Approach to hemolytic anemia

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Approach to hemolytic anemia

  1. 1. APPROACH TO HEMOLYTIC ANEMIA Candidate: Dr SARATH MENON.R K.B.ILLAVA HEMATOLOGY DIVISION DEPT.MEDICINE, MGM MEDICAL COLLEGE,INDORE
  2. 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. 3. HEMOLYTIC ANEMIA  Definition:  Those anemias which result from an increase in RBC destruction coupled with increased erythropoiesis  Classification:  Congenital / Hereditary  Acquired
  4. 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. 5. CLASSIFICATION  MAHA  Transfusion rx  PNH  Infections  Snake bite  Hemoglobinopathies  Enzymopathies  Membrane defects  AIHA Intravascular hemolysis Extravascular hemolysis
  6. 6. HOW IS HEMOLYTIC ANEMIA DIAGNOSED? Two main principles  One is to confirm that it is hemolysis  Two is to determine the etiology
  7. 7. HOW TO DIAGNOSE HEMOLYTIC ANEMIA  New onset pallor or anemia  Jaundice  Splenomegaly  Gall stones  Dark colored urine  Leg ulcers
  8. 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. 9. HEMOLYTIC FACIES- CHIPMUNK FACIES
  10. 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 + 0 0 + + + severe cases
  11. 11. POLYCHROMATOPHILIC CELLS
  12. 12. THE KEY TO THE ETIOLOGY OF HEMOLYTIC ANEMIA The history The peripheral blood film
  13. 13. PATIENT HISTORY  Acute or chronic  Medication/Drug precipitants G6PD AIHA  Family history  Concomitant medical illnesses  Clinical presentation
  14. 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. 15. PERIPHERAL SMEAR
  16. 16. WHAT IS THE DIAGNOSIS ?  SICKLE CELL ANEMIA
  17. 17. DIAGNOSIS – OTHER TESTS  Hemoglobin electrophoresis -HbS >80% -HbF -1-20% -HbA2 -2- 4.5%  Sickling test POSITIVE
  18. 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. 19. CLINICAL MANIFESTATIONS  Hemo.anemia,reticulocytosis,granulocytosis  Vasoocclusion-protean  Painful crises  Splenic sequestration crises  Hand foot syndrome  Acute chest syndrome
  20. 20. DIAGNOSIS? SICKLE THALASSEMIA`
  21. 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,gal lstones, 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. 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. 23. DIAGNOSIS?
  24. 24. TARGET CELLS
  25. 25. THALASSEMIA  Other diagnosis test-Hb electrophoresis  DNA analysis for mutations  Alpha thalassemia & beta thalassemia  Beta thalassemia- major - intermedia - minor
  26. 26. BETA THALASSEMIA  Mutn. Beta globin expression  M.C- derange splicing of m-RNA  HYPOCHROMIA ,MICROCYTIC anemia
  27. 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. 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. 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. 30. ALPHA THALASSEMIAS disease Hb A % HbH % Hb , % MCV,fl normal 97 0 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) 0 5-10 Fatal inutero or at birth
  31. 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. 32. BLISTER CELLS
  33. 33. HEINZ BODIES
  34. 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. 35.  Clinical Features:  Acute hemolysis: Drugs,infections,asso with diabetic acidosis  Favism  Neonatal jaundice  Congenital nonspherocytic hemolytic anemia
  36. 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. 37. 2. Pyruvate Kinase Deficiency  AR  Deficient ATP production, Chronic hemolytic anemia  Clinical features o hydrops fetalis o neonatal jaundice o compensated hemolytic anemia  Inv; P. Smear: PRICKLE CELLS ( Contracted rbc with spicules) Decreased enzyme activity
  38. 38. PRICKLE CELL
  39. 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. 40. DIFFERENTIAL DIAGNOSIS  Hereditary spherocytosis  Autoimmune hemolytic anemia  Other diagnostic tests- osmotic fragility - coombs test
  41. 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. 42.  C/F: Pallor Jaundice Splenomegaly Pigmented gall stones- 50%
  43. 43. COMPLICATIONS  Clinical course may be complicated with Crisis:  Hemolytic Crisis: associated with infection  Aplastic crisis: associated with Parvovirus infection
  44. 44.  Inv:  Test will confirm Hemolysis  P Smear: Spherocytes  Osmotic Fragility: Increased  Screen family members
  45. 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. 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. 47.  Inv:  hemolysis, MCV decreased  P Smear: microspherocytosis,  Confirmation: Direct Coomb’s Test / Antiglobulin test
  48. 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. 49. Inv:  e/o hemolysis  P Smear: Microspherocytosis  DAT positive with polyspecific and anticompliment antisera
  50. 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. 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. 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. 53. MICROANGIOPATHIC HEMOLYTIC ANEMIA
  54. 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. 55. MICROANGIOPATHIC HEMOLYTIC ANEMIA(MAHA)  Other findings - leukocytosis - thrombocytopenia(DIC,TTP) - hemoglobinuria - deranged RFT - PT,APTT prolonged (DIC,TTP)
  56. 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. 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. 58. CONCLUSION  Hemolytic anemia can be recogised by clinical picture- - history & physical - lab test to confirm hemolysis - peripheral smear to guide further tests
  59. 59. THANK YOU

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