Hematology

Question 1

What are the factors of the extrinsic pathway?

Answer 1

7–>X–>5–>2 (Prothrombin)–>2a (Thrombin) –>1 (Fibrinogen)–>Fibrin–>13 (Tight clot)

NB: X marks the spot for the common pathway

NB2: 13 is not measured in PTT or PT

Question 2

What are the vitamin K dependent factors?

Answer 2

10, 9, 7, 2 (1972 - it was a good year!)NB: Vitamin K is more associated with the extrinsic pathway.

Question 3

What happens if you are deficient in Protein C or Protein S?

Answer 3

You clot out of control (predisposed to major thrombosis)

Question 4

What are the factors of the intrinsic pathway?

Answer 4

TENET - Twelve, Eleven, Nine, Eight, Ten (common)Then remainder of common pathway - 5, 2, 2a, 1, Fibrin, 13

Question 5

aPTT/PTT measures coagulation in which pathway?

Answer 5

Instrinsic (PITT)

Question 6

PT measures coagulation in which pathway?

Answer 6

Extrinsic (PET)

Question 7

What is PT used for?

Answer 7

• extrinsic and common factors

* used to monitor Coumadin patients

Question 8

What happens to PT with a Vitamin K deficiency?

Answer 8

It is prolonged

Question 9

When is PTT prolonged?

Answer 9

• von Willebrand disease
• hemophilia
• lupus anticoagulant
• NB: sensitive to Heparin contamination

Question 10

What does a 1:1 mixing study tell you?

Answer 10

• if it corrects into the normal range, a factor deficiency is the likely culprit
• if it fails to correct, an inhibitor or anticoagulant is the likely suspect
• NB: 30% activity is the threshold to correct clotting times

Question 11

What is the Platelet Function Assay (PFA-100)?

Answer 11

• modern test that replaces old “bleeding time” test
• push blood through a coated filter and watch the clot formation time on the filter
• need platelets at least 100 x 109/L

Question 12

When will the Platelet Function Assay be prolonged?

Answer 12

• von Willebrand disease
• aspirin
• platelet function defects

Question 13

What does a Normal PT/PTT indciate in the presence of a bleeding disorder?

Answer 13

Factor XIII deficiencyRemember, it is not measured by PT/PTT

Question 14

What does both an abornmal PT and PTT suggest?

Answer 14

• fibrinogen deficiency/problem
• Vitamin K deficiency
• DIC
• Liver disease (PT abnormal first)

Question 15

What does an abnormal PTT with normal mixing result suggest?

Answer 15

• Hemophilia A or B
• Von Willebrand disease
• Factor XI deficiency
• Factor XII deficiency

Question 16

What might cause a fibrinogen deficiency?

Answer 16

• liver dysfunction

* DIC

Question 17

Can a reduced level of fibrinogen cause a prolonged PT, PTT or Thrombin Clot Time?

Answer 17

• Generally, no unless fibrinogen is less than 100 mg/dL

Question 18

What does Thrombin Clot Time (TT) measure?

Answer 18

Measures the time for conversion of fibriongoen to fibrinHeparin can contaminate

Question 19

What is von Willebrand disease?

Answer 19

• Caused by a deficiency or reduced functioning of von Willebrand factor
• carries and stabilizes factor VIII
• mediates platelet adhesion and aggregation

Question 20

What is the most common inherited bleeding disorder?

Answer 20

von Willebrand disease

Question 21

What is the mechanism of inheritance of von Willebrand disease?

Answer 21

Usually autosomal dominant

Question 22

What is the Rx for von Willebrand’s disease?

Answer 22

• DDAVP (Arginine vasopression) - releases stored vWf from endothelial cells
• reduced efficacy with repeated dosing (tachyphylaxis)
• Humate-P - factor VIII product that contains vWf
• Cryoprecipitate - life-threatening bleeds (infectious transmission risks)
• Aminocaproic acid - Amicar -supportive, effective for mucosal bleeding. acts by stabilizing clot. No for hematuria

Question 23

What is Hemophilia A?

Answer 23

Deficiency or lack of Factor VIII

Question 24

What is Hemophilia B?

Answer 24

Lack or deficiency of Factor IX

Question 25

How are Hemophilia A and B transmitted?

Answer 25

X-linked recessive disorders

Question 26

What are the three degrees of severity of hemophilia?

Answer 26

* Mild Hemophilia (30-40% of cases)- Factor level 6-50%/uncommon spontaneous bleeding/see sx after major trauma or surgery * Moderate hemophilia (10% cases) - factor level 1-5%/see sx after minor trauma/4-6 bleeding episodes per year * severe hemophilia (50-70%) - Factor level <1%/spontaneous bleeding occurs/2-4 x month

Question 27

What type of bleeding episode is most common in hemophila?

Answer 27

joint bleeding (60%)most common sites are knee, ankle, elbow

Question 28

What should you avoid when treating a joint bleed?

Answer 28

NSAIDS and Aspirin (you know why)

Question 29

What are the possible complications of untreated muscle bleeds?

Answer 29

* foot drop * flexed hip * volkmann's contracture (hand arm) * compartment syndrome

Question 30

What is the treatment for Hemophilia?

Answer 30

* replacement of missing factor concentrate (on demand/prophylaxis) * DDAVP/ Stimate - not for B * Antifibrionolytic agents - Amicar * Supportive measures - RICE and pain control

Question 31

What are factor inhibitors and how do you identify when they exist?  

Answer 31

* these are antibodies that develop against "foreign" infused factors in hemophilias.  They exist in 15-25% of Factor VIII pts and 1.5-3% of Factor IX pts. * median of 9-12 exposure days * consider when pt. is unresponsive to Rx * prolonged PTT after mixing 1:1 * one BU of activity causes 50% loss of Factor VIII activity

Question 32

How do you treat inhibitors in hemophilia?

Answer 32

* recombinant FVIIa - push clotting through extrinsic pathway * High-dose VIII or IX * prothrombin complex concentrates * can try to desensitize the immune system to the factor

Question 33

What is DIC?

Answer 33

* A disorder of secondary hemostasis caused by consumption of factors in the coagulation system * triggered by exposure of blood to tissue factor * present with bleeding, petechiae and purpura * causes include:  infection; major trauma; malignancy 

Question 34

What is the Rx for DIC?

Answer 34

* Most important: TREAT UNDERLYING CAUSE * hydration * RBC transfusion * if bleeding, fresh frozen plasma, cryoprecipitate, or platelets

Question 35

What are conditions that can lead to thrombosis?

