Hematology (Week 7) Flashcards

Question

Hypoproliferative anemia

Answer 1

Most common type of anemia Reticulocytopenia Low or normal MCV Impaired production of intact hemoglobin or impaired regulation of hematopoiesis

Answer 2

Disorders of: **Erythrocyte** production: congenital, acquired (deficiency of erythropoietin, chronic renal insufficiency, pure erythrocyte aplasia) Production of **mature hemoglobin**: disorder of **iron** (**deficiency**, sequestration (**anemia of chronic disease/inflammation**; **sideroblastic anemia**)), disorder of **heme** (**thalassemia**, lead intoxication, hemoglobin E, **sideroblastic anemia**) **Hematopoietic stem cell** **Bone marrow microenvironment**

Answer 3

No active secretion of iron Iron lost **only when cells lost** (urine, skin, gut, menstruation) Regulation mainly by absorption

Answer 4

20-30 mg per day is turned over between RBC destruction and production However, remember that only small amounts (1mg per day) are lost in gut, sweat urine that must be renewed by diet

Answer 5

O2 transport messed up Electron transport messed up **Anemia** **Muscle weakness**

Answer 6

**Oxidant damage** affects: Heart Liver Endocrine Joints Infection Note: more of a problem in men because women at least have menstruation to get rid of some iron every month

Answer 7

**Cannot produce mature hemoglobin** Hypoproliferative anemia Most **common** cause of anemia worldwide Get **microcytic, hypochromic RBCs, targets, anisocytosis, poikylocytosis** Negative iron stain (with Prussian blue) of marrow Can be due to **chronic blood loss** (infancy, lactation, pregnancy, GI ulcer)

Answer 8

**GI blood loss** **Menstruation** Blood loss in **pregnancy** and **lactation** Urinary blood loss Less common: **dietary** deficiency (in baby on formula), intestinal **malabsorption**, **atransferrinemia**

Answer 9

**Anemia** (hypoproliferative, reticulocytopenia, microcytic) **Epithelial** changes (koilonychia, depapillated tongue, esophageal webs and strictures) **Skeletal** changes (growth retardation, skull changes)

Answer 10

Cannot produce mature hemoglobin Iron is sequestered in **macrophages** and have erythropoietin dysfunction Lab: low serum iron, **low TIBC**, high ferritin, normal serum transferrin receptor Iron necessary for microorganism growth and division but host binds iron with ovoalbumin, transferrin, lactoferrin and ferritin --\> **inflammation** from disease leads to **cytokine** release (IL-1, TNF, IL-6) --\> macrophages increase lactoferrin receptors to **internalize** more lactoferrin-bound iron, increase ferritin synthesis and decrease iron output from the macrophage --\> overall iron sequestered in macrophages and withheld from both microorganisms and RBCs

Answer 11

**Nuclear-cytoplasmic dissociation** (nucleus doesn't mature normally and keeps cell **very big** so cannot get out into blood and is destroyed in bone marrow!) Intramedullary maturation arrest and hemolysis **Reticulocytopenia** (bc reticulocytes never get out of bone marrow!) with macrocytosis May not be restricted to hematopoiesis

Answer 12

Causes **megaloblastic anemia** Get mucosal changes Measure low folate in serum and RBCs Get folate deficiency if: poor diet, cancer, hemolysis, alcoholism, during pregnancy and lactation (increased demand), drugs, malabsorption Folic acid does not need cofactor to be absorbed, is depleted in 5 months ("nutritional" megaloblastic anemia) Folic acid does 1 carbon transfers to make thymidilate to make pyramidines and purines (for DNA synthesis)

Answer 13

Causes **megaloblastic anemia** Get **neurologic** **symptoms** (paresthesias in hands and feet, decreased vibration/position sense, ataxia, psychoses), mucosal changes Measure low B12 blood levels Get B12 deficiency if: deficiency in **intrinsic factor** activity (**pernicious** **anemia**), gastric resection/neoplasm, ileal resection/enteritis, fish tapeworm competition, diverticulosis, strict vegans Get vitamin B12 from **meat, dairy** Need intrinsic factor (secreted by parietal cells in stomach) to absorb B12 in terminal ileum Takes **years to deplete B12**, so don't just get nutritional deficiency!

