Approach to hemolytic anemia

1. Approach to hemolytic anemia Candidate: Dr SARATH MENON.R K.B.ILLAVA HEMATOLOGY DIVISION DEPT.MEDICINE , MGM MEDICAL COLLEGE,INDORE

2. objectives Lab indication of hemolysis Intravascular v/s extravascular hemolysis D/D of hemolytic anemia Diagnose hemo.anemia with peripheral smear & ancillary lab tests

3. Hemolytic Anemia Definition: Those anemias which result from an increase in RBC destruction coupled with increased erythropoiesis Classification: Congenital / Hereditary Acquired

4. CLASSIFICATION OF HEMOLYTIC ANEMIAS INTRACORPUSCULAR DEFECTS EXTRACORPUSCULAR FACTORS HEREDITARY HEMOGLOBINOPATHIES ENZYMOPATHIES MEMBRANE-CYTOSKELETAL DEFECTS FAMILIAL HEMOLYTIC UREMIC SYNDROME ACQUIRED PAROXYSMAL NOCTURNAL HEMOGLOBINURIA MECHANICAL DESTRUCTION [MICROANGIOPATHIC] TOXIC AGENTS DRUGS INFECTIOUS AUTOIMMUNE

5. Classification MAHA Transfusion rx PNH Infections Snake bite Hemoglobinopathies Enzymopathies Membrane defects AIHA Intravascular hemolysis Extravascular hemolysis

6. How is Hemolytic Anemia Diagnosed? Two main principles One is to confirm that it is hemolysis Two is to determine the etiology

7. How to diagnose hemolytic anemia New onset pallor or anemia Jaundice Splenomegaly Gall stones Dark colored urine Leg ulcers

8. GENERAL FEATURES OF HEMOLYTIC DISORDERS GENERAL EXAMINATION - JAUNDICE, PALLOR BOSSING OF SKULL PHYSICAL FINDINGS - ENLARGED SPLEEN HEMOGLOBIN - FROM NORMAL TO SEVERELY REDUCED MCV - USUALLY INCREASED RETICULOCYTES - INCREASED BILIRUBIN - INCREASED[MOSTLY UNCONJUGATED] LDH - INCREASED HAPTOGLOBULIN - REDUCED TO ABSENT

9. Hemolytic facies - chipmunk facies

10. Laboratory Evaluation of Hemolysis Extravascular Intravascular   HEMATOLOGIC Routine blood film Reticulocyte count Bone marrow examination Polychromatophilia Erythroid hyperplasia Polychromatophilia Erythroid hyperplasia   PLASMA OR SERUM Bilirubin Haptoglobin Plasma hemoglobin Lactate dehydrogenase Unconjugated , Absent N/ (Variable) Unconjugated Absent (Variable)   URINE Bilirubin Hemosiderin Hemoglobin + + + +  severe cases  

11. POLYCHROMATOPHILIC CELLS

12. The key to the etiology of hemolytic anemia The history The peripheral blood film

13. Patient History Acute or chronic Medication/Drug precipitants G6PD AIHA Family history Concomitant medical illnesses Clinical presentation

14. Case 1 3 yr old male child presenting with pallor,jaundice , Severe pain of long bones, fever CBC- anemia,reticulocytosis,increased WBC LAB - LDH -600 (normal upto 200) S.bilirubin - 5mg%

15. Peripheral smear

16. What is the diagnosis ? SICKLE CELL ANEMIA

17. DIAGNOSIS – OTHER TESTS Hemoglobin electrophoresis - HbS >80% - HbF -1-20% -HbA2 -2- 4.5% Sickling test POSITIVE

18. Sickle cell disease Mutn .beta globin-6 Glu Val. Deoxy HbS ( polymerised ) Ca influx, K leakage stiff,viscous sickle cell venocclusion dec.RBC survival microinfarctions,isch.pains anemia,jaundice , autoinfarct.spleen gallstones,leg ulcers

19. Clinical manifestations Hemo.anemia,reticulocytosis,granulocytosis Vasoocclusion -protean Painful crises Splenic sequestration crises Hand foot syndrome Acute chest syndrome

20. Diagnosis? SICKLE THALASSEMIA`

21. Clinical features of sickle hemoglobinopathies Condition Clinical abnorm Hb level g% MCV,fl Hb electropho Sickle cell trait None,rare painlss hematuria normal normal HbS /A: 40/60 Sickle cell anemia Vasocclusive crises,AVN,gallstones , priapism 7-10 80-100 HbS /A:100/0 HbF;2-25% S/beta0 thalasssemia Vasoocclusive Crises,AVN 7-10 60-80 HbS /A-100/0 HbF ; 1-10% S/beta+ thalassemia Rare crises, AVN 10-14 70-80 HbS /A: 60/40 HbSC --do--, retinopathy 10-14 80-100 HbS /A;50/0 HbC;50%

