Hematology Board Review

1. Hematology Board Review Ye Seventeenth of July Two Thousand and Fourteen Vince Herrin

2. Question #1 A 45 year old woman presents with fatigue and nausea. She has occasional palpitations and SOB with minimal exertion. Her cardiac and pulmonary exams are normal but she has spooning of her nails.

5. #1 Which of the following should be true? • Low iron, low IBC, low ferritin • Low iron, high IBC, high ferritin • Low iron, low IBC, high ferritin • Low iron, high IBC, low ferritin

6. #1 cont Your iron studies are nondiagnostic for a diagnosis of Iron deficiency. Which of the following would you order next? • Soluble transferrin receptor • Beta 2 microglobulin • RBC mass • ESR

7. #1 • However, remember the gold standard for proving Iron deficiency anemia is…… ?????

8. #1 Treatment for iron deficiency is best accomplished with…… • IV iron replacement weekly • IV iron replacement • IM iron replacement • PO iron replacement

9. Classification of Anemia: by indices microcytic/low MCV normocytic/normal MCV • iron deficiency -anemia of chronic disease • thalassemia • lead poisoning macrocytic/high MCV • B12/folate deficiency • hemolysis • liver disease

10. Classification of Anemia • by RDW • normal • Increased • by reticulocyte response • normal • increased • hemolysis

11. #2 A 38 yo male patient is referred to you for recommendations regarding their microcytic anemia. The patient has no systemic symptoms. The CBC shows: WBC 5.7 (normal differential), RBC 5.8, Hgb 12, HCT 37.1, platelets 340. MCV is 71 and RDW is 15. Ferritin is 50, iron 50, TIBC 300. Hemoglobin electrophoresis is normal.

12. #2 • Your recommendation should be: • A. Referal for EGD and colonoscopy • B. Iron infusion with a goal of replacing 1000 mg storage iron • C. Reassurance and a discussion about DNA testing testing • D. Iron absorption assay followed by 6 months of PO iron supplementation

13. #2 Know other anemias…..

14. Other types of anemia • Anemia of chronic disease • Hemoglobinopathies • Aplastic anemia • Hemolytic anemias • AIHA • Cold antibodies • microangiopathic

15. ANEMIA OF CHRONIC DISEASE • Anemia of inflammation • Unable to utilize available storage iron • Mediated by inflammatory cytokines such as TNF, IL 1, and IFN beta • Usually associated with a decreased erythropoietin state or reduced responsiveness to erythropoietin

16. ANEMIA OF CHRONIC DISEASE Clues for diagnosis • Usually normochromicnormocytic RBCs • Occasionally may be hypochromicmicrocytic • Decreased reticulocyte count

20. B12/folate deficiency • Differentiate with neurological symptoms • Check vitamin levels • Check antibodies • Suspect diagnosis but vitamin levels normal…… • Check MMA and Homocystine

22. Warm and cold auto antibodies WARM • IgG antibodies • Associated with lymphoproliferative and collagen vascular diseases COLD • IgM antibodies • Hemolysis is via the complement pathway • Associated with lymphoproliferative diseases or infection

23. RBC “CLUES” • CIGAR/PENCIL SHAPES • MACROOVALOCYTES • SPHEROCYTES • SCHISTOCYTES

24. RBC “CLUES” • BITE CELLS • BURR CELLS • SPUR CELLS • TARGET CELLS • TEARDROP CELLS

25. BLEEDING DISORDERS • Primary platelet vs. coagulopathy can be differentiated by the type of bleeding • Primary platelet bleeding is mucosal with petechia, epistaxis, gum bleeding and GI tract bleeding • Coagulation cascade bleeds are generally joint and soft tissue bleeds

26. CASE A 42 year old female with complaints of epistaxis and easy bruising for 2 weeks is seen in the ER. She has the following CBC: HGB 10 WBC 6200 HCT 30 PLTS 38,000 MCV 72 normal differential

27. CASE A differential diagnosis includes: • Systemic Lupus • Hepatitis • Drug effect • ITP • All of the above

28. THROMBOCYTOPENIA Decreased platelets result from Decreased Increased Production Destruction Sequestration

29. THROMBOCYTOPENIA As a general rule, if platelets above 20,000 the risk of spontaneous bleeding is small. When the count goes below 10,000 then the risk increases substantially and transfusions should be considered.