Answer 14

Marrow shows young nuclei that are **large** and have **no clumping of chromatin** Blood smear shows **big RBCs** with **low hemoglobin** (macrocytic and hypochromic?) Blood smear also shows **hypersegmentation of neutrophils**

Answer 15

Premature **destruction** of erythrocytes: Intravascular vs. extravascular Intracorpuscular vs. extracorpuscular

Answer 16

**Reticulocytosis** (trying to make up for RBC loss/lysis) with any MCV **Polychromatophilia** of RBCs Erythroid hyperplasia of bone marrow --\> increased indirect **bilirubin**, increased urinary and fecal **urobilinogen**, increased endogenous carbon monoxide production **Depleted unbound haptoglobin** (because lots of free hemoblobin to bind haptoglobin)

Answer 17

Increased **indirect** **bilirubin** **Scleral icterus** Serum is yellow from indirect bilirubin Peripheral blood smear used to determine cause of hemolysis Erythrocyte features: **fragmentation**, **spherocytosis**, distinct erythrocyte morphology, erythrocyte inclusion

Answer 18

IgG eats up membrane of RBC On peripheral blood smear, see **spherocytes**

Answer 19

**Trauma** to RBC: heart valve shears RBCs --\> fragmented RBCs on smear **Chronic liver or kidney disease**: RBC membrane becomes pickled due to abnormal distribution of membrane lipids **Infection**: Plasmodium falciparum infects RBCs and causes RBC lysis

Answer 20

Splenic consumption Vasculature Plasma Erythrocyte membrane Cytoplasm Hemoglobin Erythrocyte enzymatic machinery Infection

Answer 21

Normal spleen 200-300 cc/minute (4-5% cardiac output) Half cells capable of phagocytosis White and red pulp, marginal zone and germinal centers

Answer 22

Portal HTN Infiltrative disorders of spleen (lymphoma) Cardiomyopathy Autoimmune disease Subcapsular hemorrhage **Hematologic disorders** (hemolysis, hemoglobinopathy, neoplastic)

Answer 23

Macroangiopathic hemolytic anemias (**heart valve** shearing RBCs) Microangiopathic hemolytic anemias (**DIC**, malignant hypertension, thrombotic thrombocytopenic purpura, **hemolytic uremic syndrome**)

Answer 24

Membrane lysins Toxins and envenomations (clostridial sepsis, spider bites, snake bites, chemical lysins)

Answer 25

**Congenital**: **hereditary spherocytosis**, elliptocytosis, stomatocytosis, acanthocytosis **Acquired**: **immunohemolytic anemias**, immune hemolysis, **Rh incompatibility**, **autoimmune hemolytic anemia, drug-induced hemolytic anemia**

Answer 26

Change in AA can give new characteristics to hemoglobin and lead to: **Sickle cell hemoglobin** (HbS): increased hemoglobin precipitation Unstable hemoglobin **Methemoglobins**: inability to keep iron in reduced form within hemoglobin molecule High/low affinity molecules: altered O2 affinity of hemoglobin molecule

Answer 27

**Alpha** on chromosome **16** (**4** **genes** total) Betas on chromosome **11** (**2 genes** total) Also, **gamma** and **delta** on chromosome 11 Note: easier to develop beta thalassemia because only 2 beta genes!

Answer 28

**HgA**: alpha2beta2 = major adult Hg (\>95%) **HgA2**: alpha2delta2 = minor adult Hg (\<3%) **HgF**: alpha2gamma2 = major Hg in fetus (\<2% in adults)

Answer 29

**Qualitative** problem Point mutation at **6th AA** position of **beta globulin gene** from **hydrophilic** **glutamic acid** to **hydrophobic** **valine** --\> when hemoglobin **deoxygenated**, beta globulins interact with each other so hemoglobins form **polymers** within RBC --\> **rigid, sickled RBC** 10% of American Blacks have S gene Age of onset is variable (6 months - 2 years) Lab: low grade **anemia**, erythroid hyperplasia, **extravascular hemolysis** (in the spleen? indirect hyperbilirubinemia) Symptoms: **pain, bone infarcts**, lungs, CNS, heart, renal, **autosplenectomy**, infections Treatment: analgesia, fluid if dehydrated, alkalinization if acidotic, antibiotics if infected, transfusions, **hydroxyurea** (only FDA approved), bone marrow transplant (?) 85% survive to age 20; 60% survive to age 50 Cause of death in kids is **infection** (spleen infarcted --\> encapsulated bacterial infection); cause of death in adolescents/adults is **acute chest syndrome** or infection Carrier state (**HgAS** usually asymptomatic and resistant to **Malaria**)

Answer 30

**Quantitative** problem **Decrease in synthesis** of a globin chain (globin gene missing!) resulting in **unbalanced** synthesis of globin chains and decreased hemoglobin production **Microcytic, hypochromic RBCs** **Beta Thalassemia Major**: **homozygous**; severe anemia, hepatosplenomegaly, hypercellular marrow, bone changes, iron overload (due to transfusions AND hemolysis of bad RBCs), infections, HgA 0; Hg 2-6 **Beta Thalassemia Minor**: heterozygous; mild anemia or asymptomatic, may worsen with infections or pregnancy; Hg \>9 **Hydrops fetalis**: missing all **4 alpha** genes; fetus has **"Barts Hg"** (gamma 4 tetramers) and dies **Hemoglobin H disease**: missing **3 alpha** genes so get **HgH which** is tetramer of beta chains only; intra-erythrocytic **inclusions** because they **precipitate**; hemolytic anemia, microcytic, hypochromic target cells **Alpha Thalassemia Minor**: missing **2 alpha** genes; mild microcytic, hypochromic anemia or asymptomatic **Silent carrier**: missing **1 alpha** gene; asypmtomatic