22. CASE 2 6 yr old child presenting with severe pallor,jaundice growth delay Abnormal facies,hepatosplenomegaly + h/o recurrent blood transfusions CBC- Hb -3gm%, MCV-58FL(Nl-86-98), -MCH- 19pg (nl-28-33) P.S- MICROCYTIC,HYPOCHROMIA with target cells +

23. Diagnosis?

24. Target cells

25. thalassemia Other diagnosis test- Hb electrophoresis DNA analysis for mutations Alpha thalassemia & beta thalassemia Beta thalassemia - major - intermedia - minor

26. Beta thalassemia Mutn . Beta globin expression M.C- derange splicing of m-RNA HYPOCHROMIA ,MICROCYTIC anemia

27. Beta thalassemia major Severe homozygous Childhood, growth delay Severe anemia,hepatosplenomegaly,r /r transfusion Iron overload- endo.dysfnct P.Smear - severe microcytosis,target cells Hb electro- HbF - 90-96 % HbA2- 3.5 %- 5.5% HbA - 0 %

28. Beta thalassemia intermedia Similar stigmata like major Survive without c/c transfusion Less severe than major Moderate anemia,microcytosis,hypochromia Hb electrophor - HbF - 20-100% HbA2 -3.5%-5.5% HbA – 0-30%

29. Beta thalassemia minor Profound microcytosis,target cells Minimal anemia Similar bld picture of iron def.anemia Lab inv: MCV<75,Hct <30-33% Hb electr : HbA2-3.5-7.5%, HbA-80-95%,HbF-1-5%

30. Alpha thalassemias disease Hb A % Hb H % Hb , % MCV,fl normal 97 15 90 Thalassemia traits 90-95 rare 12-13 70-80 HbH (b4) 70-95 5-30 6-10 60-70 Hb Bart ( hydrops fetalis ) 5-10 Fatal inutero or at birth

31. CASE 3 45 yr old male came to opd in a remote PHC with burning micturition Urine R/M shows numerous pus cells++++ UTI diagnosed & medical officer gave cotrimoxazole 2 bd X 5days 1 wk later,pt developed severe pallor,palpitation,jaundice Lab- increased LDH, S.BILIRUBIN,RETIC COUNT P.S- shows irreg cells like

32. Blister cells

33. Heinz bodies

34. Diagnosis? G-6PD DEFICIENCY INVESTIGATION- Peripheral smear- bite cells,heinz bodies, - polychromasia G-6PD LEVEL BEUTLER FLUORESCENT SPOT TEST- Positive-if blood spot fails to flouresce in U V

35. Clinical Features: Acute hemolysis: Drugs,infections,asso with diabetic acidosis Favism Neonatal jaundice Congenital nonspherocytic hemolytic anemia

36. Definitive risk Possible risk Doubtful risk antimalarials Primaquine Dapsone cholrproguanil chloroquine quinine Sulphonamides / sulphones Sulphametoxazole Dapsone Sulfasalazine Sulfadimidine Sulfisoxazole Sulfadiazine Antibacterials / Antibiotics Cotrimoxazole Nalidixic acid Nitrofurantoin Ciprofloxacin Norfloxacin Cholramphenicol p - Aminosalicylic acid Antipyretic/ Analgesics Acetanilide Phenazopyridine [ pyridium ] Acetylsalicylic acid High dose[>3g/d] Acetylsalicylic acid [<3g/d] Acetaminophen

37. 2. Pyruvate Kinase Deficiency AR Deficient ATP production, Chronic hemolytic anemia Clinical features hydrops fetalis neonatal jaundice compensated hemolytic anemia Inv; P. Smear: PRICKLE CELLS ( Contracted rbc with spicules ) Decreased enzyme activity

38. Prickle cell

39. CASE 4 14 YR old female present with anemia, jaundice Rt hypochondrial pain o/e- vitals stable.pallor+,icterus+,splenomegaly + Usg - cholilithiasis Lab; elevated ,LDH, S.Bilirubin Peripheral smear shows-

40. Differential diagnosis Hereditary spherocytosis Autoimmune hemolytic anemia Other diagnostic tests- osmotic fragility - coombs test

41. Red Cell Membrane Defects 1.Hereditary Spherocytosis Usually inherited as AD disorder Defect: Deficiency of Beta Spectrin or Ankyrin  Loss of membrane surface area becomes more spherical Destruction in Spleen