Answer 35

``` Virchow's Triad * alterations in blood flow (stasis) * vascular endothelial injury * alterations in constituents of blood 50% of thrombotic events in pts with inherited thrombophilia are affiliated with additional risk factor ```

Question 36

What are the causes of inheritied thrombophilia?

Answer 36

* Factor V (Leiden) - most common inherited in causasians 3-8% * prothrombin gene mutation (G20210A) * Protein S deficiency * Protein C deficiency  * antithrombin deficiency

Question 37

What is the Rx for venous thromboembolism?

Answer 37

* LMW heparin, vondaparinaux, unfractioned IV heparin * overlap with and transition to Vitamin K antagonist * Target INR 2.5

Question 38

Who should be screened for thrombophilia?

Answer 38

* initial thrombus occuring before 40 without provoking factor * FH of 1st degree relatives with VTE * recurrent VTE * thrombosis in unusual vascular beds - liver, cerebral, mesenteric

Question 39

What are secondary hypercoagulable states?

Answer 39

* pregnancy * contraceptive use/HT * malignancy * systemic inflammation * post-operative state * immobilization * trauma

Question 40

Elevated Reticulocytes Indicate..

Answer 40

Hemoglobinopathies• RBC MembraneDefects• Enzyme deficiencies

Question 41

Decreased Recitulocytes indicate...

Answer 41

Fe deficiency• Lead poisoning• Inflammation• Bone marrow failures syndromes

Question 42

Hemolytic Anemia Signs/Sx:

Answer 42

Pallor, fatigue Jaundice, dark urine Splenomegaly, gallstones

Question 43

Hemolytic Anemia Lab Findings

Answer 43

Reticulocytosis, AnemiaElevated bilirubinElevated AST > ALTElevated LDH

Question 44

Hereditary Spherocytosis (HS) Characteristics

Answer 44

Spherocytes: smaller, loss of central pallorCongenital hemolytic anemia• Most common inherited anemia in individuals ofnorthern European descent • Autosomal Dominant Inheritance• ~1/3 are spontaneous mutationsMutations affect RBC membrane• Spectrin, ankyrin• Loss of membrane surface area relative to intracellularvolume

Question 45

Hereditary Spherocytosis Clinical Signs/Sx

Answer 45

Neonatal jaundice• First 24 hours of life• Exaggerated, prolonged physiologic nadirOutside the newborn period:• Incidental Laboratory findings• Acute aplastic event (Parvovirus B19)• Jaundice, Splenomegaly, early gallstones

Question 46

Parvovirus B19 infection Characteristics

Answer 46

• “5th Disease”• Clinical manifestations: URI/pharyngitis, rash (“slapped cheeks”), Very mild anemia• Infects RBC precursors for 7-10 days so rapid decrease in red calls daily• Dx: serology (IgM)

Question 47

Hereditary Spherocytosis Levels of Infection

Answer 47

Depends on Spectrin Content: Mild HS: 20-30% of cases, No anemia, sight Reticulocyte increase, Mild jaundice Moderate HS: 65-75% of cases, + anemia, +Reticulocytes, + Bilirubin, ± splenomegaly, Occasional transfusions Severe HS: 5% of cases, ++ anemia, ++Reticulocytes, ++ Bilirubin, Marked splenomegaly, Regular transfusions

Question 48

Hereditary Spherocytosis Lab Findings

Answer 48

AnemiaReticulocytosis*MCHC typically > 36% Wide RDW (small spheres and large reticulocytes) Often elevated bilirubin, LDH, AST>ALT*Presence of spherocytes on peripheral blood smear

Question 49

Hereditary Spherocytosis Diagnostic Test results

Answer 49

Negative Direct Antiglobulin Test (DAT/Coombs)Positive Osmotic Fragility Testing: decreased surface area means no room to swell so burst.

Question 50

Hereditary Elliptocytosis (HE) Characteristics:

Answer 50

• Elliptical, cigar shaped, erythrocytes• Normochromic, normocytic, may or may not be anemic• Defect in spectrin• African and Southeast Asian Variants: 1:100 in parts of Africa• Autosomal Dominant• Many asymptomatic: RBC lifespan decreased by only ~10%

Question 51

Hereditary Pyropoikilocytosis (HPP) Characteristics:

Answer 51

• Newborns with severe hemolytic anemia:– Anemia, jaundice– Poikilocytosis, elliptocytosis, and spherocytosis– Fragments of cells so intra & extravascular lysis• Gradually evolves into mild HE

Question 52

G6PD Deficiency Characteristics

Answer 52

Most common human genetic mutation: X-linked High prevalence re malaria protection> 400 missense Genetic mutations: A- variant most common among African descent Mediterranean variant more severeEffects of G6PD deficiency Incomplete protection against oxidative stressAcute hemolytic anemia after exposure to oxidative stress: Infections Sulfa drugs Naphthalene (moth balls) Fava beans

Question 53

G6PD Deficiency Signs/Sx:

Answer 53

Acute fatigue, jaundice, pallor,dark urine (intravascular hemolysis),+/- history of known trigger

Question 54

G6PD Deficiency Diagnostic Lab findings:

Answer 54

• Normocytic, normochromic anemia• Reticulocytosis Elevated LDH, Bilirubin** Hemoglobinuria (+ for blood, no RBCs on microscopic urine)** Blister cells, anisocytosis on blood smear**Assay G6PD activity after resolution of a hemolytic crisis

Question 55

Autoimmune Hemolytic Anemia (AIHA) characteristics:

Answer 55

Incidence: 1 - 3/100,000, children and adultsVariable clinical course: self-limited, short illness, waxing and waning, chronic illnessPrognosis typically good: Morbidity from treatment, Mortality <10%Erythrocyte autoantibodies: IgG, IgM, Complement fixationTypes: Warm vs. ColdLab Test: Direct Antiglobulin Test (Coombs test)

Question 56

Warm-Reactive AIHA characteristics:

Answer 56

IgG autoantibody mediated RBC destruction (G for Georgia = Warm)• Bind RBC surface at warmer temperatures* Extravascular hemolysis—Fc Receptors in the spleen• Occasionally fix complement leading to lysisTypes: -Idiopathic-Immunodeficiency -Secondary: EBV infection

Question 57

Direct Antiglobulin Test (DAT)AKA “Coombs Test”: How does it work?

Answer 57

Sensitized Erythrocytes+Coombs reagent (anti-IgG, anti-C3) =Visual RBC Agglutination (1+ to 4+)

Question 58

Warm-Reactive AIHA Signs/Sx:

Answer 58

• Typically rapid onset anemia• Can be life threatening• Fatigue, dyspnea, heart failure• Scleral Icterus, Jaundice, +/- dark urine (hemoglobinuria)• Splenomegaly

Question 59

Warm-Reactive AIHA Labs:

Answer 59

• Anemia and reticulocytosis• Spherocytes on peripheral blood smear• Positive DAT+ IgG, ± Complement (C3)

Question 60

Warm-Reactive AIHA

Answer 60

Transfusion will not be 100% compatible but may be necessary (Least Incompatible)Glucocorticoids: Once remission has been achieved, wean steroids SLOWLY and mimic physiologic dosing as much as possible (AM dosing)SplenectomyRituximab: Monoclonal antibody directed against CD20 on B-cell surface

Question 61

Cold Agglutinin Disease(Cold Reactive AIHA) Signs/Sx:

Answer 61

Erythrocyte agglutination upon exposure to cold• Mottled or numb fingers and toes• Acrocyanosis (blue extremities)

Question 62

Cold Agglutinin Disease(Cold Reactive AIHA) Labs:

Answer 62

• Mild anemia with reticulocytosis** Red cell agglutination on PBS made at room temperature (but not at 37 C)!** DAT (Coombs) will be positive for complement (C3) only

Question 63

Cold Agglutinin Disease(Cold Reactive AIHA) Treatment

Answer 63

Largely symptomatic--Avoid cold! Rituximab re active or relapsing symptomatic hemolysisSplenectomy and corticosteroids ineffective so avoidIf transfusion is needed—Warm the RBCs!

Question 64

DDX re Warm-Reactive AIHA vs Cold-Reactive AIHA

Answer 64

Warm-Reactive AIHA: IgG, DAT result: +IgG, ± C3 (C3 fixation Variable) Thermal reactivity 37C, RBC destruction: Spleen, Tx: Steroids, Splenectomy Cold-Reactive AIHA: IgM Thermal reactivity: 4C +C3 (C3 fixation) RBC destruction: Liver Common therapy: Avoid cold, Rituximab

Question 65

Hb/Hgb 

Answer 65

the concentration of hemoglobin: oxygen carrying proteins2 beta and 2 alpha chains.  each chain has associated heme group and each heme group has a central iron which binds oxygen.

Question 66

HCT (%)

Answer 66

Hematocrit percent (should be 3x hemoglobin)% of blood volume occupied by RBC

Question 67

what does MCV mean?

Answer 67

mean cell corpuscular volume: tells us the average volume of RBCs collected.relates to RBC size to tell if micro=<80, normo=80-100, or macrocytic >100neonates 110 normal, 70 at 1 year oldif larger, it's newer cells (macrocytic)

Question 68

MCH

Answer 68

Mean cell hemoglobin: average Hb concentration of the RBCs(when cell size change, 

Question 69

what is MCHC? 

Answer 69

Mean [Hg] per ONE Red blood cell

Question 70

What does a Reticulocyte Count mean?How do you evaluate for Anemia?

Answer 70

a direct reflection of rate of RBC productionindirect reflection of rate of RBC destruction (elevated in disorders with more destruction)(reported as % and an absolute number "ARC") Use ARC and %retic x RBC to get the whole pictureif pt has retic of 1% (normal) that's fine unless their Hg is low, then retic should be high and compensating.

Question 71

two classifications and 3 sub classifications of anemia

Answer 71

``` PATHOPHYSIOLOGIC: * decreased production * blood loss * increased destruction MORPHOLOGIC * Macrocytic * Normocytic * Microcytic ```

Question 72

What are disorders with destruction probs

Answer 72

HemoglobinopathiesRBC Membrane defectsenzyme deficiencies

Question 73

What is RBC chromicity

Answer 73

clues on [Hg] : color or RBCcentral palor: normalMCH, MCHC can give clues, but Peripheral blood smear is more important hyperchromic, normochromic, hypochromic, or polychromasia

Question 74

What diseases are connected with these shapes, and what are these RBC shapes:Target cells,echinocyteAcanthocyteSpherocyte

Answer 74

Target cells: looks like a target:  liver disease, HbC, HbD, HbE, Thalassemiaechinocyte: spiney like a sea urchin: Uremia, hypokalemia, artifactAcanthocyte: irregularly shaped RBC with thorny projection: liver disease, PK deficiencySpherocyte: sphere shaped, no central palor: HS Immune hemolytic anemia

Question 75

Microcytic Anemia causes

Answer 75

Fe deficiency anemiathalassemias (alpha & beta)Chronic disease/ inflammationPb toxicicty

Question 76

Most common anemia

Answer 76

Fe deficiency with 3% of young children in US8-10% have Fe deficiency with out anemia(pregnant women, adolescents, elderly)(if Fe deficient and small bodied, a small blood loss could push them over the edge to become anemic) 

Question 77

Etiology of Fe deficiency

Answer 77

Increased demand to make blood (infancy, adolescents, pregnant, making more rbcs) malnutrition (vegetarians, vegans, junk food diets) decreased absorption (gastrectomy, H. pylori, IBD, drugs) GI bleeds benign or malignant, GU bleeding heavy periods, blood donors drugs: NSAIDS, steroids chronic kidney disease, IBD, heart failure, obesity

Question 78

Stages of Fe depletion, what labs would you order and why

Answer 78

1) Depleted iron stores (marrow iron/serum ferratin) 2-3+2) Iron deficient erythropoiesis: Serum Fe <100ug/dl and %saturation is <303) Iron Deficient Anemia: HCT<40, RBC become microcytic and hypochromic*don't stop treatment too early, gotta build up stores! Serum Fe increases in one meal, Serum ferratin slower to build  

Question 79

What does low Fe look like with labs?

Answer 79

Low: Hg, MCV, MCH, MCHC, RBC countLow uncompensated retic countIncreased TIBC/transferin (nothing to bind them)Low ferritin (deficiency: <10-12ng/L, depletion: 12-20ng/Lnormal is 20-300ng/LInflammation can falsely elevate Ferratin even if you don't have iron stores

Question 80

Problems with Fe Tx

Answer 80

Ferous sulfate tastes horrible.Side effects include dyspepsia, constipation, nausea, abd pain, Helps to take with food... decreases absorption, but some is better than not taking it at all.Polysaccharide preparations sweeter

Question 81

Foods with high Fe

Answer 81

Liver, red meatbeans/ greensiron-fortified cereals/ grainsheme: meat, non-heme: vegetarian

Question 82

therapeutic response to Fe treatment of deficiency

Answer 82

Tx works within 3 days.  see less hypochromia, increased RDWincreased reticulocytes in 2-3 days, Hg & MCV goes up in a weekSerum iron 1-2 hrsTIBC goes down: 2-3 weeksSerum Ferritin goes up: 1-2 weeks, 3-4 to normal

Question 83

Why are they having Fe loss in the first place?  What would you look for?

Answer 83

GI Blood loss: guaiac (occult stool), if positive endoscopyUrea breath testTest Antibodies for H. pylori, anti-transglutaminase (celiac sprue if fails to respond to oral iron)C-reactive protein: inflammation? neoplasm? especially in elderlyMetro/menorrhagia: evaluate for bleeding disorder

Question 84

Normal Treatment for Fe deficiency

Answer 84

Iron Salts 100-200mg elemental Fe in 2 dosesFerrous Sulfate, Ferrous Gluconate Taken on empty stomach for best absorption, avoid coffee, tea, take with Vit C (acid helps absorption) Kids: 2-6mg/2 doses, NO MILK **continue Tx 3mths to replenish serum ferritin***

Question 85

when oral Fe is contraindicated, or another method is indicated

Answer 85

IV iron therapy : for those who can't take orally (gastrectomy, duodenal bypass, H. pylori, celiac, IBD, genetic IRIDA, or if needs to be immediate recovery (severe anemia in 2nd-3rd trimester, chronic renal disease, substitution for blood transfusion (religious reasons), chemo anemia (from ESA)contraindicated: 1st trimester of pregnancy, iron allergy (hypersensitivity rx)

Question 86

What is anemia of Chronic Disease

Answer 86

Anemia from a chronic state of inflammation (like cancer, chronic infection, lupus, RA, and other autoimmune disease, obesity, aging)that causes impaired production of RBCs

Question 87

What's the pathophysiology  Anemia of Chronic Disease that has to do with iron levels?

Answer 87

Hepsiden ( regulatory hormone made in liver, excreted to urine) tells Macrophages to keep iron inside cells, and not let it into circulation, and tells duodenal and intestinal cells not to absorb more Fe.  This is because it thinks it is being invaded, and Fe makes bacterial infections stronger.We expect higher hepsiden in Fe overload, and infection

Question 88

lab findings in  Anemia of Chronic Disease 

Answer 88

mild-moderate anemiaMCV: normal to lowRDW: normalRetic Count: lowFerritin: normal to high (even if Fe is low)

Question 89

treatment  Anemia of Chronic Disease

Answer 89

*  eradicate underlying disease if impossible,  * transfusions * IV iron * Erythropoesis Stimulating Agents * New experimental approaches targeting IL-6 activity

Question 90

What is macrocytic Anemia? what's it caused by

Answer 90

Larger RBCs Caused by B12 or Folate deficiency (DNA synthesis: mismatch between how much cytoplasm to put in cell and membrane so cells larger)Non-Megaloblastic causes: Phentoin, Bactrim, ART, Chemo, hypothyroid, liver disease, alcoholics, myelodysplasia, bone marrow failure, reticulocytosis 

Question 91

What labs do we order if we suspect Macrocytic Anemia?