Answer 31

**G6PD** deficiency **Pyruvate kinase** deficiency Hemolytic anemias caused by other derangement of Embden-Meyerhoff pathway (glycolysis) Abnormalities of nucleotide metabolism

Answer 32

Malaria Babesiolsis Other protozoal infections Bartonellosis

Answer 33

**Bacterial** infection **Hyphal fungal** infection

Answer 34

1) Too many WBCs (**leukocytosis**): reactive (**infection**) vs. **neoplastic** (leukemias, lymphomas) 2) WBC **dysfunction**: congenital, toxic, neoplastic 3) Too few WBCs (**leukopenia**): decreased production, increased destruction, or splenic sequestration

Answer 35

**Decreased marrow production** of (usually) all blood cells Get **pancytopenia** (decreased erythroid, myeloid and megakaryocytic cell lines); only cells that remain are ones that live a long time (plasma cells and lymphocytes) Bone marrow is **hypocellular** Symptoms: weakness, fevers, infections (bc low WBC), bleeding (bc low platelets) Signs: **peticheae**, **hemorrhage**, **pallor**, **fever** Causes: **idiopathic**, drugs/toxins (**benzene**, **chloramphenicol**), **infection**, **radiation**, **immune** **mediated**, **paroxysmal nocturnal hemoglobinuria** Treatment: **transfusion**, antibiotics, **immune** **suppression** (ATG = horse serum), **hematopoietic stem cell transplantation**

Answer 36

Abnormal **production** or **accumulation** of lymphoid cells with clinical behavior reminiscent of ontogeny of the cells Note: you can only get cancer in **dividing** **cells** so there is no such thing as neutrophilic leukemia because neutrophils can't divide

Answer 37

Decreased: cytopenias Increased: cythemias, or cytoses

Answer 38

1) Primary marrow abnormality (**neoplastic** or preneoplastic) 2) Secondary (appropriate marrow response to external signals, like **infection**!)

Answer 39

**Leukemia**: abnormal cells in **blood** and **marrow** **Lymphoma**: abnormal cells in **lymph nodes**, thymus, spleen, or other lymphoid tissues (Peyer's patches) Note: this is a relative difference, not aboslute--they overlap obviously

Answer 40

Chronic lymphocytic leukemia (**CLL**) Acute lymphocytic leukemia (**ALL**)

Answer 41

**Neoplastic** will be **clonal**: all lymphocytes have either kappa or lambda light chain but not both Infectious will be polyclonal because lots of different cells fighting infection

Answer 42

**Lymphoproliferative** disorder **Lymphocytosis**, **lymphadenopathy**, hepatosplenomegaly, infections, immunologic abnormalities (hypogammaglobulinemia, immune cytopenias, paraproteinemias), secondary malignancies Usually monoclonal mature **B-cells**, but rarely T cells, NK, Prolymphocytic, or Hairy Cell) 30% of all leukemias in US Cytogenetic abnormalities: deletion 13q14.3, trisomy 12 Lab: coexpression of **CD5** (usually T cell marker) with **CD19 and 20** (B cell markers), anemia, thrombocytopenia Treatment: only treat if **symptomatic** (alkylators, fludarabine, chemo, steroids to induce apoptosis of lymphocytes, Mab therapy, blood or marrow transplant in younger pts)

Answer 43

Stage 0: lymphocytosis of blood and marrow Stage I: lymphocytosis + lymphadenopathy Stage II: lymphocytosis + splenomegaly and/or hepatomegaly Stage III: lymphocytosis + anemia (Hg\<11) Stage IV: lymphocytosis + thrombocytopenia (plt\<100,000)

Answer 44

Body tries to control B cell clone but actually ends up **controling normal clones** and neoplastic cells still grow (reason why patients develop hypogammaglobulinemia?) CLL patients get **encapsulated bacteria infections**

Answer 45

**Lymphoproliferative** disorder Blood and marrow **lymphocytes** with **fine filamentous "hairy" projections** Usually **B cells** Stain for tartrate resistant acid phosphatase (trap), monoclonal surface immunoglobulin and Fc receptors **Pancytopenia**, splenomegaly, infections, immune abnormalities Responsive to deoxycoformycin, alpha-interferon, splenectomy **1 week of nucleoside analog can produce 10 year remission!**

Answer 46

**Mycosis fungoides/Sezary's syndrome**: **CD4+** lymphoma which produces cutaneous infiltrates, lymphadenopathy and can transform to erythrodermatous phase with circulating Sezary cells **Large granular lymphocytosis syndrome**: **T cell/NK cell** disorder (**CD8+**), severe neutropenia, pancytopenia, rheumatoid arthritis, splenomegaly **Adult T cell leukemia/lymphoma**: associated with **HTLV-1**, have lymphocytosis, lymphadenopathy, hypercalcemia, lytic bone lesions

Answer 47

1) **Vasoconstriction** (if have vascular disease and hardened vessel, can't constrict and pt will bleed!) 2) **Primary** hemostasis: **platelets** 3) **Secondary** hemostasis: **fibrin**

Answer 48

Endothelium is damaged and exposes **subendothelium** below von Wildebrand Factor (**vWF**) binds subendothelium **Platelets** then bind vWF via GpIb receptor

Answer 49

Platelet adhesion: **unactivated** platelets bind ?? Platelet activation: **activated** platelets **expose adhesion molecules** and adhere to subendothelium?

