Heme/Lymph Flashcards Preview

Step 1 AB > Heme/Lymph > Flashcards

Flashcards in Heme/Lymph Deck (302):
1

What triggers coagulation in extrinsic pathway?

Tissue injury releases tissue factor (thromboplastin)

2

What is deficiency of Hemophilia B?

Coagulation factor IX (9) deficiency

3

What is deficiency of Hemophilia A?

Factor 8

4

What is rate limited of coagulation cascade?

Convergence of extrinsic and intrinsic at Factor 10

5

Function of Protein C and S?

Inhibit Factors Va and VIIIa

6

Why does Warfarin transiently increase clot formation?

Warfarin inhibits Factors 2, 7, 9 and 10; but it also inhibits protein C and S MORE rapidly than clotting factors --> this transiently increases clot formation before the other factors are inhibited
-This is why we start Heparin first

7

What is the final common pathway?

Factor 10 -->10a
10a + 5a activate prothrombin to thrombin
Thrombin + 13a activate fibrin monomers into fibrin mesh

8

What is function of Antithrombin?

Inhibits thrombin from activating fibrin

9

What drug increases effectiveness of thrombin?

Heparin

10

How does coagulase affect coagulation pathway? What produces coagulase?

Coagulase activates thrombin
Made by Staph aureus

11

What other ions/proteins are necessary for coagulation cascade?

Calcium
Phospholipid

12

What are the functions of factor 12a?

1) 12a activates 11 --> 11a
2) 12a converts prekallikrein to kallikrein --> then kallikrein cleaves plasminogen to form plasmin --> plasmin breaks down fibrin mesh
-Kallikrein also converts HMWK to bradykinin --> Bradykinin vasodilates, increases vascular permeability and mediates pain (coagulation and inflammation are interconnected)

13

What does the prothrombin time measure?

Take plasma and add tissue factor --> measure how long it takes clot to form
Tests how effectively tissue factor can activate the tissue factor pathway and the final common pathway
Testing factors 7, 10, 5 and 2 (prothrombin)
Always reported as INR (1 is normal)

14

What does partial thromboplastin time measure?

Plasma + silica or something that activates tissue activating pathway
-Also have to add phospholipids that normally combine with tissue factor to form thromboplastin
-Tests function of contact activation pathway and final common pathway
-Tests 12, 11, 9 and 8, 10, 5 and 2

15

What does bleeding time measure?

Should take 2-9 minutes
A function of platelet function
Disorders of coagulation cascade will not affect bleeding time

16

Hemophilia A and Hemophilia B
a. effect which pathway?
b. Effects on PT and PTT

a. Intrinsic pathway
b. Increased PTT, not effect on PT or INR

17

Symptoms of Hemophilia A/B

Macrohemorrhage --> hemarthroses, easy bruising, bleeding after trauma or surgery

18

Treatment for Hemophilia A, B and C

A - Desmopressin + factor 8 concentrate
B - factor 9 concentrate
C - factor 11 concentrate

19

Vitamin K Deficiency
a. Effects on PT, PTT
b. Mechanism

a. Increased PT, PTT
b. Decreased 10, 7, 9, 2
c. Vitamin K dietary deficiency, newborns (no gut bacteria), someone taking antibiotics, patients on Warfarin, end stage liver disease

20

Factor V Leidin
a. What does Factor V do?
b. Mechanism of disease

a. Factor V is a cofactor for factor 10 --> helps it activate thrombin
b. Factor V Leiden mutations makes Va resistant to inactivation by protein C --> increased coagulation

21

Prothrombin gene mutation (G20210A)
a. Mechanism
b. Effect

a. Mutation in 3' intranslated region
b. Increased production of prothrombin --> increased plasma levels and venous clots

22

Antithrombin deficiency
a. Effect
b. PT/PTT

a. Unable to activate thrombin
b. No direct effect on PT, PTT or thrombin time but the increase in PTT is diminished after adding Heparin (reduced effect)

23

Protein C deficiency (or protein S)

Unable to activate factors 5 and 8 --> can't shut off coagulation cascade --> increased risk of thrombotic skin necrosis with hemorrhage following administration of Warfarin

24

Skin and subcutaneous tissue necrosis after warfarin administration

Protein C deficiency

25

Mechanism of Heparin

Cofactor for activation of antithrombin --> decreased thrombin and factor 10a (only prevents clot from getting bigger or new clots from forming)
VERY SHORT HALF LIFE

26

Uses of Heparin

PE, acute stroke, MI, DVT
Can be used during PREGNANCY

27

What lab do we measure to monitor Heparin?

PTT

28

S/E of Heparin

Bleeding
Bone loss, osteoporosis
Heparin-Induced Thrombocytopenia (HIT) --> heparin binds to platelet factor 4 --> autoantibody complexes can then activate platelets to aggregate --> then they get removed from circulation and destroyed --> thrombosis and thrombocytopenia

29

What do you do for Heparin Induced Thrombocytopenia?

Stop Heparin
Start different anticoagulant like direct thrombin inhibitor (dabigatran, bivalirudin)

30

Direct Thrombin Inhibitors (specifically ones derived from Hirudin from leech spit)

Lepirudin
Bivalirudin
Desirudin

31

Direct Thrombin Inhibitors (NOT from hirudin)

Argatroban
Dabigatran

32

Low-molecular weight Heparins

Enoxaparin
Dalteparin

33

Advantages of low-molecular weight Heparins
Disadvantages?