Answer 91

CBC with peripheral blood smear (hyper-segmented neutrophils/neutropenia)reticulocyte count (to see if MCV 110-140 is bigger because more retics, also to see if production or destruction prob)serum cobalamin, folate, and TSHliver function test (alcoholics)measure folate/cobalamin (needed for DNA synthesis including for RBCs)

Question 92

Signs and symptoms of macrocytic anemia

Answer 92

Both for B12 and Folate deficiency, see glossitis-smooth tongue, and dyspnea with exercise, pallor, etc.For B12, neuropathies, ataxia, seizures, psychiatric probs, decreased sensations 

Question 93

what causes B12 deficiency

Answer 93

pernicious anemia: (autoimmune) disease where autoantibodies destroy gastric parietal cells which produce intrinsic factormalabsorption: IBS, chrons disease, celiac, bowel resection Hemolytic anemia, excess blood losspregnancy: when more need is happening

Question 94

Lab results for Macrocytic Anemia from B12 deficiency

Answer 94

moderate -severe anemiaelevated MCV 110-140low reticulocyte (not compensated)hypersegmented neutrophils and macroovalecytes on smearmild thrombocytopenia and/or neutropenialow serum B12, <170 (when normal or 170-210, confirm with elevated methylmalonic acid or homocystine)

Question 95

Diagnosis for Pernicious Anemia

Answer 95

Anti-intrinsic factor antibodies (100%specific, but only 70% sensitive= false neg)Anti-parietal cell antibodies (more sensitive, but less specific=false positive)Shilling test (board answer) 

Question 96

Tx for B12 deficiency

Answer 96

IM or subcutaneous injection of 100mcg B12daily x 1 wk, then weekly x 1 month, then monthly for lifeORsublingual 1mg/day for EVER(folic acid also recommended for first few mths of B12 tx)

Question 97

Response to B12 Tx for Macrocytic Anemia

Answer 97

well-being in 1-2 days, brisk retic increase in 3-4 days, and Hg in 10 days***Hypokalemia can occur during early response because increased K+ use for RBC production*** monitor neuropathies improve totally by 6 mths

Question 98

Labs for Folate Deficiency 

Answer 98

Mod-severe anemiaelevated MCVlow retichypersegmented neutrophils/macro-ovalcytes on peripheral smearmild thrombocytopenia/neutrophilsRBC folic acid levels (better than serum folate b/c reflects body stores <150 is deficient)also measure B12.  

Question 99

Tx of folate deficiency

Answer 99

daily oral folic acid 1 mgResponse is rapid wellbeing retics in 5-7 daystotal correction of hematologic abnormals in 2 mths

Question 100

Non-megaloblastic anemia causes and Tx

Answer 100

anti-retroviral drugs, antiseizure meds, chemo, bactrimhypothyroidismnon-alcoholic liver diseasechronic alcohol use: stop alcohol use, blood returns rapidly 

Question 101

Differential for Normocytic Anemia

Answer 101

+++Reticulocyteshemolytic anemia Post-hemorrhagic anemia---Reticulocytesacute hemorrhageanemia of inflammationrenal/liver diseasemarrow infiltrationmyelodysplastic syndrome

Question 102

most common causes of inherited hemoglobin disorders

Answer 102

DNA deletions or point mutations

Question 103

what is a quantitative hemoglobin disorder

Answer 103

thalassemia

Question 104

what is a qualitative hemoglobin disorder

Answer 104

hemoglobinopathy

Question 105

normal fetal hemoglobin made of?

Answer 105

2 alpha chains and 2 gamma chains

Question 106

normal adult hemoglobin made of

Answer 106

2 alpha chains and 2 beta chains

Question 107

in thalassemia what is the balance of alpha and beta chains

Answer 107

alpha thalassemia- excess betabeta thalassemia- excess alpha

Question 108

pathophysiology of thalassemia

Answer 108

excess globins precipitate and damage the RBC membrane, ineffective erythropoiesis

Question 109

outcomes of thalassemia

Answer 109

anemia, bone marrow expansion, extramedullary hematopoiesis, increased intestinal iron absorption

Question 110

Sickle cell and thalassemia protects from what disease?

Answer 110

malaria

Question 111

silent carrier in thalassemia

Answer 111

one deletion of the functional gene

Question 112

What is alpha-thalassemia trait

Answer 112

two deletions of functional genes ( cis- more common in Asian pops or trans more common in African pop)

Question 113

HbH disease

Answer 113

3 deletions of functional genes

Question 114

hydrops fetalis

Answer 114

4 deletions of functional genes- incompatible with life

Question 115

alpha thalassemia trait definition

Answer 115

reduced alpha globin chain synthesis due to 2-gene deletion- causes an excess amount of gamma globin at birth, or beta globin as an adult

Question 116

best time to identify alpha thalassemia

Answer 116

in newborns- excess gamma globin and fast band production makes it more identifiable with testing. For adults, try to track newborn screen.

Question 117

Heinz bodies

Answer 117

detects protein precipitates, denatured proteins. Test isnot commonly used due to common false negatives

Question 118

treatment for hydrop fetalis

Answer 118

if caught in utero- can do transfusion support.then stem cell transplantation to treat after birth.

Question 119

beta thalassemia

Answer 119

beta-0- producing no beta globinbeta+ produces little beta globin

Question 120

B-thalassemia major

Answer 120

homozygoussevere anemiarequires life-long RBC transfusion

Question 121

B-thalassemia intermedia

Answer 121

mild anemiaoccasional transfusions required

Question 122

B-thalassemia trait

Answer 122

heterozygousasymptomaticconfused with iron deficiency- suspect if patient does not respond to iron therapy

Question 123

phenotypes for b thalassemiamild moderate severe

Answer 123

B+ B+Bo B+Bo Bo

Question 124

beta thalassemia trait under the microscope

Answer 124

unbalanced a:b chainselevated A2elevated Hb Fmicrocyctic anemia

Question 125

treatment of beta thalassemia intermedia

Answer 125

hydroxyurea- increase in fetal hemoglobin production.watch iron absorption- can be increased

Question 126

outcomes of thalassemia major/erythropoiesis

Answer 126

expansion of marrow cavities, extramedullary hematopoiesis, splenic destruction of RBC, hypersplenism, growth failure

Question 127

treatments for thalassemia major

Answer 127

hypertransfusion every 2-4 weekssplenectomy (in non-transfusion dependent)stem cell transplant to curetreat iron overload with chelation

Question 128

iron overload cause

Answer 128

RBC trasfusionsno body mechanism to get rid of excess ironintake of 1 gm/month in chronic transfusion patients

Question 129

iron overload complications

Answer 129

pericarditis, arrhythmias, cardia failurefibrosis, cirrhosis, hepatic failure, cancerdiabeter, growth failure, infertility

Question 130

how to test for iron overload

Answer 130

serum ferritin, liver biopsy, MRI

Question 131

treatment of iron overload

Answer 131

chelation (deferasirox or deferoxamine)- start treatment early to prevent iron overload rather than trying to reduce amount of iron in the body if possible. phlebotomy- regularly remove blood to reduce amount of iron in the blood

Question 132

sickle cell disease definition

Answer 132

group of blood disorders containing HbS

Question 133

is sickle cell dominant or recessive?

Answer 133

autosomal recessive

Question 134

sickle cell pathophysiology

Answer 134

single point mutation on the beta chainAdenine to Thymine at position 6 of the beta globin.changes RBC shape (stiff due to deoxygenation)blood flow obstruction leads to ischemia

Question 135

epidemiology of sickle cell

Answer 135

in US- 8%1/400 births3,000,000 with trait and 100,000 with diseaseglobally more than 400,000 births per year

Question 136

how does sickle cell trait protect against malaria

Answer 136

lower transmissionreduced parasitemiadecreased mortality

Question 137

how is sickle cell diagnosed in the US?

Answer 137

all newborns tested with dried blood spotsmost common disease found by newborn screening

Question 138

newborn screening resultsFA

Answer 138

normal

Question 139

newborn screening resultsFAS

Answer 139

sickle cell trait

Question 140

newborn screening resultsFS

Answer 140

sickle cell anemia

Question 141

newborn screening resultsFSA

Answer 141

sickle B+ thalassemia

Question 142

newborn screening resultsF

Answer 142

thalassemia major

Question 143

newborn screening resultsFA

Answer 143

fast band- alpha thalassemia trait

Question 144

risks for sickle cell trait

Answer 144

hematuriarenal medullary carcinomasudden death during prolonged, strenuous physical activity

Question 145

hyphema

Answer 145

increased occular pressure, loss of visionthose with sickle cell need referral to a specialist to prevent loss of vision

Question 146

clinical manifestations of sickle cell disease

Answer 146

functional asplenia, pneumococcal infectionhemolysis (partially compensated- increased reticulocytes)acute vaso-occlusive events (painful)organ damage

Question 147

most common cause of death for sickle cell disease patients

Answer 147

organ damage- spleen, kidneys, lung, brain, eyes, hips

Question 148

how to prevent sepsis in newborns with sickle cell disease

Answer 148

prophylactic therapy with oral penicillin by 3 months

Question 149

penicillin regimen for sepsis prophylaxis with sickle cell

Answer 149

125mg BID- until age 3250mg BID- until age 5usually has to be refridgerated and picked up every 2 weeks from the pharmacy- difficult to get patients to be compliant

Question 150

why stop prophylaxis at age 5

Answer 150

immunizations with HiB, prevnar, pneumovax, meningovax, no evidence of sepsis prevention beyond age 5

Question 151

what temperature is considered a medical emergency for patients with sickle cell disease?

