APPROACH TO A CHILD WITH HEMOLYTIC ANEMIA DR GRK.pptx

approach to child with hemolytic anemia it describes all cases of hemolytic anemia like thalassemia, sickle cell anemia how to approach a child with hemolytic anemia with basis of lab findings smear findings including clinical features investigations and management

1. DR G.RAJKUMAR PROFESSOR OF PAEDIATRICS CHRI APPROACH TO A CHILD WITH HEMOLYTIC ANEMIA

2. Definition : Anaemia due to increased red cell destruction outside the bone marrow resulting in shortened RBC lifespan (and increased erythropoiesis) DR GRK CHRI 2

3. Mechanisms of hemolysis: - intravascular - extravascular DR GRK CHRI 3

4. Intracorpuscular Extracorpuscular Hereditary Hemoglobinopathies Enzyme defects Membrane defects Familial HUS Acquired PNH MAHA Toxins Drugs Infections Autoimmune DR GRK CHRI 4

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

6. I. Red cell abnormality (Intracorpuscular factors) A. Hereditary 1. Membrane defect (spherocytosis, elliptocytosis) 2. Metabolic defect (Glucoze-6-Phosphate-Dehydrogenaze (G6PD) deficiency, Pyruvate kinase (PK) deficiency) 3. Hemoglobinopathies (unstable hemoglobins , thalassemias , sickle cell anemia ) B. Acquired 1. Membrane abnormality-paroxysmal nocturnal hemoglobinuria (PNH) DR GRK CHRI 6

7. II. Extracorpuscular factors A. Immune hemolytic anemias 1. Autoimmune hemolytic anemia - caused by warm-reactive antibodies - caused by cold-reactive antibodies 2. Transfusion of incompatible blood B. Nonimmune hemolytic anemias 1. Chemicals 2. Bacterial infections, parasitic infections (malaria), venons 3. Hemolysis due to physical trauma - hemolytic - uremic syndrome (HUS) - thrombotic thrombocytopenic purpura (TTP) - prosthetic heart valves 4. Hypersplenism DR GRK CHRI 7

8. Inravascular hemolysis : - red cells destruction occurs in vascular space - clinical states associated with Intravascular hemolysis: acute hemolytic transfusion reactions severe and extensive burns paroxysmal nocturnal hemoglobinuria severe microangiopathic hemolysis physical trauma bacterial infections and parasitic infections (sepsis) DR GRK CHRI 8

9. Inravascular hemolysis : - laboratory signs of intravascular hemolysis: indirect hyperbilirubinemia erythroid hyperplasia hemoglobinemia methemoalbuminemia hemoglobinuria absence or reduced of free serum haptoglobin hemosiderynuria DR GRK CHRI 9

10. Extravascular hemolysis : - red cells destruction occurs in reticuloendothelial system - clinical states associated with extravascular hemolysis : autoimmune hemolysis delayed hemolytic transfusion reactions hemoglobinopathies hereditary spherocytosis hypersplenism hemolysis with liver disease - laboratory signs of extravascular hemolysis: indirect hyperbilirubinemia increased excretion of bilirubin by bile erythroid hyperplasia hemosiderosis DR GRK CHRI 10

11. Classification : INTRACORPUSCULAR HEMOLYSIS Membrane Abnormalities Haemoglobin defects Enzyme defects EXTRACORPUSCULAR HEMOLYSIS Nonimmune Immune DR GRK CHRI 11

12. Intracorpuscular defects Membrane Defects Microskeletal defects Hereditary spherocytosis** Membrane permeability defects Hereditary stomatocytosis Increased sensitivity to complement Paroxysmal nocturnal hemoglobinuria DR GRK CHRI 12

13. Intracorpuscular defects Enzymopathies Deficiencies in Hexose Monophosphate Shunt Glucose 6-Phosphate Dehydrogenase Deficiency** Deficiencies in the EM Pathway Pyruvate Kinase Deficiency DR GRK CHRI 13