Better bioavailability
2-4 times longer half life
Administered SubQ
Don't need lab monitoring
Disadvantage - not easily reversible

34

Fondaparinux

Activates antithrombin to inhibit Factor Xa
(Not a Heparin derivative)

35

Mechanism of LMW Heparins?

Stimulate antithrombin to inactivate Factor Xa

36

Direct Factor 10a inhibitors

Rivaroxaban
Apixaban

37

Warfarin mechanism

Inhibits epoxide reductase --> interferes with gamma-carboxylation of vitamin K dependent clotting factors 2,7,9,10 Protein C and S
(Epoxide reducase recycles vitamin K)

38

Uses of Warfarin

Chronic antricoagulation --> Atrial fibrillation, DVT prophylaxis, DVT treatment, PE treatment

39

When is Warfarin C/I?

Pregnant patients - crosses placenta and is teratogenic

40

Toxicity of Warfarin

Bleeding, teratogen, skin/tissue necrosis, transient hyper coagulability

41

Reversal of Heparin

Protamine Sulfate

42

Reversal of Warfarin

Vitamin K (oral) - takes days to do anything to reverse effects because have to wait for liver to make more clotting factors
Fresh frozen plasma

43

Half life in Heparin vs. Warfarin

Short half life - Heparin
LONG half life - Warfarin

44

Onset of action in Heparin vs. Warfarin

Rapid (seconds) - Heparin
Slow - Warfarin

45

Thrombolytics
a. mechanism
b. Use

a. activated Plasmin --> lyses fibrin clot
b. EARLY ST elevation MI (< 3-6 hours), acute stroke, severe PE

46

S/E of thrombolytics

Bleeding (C/I in active bleeding, recent surgery, HTN, history of intracranial bleeding, coagulation defect)

47

Used to monitor coagulation in patient taking Warfarn

PT and INR

48

Characteristics of RBC
a. life span
b. shape
c. source of energy

a. 120 days
b. biconcave (spectrin), anucleate
c. Glucose 90% anaerobical metabolized to lactate, 10% used in HMP shunt

49

What is anisocytosis?

RBC of varying sizes

50

What is poikilocytosis?

RBC of varying shapes

51

What is a reticulocyte? What dose it reflect?

Immature RBC; reflects erythroid proliferation

52

What is polycythemia or erythrocytosis?

Too many RBCs

53

Basophilic stippling
Associated pathology?

Little purple red dots (clumps of denatured RNA in basophil)
Lead poisoning (also thalassemias, anemia of chronic disease, alcohol abuse)

54

Echinocyte (burr cell)

Regular, uniform spikes all over surface
Seen in uremia, renal failure

55

Spurr cell (Acanthocyte)

IRREGULAR spiked cells
Liver disease
Abetalipoproteinemia

56

Spherocyte

RBCs that lose biconcave shape
-seen in Hereditary Spherocytosis

57

Schistocytes

Fragments of RBC that look like helmets
-Seen in DIC, TTP/HUS, HELLP, (pathologic intravascular clotting that RBCs are being forced through) from mechanical hemolysis

58

Target cells

Look like bulls eye
THAL
Thalassemia
Hemoglobin C disease
Asplenia
Liver disease (also see acanthocytes)

59

Sickle cells

Crescent shaped
In sickle cell anemia

60

Howell Jolly body

Basophilic nuclear remnants found in RBCs
-Normally removed from RBCs by splenic macrophages; seen in patients with functional hyposplenia or asplenia (trauma, immune thrombocytopenia purpora splenic removal)

61

Heinz bodies

When hemoglobin gets oxidized and precipitates out of solution in RBC --> little clumps of Hgb
-Spleen bites the Hgb clumps out of RBCs
-Seen in G6PD deficiency (oxidative damage causes Heinz bodies)

62

How do you tell Heinz body from Howell Jolly Body?

Can only have ONE Howel jolly body but can have MANY Heinz bodies

63

Teardrop cells

Shaped like teardrops
-Seen with myelofibrosis

64

Elliptical shape cells (pencil cells)

Hereditary Elliptocytosis

65

Ring Sideroblasts

ABNORMAL
-Seen in Bone marrow
-Lead poisoning*** (big one), drugs, myelodysplastic syndromes
-Sign of underlying diagnosis

66

Sideroblasts

Nucleated RBC precursor with granules of iron in mitochondria
-Found in BM of healthy people
-If you have disorder that affects heme synthesis and body can't use all iron granules --> the granules surround and encircle the nucleus --> form ring

67

What happens if you transfuse incompatible blood type?

Antibody-mediated type II hypersensitivity

68

What is Erythroblastosis Fetalis?

Due to Rh incompatibility
Maternal Abs to fetal RBC antigens (Rh-D)
Rh- moms don't have antibodies to Rh-D but after they are exposed to babies RBCs they form them (after first pregnancy)
-If babies blood comes into contact with babies blood in first pregnancy, mom's immune system is sensitized to Rh- antigen and mom develops Abs --> then IgG can cross placenta and attack RBCs --> hemolysis --> Hgb breaks down into bilirubin and causes jaundice

69

Clinical features of Erythroblastosis Fetalis in infant

Anemia due to hemolysis of RBC by maternal Abs
Jaundice --> kernicterus possible
Hydrops fetalis (fetal edema)
Intrauterine death

70

Treatment of Erythroblastosis Fetalis

Administer RhoGAM (anti-Rh immunoglobulin) to Rh- pregnant women during 3rd trimester to prevent maternal anti-Rh IgG production (and any time there is trauma)

71

What kind of RBCs do you see in G6PD deficiency?