Answer 50

1) Adhesion 2) Activation and secretion 3) Aggregation 4) Procoagulant activity (assembly of factors in secondary hemostasis)

Answer 51

1) **Endotheluim**: covers subendothelium because as soon as subendothelium exposed, we clot 2) **Fast flow of blood**: things zipping by so fast that they can't find each other (need high enough **concentration** to make clotting happen)

Answer 52

**Intrinsic** pathway: **9 needs 8 as cofactor to activate 10** --\> 10 needs 5 as cofactor to activate 2 (thrombin) --\> thrombin turns fibrinogen to fibrin **Extrinsic** pathway: **7 activates 10** --\> 10 needs 5 as cofactor to activate 2 (thrombin) --\> thrombin turns fibrinogen to fibrin

Answer 53

**7, 9, 10, 2** (thrombin) These trigger the clotting cascade Serine proteases, synthesized in liver These zymogens (proenzymes) need to be **carboxylated** by carboxylase, but carboxylase needs **Vitamin K** as **cofactor** --\> once carboxylated, can **bind Ca2+** which they need in order to become **active**

Answer 54

Coumadin **inhibits carboxylase reaction** on **7, 9, 10, 2** so that these clotting enzymes **cannot become active**

Answer 55

Since enzymes/co-factors are **not consumed** in reaction, levels can get **very low (\<30%)** before coagulation is impaired (recessive or X-linked mutations) **Mild bleeding**: **30-5%** activity of factors **Moderate bleeding**: **5-1%** activity of factors **Severe bleeding**: \<1% activity Note: fibrinogen and vWF ARE consumed in reaction, so lower levels of those show anti-coagulation phenotype easily (autosomal dominant mutations)

Answer 56

**Petechiae** and **purpura** (usually symmetric; small bleeds) History of easy or spontaneous **bruising** Mild to moderate **mucosal membrane bleeding** (gingival, menorrhagia, epistaxis)

Answer 57

**Thrombocythemia** (primary or secondary) **Thrombocytopenia** (decreased production or increased destruction) **Loss of platelet function** (congenital or aquired)

Answer 58

**Myeloproliferative** disease (CML, PV, ET) Platelets can have **normal** or **abnormal** function

Answer 59

**Increased release of platelets** from bone marrow Due to **steroids** or **stress**, or cute phase reactant, iron deficiency, acute blood loss, post splenectomy, epinephrine, chronic infections Platelets have **normal** function

Answer 60

Marrow replacement (**space taken up** by fibrosis) **Aplastic anemia** **Viral infection** Drugs (chemical wiped out progenitors) Congenital disorders (rare)

Answer 61

**Prosthetic valves** **Hypersplenism** Immune mediated disseminated intravascular coagulation (**DIC**) Medications (**heparin**, antibiotics, H2 blockers)

Answer 62

Autoimmune (**ITP**) acute or chronic **Alloantibodies** (**neonatal** or **transfusion**) Drug induced (ie **heparin**) by creating new epitope Disease association (make antibodies you shouldn't): other autoimmune, lymphoproliferative, myeloproliferative, solid tumors, infection

Answer 63

**Acute**: **children** 2-9 years; **abrupt** onset, **after infection**, **\<20,000 platelets (very dangerous!)**; lasts 2-6 weeks but then **80% spontaneous remission** (don't need tx other than support); variable response to immunosuppression or splenectomy **Chronic**: **adults** 20-40 years; more female; **gradual** onset; no clear antecedent; **20-100,000 platelets still**; lasts years and spontaneous remission is rare; usually respond to **immunosuppression or splenectomy**

Answer 64

Uremia (not clear why) Liver disease Prosthetic valves Aspirin or NSAIDs (or other drugs) Essential thrombocythemia Congenital (vWD, intrinsic platelet defects)

Answer 65

**Platelet count** **Bone marrow** (look for megakaryocytes to determine production vs. destruction) Bleeding time (only if platelets \>100,000) Platelet aggregation assays

Answer 66

**Normal platelet count: 150-350,000** Risk of excess bleeding with **surgery**: **\<50,000** Risk of **spontaneous** bleeding: **\<20,000** **Imminent risk** of GI or cerebral hemorrhage: **\<5,000**

Answer 67

Very archaic, only used if you think there is a **vascular problem** (can't test that with other lab tests!) Normal bleeding time 10 minutes Only do this if patient has \>100,000 platelets and no liver disease, uremia, collagen vascular disease, prosthetic valves, etc because of course bleeding time will be increased!