14. Intracorpuscular defects Haemoglobin defects Haemoglobinopathies : Sickle cell anemia Thalassemias: β -thalassemia major HbH disease Double heterozygous disorders: Sickle cell β -thalassemia DR GRK CHRI 14

15. Extracorpuscular defects - IMMUNE Autoimmune Hemolysis Warm antibody Cold antibody Alloimmune Hemolysis Hemolytic Transfusion Reaction Hemolytic Disease of the Newborn Drug-Related Hemolysis DR GRK CHRI 15

16. Extracorpuscular defects - Nonimmune Mechanical Infectious Chemical Thermal DR GRK CHRI 16

17. How is Hemolytic Anemia Diagnosed? Two main principles One is to confirm that it is hemolysis Two is to determine the etiology DR GRK CHRI 17

18. How to diagnose hemolytic anemia New onset pallor or anemia Jaundice Splenomegaly Gall stones Dark colored urine Leg ulcers DR GRK CHRI 18

19. General evidences of haemolysis: Evidence of increased Hb breakdown: - jaundice and hyperbilirubinemia - reduced plasma haptoglobin( binds free Hemoglobin) / haemopexin - increased plasma LDH (RBC lysis) e/o intravascular haemolysis Haemoglobinaemia (increased free Hb) Haemoglobinuria Methaemalbuminaemia Haemosiderinuria DR GRK CHRI 19

20. Evidence of compensatory erythroid hyperplasia : - Reticulocytosis (0.5-2%) Absolute retic count= % reticulocytes X RBC count/µ l > 100000/µ l - Macrocytosis & polychromasia - BM erythroid hyperplasia M:E ratio (4:1) becomes 1:1 - Radiological changes in bones Evidence of damage to red cells: - Spherocytosis & increased fragility - Fragmented RBCs - Heinz bodies Demonstration of shortened RBC life-span DR GRK CHRI 20

21. 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 DR GRK CHRI 21

22. Extravascular Intravascular Hematologic Peripheral smear Polychromatophilia Polychromatophilia Retic count BM examination Erythroid hyperplasia Erythroid hyperplasia Plasma or Serum Bilirubin Unconjugated Unconjugated Haptoglobin Absent Absent Plasma Hb N/ LDH Variable Variable Urine Bilirubin + + Hemosiderin ___ + Hemoglobin ____ + DR GRK CHRI 22

23. POLYCHROMATOPHILIC CELLS DR GRK CHRI 23

24. The key to the etiology of hemolytic anemia The history The peripheral blood film DR GRK CHRI 24

25. Patient History Acute or chronic Medication/Drug precipitants G6PD AIHA Family history Concomitant medical illnesses Clinical presentation DR GRK CHRI 25

26. A 5.5 year old girl child came to OPD for pallor, In the 7th month, the child was hospitalized with whitish tinge & paleness of the skin (hand and feet), growth retardation, and low Hb level (5 gm /dl ). Treated with blood transfusion 1st time and recovered well. At the 11th month of age,rehospitalization was done due to chronic anemia (sudden drop in hemoglobin level). Treated with blood transfusion DR GRK CHRI 26

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28. Thalassemia - autosomal recessive - two main types, i.e., alpha and beta. DR GRK CHRI 28

29. Symptoms and Signs Fatigue/weakness/shortness of breath Pale or yellowish skin/anemia Facial bone deformity Slow growth/failure to thrive Abdominal swelling Hepatosplenomegaly DR GRK CHRI 29

30. Jaundice and pigment gallstones Hypersplenism Complications of extramedullary hematopoiesis Skeletal changes Iron overload Growth impairment Complications of iron overload Endocrine and metabolic abnormalities Heart failure and arrhythmias Pulmonary abnormalities and PH. DR GRK CHRI 30

31. Laboratory Findings DR GRK CHRI 31

32. Management DR GRK CHRI 32

33. CASE 1 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- DR GRK CHRI 33

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35. Differential diagnosis Hereditary spherocytosis Autoimmune hemolytic anemia Other diagnostic tests- osmotic fragility - coombs test DR GRK CHRI 35