Answer 151

38.5 or greater

Question 152

what to order in a SCD patient with fever

Answer 152

labs- blood cultures, cbc with retic, UAchest x-raytype and cross-match if increased pallor or splenomegaly or resp/neuro symptoms

Question 153

treatment of sepsis in SCD patients

Answer 153

IV broad spectrum antibiotics

Question 154

most common manifestation of SCD

Answer 154

acute vaso-occlusive pain- occurs as early as 6 months

Question 155

painful events with SCD

Answer 155

sudden onset in extremities, back , and sternum/ribsdactylitis/ hand-foot syndrome

Question 156

treatment of painful events

Answer 156

NSAIDs and opioidsfluids and hydrationearly pain control

Question 157

warning signs with SCD pain

Answer 157

respiratory distress, chest pain- acute chest syndromefever- infectionweakness- strokelethargy- splenic sequestrationabdominal pain/jaundice- cholelithiasis

Question 158

symptoms of acute splenic sequestation

Answer 158

tender splenomegaly, worsened anemia, increased retics, platelets less than 150,000, LUQ pain, SOB, vomiting

Question 159

typical age of onset of acute splenic sequestation

Answer 159

6 months to 3 years

Question 160

treatment of splenic sequestration

Answer 160

RBC transfusionscareful not to overshoot

Question 161

recurrence rate of splenic sequestration

Answer 161

50%

Question 162

acute chest syndrome signs/symptoms

Answer 162

+/-fever, dyspnea, pain, hypoxia, increased WBC, pleural effusion, fat embolism, atelectasis, sickling and intra-pulmonary sequestration

Question 163

acute chest syndrome treatment

Answer 163

admissionantimicrobial treatment- ceftriaxone, azithromycin, levofloxacinO2bronchodilatorsIV fluidstransfusions

Question 164

avascular necrosis (AVN)

Answer 164

osteonecrosis in limited circulation areasfemoral head most common

Question 165

AVN treatment

Answer 165

NSAIDs, PT, hip replacement

Question 166

SCD and renal manifestations

Answer 166

hyposthenuriarenal infarctionprogression to renal failure and proteinuria

Question 167

priapism

Answer 167

prolonged, painful erection40% of men with SCDblood flow is obstructed

Question 168

priapism treatment

Answer 168

analgesics and hydrationaspiration if greater than 4 hoursvasodilators can prevent attacks, but do not treat

Question 169

sickle retinopathy

Answer 169

vitreal hemorrhage and retinal detachmentcauses vision lossseen in HbSC > HbSS

Question 170

leg ulcers and SCD

Answer 170

5-10% of people > age 10 have healing problems

Question 171

incidence of stroke with SCD

Answer 171

11% by age 20 24% by age 45

Question 172

stroke symptoms

Answer 172

hemiparesis (weakness as opposed to pain)visual/language dysfunctionseizuresheadachesaltered sensationaltered mental status

Question 173

treatment of stroke with SCD

Answer 173

transfusion immediatelyCTIV fluidsMRI (can wait a few days)

Question 174

stroke recurrence with SCD

Answer 174

47-93% without treatmenttreat with blood transfusions every 3-4 weeks10-20% still experience recurrence with treatment

Question 175

stroke prevention in SCD

Answer 175

transcranial doppler (TCD) ultrasonography screeningif > 200 cm/sec- abnormal, requires transfusions

Question 176

indications for simple transfusions

Answer 176

splenic sequestrationtransient aplastic crisisanaemiaacute chest syndromepre-ops

Question 177

indications for chronic transfusions

Answer 177

clinical strokeabnormal TCD (>200 cm/sec)multisystem organ failure

Question 178

What are the signs and symptoms of platelet bleeding (i.e., primary hemostasis)?

Answer 178

* mucouos membrane bleeding * epistaxis * prolonged oozing from minor wounds * brusing * menorrhagia * abnormal intraoperative bleeding

Question 179

What is thrombocytopenia?

Answer 179

low platelet counts 

Question 180

What is a failure of secondary hemostasis?

Answer 180

* bleeding from large vessels * subcutaneous hematomas * hemarthroses * intramuscular hematomas This is a more "coagulation factor deficiency" picture

Question 181

What are some signs of congenital thrombocytopenia?

Answer 181

* umbilical cord stump bleeding | * bleeding after circumcision that won't stop

Question 182

When you see bruising on a person with suspected thrombocytopenia, what distinguishes it from ordinary bruising?

Answer 182

* indurated (hardened) * found in locations where simple trauma bruises are unlikely (e.g, abdomen) * sometimes accompanied by petechiae

Question 183

What are the etiologies of thrombocytopenia?  

Answer 183

``` Poor platelet production  * bone marrow failure * infections * drugs (sulfa) * nutritional disorders (B12, folate) * inherited Increased destruction of platelets * splenomegaly * non-immune mediated (DIC, HUS) * immune-mediated platelet destruction ```

Question 184

What do normal platelets look like?

Answer 184

* purple color * small (much smaller than RBC) * little fuzzy granulations * count and multiply in a field by 10k to get total

Question 185

What is immune thrombocytopenia (ITP)?

Answer 185

immune system mediated destruction of platelets.

Question 186

What do the practice guidelines from ASH 2011 say about treatment of ITP?

Answer 186

* mild symptoms (i.e., no "wet" bleeding) can be treated with observation alone * First line treatment includes corticosteriods, IVIG or anti-D immunoglobin * Adults:  consider for platelet less than 30x109/L try corticosteriods first, IVIG if rapid or IVIG/Anti-D if you can't do steroids * Kids:  probaby will use IVIG/Anti-D FIRST as corticosteroids can MASK underlying Leukemia and hide the diagnsosis from you.

Question 187

What are the pratical considerations in treating ITP?

Answer 187

* no bright line rules for platelet levels Individualize decisions based upon: * patient age (little people are dangerous) * clincal symptoms * platelets * parent/your concern * access to medical care (ER) * Patients at high risk of significant bleeding should be treated and monitored

Question 188

What are the symptoms of TTP?

Answer 188

* Note: Rare (congenital < acquired) * "Classic" Pentad:  thrombocytopenia; microangiopathic hemolytic anema; fluctuating neurological signs; renal impairment; fever. * Most patients present WITHOUT the full pentad

Question 189

How do you diagnose TTP?

Answer 189

* ADAMTS13 below normal range is definitive  * Normal (<5-10%) * Positive ADAMTS13 inhibitor = usually acquired * Negative ADAMTS13 inhibitor = indicates congenital TTP (Upshaw-Schulman Syndrome)

Question 190

What does ADAMTS-13 Do? 

Answer 190

* It is an enzyme that cleaves von Willebrand multimers * It is essential to prevent excessive clot formation low ADAMTS-13 causes multimers to form webs in vessels * RBC's get sheared causing shistocytes * platelets get caught in the webs, reducing their numbers

Question 191

What is Hemolytic Uremic Syndrome (HUS)?

Answer 191

A disease that causes microangiopathic hemolytic anemia; thrombocytopenia; and renal impairment (predominant)

Question 192

* What is the most common cuase of HUS?

Answer 192

* shiga-toxin producing E. Coli (STEC) absence of this classified as atypical (aHUS) * ​leads to uncontrolled activation of the complement system

Question 193

What genetic mutation is commonly seen in patients that acquire aHUS?

Answer 193

* 60% have mutation in genes that protect us from complement activation (Factor H - CFH) and I (CFI)

Question 194

Who is most likely to get HUS?

Answer 194

* Manifests in all ages (note that this is NOT what PPP says) * especially in adolescents and adults

Question 195

What is the threatment for HUS?

Answer 195

* Primarily supportive * transfusions may be required for anemia * platelet transfusion only resereved for severe bleeding * dialysis as need for renal * watch fluid load

Question 196

What is the prognosis for people with HUS?

Answer 196

* Generally favorable - renal recovery  | * hematologic manifestations typically resolve 1-2 weeks

Question 197

What is the treatment for aHUS?

Answer 197

* Plasma exchange Eculizamab - MAb to complement factor C5 * blocks complement activation

Question 198

What is the prognosis for aHUS?

Answer 198

Compared with HUS, prognosis is much poorer.  Chronic relapsing course is common and outcome overall is poorer.

Question 199

What is the etiology of immune thrombocytopenia?

Answer 199

may present 1-2 weeks after an immune trigger * viral illness * live virus immunization * allergic rxn * can be presenting symptom of broader immune disease (HIV, SLE) * can be brought on by specific infections - HepC and H. Pylori * lymphoid malignancy

Question 200

What is the pathophysiology of congenital TTP?

Answer 200

Gene that makes ADAMST13 is mutated, resulting in lowered production of the enzyme

Question 201

What is the pathophysiology of immune-mediated TTP?

Answer 201

* B-cell mediated autoantibody production against von Willebrand cleaving protease (ADAMS13)

Question 202

How do you treat TTP?

Answer 202

* early diagnosis crucial - DO NOT MISS plasmapheresis is the main treatment * replaces ADAMST13 and reduces any antibody * in acute phase, 1.5 L * maintains congenital 3-4 weeks * steroids for immune-mediated TTP * Platelet transfusions contraindicated unelss bleeding is life-threatening 

Question 203

What is the second-line treatment for TTP if plasmaphoresis fails?

Answer 203

Immune mediated: * splenectomy * corticosteriods * rituximab (MAb -  95% of case reports)

Question 204

What is secondary hemostasis (coagulative factor bleeding)?

Answer 204

* bleeding from large vessels * subcutaneous hematomoas * hemarthroses - bleeding into joint spaces * intramuscular hematomas

Question 205

What is pseudothrombocytopenia?

Answer 205

Where platelet counts are artificially reduced on CBC/peripheral smears because the platelets have all aggregated into clumps (improper handling of sample).

Question 206

What is the epidemiology of ITP?

Answer 206

* all genders, races and ages (used to be thought of as a young woman's disease - not true) * 10-40 per 100k prevalence

Question 207

What are the categories of ITP?

Answer 207

* Acute:  within three months of diagnosis * persistent: 3-12 months from diagnosis (80% of ITP in childhood will spontaneously resolve in 6-12 months) * chronic ITP:  lasting more than 12 months (80% of adult cases go on to be chronic)

Question 208

What is the pathophysiology of ITP?

Answer 208

* loss of self-tolerance autoantibodies (IgG) against platelet antigens * platelet gycoproteins (IIb/IIIa and Ib/IX) * cellular mechanisms * platelets get coated with autoantibodies * get destroyed (retiuloendothelial system) - bind to Fc receptros on macrophages, then get eaten * decreased production

Question 209

What is the key point to know about the pathophysiology of ITP?

Answer 209

Polyclonal autoantibodies may inhibit platelet production by inhibiting megakaryocyte maturation  

Question 210

What is the clinical presentation of ITP?

Answer 210

bleeding  mucocutaneous bleeding  * wet -oral bullae, epistaxis, menorrhagia, gingival and GI bleeding  * dry - bruising and petechiae

Question 211

What does the CBC/PBS of ITP look like?

Answer 211

* thrombocytopenia <100 x 109/L * normal platelet granulation occasional large platelets * normal WBC # and diff * normal RBC # and appearance (unless active bleeding) * no evidence of hemolysis

Question 212

How do you diagnose ITP?

Answer 212

* Diagnosis of exclusion * no splenomegaly, lymphadenopathy * other CBC indices normal

Question 213

ITP in adults - what additional tests should be done for new onset?

Answer 213

Test for HIV and HCV broader immune dysfunction DAT - prior to anti-D quantiative immunoglobins 

Question 214

What are the treatments for ITP?

Answer 214

* IVIg * anti-D * corticosteroids  

Question 215

What is IVIG treatment? 

Answer 215

* derived from human plasma * blocks Fc receptors on macrophages from binding with autoantibody coated platelets adverse effects include nausea, vomiting, headache (also sx of head bleed), fever * aceptic meningitis (rare) * alloimmune hemolysis (rare) * infection transmission exceedingly rare * anaphylaxis in IgA deficient pt. 

Question 216

What are the pros and cons of IVIG?

Answer 216

``` Pros * lack of long term side effects * efficacious in 1-2 doses (lasts 2-4 wks) Cons * several hour IV infusion * very $$$ * difficult side effects * derived from pooled human plasma ```

Question 217

What is Anti-D immunoglobin therapy?