Bite cells
Heinz bodies

72

When do primitive blood cell progenitors appear in yolk sac?

at 3 weeks; come from mesonephros

73

Young Liver Synthesizes Blood

Yolk Sac (week 3-8)
Liver (and spleen)
Bone marrow (at 28 weeks)

74

Which part of skeleton is hematopoietically active?

Infancy and childhood - entire skeleton (sternum, pelvis, ribs, long bones, vertebrae, cranial)
Late adolescence, adulthood - vertebrae, sternum, ribs, pelvis

75

Fetal hemoglobin?
Adult hemoglobin?

Fetal - 2 alpha chains, 2 gamma chains (gamma has lower affinity for 2,3 DPG --> higher affinity for oxygen)
Adult - 2 alpha chains, 2 beta chains

76

Hemoglobin variants
HbA
HbA2
HbA1c
HbF
HbGower

HbA - 97% of normal (a2B2)
HbA2 - 2% of normal (a2delta2)
HbA1c - poorly controlled diabetes
HbF - fetal hemoglobin (a2gamma2)
HbGower - embryonic Hgb (2 zeta and 2 episilon chains)

77

HbS

Sickle cell Hgb
alpha 2, betaS2
Glu --> val in B chain

78

HbC

Hemoglobin C disease
alpha 2, betaC2
Glu --> lys in Beta chain

79

HbBart's

Severe alpha thalassemia
gamma 4 (no alpha chain)

80

HbH

Severe alpha thalassemia
B4 (no alpha chains)

81

What is rate limiting enzyme of heme synthesis?
What does it require?

aminolevulinic acid synthase (ALA synthase)
It makes glycine and succinyl-CoA into aminolevulinic acid
Requires Vitamin B6

82

What enzyme is defective in acute intermittent porphyria?

Porphobilinogen deaminase
Can't make porphobilinogen into hydroxymethylbilane

83

Presentation of acute intermittent porphyria

Abdominal pain (neuropathic)
Port wine- colored urine
Polyneuropathy
Psychological disturbanes
Precipitated by drugs (cytochrome p450 inducers, alcohol, starvation)

84

How do you treat acute intermittent porphyria?

Glucose and heme --> inhibit ALA synthase (no build up of neuro toxic products)

85

5 P's of acute intermittent porphyria

Pain in abdomen
Polyneuropathy
Port wine-colored urine
Psychological disturbances
Precipitated by drugs

86

What enzyme is defective in Porphyria Cutanea Tarda?

Uroporphyrinogen decarboxylase
Uroporphyrin accumulates and causes tea colored urine

87

Presentation of Porphyria Cutanea Tarda

Most common form!
Blistering of skin and photosensitivity
Hypertrichosis
Facial hyperpigmentation
Tea-colored urine
Hepatitis C and alcoholism
Elevation of LFTs (AST, ALT)
(Think of homeless man)

88

How does lead poisoning affect heme synthesis pathway?

Inhibits Ferrochelatase --> Protoporphyin accumulates
Inhibits ALA dehydratase

89

Presentation of lead poisoning

Microcytic anemia (basophilic stippling) GI (abdominal colic) and Kidney disease
Mental deterioration in kids (also lead lines in bones, gingiva)
Headache, memory loss, demyelination in adults

90

Treatment of lead poisoning

EDTA or succimer to chelate lead
Dimercaprol + succimer in kids for very severe lead poisoning

91

What is Polycythemia vera?

Monoclonal proliferation of RBCs

92

Causes of polycythemia vera

Chronic hypoxia --> to increase O2 carrying capacity (pulmonary disease, cyanotic heart disease, high altitudes)
Tumors
Trisomy 21 at birth

93

Tumors that cause polycythemia vera
Potentially Really High Hematocrit

Pheochromocytoma
Renal cell carcinoma
Hepatocellular carcinoma
Hemangioblastoma

94

Relative Polycythemia

Plasma volume is reduced so that red cell count is increased relative to plasma volume

95

Absolute polycythemia

Plasma volume is normal and you have too many RBCs

96

Appropriate absolute polycythemia
a. plasma volume
b. RBC mass
c. O2 saturation
d. EPO levels
e. associations

a. no change
b. Increased
c. decreased
d. increased
e. seen in lung disease, congenital heart disease, high altitude

97

Inappropriate absolute polycythemia
a. plasma volume
b. RBC mass
c. O2 saturation
d. EPO levels
e. associations

a. no change
b. Increased
c. no change
d. increased
e. renal cell carcinoma, hepatocellular carinoma, hydronephrosis

98

Polycythemia vera
a. plasma volume
b. RBC mass
c. O2 saturation
d. EPO levels
e. associations

a. increased
b. really increased
c. no change
d. decreased
-EPO decreased due to negative feedback suppressing renal EPO production

99

Relative polycythemia
a. plasma volume
b. RBC mass
c. O2 saturation
d. EPO levels
e. Associations

a. decreased
b. no change
c. no change
d. no change
e. Decreased plasma volume like dehydration and burns

100

Microcytic Anemia

Iron Deficiency Anemia
Alpha thalassemia
Beta thalassemia
Lead poisoning
Sideroblastic anemia
Anemia of Chronic Disease

101

Iron Deficiency Anemia - causes

Poor intake
Blood loss (menstruation or GI chronic occult blood loss)

102

IDA - characteristics

Hypochromic
Microcytic

103

What is Plummer Vinson syndrome?