36. HEREDITARY SPHEROCYTOSIS

37. ETIOLOGY Usually AD . Rarely AR 25% have no F/H. New mutations Northern Europe most common Also seen in SE Asia incl. India, Nepal DR GRK CHRI 37

38. RBC CYTOSKELETON “Vertical” and “horizontal” interactions b/w proteins and lipids Lipid bilayer skeleton Spectrin and Ankyrin : major components Spectrin has α and β chains Protein 3 also present Deficiency in either of the 3 causes problem in the “vertical” interactions DR GRK CHRI 38

39. MOLECULAR PATHOPHYSIOLOGY Deficiency in spectrin, ankyrin, protein 3 Lipid bilayer skeleton uncoupling Membrane loss in the form of microvesicles Surface area deficiency Spherocytosis Impaired passage through splenic cord Sequestration DR GRK CHRI 39

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41. RBC INDEX Increased concentration of Hb per RBC area MCHC (only condition where its elevated) DR GRK CHRI 41

42. VARIOUS PRESENTATIONS Hemolytic d/s of newborn Hemolytic crisis : most common form Aplastic crisis Megaloblastic crisis HS in pregnancy DR GRK CHRI 42

43. CLINICAL CLASSIFICATION Trait Mild HS Moderate HS Moderately severe HS Severe HS DR GRK CHRI 43

44. HS IN NEONATES Hemolytic d/s of newborn Prolonged neonatal jaundice May require PT/ exchange transf. Anemia progressing to CCF Hydrops fetalis (rare) Palpable spleen Investigate parents DR GRK CHRI 44

45. HEMOLYTIC CRISIS Pptd by viral inf : Infectious mononucleosis Exercise induced Anemia,jaundice Vomiting, abd pain, tender spleen May happen also during recovery phase of aplastic crisis DR GRK CHRI 45

46. APLASTIC CRISIS Less common, more serious Parvovirus B19 Fever, chills Vomiting, diarrhea, myalgias Slapped cheek appearance Following this - sudden pallor, jaundice, weakness DR GRK CHRI 46

47. PATHOGENESIS OF APLASTIC CRISIS Parvovirus affects erythropoetic precursors -> arrests cell cycle in G2 phase -> apoptosis. Also transient neutropenia, thrombocytopenia (pancytopenia) BM: giant pronormoblasts (hallmark) Unused iron levels increase in serum Hematocrit and retic count falls Self limiting process. Self recovery after sometime DR GRK CHRI 47

48. MEGALOBLASTIC CRISIS Due to a secondary folate deficiency In patients recovering from aplastic crisis Hence supplement 1mg/day of F.A. to children with HS DR GRK CHRI 48

49. COMPLICATIONS Gall stones : young adults/ adolescence . Gout, Leg ulcers Chronic erythematous dermatitis of legs Extramedullary hematopoesis Hematologic malignancies : multiple myeloma, leukemia, hepatoma Heart disease: CCF, cardiomyopathy DR GRK CHRI 49

50. INVESTIGATIONS Hb: 6-10g/dl Increased retics Indirect hyperbilirubinemia MCV normal. MCHC increased (high Hb) PS: polychromatophilia, spherocytes (usually >15-20% of cells), central pallor absent, hyperchromic, DR GRK CHRI 50

51. INVESTIGATIONS BM: erythroid hyperplasia Decreased haptoglobin Incubated Osmotic fragility test (deprive RBC off glucose overnight): increased fragility to hypotonic saline Autohemolysis: spont cell breakdown after incubation for 48 hrs at 37C. Normally <4%, In HS >10-15% Molecular and genetic analysis DR GRK CHRI 51

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53. OSMOTIC FRAGILITY DR GRK CHRI 53