Answer 217

* polyclonal Ab derived from human Ig * Rh(D) antigen positive, non-splenectomized pts can receive  * preferential destruction of antibody-coated RBCs, spares the platelets (sacrifices RBC) * adverse events:  fever, chills, nausea, vomiting (give premedications)

Question 218

What are the pros and cons of Anti-D therapy?

Answer 218

Pros * short IV infusion * efficacious * fewer donors per dose than IVIG Cons * side effect of hemolysis * really small chance <0.05% massive intravascular hemolysis  * no no if baseline hemolysis (DAT/Coombs BEFORE starting therapy) * have to avoid in anemia, acute illness, abormal renal function, patients > 65

Question 219

What is the biggest risk to avoid in ITP?

Answer 219

Intracranial hemorrhage * rare <1%, but deadly * patients with lowest platelet counts at highest risk <20k * life-threatening spontaneous bleeding at very low counts * eliminate anti-platelet medications and high risk activity

Question 220

How is corticosteriod therapy used in treating ITP?

Answer 220

* 1st line in adult ITP patients * masks leukemia, so you need to avoid as first line in children * predinose, methylprednisone, dexamethasone * less rapid platelet rise than in other therapies * get massive weight gain

Question 221

What are the urgent treatment options for ITP?

Answer 221

platelet infusions/drip emergency splenectomy IV methylprednismoe IVIG recombinant FVIIa (extrinsic pathway that will push toward clotting)

Question 222

What is the treatment for chronic ITP?

Answer 222

splenectomy * effective 75% * but many post-splenectomy complications  * Rituximab (specifically against B cells) * thrombopoietin receptor agonists - binds to megakaryocytes and stimulates platelet production * Azathioprine - immunosuppressant

Question 223

ITP vs TTP - How do you tell them apart?

Answer 223

Patient Population:Young child - suspect ITP over TTP (note congenital TTP)Clinical Symptoms:  ITP often has no symptoms other than mucocutaneous bleeding. NO splenomegaly and no hemolytic anemia or neuro symptoms.  Diagnosis:  ITP is isolated thrombocytopenia, but TTP has hemolytic anemia, increased indirect bilirubin, decreased haptoglobin 

Question 224

What is unilineage bone marrow failure

Answer 224

one cytopenia:anemia (RBC) ORneutropenia (WBC) ORthrombocytopenia (platelets)

Question 225

What is multilineage bone marrow failure

Answer 225

multiple cytopenias:anemia (RBC) ANDneutropenia (WBC) ANDthrombocytopenia (platelets)AKA pancytopenia

Question 226

define pancytopenia

Answer 226

all three cell lines (RBCs, WBCs, and platelets) are decreased

Question 227

What are RBCs, WBC, and platelets made from

Answer 227

hematopoietic stem cells in the bone marrow

Question 228

Define hematopoiesis

Answer 228

process of making blood cells

Question 229

Define erythropoiesis

Answer 229

making erythrocytes

Question 230

Define myelopoiesis

Answer 230

making neutrophils

Question 231

Define thrombopoiesis

Answer 231

making platelets

Question 232

Define bone marrow failure (BMF)

Answer 232

refers to peripheral blood cytopenias resulting from decreased or absent blood cell production in the bone marrow

Question 233

Is bone marrow failure (BMF) acquired or inherited (genetics)

Answer 233

bothVERY important to distinguish between the two

Question 234

Classifications of bone marrow failure (BMF)

Answer 234

severe: bone marrow with less than or equal to 25% cellularity AND meets at lest two criteria of cytopenias (ANC less than 500, platelets less than 20K, or ARC less than 40K)moderatemild

Question 235

ANCARC

Answer 235

absolute neutrophil countabsolute retic count

Question 236

Clinical manifestations of bone marrow failure (BMF)

Answer 236

as per their cytopeniasie) symptomatic anemia or bleeding or...etc)

Question 237

Diagnosis of bone marrow failure (BMF)

Answer 237

examination of bone marrow so do a bone marrow biopsyunexplained inc or dec in blood cell countsunexplained inc or dec in abnormal cells

Question 238

Difference between BMF and Aplastic Anemia (AA)

Answer 238

see picture

Question 239

Diff Dx for hematopoietic stem cell (HSC) injury

Answer 239

aplastic anemia or bone marrow failure:idiopathicimmune mediateddue to drugs, toxin, virusesinherited BMF syndorme (fanconi anemia or dyskeratosis congenita)

Question 240

Acquired AA/BMF

Answer 240

idiopathic (80% of acquired AA/BMF)post-hepatitisdrugstoxinsinfection

Question 241

Congenital AA/BMF

Answer 241

Falconi AnemiaDyskeratosis CongenitaDiamond Blackfan Anemia

Question 242

Clinical presentation of AA/BMF

Answer 242

sign and symptoms of:anemia (fatigue, pallor)thrombocytopenia (bruising, bleeding)leukopenia/neutropenia (fever, signs/symptoms of severe infection)

Question 243

Diagnostic tests

Answer 243

CBC with diffbone marrow aspirate and biopsy

Question 244

Other diagnostic tests for acquired AA/BMF

Answer 244

viral studies (parvovirus B19)liver panelvit B12ANA profile (antinuclear antibody: screens for Lupus)PNH (paroxysmal nocturnal hemoglobinuria) by flow cytometry

Question 245

Other diagnostic tests for congenital AA/BMF

Answer 245

elevated Hgb Felevated MCVchromosome breakage analysis*telomere length testing*genetic panel

Question 246

Treatment for AA/BMF

Answer 246

depends on underlying etiology

Question 247

pathophysiology of acquired idiopathic AA

Answer 247

not sure, but maybe immune mediated destruction of hematopoietic stem cells (HSC)

Question 248

diagnostic test for acquired idiopathic AA

Answer 248

no confirmatory testrule out genetic/congential causes

Question 249

is acquired idiopathic AA life threatening

Answer 249

yes, requires urgent evaluations and care as patients are at high risk for serious bacterial infection

Question 250

treatment of acquired idiopathic AA

Answer 250

Best/1st choice: hematopoietic stem cell (HSC) transplant2nd choice: immunosuppressive therapy (combo of antithymocyte globulin (ATG) and cyclosporine (CSA): unclear why works but they are lymphocytotoxic so they may decrease immune mediated destruction of HSC) (about 1/3 relapse)also: supportive care with blood transfusions util definitive therapy

Question 251

treatment of acquired post-hepatits AA

Answer 251

similar to acquired idiopathic AA

Question 252

treatment of acquired AA due to infection

Answer 252

similar to acquired idiopathic AA

Question 253

treatment of acquired AA due to drugs

Answer 253

remove offending agent

Question 254

treatment of acquired AA due to toxins

Answer 254

remove offending agent

Question 255

another name for congenital/inherited/genetic AA

Answer 255

inherited bone marrow failure syndrome (IBMFS)

Question 256

the three IBMFS

Answer 256

Falcon AnemiaDyskeratosis CongentiaDiamond Blackfan Anemai

Question 257

why is it important to rule out IBMFS before looking at acquired AA causes for patients with AA prior to initiation of therapy (another way to ask this question: why is it important to distinguish if AA is acquired or congenital

Answer 257

IBMFS will not respond to immunosuppressive therapy (have exposed them to drugs that could have nasty side effects and have delayed definitive Dx)other family members may be affected (this is important info if matched related bone marrow transplant is planned)

Question 258

Common phenotypes of IBMFS

Answer 258

poor growthendocrinopathiesanatomical abnormalities of the limbs/digits (i.e. thumbs)anatomical abnormalities of genitourinary tractanatomical abnormalities of heart

Question 259

Persons with IBMFS are predisposed to develop what

Answer 259

leukemia or other cancers

Question 260

diagnosis of IBMFS

Answer 260

genetic testing

Question 261

treatment of IBMFS

Answer 261

HSC transplant is curative but not always indicated for IBMFS

Question 262

define falconi anemia (FA)

Answer 262

mostly autosomal recessive disorder characterized by PROGRESSIVE BMF leading to pancytopenia (often starts with isolated thrombocytopenia and/or macrocytosis)

Question 263

common congenital abnormalities of falconi anemia (FA)

Answer 263

abnormal skin pigment (cafe au lait spot), short stature, skeletal abnormalities (microophthalmia: small eyes), upper limb abnormalities (thumbs), and reproductive organ abnormalities (25% may have no anatomical abnormalities)

Question 264

when are hematologic abnormalities noticed in Falconi Anemia (FA)

Answer 264

median age 7

Question 265

diagnostic test for Fanconi Anemia (FA)

Answer 265

chromosome breakage: increased chromosome breakage when exposed to DNA cross linking agents

Question 266

treatment of Fanconi Anemia (FA)

Answer 266

HSC transplantsupportive blood transfusions until HSCT

Question 267

prognosis of Fanconi Anemia (FA)

Answer 267

800-1000x higher risk of developing cancerinc risk of myelodysplastic syndrome (MDS) and progression to acute myeloid leukemia (AML)requires continued monitoring for development of endocrinopathies, cancer surveillance, and anatomic abnormalities

Question 268

characteristics of Dyskeratosis Congenita

Answer 268

BMF (may present early on with mild cytopenia, most often thrombocytopenia)high incidence of cancerlung and liver fibrosis

Question 269

what are those with Dyskeratosis Congenita at risk for

Answer 269

MDSleukemiahead/neck cancer

Question 270

what percent of those with Dyskeratosis Congentia develop BMF by age 30

Answer 270

90%

Question 271

Clinical presentation of Dyskeratosis Congentia

Answer 271

leukoplakia (oral)hypo/hyper-pigmentation (reticulate)nail dystrophycan show all together as classic mucocutaneous triad

Question 272

Common family Hx of Dyskeratosis Congentia

Answer 272

MDSearly graying of hairnail abnormalitieslung fibrosis

Question 273

Pathogenesis of Dyskeratosis Congenita

Answer 273

mutations in genes encoding for factors implicated in telomere function

Question 274

diagnostic test for Dyskeratosis Congenita

Answer 274

test for telomere length (will be very short for age)

Question 275

define Diamond Blackfan Anemia (DBA)

Answer 275

genetically and clinically heterogeneous due to mutations in the ribosomal subunit, bone marrow will have paucity of erythroid precursors but normal myeloid precursors and megakaryocytic

Question 276

Presentation of Diamond Blackfan Anemia (DBA)

Answer 276

isolated macroytic anemia within first year of life, generally rest of CBC looks normal

Question 277

characteristics of Diamond Blackfan Anemia (DBA)