42. C/F: Pallor Jaundice Splenomegaly Pigmented gall stones- 50%

43. Complications Clinical course may be complicated with Crisis: Hemolytic Crisis : associated with infection Aplastic crisis : associated with Parvovirus infection

44. Inv: Test will confirm Hemolysis P Smear: Spherocytes Osmotic Fragility: Increased Screen family members

45. Autoimmune Hemolytic Anemia Result from RBC destruction due to RBC autoantibodies : Ig G, M, E, A Most commonly-idiopathic Classification Warm AI hemolysis:Ab binds at 37degree Celsius Cold AI Hemolysis : Ab binds at 4 degree Celsius

46. 1.Warm AI Hemolysis : Can occurs at all age groups F > M Causes: 50% Idiopathic Rest - secondary causes: 1.Lymphoid neoplasm: CLL, Lymphoma, Myeloma 2.Solid Tumors: Lung, Colon, Kidney, Ovary, Thymoma 3.CTD: SLE,RA 4.Drugs: Alpha methyl DOPA, Penicillin , Quinine, Chloroquine 5. UC, HIV

47. Inv: hemolysis , MCV decreased P Smear: microspherocytosis , Confirmation: Direct Coomb’s Test / Antiglobulin test

48. 2. Cold AI Hemolysis Usually Ig M directed at the RBC I antigen Infection: Mycoplasma pneumonia, Infec Mononucleosis Neoplasms : waldenstrom macroglobulinemia , lymphoma,CLL,kaposi sarcoma, myeloma. C/F: Elderly patients Exacerbations in the winter Cold , painful & often blue fingers, toes, ears, or nose ( Acrocyanosis )

49. Inv: e/o hemolysis P Smear: Microspherocytosis DAT positive with polyspecific and anticompliment antisera

50. Case 5 32 yr old presented 4 days history of distention of abdomen and rt hypochondrial pain and has h/o passage of dark colored urine at night for weeks On USG- hepatomegaly,gross ascites,hepatic vein thrombosis Lab : Hb – 7gm%. WBC- 2200, PLC- 80,000 LDH- 600, S.BR- 4 mg% urine bile pigment +, heme dip stick++ What is the diagnosis?

51. Paroxysmal nocturnal hemoglobinuria Acquired chronic H.A Persistent intra vascular hemolysis Pancytopenia Lab : hburia,hemosiderinuria,increased LDH,bilirubin Risk of venous thrombosis C/F – hemoglobinuria during night P.S – polychromatophilia , normoblasts B.M – normoblastic hyperplasia Def.diagnosis -flow cytometry CD59-,CD55- RBC,WBC - Hams’ acidified serum test

52. Case 6 25 yr old male with RHD – severe MR done MVR,after 10 days presented with pallor, palpitation,jaundice CBC shows Hb – 7.5 gm %, Hct -22 % Lab : S.bilirubin -4.5mg% LDH -600 Retic count 10% Peripheral smear –

53. Microangiopathic hemolytic anemia

54. Non-Immune Acquired Hemolytic Anemia 1. Mechanical Trauma A). Mechanical heart valves, Arterial grafts: cause shear stress damage B).March hemoglobinuria: Red cell damage in capillaries of feet C). Thermal injury: burns D). Microangiopathic hemolytic anemia (MAHA): by passage of RBC through fibrin strands deposited in small vessels  disruption of RBC eg: DIC,PIH, Malignant HTN,TTP,HUS

55. Microangiopathic hemolytic anemia( maha ) Other findings - leukocytosis - thrombocytopenia(DIC,TTP) - hemoglobinuria - deranged RFT - PT,APTT prolonged (DIC,TTP)

56. Acquired hemolysis Infection F. malaria: intravascular hemolysis: severe called ‘ Blackwater fever’ Cl. perfringens septicemia Chemical/Drugs: oxidant denaturation of hemoglobin Eg : Dapsone , sulphasalazine , Arsenic gas, Cu, Nitrates & Nitrobenzene

57. Peripheral blood smear Spherocytes AIHA, hereditary spherocytosis Schistocytes With thrombocytopenia-Familial HUS TTP or DIC Without thrombocytopenia- heart valve hemolysis Blister Cells oxidative damage- G6PD Sickle cells sickle cell anemia Heinz bodies Alpha thalassemia G6PD deficiency

58. conclusion Hemolytic anemia can be recogised by clinical picture- - history & physical - lab test to confirm hemolysis - peripheral smear to guide further tests

59. Thank you