Iron deficiency anemia
Esophageal web
Atrophic glossitis

104

Alpha Thalassemia - cause
Affects who?

Defect in alpha globin gene deletions --> defect in alpha globin synthesis
African/Asian populations

105

alpha thalassemia
a. mutation of one allele
b. mutation in 2 alleles
c. mutate 3 alleles
d. mutate 4 alleles

a. no anemia
b. alpha thal trait, no anemia
c. Hemoglobin H disease (beta globins pair up with each other )
d. incompatible with life - Hemoglobin Barts - four gamma globes --> causes hydrous fetalis and death

106

Beta thalassemia cause
Affects who?

Defect in beta globin gene (point mutation) --> decreased beta globin synthesis
Mediterranean populations

107

B-thalassemia minor (heterozygote)

B chain is underproduced
Usually asymptomatic
Diagnosis confirmed by increased HbA2 (>3.5%) on electrophoresis

108

B-thalassemia major (homozygote)

B chain is absent --> severe anemia requiring blood transfusion
Marrow expansion (crew cut on skull X-ray) --> skeletal deformities, chipmunk facies
Extramedullary hematopoiesis leads to hepatosplenomegaly
-Increased risk of parvovirus B19 induced aplastic crisis

109

Why do you have to confirm diagnosis of iron deficiency in patients with microcytic anemia before you start iron supplements?

They might have beta thalassemia in which case they would have increased iron from thalassemia

110

Peripheral smear of thalassemia shows...

Target cells

111

What are two enzymes in heme synthesis that are affected by lead poisoning?

Ferrochelatase
ALA dehydratase

112

Causes of sideroblastic anemia

Lead poisoning
Alcohol
Drugs (seizure drugs, Rifampin)
Hereditary X linked defect in ALA synthase

113

Anemia of chronic disease
Iron, Ferritin levels

From defective iron utilization
Iron is trapped in macrophages so serum iron is LOW
Ferritin is normal or HIGH

114

Macrocytic anemia
a. Megaloblastic anemia
b. Non-megaloblastic anemia

a. B12 deficiency, Folate deficiency , orotic aciduria
b. Liver disease, Alcoholism, Reticulocytes

115

RBC appearance in B12/folate deficiency

Hypersegmented neutrophils (>6 lobes)

116

Causes of B12 deficiency

Insufficient intake
Malabsorption (Crohn, removal of terminal ileum)
Pernicious anemia
Diphyllobothrium latum (fish tapeworm)
Gastrectomy

117

Causes of folate deficiency

Malnutrition (alcoholics)
Malabsorption
Drugs (methotrexate, phenytoin, trimethoprim)
Increased requirement (pregnancy, hemolytic anemia)

118

Findings in
a. Folate deficiency
b. B12 deficiency

a. NO NEUROLOGIC SYMPTOMS; increased homocysteine, normal methylmalonic acid; megaloblastic anemia
b. Neurologic symptoms (subacute combined degeneration, spinocerebellar tract, lateral corticospinal tract, dorsal column dysfunction, dementia, neuropathy); Methylmalonic acid INCREASED, increased homocysteine

119

Why does B12 deficiency cause subacute combined degeneration?

B12 is involved in fatty acid pathways and myelin synthesis

120

Why should you not treat with empiric folic acid for megaloblastic anemia?

It might fix anemia but if B12 is deficient it will NOT correct neurologic deficits

121

What is orotic aciduria?

Defect in UMP synthase (pyrmidine synthase)
Causes orotic acid in urine, megaloblastic anemia Developmental delay
Failure to thrive
NO hyperammonemia (vs. ornithine transcarbamylase deficiency)

122

NON-megaloblastic macrocytic anemia cause

DNA synthesis is NOT impaired
Alcoholism
Liver disease
Hypothyroidism
Reticulocytosis
Drugs (5-FU, Zidovudine, Hydroxyurea)

123

Normocytic NON-hemolytic anemia causes

Anemia of chronic disease
Aplastic anemia

124

Anemia of chronic disease
a. cause
b. Iron, TIBC, Ferritin levels

a. Lots of inflammation causes lots of inflammatory mediators like Hepcidin to be increased --> inhibits iron transport because iron is trapped in macrophages
b. Decreased iron, decreased TIBC, Increased Ferritin

125

Conditions associated with anemia of chronic disease

SLE, RA, Neoplastic disorders, CKD

126

Aplastic anemia
a. causes
b. Findings
c. symptoms

a. Radiation***** and drugs, Viral agents (parvovirus B19, EBV, HIV, HCV), Fanconi anemia (DNA repair defect), Idiopathic (immune mediated)
b. Pancytopenia (anemia, leukopenia, thrombocytopenia)
Normal cell morphology but HYPOCELLULAR BONE MARROW With fatty infiltration
c. Fatigue, malaise, pallor, purpura, petechiae, infection

127

Treatment of aplastic anemia

Withdrawal of offending agent
Bone marrow allograft
RBC/platelet transfusion
Bone marrow stimulation

128

What test can be used to diagnose Beta thalassemia minor?