Answer 277

skeletal abnormalities (thumb)renal issuescraniofacial or cardiac abnormalitiesshort stature

Question 278

diagnosis of Diamond Blackfan Anemia

Answer 278

RBC have inc activity of adenosine deaminase (eADA)

Question 279

what are patients with Diamond Blackfan Anemia at risk for

Answer 279

malignancies

Question 280

treatment of Diamond Blackfan Anemia

Answer 280

supportive care with RBC transfusionsanemia may respond to steroid therapyHSC transplant if indicated

Question 281

what is the only curative option for congenital/inherited BMF

Answer 281

HSC transplant

Question 282

what are your options to treat acquired BMF

Answer 282

HSC transplantimmune suppressive therapy

Question 283

HLA matching best source

Answer 283

MRD (matched related donor)usually sibling

Question 284

other sources for HLA matching

Answer 284

MUD (matched unrelated donor)haploidentical (50% match of related donor so usually parent: not the best outcomes: in emergency situations)

Question 285

complications of HSC transplant

Answer 285

graft rejection (original disease returns because recipients immune system attacked and killed donated stem cells)graft vs host disease (when donor stem cells attack the recipients native tissues)above increased with mismatching between donor and recipient

Question 286

complications of HSC transplant if use autologous source (from donor)

Answer 286

no complications except that there is a risk of same disease returning

Question 287

define neutropenia

Answer 287

absolute dec in number of circulating neutrophils so dec ANC (absolute neutrophil count)

Question 288

what is the lower limit of ANC

Answer 288

1500

Question 289

neutropenia classifications

Answer 289

mild 1000-1500moderate 500-1000severe less than 500

Question 290

etiology of neutropenia

Answer 290

defects in myelopoiesis, drugs, infections, autoantibodies

Question 291

what does a neutrophil do

Answer 291

primary cell in immune response to pyogenic (pus) organisms and predominate cell in acute inflammatory infiltrates: so they are the big guns

Question 292

what does neutropenia inc your susceptibility to

Answer 292

bacterial and fungal infectionsskin and oral cavity most commonly affectedsepsis is a common complication (morbidity and mortality)signs and symptoms may be altered with neutropenic patient: infection may not look normal because don't have and WBCs to fight it so no pus forming no inflammation maybe...

Question 293

can you have normal WBC and still have neutropenia

Answer 293

yes so look at differential

Question 294

other names for neutrophils

Answer 294

granulocytes (GRAN%)segmented neutrophils (SEG%)

Question 295

what are "bands" or banded neutrophils

Answer 295

less mature neutrophilsmature neutrophils are segmentedbands can be listed may or may not be listed separately in differentiated CBC

Question 296

gene mutations of severe congenital neutropenia (SCN)

Answer 296

autosomal dominant (ELA2 gene) orrecessive disorder (HAX1 gene)

Question 297

characteristics/clinical presentation of severe congenital neutropenia (SCN)

Answer 297

ANC < 200 from birthrecurrent fevers and infections from early infancy

Question 298

treatment of severe congenital neutropenia (SCN)

Answer 298

as soon as possible: start granulocyte colony stimulating factor (G-CSF): given as a shotfever precautionsappropriate oral/hand hygieneannual surveillance of marrowmanaged by specialist

Question 299

define cyclic neutropenia

Answer 299

regular, periodic oscillations in ANCevery 21 days or so (period for your neutrophils!)classically, monocyte count inc with dec ANC

Question 300

gene mutation of cyclic neutropenia

Answer 300

autosomal dominant inheritance (ELA2 mutation)

Question 301

diagnosis of cyclic neutropenia

Answer 301

identifying cycle or genetic testing

Question 302

can cyclic neutropenia present later in life

Answer 302

yes, with Hx of recurrent mouth sores and fever

Question 303

treatment of cyclic neutropenia

Answer 303

granulocyte colony stimulating factor (G-CSF)managed by specialist

Question 304

characteristics of autoimmune neutropenia (AIN)

Answer 304

isolated neutropenia: no other underlying condition causing neutropenia: immune system attacking neutrophils

Question 305

who normally gets autoimmune neutropenia (AIN)

Answer 305

young kids mostly: self resolving condition

Question 306

clue it may be autoimmune neutropenia (AIN)

Answer 306

neutropenia is out of proportion to infectious Hx ie) ANC < 200 but otherwise healthy kid

Question 307

diagnosis of autoimmune neutropenia (AIN)

Answer 307

anti-neutrophil antibody is helpful but not always diagnosticfollowed by specialist to rule out other causes of neutropenia

Question 308

treatment of autoimmune neutropenia (AIN)

Answer 308

can be self resolvingrarely use G-CSFfollows fever precautions

Question 309

what are causes of secondary autoimmune neutropenia (AIN)

Answer 309

broader autoimmune disorders (i.e.: Lupus or Sjogren's)infectionmedications (hydralazine or procainamide)

Question 310

ethnic neutropenia

Answer 310

benign mild-moderate neutropeniamostly in Africans, Jewish, and Arab poplnotherwise normal leukocytes/bone marrowNO Hx or RISK of recurrent infectionsdoes NOT require specialist care

Question 311

other causes of neturopenia

Answer 311

acquired or inherited BMFinfectiondrugimmune dysfunctionneonatal alloimmune neutropeniametabolic disordersnutritional deficiencies (vit B12 or folate)marrow infiltration (tumors)

Question 312

is severe neutropenia in an ill or febrile patient an emergency

Answer 312

yes

Question 313

can neutropenia (even severe) be observed initially in an otherwise healthy person

Answer 313

yes

Question 314

diagnostics for neutropenia

Answer 314

blood culturesCBC with differentialHx and physical

Question 315

what are the other granulocytes besides neutrophils

Answer 315

basophils and eosinophils

Question 316

results of dec absolute eosinophil count so less than 500

Answer 316

allergyasthmaparasitic infectionsmalignanciesrheumatologic disordersimmunodeficiencieshypereosinophilic syndrome

Question 317

results of basophilia

Answer 317

hypersensitivity reactionsanaphylaxisinfectionschronic myelogenous leukemia (CML)

Question 318

agranulocytes (other leukocytes)

Answer 318

lymphocytes and monocytes

Question 319

what are lymphocytes

Answer 319

T cellsB cellsNK cellsNKT cellsprimary cell of specific immune recognitionmemory aspectdifferentiate between self and non-self

Question 320

disorders/diseases of lymphocytes

Answer 320

lymphocytosis (infection especially viral and leukemias)lymphopenia (rheumatologic diseases)

Question 321

what are monocytes

Answer 321

have multiple functions including phagocytosis and antigen presentation

Question 322

disorders/diseases of lymphocytes

Answer 322

monocytosis: infections like SBE or TBmalignanciesrheumatologic diseasesSCN

Question 323

A diagnosis of cancer must be based upon....

Answer 323

Pathology: usuaully based upon a biopsy obtained EARLY in the evaluation.

Question 324

What are the basics of cytology?

Answer 324

Cytology: cellular morphology▪ Aspiration of tumor (fine needle aspiration)▪ Removal and analysis of abnormal fluid (eg: pleuralfluid, ascites)▪ Review and analysis of normal fluid (e.g. CSF)▪ Washings/lavage with saline (e.g., bladder, lung)

Question 325

What are the pros and cons of cytology?

Answer 325

* Advantages: Less invasive; may distinguish malignancy vs. benign disease▪ Disadvantage: CELLULAR samples only (not tissue), so may limit further classification

Question 326

What are the basics of pathologic sampling?

Answer 326

Pathology: tissue morphology* core needle biopsy* surgical biopsy* excisional biopsy

Question 327

What are the pros and cons of pathologic sampling?

Answer 327

Pros: TISSUE collection allows for further classification may be determined▪ Determination of invasiveness▪ Evaluation of malignant tissue in relationship tonormal tissueCons: more invasive

Question 328

Name the six types of neoplasm

Answer 328

CarcinomaMelanomaLymphomaSarcomaGerm CellCNS Tumors

Question 329

Name the 7 types of Carcinoma

Answer 329

Adenocarcinoma (most common)Squamous Cell (most common)NeuroendocrineHepatocellularThyroidRenal CellOther

Question 330

What 3 things do you consider when trying to find out if the cancer is primary or metastatic?

Answer 330

▪ Clinical presentation▪ Location and number of tumor(s)▪ Pattern of metastatic spread

Question 331

What 3 factors might you consider when deciding what/where to biopsy?

Answer 331

* Most accessible site▪ Site most likely to yield diagnostic results▪ Site most likely to influence treatment

Question 332

What is cancer staging?

Answer 332

Determining:*HOW MUCH cancer is in the body*WHERE the cancer is located.Describes SEVERITY of the cancer based on: *Characteristics of the primary tumor*Extent of the SPREAD around the body.

Question 333

Why do cancer staging?

Answer 333

▪ Indication of PROGNOSIS▪ Establish the best TREATMENT PLAN ▪ Evaluate EFFECTIVENESS of treatment▪ COMMUNICATE “the same language” to other clinicians ▪ Provide standardization for valid RESEARCH

Question 334

What are the three parameters of Clinical Staging?

Answer 334

T =Tumor: The extent of the primary tumorN =Nodes: The absence or presence and extent of REGIONAL lymph node metastasisM =Mets: The absence or presence of distant METASTASIS

Question 335

Tumor (T) Stage: Which types of cancer are staged by SIZE and which are staged by DEPTH of penetration?

Answer 335

Size: Lung, Breast, Ovarian, ProstateDepth: Bowel, Bladder, Melanoma

Question 336

Nodal (N) Stage: What do you consider when assigning the nodal stage?

Answer 336

Based on number and location of regional nodes (distant node is metastasis via hematologic spread)Nodes can be assessed by*Clinical evaluation if PALPABLE*Imaging for size and appearance (CT,MRI,U/S)*Biopsy or aspiration (IF it will affect treatment!)*Surgically (at time of primary tumor resection)

Question 337

Metastasis (M) Stage: What do you consider when assigning the metastasis stage?

Answer 337

* History and PE * Patterns of metastasis* Consensus guidelines about radiologic evaluation* Surgical evaluation is rarely used for metastatic staging

Question 338

What do the staging numbers signify for Primary Tumor (T)

Answer 338

TX Primary tumor cannot be evaluatedT0 No evidence of a primary tumorTis Carcinoma In SituT1, T2, T3, T4 Increasing size and extent of tumor

Question 339

What do the staging numbers signify for Regional Lymph Nodes? (N)

Answer 339

NX Regional lymph nodes cannot be evaluatedN0 No evidence of disease in lymph nodesN1, N2, N3 Increasing disease involvement in regional lymph nodes

Question 340

What do the staging numbers signify for Distant Metastasis (M)?

Answer 340

MX Distant metastasis cannot be evaluatedM0 No evidence of metastasisM1 Distant metastasis

Question 341

What is the difference between clinical and pathological staging?

Answer 341

* Clinical Stage: before starting therapy or having surgery▪ Pathological Stage: surgical exploration and tissue histology.▪ Both should be recorded if possible.

