1. HEREDITARY/ACQUIRED ANEMIA DR. BATIZY, D.O. PREPARED BY JEFFREY L PAY, D.O. NOVEMBER 3, 2003

2. HEREDITARY HEMOLYTIC ANEMIA CHARACTERIZED BY: - DEFECTS OF HEMOGLOBIN OR - DEFECTS OF THE RBC MEMBRANE RESULTS IN PREMATURE DESTRUCTION OF RED CELLS

3. TYPES OF HA SICKLE CELL DISEASE THALASSEMIAS G6PD DEFICIENCY HEREDITARY SPHEROCYTOSIS

4. SICKLE CELL DISEASE INHERITED, AUTOSOMAL RECESSIVE TRAIT; DISEASE SEEN IN PTS WHO ARE HOMOZYGOUS FOR THE SICKLE CELL GENE (HbSS) MOST COMMON REASON TO ER – PAINFUL VASO-OCCLUSIVE CRISIS ACUTE CHEST SYNDROME (ACS) LEADING CAUSE OF DEATH FROM SCD IN US

5. SICKLE CELL ANEMIA SICKLE CELL TRAIT IN 8% OF THE U.S. BLACK POPULATION PEOPLE WITH TRAIT HAVE A NORMAL LIFE SPAN AND USUALLY ASYMPTOMATIC SICKLE CELL TRAIT THOUGHT TO BE PROTECTIVE AGAINST MALARIA

6. SCD - PATHOPHYS HEMOGLOBIN S CAUSED BY MUTATION OF ß CHAIN; substitution of the AA valine for glutamine at position 6 of the β-globin chain DEOXYGENATED HEMOGLOBIN S POLYMERIZES, WHICH DEFORMS RBC AND CAUSES SICKLED APPEARANCE SICKLED CELL INCREASES VISCOSITY OF BLOOD, OBSTRUCTS MICROVASC VASO-OCCLUSIVE CRISIS OCCURS FROM SICKLING IN MICROCIRCULATION

7. SCD – CLINICAL SX PTS ARE FUNCTIONALLY ASPLENIC AFTER EARLY CHILDHOOD, AT RISK FOR SERIOIUS INFECTION FROM ENCAPSULATED ORGANISMS PTS MAY HAVE CHF, CM, COR PULMONALE, LE ULCERATIONS, ICTERUS, & HEPATOMEGALY PTS WITH ACS WILL HAVE PULMONARY SX: PLEURITIC CP, FEVER, HYPOXIA

8. SCD – CLINICAL SX NEUROLOGIC SX: CEREBRAL INFARCT IN KIDS, HEMORRAGE IN ADULTS; TIA, SEIZURES, HA, COMA PRIAPISM SWELLING OF HANDS & FEET DUE TO VASO-OCCLUSION INFARCTION OF RENAL MEDULLA, ASSOC WITH FLANK PAIN AND HEMATURIA

9. SCD – CAUSES OF VASO-OCCLUSIVE CRISES COLD EXPOSURE, DEHYDRATION, HIGH ALTITUDE INFECTIONS (ENCAPSULATED – H. influenza & PNEUMOCOCCI

10. SCD – DIAGNOSIS SCD USUALLY DX EARLY IN PT LIFE PRESCENCE OF SICKLING RBC’S ON PERIPHERAL BLOOD SMEAR IS DX DROP IN HBG BY 2 g/dL FROM BASELINE SUGGESTS ACUTE APLASTIC CRISIS RETIC COUNT – COUNT LESS THAN BASELINE OF 5-15% MAY REFLECT APLASTIC CRISIS LEUKOCYTOSIS WITH LEFT SHIFT – INFECTION MAYBE CAUSE OF CRISIS

