APPROACH TO A PATIENT WITH HEMOLYTIC ANAEMIA

APPROACH TO A PATIENT WITH HEMOLYTIC ANAEMIAMODERATOR-DR.AMIT VARMAPRESENTAOR DR.SUNIL BHATT

Normal shape of RBC- biconcaveNormal life span of RBC-120 day

Hemolytic anemia is a form of anemia due to haemolysis ,the abnormal premature breakdown of red blood cells (RBCs)either in the blood vessel (intravascular haemolysis)or elsewhere in the human body(extravascular ) and bone marrow is not compensating for red blood cell loss.

Compensatory action of bone marrowIn response to haemolytic anaemia dec haemoglobinOxygen supply to kidney is dec,Inc erythropoiten from peritubular capillaries around PCTErythropoiten prevents apoptosis of erthroblast .causes erythroid hyperplasia

Bone marrow can inc prod.of RBC 8 to 10 times.(compensated haemolytic disease)

evidence of haemolyisJaundice due to unconjugated hyperbilirubinemia. jaundice is mild to moderate. lemon yellow color of skin(Pale color of aneamia and yellow color of jaundice )Dark color stoolInc urobilinogen in urine(acholuric jaundice)LDH level are raisedHaptoglobin (macrophages destroy haptoglobin and haemoglobin)Slightly less haptoglobin in extravascularVery less haptoglobin in intravascular.

PERIPHERAL BLOOD FILM evidence of haemolysisNormal reticulocyte count in blood is 1 to 2%In haemolysis reticulocyte count is upto 20%MCV-Increses(105fl)normal is 80 to 100flMacrocytosisPolychromasia(multiple color and shade)

BONE MARROWHypercelluar bone marrow

EXTRAVASCULAR OR INTRAVASCULARextravascularSPLENOMEGALYintravasculardec haptoglobin or absent haptoglobinHaemoglobinemiaMethaemoglobinemiaTetrameric to dimer structure of haemoglobin --endocytosis by PCT cells ---release of iron-- Acute tubular necrosis renal failureHaemoglobinurea.

FEATURES OF EXTRAVASCULAR HAEMOLYSIS(HERIDITARY SPHEROCYTOSIS)PBFMCV DECMCH -NORMALMCHC HIGHRBC SHAPE SPHERICALRBC COLOR- DARK RED WITH LOSS OF CENTRAL PALLOROTHER FINDINGSSPLENOMEGALY

ACUTE OR CHRONIC intravascular haemolysisACUTEHaemoglobinemia,methaemoglobinemia,low haptoglobinHaemoglobinuria

CHRONICDeposition of bilirubin in gall bladdergall stones.Splenomegaly.

Haemosiderinureadue to chronic haemolysis haemosiderin is formed in PCT.Stained by persian blue.

Intrinsic and extrinsic causesINTRINSIC CAUSES cause is related to RBC itself.

EXTRINSIC CAUSES-where factors external to the RBC dominate.

Intrinsic causesINHERITEDMembrane defectsEnzymes defect

INTRINSIC CAUSESINHERITEDHeriditary spherocytosisHeriditary elliptosytosis

ACQUIREDPNH

PNHAcquiredMutation of myeloid cellsOn x chromosomes on short armPIG-A gene-GPI PHOSPHOLIPIDS on cell membrane which is attached to PIG tailed protein(CD55,CD59,C-8 BINDER)Haemolysis of RBC,WBC and platelets.HAEMOTOLOGICAL CHIMERAASSOSIATION WITH APLASTIC ANAEMIAAUTOREACTIVE REACTIVE T CELLS DESTROYS THOSE MYELOID CELL WHICH ARE LOADED WITH NORMAL GPI PROTEIN WHICH WILL CAUSE CELLS DEFICIENT IN GPI WILL PROLIFERATE.THESE PATHOLOGICAL CELLS WILL MULTIPLY.In severe case pancytopenia

Haemolysis occur all the timeDuring sleep occurs moreBreathing become slow inc in co2---produce acidic enviornment-alternate compliment acivated.

Thrombi formation(hepatic vein,cerebral vein,deep vein of legs)Free Hb combine with NO Smooth muscle fail to relaxerectile dysfuntion,odynophagiaInc infectionLAP score dec

TESTSHAM TESTSUCROSE HAEMOLYSIS TESTFLOW CYTOMETRY

IMMUNOSUPPRESIVE DRUGSMONOCLONAL ANTIBODIESBINDS WITH C5 PREVENTS BREAKDOWN OF C5 TO A AND B COMPONENT.

Enzyme defectHexokinase Pyruvate kinaseG6PD DeficiencyGlutathione syntheseGlycolysis pathway disturbed

Haemoglobin synthesis defect

GLOBIN CHAIN SYNTHESIS IS QUANTITATIVELY REDUCEDTHALASEMIA(ALPHA OR BETA )

QUALITATIVE DEFECT IN GLOBIN CHAINHAEMOGLOBINOPATHIESSICKLE CELL ANAEMIA(GENE defect POSITION NO 6 .GLUTAMIC ACID IS REPLACED BY VALINE)

Extrinsic causesImmune mediated causes likeISO ANTIBODY---ABO ,RhAUTO ANTIBODY---

Warm cold agglutinins cold haemolysins

WARM ANTIBODY

IgG37 DEGREE CENTIGRADEDIRECTED AGAINST -Rh antigenMonomeric cannot agglutinateCompliment system cannot be activated(RBC has cd59 and cd55)RBC when they pass through spleen converts to spherocytes.(differentiated by direct coombs test)Cause-idiopathic,lymphoma,leukemia,SLE,drugs(penicillin,cephalosparin,quinidine,alpha methyl dopa)

Cold antibodyIgMAgglutinate