Hemoglobin electrophoresis to look for higher than normal levels of HbA2

129

Megaloblastic anemia not correctable by B12 or Folate

Orotic Aciduria

130

Microcytic anemia reversible with B6

Sideroblastic anemia

131

Drugs that can cause sideroblastic anemia

Isoniazid (inhibits B6)
Lead
Copper deficiency
B6 deficiency

132

HIV patient with macrocytic anemia

Zidovudine

133

Normocytic anemia with elevated creatinine

Chronic kidney disease resulting in low EPO

134

Skull x-ray shows "hair on end" appearance

Result of marrow hyperplasia (crew cut)

135

Basophilic stippling of RBCs

Lead poisoning

136

Co-factor required for pyruvate dehydrogenase
Tender Loving Care For No-one
What other enzyme requires these?

Thiamine
Lipoid acid
Coenzyme A
FAD
NAD
-Also required by Alpha-ketoglutarate dehydrogenase

137

Intravascular or Extravascular hemolysis?
a. Decreased serum haptoglobin
b. Increased LDH
c. Increased unconjugated bilirubin

a. Massive intravascular hemolysis causes haptoglobin to bind all free hemoglobin
b. released from RBCs (intravascular OR extravascular hemolysis)
c. Seen in extravascular hemolysis (with intravascular all the heme would be bound by haptoglobin)

138

Intravascular hemolysis Causes

Autoimmune hemolytic anemia
Paroxysmal nocturnal hemoglobinuria
Mechanical destruction of RBCs

139

Extravascular hemolysis
Causes

Hereditary spherocytosis (spleen recognizes abnormal cells)
G6PD Deficiency (extravascular AND intravascular)
Pyruvate kinase deficiency
Sickle cell
Hemoglobin C disease

140

Hereditary spherocytosis defect

Defect in Ankyrin and spectrin (proteins interacting with RBC membrane skeleton and plasma membrane) --> red cells are small round spheres with NO central pallor and less surface area

141

Hereditary spherocytosis
a. Increased MCHC - why?
b. increased RDW - why?
c. Why does it cause hemolysis

a. Increased Mean corpuscular hemoglobin content; same amount of Hgb but they are smaller so it is more concentrated
b. Not as much variability with red cell size
c. Spleen recognizes cells as normal and removes them --> splenomegaly

142

Diagnostic test for Hereditary spherocytosis

Osmotic fragility test (high percentage of lysis in NaCl)

143

Treatment for hereditary spherocytosis

Splenectomy (so that it doesn't remove red cells) --> then you see Howell Jolly bodies

144

G6PD deficiency defect

X linked recessive
Defect in G6PD --> causes decreased glutathione and increased RBC susceptibility to oxidative stress

145

Stressors that cause anemia in G6PD deficiency

Fava beans
Sulfa drugs
Anti-malarials
Infections

146

Symptoms of G6PD deficiency

Back pain, hemoglobinuria a few days after oxidant stress

147

Pyruvate kinase deficiency causes...

Intrinsic hemolytic anemia
Defect in pyruvate kinase --> decreased ATP --> rigid RBCs
Hemolytic anemia in newborn

148

Paroxysmal Nocturnal Hemoglobinuria defect

Red cells missing surface markers CD55 and CD59 so complement attacks them and lyses them

149

What is test for PNH?

Ham's test - add acid to lower pH and that activates complement and lyses RBCs

150

Triad of PNH

Coombs - hemolytic anemia
Pancytopenia
Venous thrombosis

151

Sickle cell disease defect

Hemoglobin S mutation is single aa replacement where valine is used instead of glutamic acid at position 6 --> allow Hgb to polymerize in RBC

152

What triggers sickling in SCD?

Hypoxemia
Dehydration
Acidosis

153

Complications of Sickle Cell Disease

Aplastic crisis
Autosplenectomy
Splenic infarct
Salmonella osteomyelitis
Painful crises (vaso-occlusive)--> acute chest syndrome, avascular necrosis, stroke, dactylitis
Renal papillary necrosis and microhematuria

154

What organism causes osteomyelitis in SCD?

Salmonella

155

Treatment for SCD

Hydroxyurea
BM transplantation

156

Hemoglobin C disease defect

Glutamic acid--> Lysine mutation in B globin

157

Microangiopathic anemia cause

RBCs are mechanically damaged as they pass through lumen of obstructed vessel --> in DIC, TIP/HUS, lupus, malignant HTN --> RBC gets chopped up by shear force or fibrin strands

158

Macroangiopathic anemia cause

Damage to cells by forces in LARGER vessels (prosthetic heart valves, aortic stenosis)

159

Autoimmune Hemolytic Anemia a. Warm agglutinins
b. Cold agglutinins

a. IgG Abs attach to red cells and cause them to agglutinate AT BODY TEMP
b. IgM Abs that only cause problems when temp is lower

160

Cold agglutinins occur in...

Infections with EBV, mycoplasma
Malignancies (CLL)

161

Warm agglutinins occur in...