11. SCD – DIFF DX OSTEOMYELITIS ACUTE ARTHRITIS PANCREATITIS HEPATITIS PE MENINGITIS PID PYELONEPHRITIS

12. SCD – ER TREATMENT PTS WITH DEHYDRATION OR ACUTE PAIN REHYDRATED ORALLY OR WITH IV FLUIDS NORMAL SALINE @ 1.5 TIMES MAINTENANCE NARCOTICS PROMPTLY FOR SEVERE PAIN, BEWARE OF DRUG SEEKERS INFECTION OR TEMP > 38C HAVE CULTURES DRAWN; START BROAD-SPEC ABX: CEFUROXIME OR CEFTRIAXONE

13. SCD – ER TREATMENT TRANSFUSION FOR SC CRISIS OR COMPLICATIONS IS RESERVED FOR SPECIFIC INDICATIONS: APLASTIC CRISIS, PREGNANCY, STROKE, RESP FAILURE, SURGERY, PRIAPISM PTS WITH PRIAPISM NEED HYDRATION, ANALGESIA, AND IMMEDIATE UROLOGY CONSULT

14. SCD – ER TREATMENT PTS WITH ACUTE BONE PAIN – THINK OSTEOMYELITIS DRAW CULTURES AND START IV ABX COVERING Staph aureus and Salmonella typhimurium

15. SCD – ADMIT/DISPO ADMISSION CRITERIA INCLUDE PULM, NEURO, APLASTIC, OR INFECTIOUS CRISES; SPLENIC SEQUESTRATION; INTRACTIBLE PAIN; PERSISTENT N/V; OR UNCERTAIN DX DISCHARGED PTS SHOULD RECEIVE ORAL ANALGESICS, CLOSE FOLLOW UP, AND INSTRUCTIONS TO RETURN TO ER IMMEDIATELY FOR FEVER >38C OR WORSENING SX

16. THALASSEMIAS MICROCYTIC, HYPOCHROMIC, HEMOLYTIC ANEMIA MOST COMMON IN AFRICAN, MEDITERRANEAN, MIDDLE EASTERN, & SOUTHEAST ASIAN DESCENT MULTIPLE VARIANTS

17. THALASSEMIAS CHARACTERIZED BY DEFECTIVE SYNTHESIS OF GLOBIN CHAINS, UNABLE TO PRODUCE NORMAL ADULT HEMOGLOBIN TRAIT THOUGHT TO BE PROTECTIVE AGAINST MALARIA AS WELL

18. HEMOGLOBIN NORMAL ADULT RBC CONSISTS OF 3 FORMS OF Hb: - HbA - 2 α and 2 β globin chains - HbA2 – 2 α and 2 δ globin chains - HbF - 2 α and 2 γ globin chains THALASSEMIAS α and β

19. THALASSEMIAS TYPES OF DZ CHARACTERIZED BY DEFFERING EXTREMES OF ANEMIA DEPENDS ON AMOUNT OF INEFFECTIVE ERYTHROPOIESIS AND PREMATURE DESTRUCTION OF CIRCULATING RBC’S HYPOXIA IN SEVERE CASES

20. G6PD DEFICIENCY MOST COMMON HUMAN ENZYME DEFECT X-LINKED DISORDER AFFECTS 15% OF U.S. BLACK MALES DECREASE IN GLUTATHIONE LEVELS

21. G6PD DEFICIENCY HEINZ BODIES SEEN ON PERIPHERAL BLOOD SMEAR NEONATAL JAUNDICE 1-4 DAYS AFTER BIRTH IN SEVERE VARIANTS INCREASE INCIDENCE OF PIDMENTED GALLSTONES AND SPLENOMEGALY

22. G6PD DEFICIENCY ACUTE HEMOLYTIC CRISIS DUE TO: - BACTERIAL/VIRAL INFECTION - OXIDANT DRUGS ( SULFAMETHOXAZOLE ) - METABOLIC ACIDOSIS (DKA) - RENAL FAILURE - INGESTION OF FAVA BEANS

23. G6PD DEFICIENCY DIAGNOSIS – QUANTITATIVE ASSAY DETECTING LOW ENZYME TREATMENT – SUPPORTIVE AND PREVENTATIVE

24. HEREDITARY SPHEROCYTOSIS RBS MEMBRANE DEFECT MOST COMMON HEREDITARY ANEMIA FROM PTS OF NORTHERN EUROPEAN DESCENT AUTOSOMAL DOMINANT MUTATIONS IN SPECTRIN AND ANKYRIN (MEMBRANE PROTEINS)