30. ITP • Not always idiopathic • 30-30-30-10 rule • Idiopathic • Drugs • Disease states such as lymphoma, CLL, collagen vascular diseases • Viral illnesses such as HCV, HIV

31. ITP Treatment options: • Platelets > 30,000---observation • Platelets< 30,000---treatment • Steroids • IVIG • Splenectomy • Up to 80% improved with these maneuvers

32. Question • You are evaluating a 40 yo female patient who fell at home. She has no known significant medical history. She is awake but lethargic and has the following test results of concern: • HCT 27, platelets 45, schistocytes on peripheral smear • BUN 40, creatinine 1.8, LDH 800 • Coags are within normal limits; tox screen negative

33. Question • Your next move after completing your assessment should be: • A. Send an ADAMTS13 and consult Hematology for urgent plasmapheresis • B. Order a d-dimer to rule out early DIC • C. One unit random-donor apheresed irradiated platelets • D. CT Chest/Abdomen/Pelvis to look for occult injury or PE

35. THROMBOTIC THROMBOCYTOPENIC PURPURA DIAGNOSTIC PENTAD • Fever • Neurological signs • Microangiopathic hemolytic anemia • Thrombocytopenia • Renal dysfunction

36. TTP • Newly determined genetic determinant for TTP • ADAMTS13 gene defect found in many patients • Encodes for a vW antigen protease responsible for cleaving unusually large vW multimers • This syndrome is considered a medical emergency and treatment should be instituted immediately

37. HEPARIN INDUCED THROMBOCYTOPENIA • Affects about 3% of patients treated with heparin • Less risk with porcine heparin • Less risk with LMWHs • Occurs 5-8 days after starting heparin therapy unless there has been prior exposure • Amnestic response after prior exposure and can develop thrombocytopenia within 1-2 days • If platelet count falls by 50% or falls below 100,000 should immediately stop heparin

38. Question • You are doing a pre-op physical on a healthy 55 yo man who injured his knee. He has a history of nosebleeds as a child and his mother was a “free-bleeder” but had no major episodes and died of an MI at age 74. He tells you he was once tested for von-Willebrands, but that it was negative. • His CBC is entirely normal, as are his chemistries. • His coags reveal a PT of 12.5 and a PTT of 40.

39. Question • You ordered a repeat PTT with a 1:1 mix, which corrected. Your next step will be: • A. Reassurance and clearance for surgery. • B. Repeat testing for von Willebrand’s disease • C. Order a bleeding time and clear the patient for surgery if the result is normal. • D. Recommend FFP prior to surgery at a dose of 15 mg/kg to cover whatever coagulation abnormality he has.

40. VON WILLEBRAND DISEASE • Most common inherited bleeding disorder • Autosomal dominant inheritance • Affected individuals are heterozygous • Bleeding ranges from mild to severe and spontaneous • Prolonged PT/PTT, BT, abnl platelet aggregation with ristocetin

41. vWD • Von Willebrand factor is a multimeric protein with two functions • Platelet adhesion---links platelet receptors to exposed subendothelium • Carrier protein for factorVIII • Type I – quantitative defect • Type 2 – qualitative defects • 2b – thrombocytopenia associated • Type 3 – no protein detectable

42. BERNARD-SOULIER SYNDROME • Also called the giant platelet syndrome • Glycoprotein Ib platelet defect • Unable to bind vWF which is important for adhesion to the endothelium • Have abnormal ristocetin aggregation • Have mild thrombocytopenia

43. GLANZMANN’S THROMBASTHENIA • Autosomal recessive inheritance • Mucosal bleeding • Glycoprotein IIb-IIIa defect • Unable to crosslink fibrinogen which is important for aggregation • Have abnormal ADP and EPI aggregation

44. EVALUATION OF PROLONGED PT OR PTT • 1:1 mix of patient and normal plasma • Will detect a factor deficiency---should see correction with mix • Will allow detection of an inhibitor---doesn’t correct with mixing • May need to do a 2 hour incubation to reveal an inhibitor--- may correct initially put prolong with incubation if a weak (slow) inhibitor is present • Hemophilia A and B most common

45. FACTOR XI • Third most common • Autosomal recessive inheritance • Correlation between factor level and bleeding tendency is poor • Less spontaneous bleeding • Treat with FFP

46. FACTOR X • Deficiency is very rare • Acquired deficiency occurs with amyloidosis**** • Treat with FFP

47. FACTOR XII • XII is also known as the Hageman factor • Have very prolonged PTT • No evidence of clinical bleeding and have normal hemostasis

48. Question • A healthy 50 yo female has followed with your for several years and comes in with right leg swelling that has been present for about 3 weeks. She is on no medications except amlodipine. She has not injured herself, been ill lately, or been on any trips. Her BMI is 24. • You are suspicious based on the exam and order a Doppler which reveals subacute nearly occlusive clot in the right superficial femoral vein.

49. Question • Her CBC, chemistries, and coags are all wnl. Your recommendation to her is: A. Take aspirin, use warm soaks and wear support hose because this is superficial thrombophlebitis. B. Admit to the hospital for tPA infusion to prevent varicose vein formation. C. Order a JAK-2 analysis to assess occult myeloproliferative disease D. Recommend at least 6 months of anticoagulation, initiating LMW heparin and warfarin today. E. 3 months of anticoagulation beginning with Lovenox for a week and then warfarin loading at 10mg per day for 3 days

50. THROMBOTIC DISORDERS • Hypercoaguable states result in unprovoked thrombosis • Generally there is a family history of thrombosis • Most are undefined but there are several deficiencies of the natural occurring anticoagulants that are described