Question 342

Based on TNM score, how do you decide whether the cancer is Stage I, II, III or IV?

Answer 342

Depends on the cancer

Question 343

If a patient has M1 cancer, what stages are possible?

Answer 343

Stage IV only

Question 344

Can a patient have N1 and have Stage I cancer?

Answer 344

No. Regardless of cancer, Stage I must have N=0

Question 345

What is the basis of histopathologic grading?

Answer 345

Histology and morphology of cancerous cells seen with a microscope

Question 346

Which is more important: grading or staging?

Answer 346

Equally important: a small but aggressive cancer can be more dangerous than a large, indolent cancer.

Question 347

What are Grades GX through G4?

Answer 347

GX: Grade cannot be evaluatedG1: Well-differentiatedG2: Moderately differentiatedG3: Poorly differentiatedG4: Very poorly differentiated/Anaplastic

Question 348

What is the difference between well-differentiated cells and poorly-differentiated cells?

Answer 348

Well-differentiated: closely resemble the normal cells in architecture (and less aggressive)Poorly-differentiated: do not resemble the normal cells (more aggressive)

Question 349

What are other kinds of cancer qualifiers in considering prognosis and therapies besides Stage and Grade?

Answer 349

AgeSerum Markers (eg: PSA, CEA-125)Tumor Genetics (eg: EGFA expression in lung cancer)Patient Genetics (eg: BRCA)

Question 350

If the patient has a stage I cancer, what is theeffective treatment most likely to be?

Answer 350

Depends on the location: surgical resection (because it is self-contained) with or without chemo or radiation

Question 351

Why are biopsies of tissue so important fordetermining cancer treatment?

Answer 351

Staging, histology/grading, treatment, gene therapy

Question 352

At which stage(s) of cancer is radiation therapy themost likely to be useful?

Answer 352

When it is still localized, so stages I, II and III.

Question 353

If the patient has a stage IV cancer, which treatmentis most likely to be effective?

Answer 353

Chemo and/or radiation to shrink the tumor, then resection if possible

Question 354

What are the sequential steps that arrest bleeding?

Answer 354

* vascular reaction - vasoconstriction * formation of platelet plug (primary hemo) * activation of the coagulation cascase (stable fibrin clot - secondary hemo)

Question 355

Describe what happens during primary hemostasis?

Answer 355

* collagen and von Willebrand factor is exposed due to injury to endothelial cell wall * platelets roll over that and stick

Question 356

What are the factors of the extrinsic pathway?

Answer 356

7-->X-->5-->2 (Prothrombin)-->2a (Thrombin) -->1 (Fibrinogen)-->Fibrin-->13 (Tight clot) NB:  X marks the spot for the common pathwayNB2:  13 is not measured in PTT or PT  

Question 357

What are the vitamin K dependent factors?

Answer 357

10, 9, 7, 2 (1972 - it was a good year!) NB:  Vitamin K is more associated with the extrinsic pathway, but really, there are factors on both sides of the pathway. Mortier told me it is more important for 7 than 9.  

Question 358

What happens if you are deficient in Protein C or Protein S?

Answer 358

You clot out of control (predisposed to major thrombosis)

Question 359

What are the factors of the intrinsic pathway?

Answer 359

TENET - Twelve, Eleven, Nine, Eight, Ten (common)Then remainder of common pathway -  5, 2, 2a, 1, Fibrin, 13

Question 360

aPTT/PTT measures coagulation in which pathway?

Answer 360

Instrinsic (PITT)

Question 361

PT measures coagulation in which pathway?

Answer 361

Extrinsic (PET) 

Question 362

What are the important PMH and FH questions to ask a patient regarding bleeding?

Answer 362

* Bleeding Hx - bruises, petechhaie, gingival bleeding, etc. * deep muscle and joint bleeding * hematemesis, melena, hematuria, hemotypsis * liver or kidney disease * aspirin, NSAIDs, Plavix, warfarin, heparin use? * menstrual bleeding hx * bleeding during or after surgery that was hard to control * blood relative with bleeding disorder * anemia 

Question 363

What are the common pitfalls of laboratory studies?

Answer 363

* heparin in sample * traumatic venipuncture (slow draw) * too little sample in tube * polycythemia (too much anticoag in vaccutainer) * anemia (too little anticoag) * specimen sits at room temperature * PFA shaken and stirred (too much disruption)

Question 364

What is PT used for?

Answer 364

* extrinsic and common factors | * used to monitor Coumadin patients

Question 365

What happens to PT with a Vitamin K deficiency?

Answer 365

It is prolonged

Question 366

When is PTT prolonged?

Answer 366

* von Willebrand disease * hemophilia * lupus anticoagulant * NB:  sensitive to Heparin contamination

Question 367

What does a 1:1 mixing study tell you?

Answer 367

* if it corrects into the normal range, a factor deficiency is the likely culprit * if it fails to correct, an inhibitor or anticoagulant is the likely suspect * NB:  30% activity is the threshold to correct clotting times

Question 368

What is the Platelet Function Assay (PFA-100)?

Answer 368

* modern test that replaces old "bleeding time" test * push blood through a coated filter and watch the clot formation time on the filter * need platelets at least 100 x 109/L

Question 369

When will the Platelet Function Assay be prolonged?

Answer 369

* von Willebrand disease * aspirin * platelet function defects

Question 370

What does a Normal PT/PTT indciate in the presence of a bleeding disorder?

Answer 370

Factor XIII deficiency Remember, it is not measured by PT/PTT

Question 371

What does both an abornmal PT and PTT suggest?

Answer 371

* fibrinogen deficiency/problem * Vitamin K deficiency * DIC * Liver disease (PT abnormal first)

Question 372

What does an abnormal PTT with normal mixing result suggest?

Answer 372

* Hemophilia A or B * Von Willebrand disease * Factor XI deficiency * Factor XII deficiency

Question 373

What might cause a fibrinogen deficiency?

Answer 373

* liver dysfunction | * DIC

Question 374

Can a reduced level of fibrinogen cause a prolonged PT, PTT or Thrombin Clot Time?

Answer 374

* Generally, no unless fibrinogen is less than 100 mg/dL

Question 375

What does Thrombin Clot Time (TT) measure?

Answer 375

Measures the time for conversion of fibriongoen to fibrin Heparin can contaminate

Question 376

What is von Willebrand disease?

Answer 376

* Caused by a deficiency or reduced functioning of von Willebrand factor * carries and stabilizes factor VIII * mediates platelet adhesion and aggregation   

Question 377

What is the most common inherited bleeding disorder?

Answer 377

von Willebrand disease

Question 378

What is the mechanism of inheritance of von Willebrand disease?

Answer 378

Usually autosomal dominant

Question 379

What kind of bleeding do you see in von Willebrand disease?

Answer 379

platelet bleeding or primary hemostasis bleeding

Question 380

What is the Rx for von Willebrand's disease?

Answer 380

* DDAVP (Arginine vasopression) - releases stored vWf from endothelial cells * reduced efficacy with repeated dosing (tachyphylaxis) * Humate-P - factor VIII product that contains vWf * Cryoprecipitate - life-threatening bleeds (infectious transmission risks) * Aminocaproic acid - Amicar - supportive, effective for mucosal bleeding.  acts by stabilizing clot.  No for hematuria

Question 381

What is Hemophilia A?

Answer 381

Deficiency or lack of Factor VIII

Question 382

What is Hemophilia B?

Answer 382

Lack or deficiency of Factor IX

Question 383

How are Hemophilia A and B transmitted?

Answer 383

X-linked recessive disorders

Question 384

Hemophilia - Epidemiology

Answer 384

* Factor VIII (80%) * Factor IX (15%)  * Expressed in males, carried in females (some females can have prolonged bleeding in surgery or trauma) * approx. 30% new mutations

Question 385

What are the three degrees of severity of hemophilia?

Answer 385

* Mild Hemophilia (30-40% of cases)- Factor level 6-50%/uncommon spontaneous bleeding/see sx after major trauma or surgery * Moderate hemophilia (10% cases) - factor level 1-5%/see sx after minor trauma/4-6 bleeding episodes per year * severe hemophilia (50-70%) - Factor level <1%/spontaneous bleeding occurs/2-4 x month

Question 386

What are some of the history questions to ask about hemophilia?

Answer 386

* family history * bleeding with circumcision * prolonged bleeding with heel stick or vaccination * easy bruising * intracranial hemorrhage (esp. during childbirth) * milder phenotypes may not present until later ages

Question 387

What type of bleeding episode is most common in hemophila?

Answer 387

joint bleeding (60%)most common sites are knee, ankle, elbow

Question 388

What should you avoid when treating a joint bleed?

Answer 388

NSAIDS and Aspirin (you know why)

Question 389

Where are common sites for muscle bleeds in hemophilia?

Answer 389

* gluteus * hamstrings * iliopsoas * calf * quadriceps * deltoid * biceps

Question 390

What are the possible complications of untreated muscle bleeds?

Answer 390

* foot drop * flexed hip * volkmann's contracture (hand arm) * compartment syndrome

Question 391

What are the key points of assessment for a joint/muscle bleed?

Answer 391

* pain - tingling or burning  * disuse or immobility * abnormal appearance - circumference * tenderness and heat * nerve involvement

Question 392

What is the treatment for Hemophilia?

Answer 392

* replacement of missing factor concentrate (on demand/prophylaxis) * DDAVP/ Stimate * Antifibrionolytic agents - Amicar * Supportive measures - RICE and pain control

Question 393

What are factor inhibitors and how do you identify when they exist?  

Answer 393

* these are antibodies that develop against "foreign" infused factors in hemophilias.  They exist in 15-25% of Factor VIII pts and 1.5-3% of Factor IX pts. * median of 9-12 exposure days * consider when pt. is unresponsive to Rx * prolonged PTT after mixing 1:1 * one BU of activity causes 50% loss of Factor VIII activity

Question 394

How do you treat inhibitors in hemophilia?

Answer 394

* recombinant FVIIa - push clotting through extrinsic pathway * High-dose VIII or IX * prothrombin complex concentrates * can try to desensitize the immune system to the factor

Question 395

What do you do first when a pt. with hemophilia presents with major bleed symptoms?

Answer 395

* TREAT FIRST

Question 396

What is DIC?

Answer 396

* A disorder of secondary hemostasis caused by consumption of factors in the coagulation system * triggered by exposure of blood to tissue factor * present with bleeding, petechiae and purpura * causes include:  infection; major trauma; malignancy 

Question 397

What is the Rx for DIC?

Answer 397

* Most important: TREAT UNDERLYING CAUSE * hydration * RBC transfusion * if bleeding, fresh frozen plasma, cryoprecipitate, or platelets

Question 398

What are conditions that can lead to thrombosis?