54. Other conditions associated with spherocytes on PS : Auto-immune hemolytic anemia Burns Wilson’s disease Chemical injury Infections HDN due to anti-A DR GRK CHRI 54

55. Treatment: If Hb > 10 gm/dl and retics < 10%- no Rx If severe anemia, poor growth, aplastic crises and age < 2 yrs - transfusion If Hb < 10 gm/dl and retics > 10 % or massive spleen- splenectomy Folic acid- 1 mg/day Cholecystectomy for gall stones DR GRK CHRI 55

56. SPLENECTOMY Indications: Hypoplastic/aplastic crisis Poor skeletal growth Cardiomegaly DR GRK CHRI 56

57. SPLENECTOMY Recommended >5-6 yrs Post splenectomy sepsis with encapsulated org Prophylactic vaccinations : Hib, Pneumococcus, meningococcus Prophylactic penicillin V: <5yr: 125mgBD >5yr to adulthood: 250mg BD Post splenectomy Thrombocytopenia : self limiting Partial splenectomy/embolization if <5yrs DR GRK CHRI 57

58. Case 2 3 yr old male child presenting with pallor, jaundice, Severe pain of long bones, fever CBC- anemia, reticulocytosis, increased WBC LAB - LDH -600 (normal up to 200) S. bilirubin- 5mg% DR GRK CHRI 58

59. Peripheral smear SICKLE CELL ANEMIA DR GRK CHRI 59

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62. Valine replaces Glutamine Abnormal hemoglobin Change in surface tension of RBC Sickling of RBCs DR GRK CHRI 62

63. Types Homozygotes ( AR)- Sickle cell disease-Median life expectancy 40s- no normal matured Hb-Africans & Caucasians Heterozygotes- Sickle cell trait-8-10% of African Americans- Normal life span- 60% N Hb A, 40 % Hb S DR GRK CHRI 63

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65. DIAGNOSIS Hemoglobin electrophoresis -HbS >80% - HbF -1-20% -HbA2 -2- 4.5% Sickling test POSITIVE DR GRK CHRI 65

66. Sickle cell disease Mutation.beta globin-6 Glutamine Valine Deoxy HbS (polymerized) Ca influx, K leakage stiff, viscous sickle cell venocclusion dec.RBC survival microinfarctions, isch.pains anemia, jaundice, autoinfarct . spleen gallstones, leg ulcers DR GRK CHRI 66

67. Clinical manifestations Hemolytic anemia (Hb 6-10 mg Retic count 3-15%) age at presentation infancy, 61% by 2 yrs , 96% by 8 yrs , reticulocytosis, granulocytosis Vasoocclusion-protean Acute Painful crises Splenic sequestration crises Hand foot syndrome- Dactylitis Acute chest syndrome DR GRK CHRI 67

68. Sickle dactylitis One of the first complications- highest incidence b/w 6 m -2 yrs Painful swelling of hand & feet Treated with IVF & NSAIDs Spontaneous resolution without complications DR GRK CHRI 68

69. Painful crisis Ppting factors- deoxygenation, dehydration, infection, stress, menses, cold Widespread occlusion of microvasculature Severe pain in back, chest, extremities & abdomen, fever, swelling, tenderness, tachypnea, nausea, vomiting Lasts for few hrs-2 weeks MOHA Morphine, Oxygenation, Hydration, analgesics DR GRK CHRI 69

70. Infection Splenic congestion with abnormal RBCs Autosplenectomy d/t Infarction (Caucasians>>>>Africans) Commonest cause of death in children Pneumonia, meningitis, sepsis, osteomyelitis Pneumococcus, Hib, Salmonella, Staph. aureus DR GRK CHRI 70

71. Acute Chest Syndrome 30% of pts Shortness of breath, fever, tachypnea, leukocytosis, X ray infiltrates DR GRK CHRI 71

72. Neurological complication TIA Cerebral infarction ( Transcranial doppler to assess early) Seizures Cerebral Hemorrhage Renal Reduced concentrating ability, glomerular disease, CRF Increased risk of UTI Priapism DR GRK CHRI 72