Answer 68

**Decreased factor production**: acquired (liver disease, Vitamin K deficiency), congenital (hemophilia) **Increased factor consumption**: acquired (DIC), congenital (rare: alpha2-anti-plasmin)

Answer 69

**Von Willebrand's Disease** (autosomal dominant) **Hemophilia A** (factor 8; X-linked) **Hemophilia B** (factor 9; X-linked) Other factors (autosomal recessive) Fibrinogen (dominant or recessive)

Answer 70

Made in endothelial cells Glues platelets down to exposed collagen to start **primary hemostasis** Consumed in reaction so mutation is autosomal dominant (unlike enzymes!) Also **stabilizes factor 8**, so can affect secondary hemostasis --\> larger bleeds

Answer 71

Common: bleeding in major muscles and **joints**, large bruises Rare: mucosal hemorrhage, intracranial bleeds, bleeding from minor cuts and abrasions

Answer 72

**Plasmin**: degrades fibrin (degrades clot) **Protein C**: serine protease (like 7, 9, 10, 2) with co-factor Protein S that degrades other co-factors 8 and 5; has shortest half-life **Anti-thrombin III:** serine protease inhibitor; in presence of heparin, inhibits 2, 9, 10 (not 7 because doesn't fit)

Answer 73

Potentiates anti-thrombin III to inhibit factors **2, 9, 10** Starts working **immediately!**

Answer 74

Give **heparin** first because starts anti-coagulating immediately (works to inhibit factors 2, 9, 10 by potentiating anti-thrombin III) Give coumadin a few days later because coumadin only works on NEWLY synthesized factors (prevents carboxylation/inhibits protein C first to get **slight clotting** which you don't wait--then prevents carboxylation/inhibits factor 7, 9, 10, 2 to anti-coagulate); coumadin will KEEP factors 7, 9, 10, 2 from working long-term

Answer 75

Note: clotting disorders are all **autosomal dominant with incomplete penetrance** (most symptomatic patients have **\>1 mutation** and other contributing factors); homozygous mutation is incompatible with life! Antiphospholipid syndrome (often seen in lupus) Factor V Leiden mutation (resistance to Protein C) Protein C deficiency Protein S deficiency ATIII deficiency Prothrombin mutation Homocysteinemia

Answer 76

Result of something else bad going on: **major tissue trauma**, brain trauma, **shock** (to treat DIC, fix initial problem; short term treatment has no protocol, either can fix clotting or bleeding) Generalized **intravascular** **clotting** AND **fibrinolysis** (dissolving clots) Disseminated **microvascular** **thrombi** cause tissue injury Consumption of coagulation factors and platelets causes **hemorrhage** See **low platelets, factors, fibrinogen**, and **high fibrin degradation products**

Answer 77

Direct intravascular factor activation by proteases: snake **venom**, proteases released in acute **pancreatitis**, crude factor concentrates Release of cellular procoagulants (**tissue factor**) causes intravascular **cell lysis** (hemolysis, leukemia, granulocyte lysis in sepsis), extravascular cell lysis (tumor, trauma, surgery), ascitic or amniotic fluid emboli Vascular factors: endothelial cell damage by endotoxin, hypotension and stasis (**shock**), **hemangiomas** Note: with shock, coagulation factors going really slowly and can aggregate easier

Answer 78

**Glomerular** **capillaries** frequently affected because plugged with microthrombi (fibrin-platelet thrombi) Widespread focal **ischemia** AND **hemorrhage** damages kidney, skin, brain, lung, GI, mucous membranes

Answer 79

Prothrombin time (**PT**): 9-12 sec Partial thromboplastin time (**PTT**): 22-33 sec **Fibrinogen**: 200-400 mg/dl Specific factor/co-factor assays: \>50% activity APC resistance/Factor V Leiden **D-dimer** assay: should be negative (measures plasma degraded fibrin)

Answer 80

Remember, PT measures extrinsic pathway (factor 7) and PTT measures intrinsic pathway (factor 9 and 8) Mutation in **7** --\> prolonged **PT** **Hemophilia A** --\> prolonged **PTT** **Hemophilia B** --\> prolonged **PTT** Mutation in **10** --\> **both** **Liver disease** --\> **both** **Vitamin K deficiency** --\> **both** Give **heparin** --\> prolonged **PTT** (doesn't affect 7!) Give **coumadin** --\> prolonged **PT** (7 has shortest half life!)

