1. HEMATOLOGY for step 1 Lauren Meshkov, MS-3 lmeshkov@med.miami.edu

2. Tips Memorize non-deducible info Predict board-style ?’s (2-3 step thinking) Make connections between subjects Who cares about other people!

3. Overview Anemia Platelets vs. Coagulation Aspirin vs. Heparin vs. Warfarin vs…. Lists to Memorize Questions

4. Anemia Mania! Alcoholism * Anemia of Chronic Dz * Autoimmune * AZT * B12 * DIC/TTP/HUS * Fe def * Folate def * G6PD * HbC * Lead * Liver dz * MAHA * Meds * Parvo B19 * PNH * Pyruvate kinase def * Reticulocytosis * Sickle Cell * Sideroblastic * Spherocytosis * Thalassemia *

5. Anemia Break Down 1.Microcytic, Macrocytic, or Normocytic? – MCV is your best clue!!! Normal = 80-100 2. Intrinsic vs. Extrinsic – RBC naturally f’d up or being attacked (hemolysis) 3. Intravascular vs. Extravascular – Is RBC getting whacked in the blood or the spleen? 4. How does the retic count look? – Bone marrow problems  leukemia?

6. Microcytic: Heme Synth (MCV < 80) Fe deficiency vs. Thalassemia Sxs – fatigue, pallor, pica Labs – everything normal but H&H Fe studies – low Fe, high TIBC, low ferritin, very low %sat Differential based on pt ID: 1.Old folks – chronic GI bleed! 2.Young person – malabsorb, IBD 3.The Ladies – pregnancy, menses 4.Plummer Vinson – esophageal web and glossitis Treat? Ferrous Sulfate (also for dx) Sxs – depends on type  : African/Asian missing 4 genes? Hb Barts (  4)  death (hydrops fetalis) missing 3 genes? HbH dz (  4)  symptoms missing 1-2 genes? Carrier  asymptomatic  : Mediterranean w/ pt mutations Labs – everything normal but H&H Fe studies – NORMAL Electrophoresis – btw  Major homozygote (HbF) Marrow expansion, skull crew cut xray, chipmunk Minor heterozygote Asymptomatic

7. Macrocytic: DNA Synth (MCV > 100) Folate deficiency vs. B12 deficiency Sxs – Glossitis sxs from underlying condition Labs – folate low, high homocysteine Normal methylmalonic acid Differential based on pt ID: 1.*Alcoholics – Malnutrition 2.IBD pts - Malabsorption 3.On bactrim or MTX 4.The Ladies – pregnancy 5.Hemolytic Anemias (demand) Smear – hypersegmented polys Sxs – Glossitis Neurologic, posterior columns (periph neuropathy, dementia) Labs – B12 low, high homocysteine high methylmalonic acid! Smear – hypersegmented polys *Years to lose B12 stores (vegans? Grandma “tea and toast”) (B12) DNA: Homocysteine  Methionine + THF (B12) FA’s: Methylmalonic acid  Succinyl CoA  TCA for energy

8. Identifying other Anemias G6PD – recent meds (sulfa, ASA, bactrim), x-linked! Spherocytosis – smear, excess membrane Sickle cell – osteomyelitis, pain crises (low O2 or dehydration), SHiNS, aplastic crisis. *Biochem: Valine put in place of glutamic acid PNH – dark a.m. urine that fades through day, decay accelerating factor, complement mediated MAHA – valve dz, DIC (all coags high), TTP, HUS Autoimmune – other autoimmune dz Parvo B19 – sickle cell aplastic anemia Anemia of chronic disease – other dz! (CA), high ferritin Lead poisoning – new home, colic, neuro, lead lines, stippling, *Biochem: blocks ferrochetalase and ALA dehydratase

9. Iron Deficiency Anemia of Chronic Dz Hemo- chroma- tosis Pregnancy OCP use Lead poisoning Serum FeLow HighNo changeHigh (blocks ferrochetala seso no heme made) Transferrin (TIBC) HighLow High (liver)Low FerritinLowNormal or high HighNo change Transferrin % saturation (Fe/TIBC) Low/High = Very Low Low/Low = No change High/Low = Very high No change/High = Low High/Low = High

10. Platelets vs. Coagulation PT (9-13 sec) and PT (29-34 sec)? Normal! Petechiae, Purpura, Epistaxis, Bleeding gums Factor VII Factor II, V, X, VII, IX, XI, XII

11. Platelets vs. Coagulation PT (9-13 sec) and PT (29-34 sec)? Prolonged! Easy bruising D-dimer  Fibrin being broken down in PE? – Not necessarily. Better negative predictive value. Factor VII Factor II, V, X, VII, IX, XI, XII COAGULATION Plasminogen--plasmin Hemophilia A or B Heparin (ATIII) Warfarin (epoxide reductase) tPA, streptokinase thrombolytics Vit K (epoxide reductase)  II, VII, IX, XX Antithrombin III def Protein C or S def Factor V Leiden

12. Platelets vs. Coagulation (what’s messed up?) Hemophilia A: VIII Hemophilia B: IX Vitamin K def: epoxide reductase  II, VII, IX, X Antithrombin III def:  can’t break down Factor V Leiden:  mutated V can’t be broken down Bernard Soulier: Gp1b Glanzmann’s: GpIIb/IIIa Abciximab: GpIIb/IIIa von Willebrand: vWF Clopidogrel: ADP rec Ticlopidine: ADP rec Aspirin: COX  TXA2 ITP: autoimmune TTP:

13. Bernard- Soulier Glanz- mann’s ITPTTPHemo- philia A or B vWFDIC PTNormal Increased PTTNormal IncreasedNormal or increased Increased BTIncreased NormalIncreased Platelet Count DownNormalDown Normal Down Clinical or MOA Platelet can’t hook onto collagen Platelets can’t aggregate Antibody vs. GpIIb/IIIa. Megakar- yocyte up Fever, Neuro, AKF, low pltlts, maha. ADAMS13 clumps of vWF, traffic jam Hem- arthrosis. Little boy Platelet can’t hook onto collagen, can’t carry VIII. Tx: FFP or cryo, ddvap “STOP making new Thrombi” Huge clotting, factors all used up so bleed! D-dimer+

14. ASA vs. Heparin vs. Warfarin ASA MOA: Irreversibly inhibits COX-1 and COX-2. (Arachidonic acid  TXA2) Why take it? Fever, analgesic, anti-inflammatory, antiplatelet. *Kawasaki’s AEs: Gastric ulcer, bleeding, hyperventilation (acid-base), Reye’s, tinnitus Antidotes: NaHCO3, alkalinze the urine Heparin MOA: Activates Antithrombin, which breaks down thrombin and Xa. Why takes it? PE, DVT, stroke, ACS, MI. Bridge to Warfarin *Ok in pregnancy AEs: Bleeding (PTT), thrombocytopenia (*HIT), osteoporosis, drug- interactions Antidotes: 1. Stop the heparin 2. Protamine sulfate Warfarin MOA: Stops epoxide reductase and  -carboxylation of Vit K (II, VII, IX, X) Why take it? Chronic anti-coagulation (heparin bridge), no good in preggo AEs: Bleeding (PT), teratogenic, *skin necrosis, *P-450 drug interactions (INR) Antidotes: Vit K, FFP

15. Things to Memorize 1.Blood cell smears 2.Heme synthesis and the porphyrias

16. Question 1 A 33 yo F comes to the office with fatigue and heavy menstrual cycle. Her H&H is 10.2/76.2 and RDW 18.5. A pregnancy test is negative and she is otherwise healthy. What do you recommend? a)Colonoscopy b)Blood Transfusion c)Trial of ferrous sulfate d)Schilling Test e)Bone Marrow Biopsy

17. Question 2 A Greek woman brings her 10 yo son to your office complaining that he tires too easily on the soccer field and the iron pills from a different doctor aren’t helping. On PE you note he has puffy cheeks. You do an electrophoresis of his hemoglobin and are most likely to see which of the following? a)HbA2 b)HbF c)HbS d)HbC e)HbM f)HbH

18. Question 3 A 32 yo F has heavy menstrual bleeding, easy bruising, gingival bleeding when she brushes her teeth, and nose bleeds. She required a blood transfusion when she gave birth. Labs: Hb 10.8, MCV 78.1, WBC 4.3, Platelet 275 BT 14 (high), PT 11 (normal), PTT 40 (high) What is the most likely diagnosis? a) Hemophilia A b) Hemophilia B c) vonWillebrand’s disease d) Disseminated Intravascular Coagulation e) Hemolytic Uremic Syndrome

19. Question 4 A 72 yo F comes has increasing memory problems and weakness over the last 7 months but can take care of her ADLs. She has a PMH of HTN. Labs: Hb 8.2LDH 450B12 324 (normal) Hct 22Tbili 4.8Folate 12 (normal) WBC 3.9Dbili 0.3Homocysteine 20 (high) MCV 110Platelet 234Methylmalo 400 (high) What is the most likely diagnosis? a) Autoimmune hemolytic anemia a)Folate deficiency b)Myelodysplasia c)Vitamin B12 deficiency d)Gilbert Syndrome

20. Question 5 A family new to the area reports the strange behavior of their 2 yo girl and her constant belly aches. Her blood smear is shown. What is the best treatment? a)Succimer and EDTA b)N-acetylcysteine c)Naloxone d)Glucagon e)Protamine sulfate f)Atropine g)Thiosulfate

21. Question 6 A 59-yo who takes warfarin for a mechanical heart valve is brought to the hospital after a car accident. What would you give to help stop his bleeding? a)Protamine sulfate b)2 units of packed RBCs c)Fresh Frozen Plasma d)Multiple doses of Vit K e)Isolated factor VIII f)DDVAP

22. Question 7 A 31yo F comes in with blistering lesions all over the skin after a weekend escape to the beach. She also reports tea colored urine. What enzyme is likely defective? a)  -aminolevulinic acid synthase  -aminolevulinic acid dehydratase c) Porphobilinogen deaminase d)Uroporphyrinogen decarboxylase e)Ferrochetalase

23. Question 8 A previously healthy 9 yo M is currently being treated for a UTI that began 5 days ago. He returns with his Mom, who is scared that her son’s urine is now dark in color and he has excessive fatigue. What are you likely to see on his blood smear? a)Bite cells b)Schistocytes c)Spur cells d)Elliptocytes e)Howell Jolly bodies f)Target cells