73. Aseptic necrosis of femoral head Leg ulcers (static ulcers) Major cause of morbidity Teenagers- medial & lateral malleolus Occlusion & stasis of skin microvasculatre DR GRK CHRI 73

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76. Splenic Sequestration- enlarged & congested with RBCs- may lead to shock d/t hypovolemia Retinopathy- d/t hemorrhage & detachment ( retinal evaluation at school age) Rhabdomyolysis- prolonged physical activity & high altitude DR GRK CHRI 76

77. Management Immunisation Penicillin prophylaxis- < 5 yrs 125 mg BD up to 2- 3 yrs then 250 mg BD Hydroxyurea(±Erythropoietin)- increases fetal Hb BMT & cord blood of Siblings DR GRK CHRI 77

78. Case 3 7 year old boy, otherwise healthy developed burning micturition R/E of Urine showed pus cells patient was started on Septran 3 days back Presented with sudden pallor, malaise, fatigue, he mentioned that he passed tea color urine. His mother noticed that he is jaundiced too. He was pale, jaundiced, inactive, PR 120 beats/minute, no organomegaly. DR GRK CHRI 78

79. GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY DR GRK CHRI 79

80. Two clinical syndromes: - Episodic / induced hemolytic A - Spontaneous chronic non- spherocytic hemolytic A Inheritance of abnormal alleles of gene responsible for synthesis of G6PD molecules DR GRK CHRI 80

81. ETIOLOGY X-Linked recessive Evolutionary advantage of resistance to falciparum malaria 90 mutations of G6PD gene Normal enzyme : G6PD B+ Variant: G6PD A+ (African-American) G6PD A - DR GRK CHRI 81

82. Synthesis of G6PD determined by X chromosome Usually only males affected Heterozygous females (intermediate enzyme activity) usually not symptomatic…unless random inactivation of normal X chromosome (rarely)  Lyon’s hypothesis DR GRK CHRI 82

83. FUNCTION OF G6PD Regenerates NADPH, allowing regeneration of glutathione Protects against oxidative stress Lack of G6PD leads to hemolysis during oxidative stress- infection, medication, fava beans Oxidative stress leads to Heinz body formation, extravascular hemolysis DR GRK CHRI 83

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86. PRECIPITATING FACTORS Antimalarials: primaquine, quinine, chloroquine Antibiotics - nitrofuantoin , furazolidine , cotrimoxazole, Nalidixic acid, Chloramphenicol, Others : Vitamin K – large doses Naphthalene (moth balls) Benzene, Methylene blue Probenecid Acetyl salicylic acid (aspirin) Fava beans Septicemia and viral hepatitis in def. pts Diabetic ketoacidosis DR GRK CHRI 86

87. FAVA BEANS DR GRK CHRI 87

88. TYPES Type 1 : mild (G6PD A-): Afro- americans Type 2 : moderately severe (G6PD B- and G6PD Canton): SE Asia, Mediterranean Type 3 : chronic: North America and Europe OR Episodic hemolytic anemia Spontaneous chronic non spherocytic hemolytic anemia DR GRK CHRI 88

89. CLINICAL FEATURES Exposure to drug 24-48 hr Severe progressive anemia, cardiac failure and jaundice Favism: hemolysis after ingestion of fava beans DR GRK CHRI 89

90. TYPE 1 Mildest form (enzymes 8-15 % of normal) Episodic form Sensitive to strong oxidants Usual doses of aspirin and Co- trimox well tolerated Young RBC have high conc of enzyme -> hence no neonatal jaundice Hemolysis doesn’t continue after intial hemolysis as ageing G6PD cells dead and young ones have enzyme DR GRK CHRI 90

91. TYPE 2 Moderately severe Episodic form Fava exposure + oxidants Neonatal Jaundice present Hemolysis continuous with continuous administration of drug Assoc with viral hepatitis – severe jaundice Encephalopathy sometimes DR GRK CHRI 91