Answer 81

Ends of long bones Iliac crest

Answer 82

Iron B-12 Folate

Answer 83

2/3 mature in the **marrow** and then are released into circulation 1/3 are put into circulation and THEN mature in the circulation

Answer 84

Depends, but can be up to 10x higher % (normal is 0.5 - 1.5%, so could be **5 - 15%**)

Answer 85

Spectrin Ankyrin Actin Note: these hold bilayer together and keep RBC in its normal shape; if defect in proteins, form spherocytes

Answer 86

**Microcytic**: iron deficiency, thalassemia **Macrocytic**: folate or B12 deficiency **Normocytic** but with **abnormal** **shapes**: hereditary spherocytosis, sickle cell disease

Answer 87

**Fatigue**, **breathlessness** **Pica** (persistent compulsive desire to ingest certain food or non-edible items like ice, clay, plaster) **Sore mouth,** angular stomatitis, **palor**

Answer 88

**B12** and **folic acid deficiency** **Hypercellular** bone marrow with increased **megaloblasts** All hematopoetic lineages show **nuclear to cytoplasmic dyssynchrony** **Hypersegmented neutrophils** Treat with B12 and see increase in **reticulocyte** count in first **week** and disappearance of **hypersegmented** **neutrophils** in **2-3 weeks**

Answer 89

Primary granules: MPO, elastase, defensins, cathepsins Secondary granules: lactoferrin Tertiary granules: cathepsin, gelatinase Note: these enzymes play important role in killing microorganisms

Answer 90

ANC = WBC x (% bands + % mature neutrophils) x 0.01

Answer 91

Severe neutropenia **\<500 per mm³** Get **infections** (chills, fever, weakness), ulcerating, necrotizing oral/pharyngeal lesions with massive growth of bacteria and no granulocyte response Treatment includes recombinant hematopoietic growth factors (G-CSF)

Answer 92

Neoplasm of malignant **plasma cells** Normal hematopoietic elements replaced by malignant plasma cells Neoplastic plasma cells secrete **paraproteins** which cause kidney problems and interfere with normal antibody secretion by plasma cells Clinical features: **CRAB** = calcemia, renal failure, anemia, bone lesions (lytic) Diagnosis: **M-protein** (paraproteins) in serum or urine, bone marrow with clonal plasma cells or plasmacytoma, CRAB

Answer 93

Hormone responsible for platelet production Produced by liver and kidney

Answer 94

**Uremia** (renal failure) **Liver disease** **Prosthetic valves** **Aspirin** or **NSAIDs** (or other drugs) Congenital (intrinsic platelet defects): **Bernard Soullier syndrome** (Gp1b deficiency), Glanzmann's thrombasthenia

Answer 95

If prevalence of disease in a population is **low**, even tests with high specificity or sensitivity will have **low positive predictive values** Makes sense because if prevalence is low, **more positives will be false positive** and more negatives will be truly negative

Answer 96

If very **low HIV prevalence**, positive predictive value (PPV) is very low but NPV is very high --\> just have to do **confirmatory test on positive results** Note: **ELISA** used for screening and **nucleic acid test** used for confirmation (not western blot anymore because that misses patients with early HIV infection)

Answer 97

Strategy used **to diagnose "recent" infection** First test with threshold of 50, see positive result, then test with threshold of 100 and see negative result --\> means **antibody titer is low** which means person was just recently infected with HIV This strategy "tunes down sensitivity of the test" (**increase threshold to call test positive**)

Answer 98

ABH antigens are located on transport proteins of the RBC membrane Antigens differ only with respect to one terminal sugar O: no terminal sugars (H antigen) A: N-acetyl-D-galactosamine B: D-galactose

Answer 99

Blood type A (has A antigen) can receive RBCs from A, O; plasma from A, AB Blood type B (has B antigen) can receive RBCs from B, O; plasma from B, AB Blood type O (no antigens) can receive RBCs from O; plasma from O, A, B, AB

Answer 100

Add recipient plasma to donor RBC and see if there is a reaction (should be NO reaction if ABO matched!) Use secondary antibody to Fc region of human antibodies to allow for clumping if the recipient's antibody did bind to donor's RBC

Answer 101

1 unit of packed RBCs = 250-300ml One unit will **increase hemoglobin** by **1 gm/dL (Hct, 2-3%)**

Answer 102

Not based upon numbers, but upon **symptoms**! To restore O2 carrying capacity in symptomatic anemia (exertional dyspnea, dyspnea at rest, fatigue, hyperdynamic state, lethargy and confusion, CHF, angina, arrhythmia, MI) or acute bleeding In general, transfuse **high risk patients** (acute MI, unstable angina) at Hgb **\< 10g/dL**; **low risk patients** at Hgb **\< 7g/dL** Note: if someone anemic (Hg = 6) but doesn't have symptoms, don't transfuse them!

Answer 103

What we're **most scared of** during transfusion! Occurs within **minutes to hours** after transfusion Signs and symptoms: chills, fever, hemoglobinuria, hypotension, renal failure with oliguria, DIC (oozing from IV sites), back pain, pain at infusion site, anxiety Management: **supportive** (maintain hydration, analgesics, pressors, hemostasis, follow-up labs), prevention Incidence = 1:38,000 - 1:70,000 Etiology: clerical error 70% of time ABO incompatible transfusions are the worst (can also have incompatibilities in other proteins?)