25. HEREDITARY SPHEROCYTOSIS SPHEROCYTES – IN PERIPHERAL BLOOD SMEAR SPHEROCYTES UNABLE TO PASS THROUGH THE SPLEEN SEVERE CASES REQUIRE A SPLENECTOMY

26. HEREDITARY SPHEROCYTOSIS NEONATAL JAUNDICE IN 1 ST WEEK OCCURS IN 30-50% OF HS PTS ANEMIA, SPLENOMEGALY, JAUNDICE, AND TRANSFUSIONS NEEDED VARY DEPENDING ON SEVERITY OF DZ

27. ACQUIRED HEMOLYTIC ANEMIA DESTRUCTION OF RBC’S NO DUE TO GENETIC/CONGENITAL DISORDER OF HGB SYNTHESIS OR RBC MEMBRANE AUTOIMMUNE, ALLOIMMUNE, DRUG-RELATED CAUSES MICROANGIOPATHIC SYNDROMES (TTP, HUS)

28. AUTOIMMUNE HA PTS MAKE ANITBODIES AGAINST THEIR OWN RBC’S WARM-TYPE AIHA – 70% CASES - IgG MEDIATED COLD-TYPE AIHA – IgM MEDIATED - 2 SUBTYPES

29. DRUG RELATED HA ALPHA- METHYLDOPA LEVODOPA PROCAINAMIDE SULFA DRUGS PENICILLIN CEFTRIAXONE CEFOTETAN QUINIDINE

30. ALLOIMMUNE HA HEMOLYTIC DZ OF NEWBORN HEMOLYTIC TRANSFUSION REACTIONS

31. ALLOIMMUNE HA - NEWBORN MATERNAL ALLOANTIBODIES FORM AFTER RhD-NEGATIVE MATERNAL RBC’S EXPOSED TO RhD- POSITIVE FETAL BLOOD ABS CROSS PLACENTA AND DESTROY FETAL RBC’S - ANEMIA, FETAL HYDROPS, DEATH, JAUNDICE

32. ALLOIMMUNE HA - TRANSFUSION PT HAS PREVIOUS TRANSFUSION SENSITIZATION TO ALLOGENIC RBC ANTIGEN OCCURS LATER TRANSFUSIONS, PT MAY DEVELOP FEVER, CP, TACHYPNEA, TACHYCARDIA, HYPOTENSION, HEMOGLOBINURIA, OLIGURIA

33. MICROANGIOPATHIC SYNDROMES THROMBOCYTOPENIC PURPURA HEMOLYTIC UREMIC SYNDROME

34. TTP & HUS - PATHOPHYS PLATELET AGGREGATION IN THE MICROVASCULATURE CIRCULATION VIA MEDIATION OF von WILLEBRAND’S FACTOR LEADS TO THROMBOCYTOPENIA AND FRAGMENTATION OF RBC’S AS THEY PASS THROUGH THESE OCCLUDED ARTERIOLES AND CAPILLARIES

35. THROMBOCYTOPENIC PURPURA (TTP) PLATLET COUNTS < 20,000 MORE COMMON IN WOMEN AGES 10-60 FEVER, NEUROLOGIC DEFICITS, HEMORRAGE, AND RENAL INSUFFICIENCY UNTREATED – 80-90% MORTALITY

36. TTP SCHISTOCYTES OR HELMET CELLS SEEN OF PERIPHERAL SMEAR INCREASED BUN/Cr LEVELS

37. TTP PREGNANCY IS THE MOST COMMON PRECIPITATING EVENT FOR TTP PREECLAMPSIA SIMILAR TO TTP; DELIVERY TX FOR PREECLAMPSIA, NOT CURE TTP