Answer 398

``` Virchow's Triad * alterations in blood flow (stasis) * vascular endothelial injury * alterations in constituents of blood 50% of thrombotic events in pts with inherited thrombophilia are affiliated with additional risk factor ```

Question 399

What are the causes of inheritied thrombophilia?

Answer 399

* Factor V (Leiden) - most common inherited in causasians 3-8% * prothrombin gene mutation (G20210A) * Protein S deficiency * Protein C deficiency  * antithrombin deficiency

Question 400

What is the Rx for venous thromboembolism?

Answer 400

* LMW heparin, vondaparinaux, unfractioned IV heparin * overlap with and transition to Vitamin K antagonist * Target INR 2.5

Question 401

Who should be screened for thrombophilia?

Answer 401

* initial thrombus occuring before 40 without provoking factor * FH of 1st degree relatives with VTE * recurrent VTE * thrombosis in unusual vascular beds - liver, cerebral, mesenteric

Question 402

What are secondary hypercoagulable states?

Answer 402

* pregnancy * contraceptive use/HT * malignancy * systemic inflammation * post-operative state * immobilization * trauma

Question 403

von Willebrand Disease Panel has what tests?

Answer 403

* vWF:RCo (Ristocetin) - decreased in vW * vWF:Ag (Antigen) - decreased (but can be normal with non-functional vW) * FVIII (can be normal)

Question 404

prevalence of acute in leukemia in children vs adults

Answer 404

30% of childhood cancers2.3% of adult cancers

Question 405

define leukemia

Answer 405

neoplastic disease, abnormal proliferation of WBCs

Question 406

name the 4 types of leukemia (that we need to know)

Answer 406

acute lymphoblastic leukemiachronic lymphoblastic leukemiaacute myelogenous leukemiachronic myelogenour leukemia

Question 407

difference between acute and chronic leukemia

Answer 407

acute is associated with proliferation of immature precursors in blood and marrow, chronic is associated with mature precursors

Question 408

which genetic conditions predispose you to leukemia

Answer 408

down syndrome, neurofibromatosis, BMF syndromes

Question 409

what environmental/iatrogenic factors predispose you to leukemia?

Answer 409

ionizing radiation, occupational exposure (benzene), prior radiation therapy, prior malignancy

Question 410

in acute leukemia, what is the outcome of malignancy in immature precursors/ early hematopoietic precursors?

Answer 410

cell progeny does not differentiate/mature but proliferates uncontrollably. These "blasts" overtake the bone marrow, peripheral blood stream, lymph nodes

Question 411

what is a typical WBC count with leukemia

Answer 411

varies widely50% have normal-mild elevation25% very high25% decreased

Question 412

what does a bone marrow biopsy show in leukemia

Answer 412

hypercellular marrowmarrow fibrosis (AML)

Question 413

when do you order a lumbar puncture?

Answer 413

with ALL alwaysif there are neurologic symptoms in a patient with AML

Question 414

what disease presents with a mediastinal mass? (50%)

Answer 414

T-cell ALL

Question 415

What is the characteristic histology finding with AML?

Answer 415

Auer rods (found in 30% of patients)

Question 416

How long is induction with AML

Answer 416

10 days

Question 417

What is the most common form of cancer in children

Answer 417

acute lymphoblastic leukemia (ALL)

Question 418

associates symptoms common with ALL

Answer 418

splenomegaly, lymphadenopathy, bone pain

Question 419

How long is induction with ALL

Answer 419

4 weeks

Question 420

what is the management of ALL after induction?

Answer 420

post-remission consolidation for 6-8 weeksmaintenance doses daily or weekly for 2-3 yearsCNS prophylaxis (intrathecal chemo)

Question 421

What disease is associated with the Philadelphia Chromosome

Answer 421

Characteristic finding of CML, but also seen in ALL- means worse prognosis- lower remission rates

Question 422

major sequelae of leukemia

Answer 422

subsequent cancers

Question 423

complications associated with chemo

Answer 423

osteopenia, endcrine abnormalities, poor cardiac function

Question 424

how does treatment of children with ALL differ from adults?

Answer 424

intensive multi-agent inductionless intensive maintenancebone marrow transplant in 5%

Question 425

treatment of children with AML?

Answer 425

6 months inpatients treatment- intensive and toxicbone marrow transplant in 30%

Question 426

Chronic lymphocytic leukemia (CLL) epidemiology

Answer 426

most common adult leukemia (western world)male to female 2:1median age of onset 72

Question 427

CLL definition

Answer 427

proliferation of mature B cells, accumulation of long-lived mature lymphocytes, hypogammaglobulinemia

Question 428

CLL clinical presentation

Answer 428

often asymptomatic- incidental findingfatigueappetite losslymphadenopathyhepatosplenomegaly

Question 429

CLL immunologic abnormalities

Answer 429

auto-immune hemolytic anemiaauto-immune thrombocytopenic purpuramonoclonal spikehypogammaglobulinemia

Question 430

how do you Dx CLL?

Answer 430

Flow cytometry

Question 431

CLL staging

Answer 431

Rai StageStage 0 Lymphocytosis onlyStage I LymphadenopathyStage II SplenomegalyStage III AnemiaStage IV Thrombocytopenia

Question 432

CLL staging- ABC

Answer 432

Binet StageA: <3 areas of lymphadenopathy. No anemia/ thrombocytopeniaB: 3 or more involved LN areas. No anemia/ thrombocytopeniaC: Hemoglobin <10 g/dl or <100,000 platelets

Question 433

Treatment of CLL

Answer 433

usually none, only if progressive/severe symptoms

Question 434

Define CML

Answer 434

proliferative hematopoeitic stem cells

Question 435

characteristic abnormalities

Answer 435

Philadelphia chromosomeBCR-ABL tyrosine kinase

Question 436

epi of CML

Answer 436

median age 45-65slightly maleincrease risk with age

Question 437

3 phases of CML

Answer 437

chronicacceleratedblastic crisis

Question 438

presentation of CML

Answer 438

often asymptomaticfatigueanorexiaabdominal fullnesssplenomegaly

Question 439

CML CBC findings

Answer 439

leukocytosisthrombocytosisanemiabasophilia

Question 440

lymphoma symptoms

Answer 440

painless lymphadenopathyconstitutional symptomsextranodal involvement

Question 441

hodgkin lymphoma epi

Answer 441

bimodal- 15-34 years and >60maleassociated with viral infections

Question 442

key finding to suggest hodgkin lymphoma

Answer 442

painless, mobile, rubbery lymph nodesworse/painful with alcoholB symptomsReed Sternberg Cells

Question 443

how to Dx hodgkin lymphoma

Answer 443

biopsy- see Reed Sternberg cell

Question 444

treatment of hodgkin lymphoma

Answer 444

radiotherapy and chemotherapy, length depends on stage

Question 445

complications of hodgkin lymphoma treatment

Answer 445

immunologic deficitthyroid dysfunctioncardiac dysfunctionsecondary malignancies

Question 446

non-hodgkin lymphoma epi

Answer 446

increasing prevalence- unknown whycommon in AIDS patientsaverage age at Dx- 42risk groups- occupational exposure to hazardous material, viral exposure, low veggie/high red meat dietdrink a little wine to protect yourselves ladies

Question 447

clinical presentation of non-hodgkin lymphoma

Answer 447

lymph node involvementsplenomegalyB symptoms

Question 448

non-hodgkin lymphoma staging

Answer 448

Stage I– Involvement of single lymph node (LN) regionStage II– >2 LN regions on same side of diaphragmStage III– LNs on both sides of diaphragmStage IV– Multifocal involvement of >1 extra-lymphatic sites (e.g., liver, bone marrow, lung)

Question 449

non-hodgkin treatment

Answer 449

chemotherapy +/- radiation depending on stagingprognosis variable depending on staging

Question 450

what is multiple myeloma characterized by

Answer 450

neoplastic proliferation of plasma cells that produce an abnormal monoclonal immunoglobulin or light chain kappa or lambda (IgG, IgM, IgA...and rarely IgD or IgE)

Question 451

examples of the extensive skeletal destruction caused by plasma cells proliferating in the bone marrow

Answer 451

osteolytic lesionsosteopeniapathologic fracturesbone painhypercalcemiaanemia

Question 452

median age to present with multiple myeloma

Answer 452

70

Question 453

who is more likely to get multiple myeloma

Answer 453

occurs in all racesblacks 2x higher than whites3.7x more likely to get if 1st degree relative with MM

Question 454

clinical presentation of multiple myeloma

Answer 454

normocytic anemiabone painelevated creatininefatigue/general weaknesshypercalcemiaweight lossparesthesis

Question 455

how many people with multiple myeloma are asymptomatic

Answer 455

up to 1/3

Question 456

initial testing for multiple myeloma

Answer 456

CBC with diffserum chemistries (Ca, Cr, BUN, albumin)

Question 457

confirmatory testing for multiple myeloma

Answer 457

24 hr urine proteinbeta 2 microglobulinLDHserum free light chain assayserum protein electrophoresisurine protein electrophoresisserum immunofixation electrophoresisquantitative immunoglobulinsskeletal survey

Question 458

testing with oncology consult for multiple myeloma

Answer 458

bone marrow aspirate and biopsyBM cytogeneticsflow cytometryFISHimmunohistochemistry

Question 459

97% of patients with MM will have a monoclonal (M) protein produced and secreted by the malignant plasma cells...this M protein spike is detected on what region on electrophoresis

Answer 459

gamma region

Question 460

key test in diagnosis of MM

Answer 460

bone marrow aspirate and biopsy

Question 461

what two criteria must be met to diagnose MM

Answer 461

clonal bone marrow plasma cells greater than or equal to 10% or biopsy proven extra medullary plasmacytoma AND one or more myeloma-defining events (listed on diff flashcard)

Question 462

what are the myeloma-defining events

Answer 462

evidence of end organ damage attributed to underlying plasma cell proliferative disorder (listed on diff flashcard)clonal bone marrow plasma cells greater than or equal to 60%serum free light chain ratio greater than or equal to 100more than one focal lesion on MRI studies

Question 463

plasma cell proliferative disorder (CRAB)

Answer 463

hyperCalcemiaRenal insufficiencyAnemiaBone lesions: one or more lytic lesions

Question 464

treatment if not a transplant candidate

Answer 464

chemotherapy

Question 465

treatment if a transplant candidate

Answer 465

myeloablative chemotherapyautologous stem cell transplant then consolidation and maintenance chemotherapy

Question 466

treatment of bone disease

Answer 466

IV zoledronic acid (Recast)pamidronatecalcium and vit D supplements

Question 467

treatment of thromboembolic events

Answer 467

thromboprophylaxis: heparin or warfarin

Question 468

treatment of infection

Answer 468

prophylactic antibiotics

Question 469

what is MGUS (monoclonal gammopathy of undetermined significance)

Answer 469

clinically asymptomatic premalignant clonal plasma cell or lymphoplasmacytic proliferative disorderserum monoclonal protein M less than 3 gm/dL, bone marrow with less than 10% monoclonal plasma cells, and NO CRAB

Question 470

why should patients with MGUS be monitored

Answer 470

associated with small risk of progressing to malignant plasma cell dyscrasia or lymphoproliferative disorder