Answer 104

Occurs secondary to **anti-D (anti-Rh) antibodies** **Mother** lacks antigen (**Rh-**) **Fetus** possesses antigen (**Rh+**) First baby's fetal red cells stimulate maternal IgG response during birth (?) If **second** **baby** is Rh+, antibody from mother crosses the placenta and binds/destroys fetal RBCs --\> fetal anemia (cardiac failure and edema, hydrops fetalis, jaundice, kernicterus) Note: mother can be sensitized by transfusion or previous pregnancy (maybe not enough of antibody response to cause anemia in first baby? Maybe just IgM with first baby..?)

Answer 105

**Rho(D) immune globulin** (Rhogam) is given to **all Rh- mothers** at 28 weeks gestation If baby is Rh+, the Rho(D) immune globulins will **coat baby's RBCs so that mother never "sees" the antigen** and never makes Rh antibodies! When baby is born, can type the baby to see if it's actually Rh+ --\> if baby was Rh+, keep giving mother Rhogam until all baby's blood out of her system?

Answer 106

Take **serial titers every 2-4 weeks** Measure Rh antibody in mother If baseline **increase by two dilutions**, means baby is at risk for hemolytic disease of newborn (baby is Rh+ and mother is reacting to it!) Note: you can also look at the **paternal genotype** to see if he is Rh+ Can also use **serial doppler ultrasound** to measure peak systolic velocity of fetal MCA (if anemic, lower blood viscosity and increased cardiac output); this is performed at 18 - 35 weeks

Answer 107

Can do this if **baby is anemic** Cord blood obtained by cordocentesis to measure hemoglobin level Transfuse fresh **O and Rh negative blood** using umbilical vein Goal is to suppress fetal red cell production Do transfusions until birth

Answer 108

Do this if someone has platelet count \<10-20,000 (myelosuppression from chemotherapy or primary aplasa (ALL)) **Apheresis platelets**: platelets in small vol of plasma with minimal RBC/WBC; 150-250 ml/unit; raises platelet count by 30,000 **Platelet concentrate** (PC): platelets in small vol of plasma with minimal RBC/WBC; 50-70 ml/unit

Answer 109

Second most common reaction **IgE** to donor plasma proteins (FFP \> platelets \> RBC \> cryo) Signs and symptoms: **urticaria**, **pruritis**, flushing Therapy: stop transfusion, give antihistamine, then can **restart** transfusion; or give antihistamine prophylactically if know will have this rxn

Answer 110

Antibody to donor **WBCs**, or transfusion of pre-formed **cytokines** in blood products (platelets most common) Signs and symptoms: fever, chills, rigors, headaches, possibly changes in BP, HR, dyspnea, nausea Not life-threatening but uncomfortable Therapy: **antipyretic**; use **leukocyte-reduced** blood products

Answer 111

FFP contains all **coagulation factors**, so give to someone who is not clotting well (liver disease, DIC, factor deficiency, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome being treated by plasma replacement, coumadin reversal) Therapy guided by coag studies (PT, aPTT) 1 unit plasma increases most factors 2.5%; **4 units** plasma increases most factors **10%** Contraindications: available specific therapy (factor 8, 9, vitamin K), volume expansion

Answer 112

Causes **death** more often than any other transfusion reaction (mortality 5-10%) Leakage of **fluid into alveolar space** due to diffuse alveolar **damage** (**antibody-mediated** or cytokines) Signs and symptoms: acute respiratory distress, **frothy fluid coming from endotracheal tube**, tachycardia, fever, hypo/hypertension, cyanosis Consequences: lung injury and prolonged ventilatory time, predispose to pulmonary infection, death Therapy: **supportive** care until recovery; test for WBC antibody (HLA, granulocyte) in donor and recipient Note: this is a **clinical diagnosis** (act fast and lab test takes a week!)

Answer 113

**Volume** **overload** temporally associated with transfusion Signs and symptoms: SOB, increased RR, hypoxemia, cough, tachycardia, JVD, headache Therapy: upright posture, O2, IV diuretic, **transfuse split unit**

Answer 114

**HIV** **HepB** **HepC** **HTLV-1, 2** **WNV** **Syphilis** CMV (sometimes?) Chagas (not yet FDA mandated)

Answer 115

**Oxygen carrying protein** within RBCs Normal adult HbA contains 4 subunits: 2 alpha chains and 2 beta chains Each subunit has a **globin** (polypeptide chain) and a **heme** (iron-containing prosthetic group)

Answer 116

Because **alpha** is expressed during **fetal life** and **beta** is not expressed until **after birth**

Answer 117

**Ordered** **regulation** of developmental gene expression Genes in each cluster **arranged** in same transcriptional orientation and same **sequential** order as **developmental** expression