38. TTP – ER TREATMENT PREDNISONE 1-2mg/kg/day INITIALLY PLASMA EXCHANGE TRANSFUSION IS FOUNDATION FOR TX (INFUSE FRESH FROZEN PLASMA IF TRANSFUSION UNAVAILABLE AVOID PLATELET TRANSFUSION NEVER USE ASPIRIN

39. TTP – ER TREATMENT PT MAY NEED SPLENECTOMY AZATHIOPRINE AND CYCLOPHOSPHAMIDE FOR THOSE WHO FAIL OR CANNOT TOLERATE STEROIDS

40. HUS DZ OF EARLY CHILDHOOD PEAK INCIDENCE BETWEEN 6mo-4yr OFTEN FOLLOWS BACTERIAL/VIRAL ILLNESS MORTALILY 5-15%, WORSE IN OLDER CHILDREN & ADULTS

41. HUS CHARACTERIZED BY -ACUTE RENAL FAILURE -MICROANGIOPATHIC HA -FEVER -THROMBOCYTOPENIA (NOT AS SEVERE AS TTP)

42. HUS THE MOST COMMON CAUSE OF ACUTE RENAL FAILURE IN CHILDHOOD E.Coli O157:H7 COMMON CAUSE MICROTHORMBI ARE CONFINED MAINLY TO KIDENYS, WHERE TTP MORE WIDESPREAD

43. HUS – ER TREATMENT MILD HUS < 24hr OF URINARY SX NEELS ONLY FLUID/ELECTROLYTE CORRECTION AND SUPPORT CARE STEROID THERAPY HEMODIAYLSIS IF ACUTE RENAL FAILURE PRESENT ABX TX CONTROVERSIAL WHEN E.Coli PRESNENT; DO NOT USE ANTIMOLITY DRUG, INCREASE RISK OF DEVELOP HUS

44. HELLP SYNDROME HEMOLYSIS ELEVATED LIVER ENZYMES LOW PLATLET COUNTS

45. HELLP SYNDROME 1 IN 1OOO PREGNANCIES SEEN IN PRESENCE OF ECLAMPSIA, PREECLAMPSIA, AND PLACENTAL ABRUPTION MAY EXTEND UP TO 6 DAYS POSTPARTUM

46. HELLP SYNDROME RUQ AND EPIGASTRIC PAIN – SEEN IN 90% OF PTS (POSSIBLE HEPATIC RUPTURE) DX BASED ON LAB DATA DECREASED SERUM HAPTOGLOBIN LEVEL MOST SENSITIVE

47. HELLP SYNDROME - TX PROMPT DELIVERY OF INFANT SUPPORTIVE CARE FOR SEIZURES AND HTN CRISIS STEROIDS MAY HELP FETAL LUNGS, BUT NO BENEFIT TO HELLP SYNDROME

48. THE END QUESTIONS????

49. 1. PT WITH SICKLE CELL DISEASE ARE AT RISK FOR SERIOUS INFECTIONS BY WHICH? A) CAPSULATED ORGANISMS B) ENCAPSULATED ORGANISMS C) BOTH A & B D) NEITHER A OR B

50. T OR F 2. PT WITH THE SICKLE CELL TRAIT ARE OFTEN SYMPTOMATIC AND WILL NEED A SPLENECTOMY

51. 3. G6PD DEFICIENCY RESULTS IN A LOW LEVEL OF WHICH ENZYME? A) FOLIC ACID B) GLUTATHIONE C) SPHINGOMYELIN D) B12

52. 4. WHICH OF THE FOLLOWING STATEMENTS IS TRUE? A) TTP IS MORE COMMON IN MEN 20-40 YEARS OF AGE B) TTP HAS NORMAL PLATELET LEVELS C) HUS DOES NOT USUALLY AFFECT THE KIDNEYS D) HUS IS DISEASE OF THE YOUNG, USUALLY 6MO-4YRS OF AGE

53. 5) WHICH OF THE FOLLOWING IS NOT PART OF THE HELLP SYNDROME? A) HIGH BUN/CR B) LOW PLATELETS C) ELEVATED LIVER ENZYMES D) HEMOLYSIS E) THROMBOCYTOPENIA