SLE
Malignancies (CLL)
Drugs (methyldopa)
Viruses (EBV, HIV)
Congenital immune abnormality

162

Direct Coombs Test

Anti-Ig antibody (Coombs reagent) is added to patient's blood --> the RBCs agglutinate if RBCs are coated with Ig

163

Indirect Coombs Test

Normal RBCs added to patient's serum --> if serum has anti-RBC surface Ig, RBCs agglutinate when Coombs reagent is added

164

Direct Coombs test is positive in:

Hemolytic disease of newborn
Drug-induced autoimmune hemolysis anemia
Hemolytic transfusion reactions

165

Indirect Coombs test positive when:

Abs present to foreign blood (test blood prior to transfusion, screen maternal antibodies to a fetus' blood)

166

Painful cyanosis of fingers and toes with hemolytic anemia

Cold autoimmune hemolytic anemia

167

Red urine in the morning, and fragile RBCs

PNH

168

Basophilic nuclear remnants in RBCs

Howell-Jolly bodies

169

Autosplenectomy

Sickle cell (from auto-infarcting)

170

Drug used to treat sickle cell disease

Hydroxyurea

171

Where do platelets come from?

Megakaryocytes

172

How long do platelets live?

8-10 days; have no nucleus

173

What is vWF? Where does it come from?
What is it's function?

It comes from Weibel-Palade bodies of endothelial cells and alpha granules of platelets
It complexes with and stabilizes factor 8 (elevated PTT with deficiency)
It binds to exposed collagen and then platelets binds vWF via Gp2b receptor at site of injury

174

How do platelets become activated after adhesion?

They change shape and ADP binding to receptor induces Gp2b/3a expression at platelet surface

175

How do platelets aggregate after activation?

Fibrinogen binds Gp2b/3a and link platelets

176

Pro-aggregation of platelet factors

TXA2 (released by platelets)
Decreased blood flow
Increased platelet aggregation

177

Anti-aggregation of platelet factors

PGI2 and NO (endothelial cells)
Increased blood flow
Decreased platelet aggregation

178

Aspirin mechanism

Inhibits cyclooxygenase --> permanently blocks the conversion of arachidonic acid to thromboxane A2

179

Effects of Aspirin on bleeding, PT, PTT

Increased bleeding time
No effect on PT, PTT

180

Uses of Aspirin

Reduce fever
Treat pain
Anti-inflammatory
Anti-platelet

181

S/E of Aspirin

Bleeding
Peptic ulcers (no protective prostaglandins)
Hyperventilation (stimulates respiratory centers of brain) --> respiratory alkalosis (but transitions to metabolic acidosis)
Reye's syndrome (Hepatoencephalopathy)

182

Mechanism of Clopidogrel

ADP receptor inhibitor (inhibits platelet aggregation by preventing expression of GP2b/3a)

183

Uses of Clopidogrel

ACS, Coronary stenting

184

2b/3a INhibitors

Abciximab
Eptifibatide
Tirofiban

185

ADP receptor blockers

Clopidogrel
Prasugrel
Ticagrelor (reversible)
Ticlopidine (causes neutropenia)

186

Uses for Gp2b/3a inhbitors

NSTEMI
Acute coronary syndrome
unstable angina
Percutaneous transluminal coronary angioplasty

187

Platelet abnormalities symptoms

Mucous membrane bleeding
Epistaxis
Petechiae
Purpura
Increased bleeding time

188

Immune Thrombocytopenia
a. mechanism
b. Signs
c. BM biopsy shows...

a. Autoimmune disease with Abs to Gp2b/3a --> immune system removes and destroys them
b. Platelet count is low
c. Increased megakaryocytic on BM biopsy

189

Treatment for ITP

Steroids
IV immunoglobulin
Splenectomy

190

Thrombotic thrombocytopenia purpura
a. mechanism
b. signs/symptoms
c.

a. platelets are excessively activated because of increased large vWF multimers --> widespread thrombosis --> uses up all the platelets and causes thrombocytopenia and bleeding
b. pentad of neurologic and renal symptoms: fever, thrombocytopenia, microangiopathic hemolytic anemia

191

Defect in TTP

Inhibition or deficiency of ADAMTS13 (metalloproteases) that cleaves and degrades vWF multimers

192

Treatment for TTP

Plasmapheresis
Steroids

193

What condition is TTP closely linked to?

Hemolytic Uremic Syndrome

194

What is triad of findings in HUS?

Microangiopathic hemolytic anemia
Renal symptoms
Thrombocytopenia

195

Five features of TTP/HUS
Nasty Fever Torched His Kidneys

Neurologic
Fever
Thrombocytopenia
Hemolysis
Kidney failure

196

What is HUS associated with in kids?

E. coli 0157H7

197

Bernard Soulier syndrome defect

Defect in glycoprotein 1b --> platelet can't bind collagen --> defect of platelet plug formation from defect in adhesion

198

Glanzmann thrombasthenia defect

Defect in Gp2b/3a --> defect in platelet aggregation --> platelet count normal, bleeding time prolonged

199

von Willebrand disease
a. defect
b. causes

a. defect in vonWillebrand factor
b. defect in platelet plug formation from defect in adhesion AND intrinsic pathway coagulation defect
c. Increased PTT and increased bleeding time

200

Treatment of vWF disease

Desmopressin (increased release of vWF in storage sites of endothelial cells)

201

Disseminated Intravascular Coagulation
a. mechanism

a. widespread activation of clotting --> deficiency in clotting factors and platelets --> bleeding state

202

Causes of DIC
STOP Making New Thrombi

Sepsis
Trauma
Obstetric complications!!!!!
acute Pancreatitis
Malignancy
Nephrotic syndrome
Transfusion

203

DIC
a. PT and PTT
b. Bleeding time
c. Fibrinogen
d. D-dimer

a. Prolonged
b. increased bleeding time
c. low fibrinogen
d. high fibrin split products (d-dimer)

204

peripheral smear of DIC

Schistocytes

205

Presentation of DIC

Multi organ failure
Bleeding

206

Most common inherited bleeding disorder

vWF disease

207

What does leukemia affect?
What does lymphoma affect?