Answer 118

**Embryonic** hemoglobin: **zeta2epsilon2** **Fetal** hemoglobin (**HbF**): **alpha2gamma2** (predominates 5 weeks gestation to birth; 70% of total Hb at birth; \<1% of total Hb in adulthood)

Answer 119

**HbA:** alpha2beta2 (nearly all is HbA by 3 months old) **HbA2**: alpha2delta2 (\<2% of adult Hb)

Answer 120

Relative **imbalance** (NOT instability!) in relative amounts of alpha and beta chains, due to mutations resulting in **decreased synthesis** of one or more globin chains **Excess normal chains precipitate** in red cell to damage cell membrane and **destroy RBCs** prematurely Results in **hypochromic** **microcytic** anemia and **tissue iron overload** Seen in Mediterraneans

Answer 121

Clinically "**benign**" and not associated with disease Mutations **impair perinatal switch** from gamma to beta globin synthesis At least one **gamma** gene remains **intact** Increased gamma chain production so **increased HbF** in adult HPFH heterozygotes have 17-35% HbF

Answer 122

**Autosomal recessive** disorder **HbSS** HbS is mutation of **6th** codon of **beta** **globin** **gene** turning **hydrophilic** **glutamic** **acid** to **hydrophobic** **valine** When **deoxygenated**, hemoglobin S interacts with other hemoglobin S to **polymerize** and cause RBC to be r**igid and sickled** Found in "Malaria Belt" but mutation emerged outside of Africa separately too (heterozygote confers resistance to malaria)

Answer 123

Presentation in first **2 years** of life **Infections**, **anemia**, failure to thrive, **splenomegaly**, dactylitis **Vaso-occlusive infarctions**: strokes, acute chest syndrome, renal papillary necrosis, **autosplenectomy**, leg ulcers, priapism, **bone** **aseptic** **necrosis**, visual loss However as many as **70% of people have no symptoms** Causes of death: progressive **renal/cardio-pulmonary failure** (in 30s and 40s), **parvovirus** **infections** (high risk of life-threatening aplastic anemias, temporary cessation of RBC production)

Answer 124

Disorder of alpha globin production Affects formation of both **fetal** and **adult** hemoglobins (can cause **intrauterine** and **postnatal** disease) In absence of alpha globin chains, beta globin **tetramers** form (**gamma4** is **Hb Bart's** and **beta4** is **HbH**) which **cannot release O2** to tissues normally Normal = 4 functional alpha genes Silent carrier = 3 functional alpha genes **Alpha-thal mild** = 2 functional alpha genes **Alpha-thal HbH** = 1 functional alpha genes **Hydrops fetalis** = 0 functional alpha genes

Answer 125

High level of **Hb Bart's** (**gamma4**) Marked **intrauterine** **hypoxia** Seen most commonly in **Southeast Asia** (high gene frequency, predominant form of alpha thal trait there is --/aa, so have risk of --/-- whereas elsewhere it's -a/-a!) Note: hydrops fetalis is massive generalized fluid accumulation in utero

Answer 126

Anemia develops because of **gradual precipitation** of **HbH** in erythrocytes

Answer 127

**Excess alpha chains** Alpha chains are insoluble, **precipitate** in RBC precursors and cause **RBCs to be destroyed** in bone marrow (ineffective erythropoiesis) Not apparent until a few **months after birth** Beta thalassemia **minor** = **heterozygote** Beta thalassemia **major** = **homozygous**

Answer 128

**Heterozygote** (**one normal** beta globin gene, the **other mutated**) **Hypochromic**, **microcytic** anemia May be **misdiagnosed as iron deficiency anemia** **HbA2** **elevation** only in these heterozygotes (alpha2delta2) **HbF** is also **increased** (not due to reactivation of gamma globin gene but increased selective survival and possibly increased production of minor population of HbF-containing adult RBCs)

Answer 129

There are **many** different mutations in the beta globin gene that can lead to beta thalassemia!

Answer 130

Usually genetic compounds that create **homozygote** (two genes with mutations in beta globin though) Severe **anemia** with phenotype due to combined effects of two alleles **Beta0** thal: **no HbA** present **Beta+** thal: **HbA** present Severe **hypochromic** anemia Treatment: blood transfusion and iron chelation; bone marrow transplantation if appropriate match

Answer 131

If the beta thal gene is **beta0**: like **sickle** **cell** **disease** If the beta thal gene is **beta+**: may be **mild** phenotype

Answer 132

Beta thal homozygotes (beta thal major) who also inherit alpha thal allele may have **LESS** **severe beta thalassemia** because there is **LESS imbalance** of alpha vs. beta globins!

Answer 133

**Pica** (eating ice) **Glossitis** (sore tongue) **Dysphagia** (esophageal webs)

Answer 134

Due to defect in **membrane skeleton protein** of RBC **Intracorpuscular hemolysis**

Hematology (Week 7) Flashcards

(158 cards)