92. TYPE 3 Chronic type Spontaneous, without any ppt factor If ppt factor given -> severe hemolysis with hemoglobinuria Severe neonatal jaundice -> kernicterus Hemolysis after febrile episode Enzyme level very very low DR GRK CHRI 92

93. INVESTIGATIONS During hemolysis : Hb decreased Elevated retics (5-15 %) PS: Normocytic normochromic anemia Polychromasia, fragmented cells Heinz bodies :- ppted hemoglobin- supravital staining Hemoglobinuria Indirect hyperbilirubinemia DR GRK CHRI 93

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95. Blister cells DR GRK CHRI 95

96. 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 DR GRK CHRI 96

97. NEVER ASSESS G6PD LEVELS DURING ACUTE HEMOLYSIS DR GRK CHRI 97

98. WHY? During acute hemolysis- all deficient cells have been hemolyzed Young cells will be in circulation Young surviving cells may have normal levels of the enzyme Hence falsely normal during acute episode Assess 2-4 months later Deficient G6PD levels will be evident Usually affected have <10% of normal level DR GRK CHRI 98

99. TREATMENT Avoid the oxidants Blood transfusion Sodium bicarbonate to alkalinise urine in severe Hburia… or else acid hematin ppt in renal tubules DR GRK CHRI 99

100. Pyruvate Kinase Deficiency AR Deficient ATP production, Chronic hemolytic anemia Clinical features Hydrops fetalis Neonatal jaundice compensated hemolytic aa P. Smear: PRICKLE CELLS ( Contracted RBCs with spicules) Decreased enzyme activity DR GRK CHRI 100

101. Autoimmune Hemolytic Anemia Result from RBC destruction due to RBC autoantibodies : Ig G, M, E, A Compliment activation Most commonly-idiopathic Classification Warm AI hemolysis: Ab binds at 37degree Celsius Cold AI Hemolysis: Ab binds at 4 degree Celsius DR GRK CHRI 101

102. 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.Connective Tissue Disorder: SLE,RA 4.Drugs: Alpha methyl DOPA, Penicillin , Quinine, Chloroquine, NSAIDS, Quinidine 5. HIV DR GRK CHRI 102

103. Inv: hemolysis, MCV decreased P Smear: microspherocytosis, Confirmation: Direct Coomb’s Test / Antiglobulin test DR GRK CHRI 103

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105. 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) DR GRK CHRI 105

106. Inv: e/o hemolysis P Smear: Microspherocytosis DAT positive with polyspecific and anticompliment antisera DR GRK CHRI 106

107. Treatment Steroids Cytotoxic drug-cyclophosphamide, azathioprine Splenectomy DR GRK CHRI 107

108. 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? DR GRK CHRI 108

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110. Paroxysmal nocturnal hemoglobinuria Acquired chronic H.A Persistent intra vascular hemolysis Pancytopenia Lab : Hemoglobinuria, hemosiderinuria, increased LDH, bilirubin Risk of venous thrombosis C/F – hemoglobinuria during night P.S – polychromatophilia, normoblasts B.M – normoblastic hyperplasia DD-flow cytometry CD59-,CD55- RBC,WBC - Hams’ acidified serum test DR GRK CHRI 110

111. 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 – DR GRK CHRI 111

112. Microangiopathic hemolytic anemia DR GRK CHRI 112

113. 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 DR GRK CHRI 113

114. Microangiopathic hemolytic anemia(MAHA) Other findings - leukocytosis - thrombocytopenia(DIC,TTP) - hemoglobinuria - deranged RFT - PT,APTT prolonged (DIC,TTP) DR GRK CHRI 114

115. 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 DR GRK CHRI 115

116. Conclusion Hemolytic anemia can be recognized by clinical picture- - history & physical - lab test to confirm hemolysis - peripheral smear to guide further tests DR GRK CHRI 116

117. Hemolytic facies- chipmunk facies DR GRK CHRI 117