Bone marrow, maybe peripheral blood
Lymphoma is tumor in lymph nodes

208

What makes lymphoma a Hodgkin lymphoma?

-Presence of Reed Sternberg cells (bilobed nuclear, clearing around nuclei, owl eye appearance, clearing around cell from cell shrinking)
-Found in single group of lymph nodes (extra nodal involvement is rare)
-Painless, nontender lymphadenopathy (nodes feel firm and rubbery)
-Lymphadenopathy in mediastinum
-Constitutional B symptoms: Low grade fever, night sweats, weight loss

209

Who gets Hodgkin lymphoma?

-Bimodal age (age 20 and 65)
-More common in men (except nodular sclerosing)

210

What are most non-Hodgkin lymphomas? Age distribution?

B cell lymphomas
Age distribution is widely variable

211

How do symptoms of non-Hodgkin compare to Hodgkin?

Fewer constitutional symptoms

212

What are certain types of non-Hodgkin lymphoma associated with?

HIV and immunocompromised

213

How do Reed Sternberg cells relate to prognosis?

The fewer cells the better prognosis

214

What is the most common type of Hodgkin lymphoma?

Nodular sclerosing type

215

Which type of Nodular sclerosing Hodgkin lymphoma has the best prognosis?

Lymphocyte rich form
Lymphocyte mixed or depleted form has worst prognosis

216

What are cell markers of Reed Sternberg cells?

CD15+
CD30+

217

Most common type of NH lymphoma in adults

Diffuse large B cell lymphoma

218

Translocation in diffuse large B cell lymphomas

t(14:18)

219

Follicular lymphoma translocation

t(14;18) of heavy chain Ig (14) and BCL-2 (18) --> BCL2 inhibits apoptosis

220

Burkitt lymphoma translocation

t(8;14) --> translocation of c-myc and heavy chain Ig

221

Mantle cell lymphoma translocation

t(11;14) --> translocation of cyclin D1 and heavy chain Ig

222

Starry sky appearance (sheets of lymphocytes with interspersed macrophages)

Burkitt lymphoma

223

Associated with EBV

Burkitt lymphoma

224

Endemic form of Burkitt lymphoma

Jaw lesion

225

Indolent course of lymphoma; painless waxing and waning lymphadenopathy

Follicular lymphoma

226

Associated with Sjogrens, Hashimotos, and H. pylori

Marginal cell MALToma

227

Adults present with cutaneous lesions (Japan, West African, Caribbean)

Adult T cell Lymphoma

228

Lytic bone lesions, Hypercalcemia

Adult T cell Lymphoma

229

Caused by HTLV (associated with IV drug abuse)

Adult T cell Lymphoma

230

Presents with skin patches/plaques characterized by atypical CD4 cells with cerebriform nuclei

Mycosis fungoides

231

If mycosis fungoides progresses to blood

Sezary syndrome

232

Associated with long term celiac disease

Intestinal T cell lymphoma

233

Lymphoma equivalent of CLL

Small lymphocytic lymphoma

234

Cancer most commonly associated with a non-infectious fever

Hodgkin lymphoma

235

Large B cells with bilobed nuclei and prominent owl's eye inclusions

Reed Sternberg Cells seen in Hodgkin Lymphoma

236

Large B cells with bilobed nuclei and prominent owl's eye inclusions

Reed Sternberg Cells seen in Hodgkin Lymphoma

237

What's the difference between acute and chronic leukemia?

Acute - rapid onset and rapidly progressive, >50% blasts on BM biopsy, (myeloblasts in AML, Lymphoblasts in ALL), numerous blast cells (>20% blasts), often associated with pancytopenia
Chronic -

238

ALL is most common in...

Children Female
Whites > Blacks

239

Common presentation of T-ALL

Mediastinal mass presenting as SVC like syndrome

240

Prognosis of ALL

Good prognosis in children (up to 90% remission)

241

TdT+, CD10+

TdT+ is a marker of preT and preB cells
CD10+ is markers of preB cells

242

ALL translocation that equals better prognosis

t(12;21)

243

ALL association

Down syndrome

244

Common ALL symptom

Bone pain

245

ALL association
(We all fall down)

Down syndrome

246

Common ALL symptom

Bone pain

247

Age of onset for AML

median onset 65 years

248

AML blood smear shows:

Auer rods (peroxidase cytoplasmic inclusions seen in M3 AML)
Increased circulating myeloblasts

249

Risk factors for AML

Prior exposure to alkylating chemotherapy, radiation, myeloproliferaetive disorders, Down syndrome

250

t(15;17)

M3 AML subtype responds to all-trans retinoid acid (vitamin A), inducing differentiation of myeloblasts (Acute promyelocytic AML)

251

DIC common presentation of:

M3 AML

252

CD13/33+

AML

253

PAS (-)

AML

254

What's the difference between acute and chronic leukemia?

Acute - rapid onset and rapidly progressive, >50% blasts on BM biopsy, (myeloblasts in AML, Lymphoblasts in ALL), numerous blast cells (>20% blasts), often associated with pancytopenia
Chronic - Insidious onset and gradual progression (months to years), mature cells (

255

PAS (-)

AML

256

Most common adult leukemia seen in western countries

CLL

257

Who does CLL affect?

Adults over age 50

258

95% have B cell markers

CLL

259

Smudge cells

CLL

260

Autoimmune hemolytic anemia

CLL

261

Autoimmune hemolytic anemia

CLL

262

CD20+, CD5+ B cell Neoplasm

SLL/CLL

263

Defined by the Philadelphia chromosome t(9;22), BCR-ABL

CML

264

Presents with increased neutrophils, metamyelocytes, basophils; splenomegaly

CML

265

Responds to Imatinib

CML

266

Very low LAP as a result of low activity in mature granulocytes

(vs. Leukemoid reaction which has Increased LAP)
CML

267

Autoimmune hemolytic anemia
(warm or cold agglutinins)

CLL

268

Presents with increased neutrophils, metamyelocytes, basophils; splenomegaly, fatigue, abdominal pain

CML

269

Very low LAP as a result of low activity in mature granulocytes

(vs. Leukemoid reaction which has Increased LAP)
CML

270

Age of presentation of CML

25-60

271

a. CLL progress to ALL?
b. CML progress to AML?

a. 10% progress to ALL
b. 80% progress to AML; this is Blast crisis

272

What is Philadelphia chromosome?

t(9;22) BCR ABL mutation
Encodes constitutively activated tyrosine kinase --> malignant transformation

273

What is Philadelphia chromosome?

t(9;22) BCR ABL mutation
Encodes constitutively activated tyrosine kinase --> malignant transformation

274

t(8;14)

Burkitt lymphoma

275

t(15;17)

M3 AML (auer rods); treated with ATRA

276

t(8;21)

AML
This is why patients with Trisomy 21 have increased incidence of AML.

277

What is Leukemoid reaction?

Increased WBC as a reaction to a stressor
Predominantly neutrophils
Left shift (5-10% immature bands)
Increased LAP (CML has decreased LAP)

278

What is Myelodysplastic syndrome?

Dysplasia of the hematopoietic cells in the myeloid tissue

279

What is Pseudo-Pelger Huet anomaly?

Neutrophils with bilobed nuclei; seen after chemotherapy

280

What are myeloproliferative disorders?

Neoplastic transformation of a single myeloid precursor -->
Monoclonal proliferation of mature myeloid cells
Polycythemia vera
Essential thrombocytosis
Myelofibrosis

281

Mutation common in myeloproliferative disorders

JAk2 --> encodes Janus kinase 2 --> switched on all the time --> constantly getting growth factor signal to make more cells

282

What is Polycythemia vera? What is the mutation?

Jak2 mutation in red cell precursor; causes increased hematocrit without elevated EPO

283

Presentation of polycythemia vera

Intense itching after hot shower (from increased basophils)
Erythromelalgia (severe, burning pain and red-blue coloration) from episode blood clots in vessels of extremities
Plethora (redness of face)
Hyper viscosity of blood
Splenomegaly
Headache

284

What is essential thrombocytosis

Overproduction of abnormal platelets --> bleeding, thrombosis

285

What does BM look like in Essential thrombocytosis?

Has enlarged megakaryocytes

286

What is myelofibrosis?

Fibrosis and obliteration of the marrow space
Causes teardrop red cells

287

What is myelofibrosis?

Fibrosis and obliteration of the marrow space
Causes teardrop red cells

288

What is multiple myeloma?

Monoclonal plasma cell cancer that arises in marrow and produces lots of IgG (55%) or IgA (25%)

289

Most common primary tumor arising within bone in people >40-50

Multiple myeloma

290

Most common primary tumor arising within bone in people >40-50

Multiple myeloma

291

How do you identify plasma cells?

Clock face chromatin and intracytoplasmic inclusions containing immunoglobulin

292

Presentation of multiple myeloma

Anemia (plasma cells interfere with production of other cells in BM)
Renal insufficiency (form casts and plug up kidneys)
Back Pain (bc they secrete ostend cytokines) Punched out lytic bone lesions!
Hypercalcemia
Susceptibilty to infection (decreased production of healthy immune cells)
Amyloidosis

293

Serum protein electrophoresis for Multiple myeloma shows:

Monoclonal antibody (M) spike

294

Bence Jones proteins

Immunoglobulin light chains in urine detected on urine protein electrophoresis
BUT Do NOT see elevated protein on regular urinalysis

295

Peripheral smear of multiple myeloma

Rouleaux formation (RBCs stacked like poker chips in bloos smear)

296

Peripheral smear of multiple myeloma

Rouleaux formation (RBCs stacked like poker chips in bloos smear)

297

What is Waldenstrom macroglobulinemia?

Shows M spike that is IgM
Hyperviscosity syndrome and Amyloidosis (blurred vision, Raynaud phenomenon)
No CRAB findings

298

Plasmacytoma

2 types: solitary plasmacytoma of bone and extra medullary plasmacytoma (predilection for head and neck -specifically nose)

299

What is Monoclonal Gammopathy of Undetermined significance?

Monoclonal expansion of plasma cells, asymptomatic, may lead to multiple myeloma
Need to be monitored

300

What is Monoclonal Gammopathy of Undetermined significance?

Monoclonal expansion of plasma cells, asymptomatic, may lead to multiple myeloma
Need to be monitored

301

Most common leukemia in children

ALL

302

Acute leukemia positive for peroxidase

AML