acquired haemolytic anaemia
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Acquired Haemolytic anaemia
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Acquired Haemolytic Anaemia
Immune1.Autoimmune*warm Ab*cold Ab
2.Alloimmune*Transfusion rn*HDN
Non Immune1.Mechanical *March haemoglobinuria*Prosthetic heart valves2.MAHA3.Infections *Malaria*Clostridium welchii4.Burns5.Drugs*Dapsone6.PNH
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18 year old girl
C/O - fever, yellow discolourationof eyes and abdominal pain – 2 weeks
O/E – Pale ++ , Icteric +, Spleen – 1cm
1. How would you confirm haemolysis?2. What are the possible causes?
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Warm autoimmune haemolytic anaemia
Antibodies optimally active at 370. IgG
Causes*Idiopathic*secondary
SLECLLLymphomasDrugs- Methyl dopa
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Warm autoimmune haemolytic anaemia cont.
Pathogenesis IgG antibodies are present on the red cells, some of
them also bind complement(C3)
Red cells are destroyed mainly in the RE system (preferentially spleen)
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Warm autoimmune haemolytic anaemia cont.
Clinical features Haemolytic anaemia Jaundice Splenomegaly
Investigations Reticulocytosis Spherocytes Increased serum bilirubin Positive direct coomb test
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Warm autoimmune haemolytic anaemia cont.
Treatment Corticosteroids
Splenectomy
Immunosuppresives- Azathioprine
Folic acid
Treat underlying cause
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Cold autoimmune haemolytic anaemia
Auto antibodies (IgM) that react best at temp. <370 (0-40)
Causes*Idiopathic (CHAD)*secondary
MycoplasmaInfectious mononucleosisLymphomaSLE
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Cold autoimmune haemolytic anaemia cont.
Investigations Anaemia with red cell agglutinates Macrocytosis Reticulocytosis Positive direct coomb test Features of IV haemolysis
RBC – 1.1x1012/l HB - 6.2g/dl MCV – 112fl
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Cold autoimmune haemolytic anaemia cont.
Clinical features Some have acute IV haemolysis & Hburia in cold
weather but maintain a normal Hb in warm weather
Others have a compensated chronic haemolysis with a mild to moderate reduction of Hb.
Acrocyanosis, Raynauds phenomenon due to agglutinates.
Spleen may not be enlarged
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Cold autoimmune haemolytic anaemia cont.
Investigations
Anaemia with red cell agglutinates Macrocytosis Reticulocytosis Positive direct coomb test Features of IV haemolysis
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Cold autoimmune haemolytic anaemia cont.
Treatment
Avoid cold May need blood transfusions Rituximab (monoclonal anti CD20) Chlorambucil Plasmapheresis has been used Corticosteroids and splenectomy are rarely of any
benefit
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Allo immune
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ABO & Rh incompatibilty Haemolytic transfusion reactions may be immediate or
delayed.
Immediate life threatening reactions associated with massive IV haemolysis is seen with complement activating antibodies of IgM & IgG classes(ABO antibodies)
Severity of the reaction depends on the recipient’s titre of antibody
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ABO & Rh incompatibilty cont.
Extra vascular haemolytic transfusion reactions are seen with the immune antibodies( IgG, unable to bind complement).
The only feature may be unexplained anaemia with jaundice
Non immune causes of haemolysis
Mechanical causes of haemolysis
Red cells may be injured by excess physical trauma as they circulate through the vascular system.
Mechanical haemolytic anaemia
Cardiac – Occasional complication of open heart surgical procedures eg. valve prostheses. In severe cases marked anaemia with intravascular haemolysis.
March haemoglobinuria – Hbnaemia & Hburia following strenuous exercise in healthy young adult males.
Traumatic effect on the blood within vessels of sole.
soldiers, athletes, karatekas.
Microangiopathic haemolytic anaemia Mechanical haemolytic anaemia in which the red cell
fragmentation is due to contact between red cells & abnormal intima of partly thrombosed, narrowed, or necrotic small vessels.
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Microangiopathic haemolytic anaemia
With associated thrombocytopaenia
1.Disseminated intravascular coagulation
2.Haemolytic uraemic syndrome
3.Thrombotic thrombocytopaenic purpura
4. HELLP syndrome
DIC Widespread intra vascular coagulation induced by pro
coagulants (that overcome the natural anti coagulant mechanisms), resulting in the formation of thrombin.
These pro coagulants may be produced in the blood or introduced from out side the circulatory system eg- snake venom
This results in- Formation of micro thrombi Ischemia
Consumption of platelets & clotting factors Bleeding
DIC cont.
Causes*Trauma*Cancers*Bacteraemia*Severe Haemorrhage*Obstetric & surgical events
DIC cont.Investigations Fragmented red cells
Low platelet count
Prolongation of PT, aPTT, TT, Low fibrinogen
Elevated FDP, D dimers
HUS-TTP Initially described as two distinct entities but thereafter
thought to be two ends of the same spectrum. ? Two distinct entities
Formation of platelet thrombi (hyaline thrombi) in terminal arterioles & capillaries.
Microangiopathic haemolytic anaemia with Thrombocytopaenia
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HUS-TTPClinical features
Fever
Neurological symptoms
Renal failure
+
MAHA Thrombocytopenia Coagulation screen – NORMAL LDH - high
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Causes of HUS
E.Coli o157 toxin Shigella dysenteriae
TTP Pathogenesis
Presence of abnormal vwf (platelet adhesion)
Deficiency of vwf cleaving proteases ADAMTS-13
Increase in vwf activity, platelet aggregation
Microthrombi formation
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Causes of TTP
Inherited deficiency of ADAMTS 13• Present in neonatal period
Acquired deficiency of ADAMTS 13• Drugs- clopidogrel, ticlopidine, ciclosporine • Post transplant• Pregnancy• SLE
TTP
Treatment Plasma exchange
FFP/CPP
Steroids / immunosuppresion
Platelets not given
Rituximab
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HELLP syndrome
HELLP syndrome occurs in approximately 0.2 to 0.6 % of all pregnancies.
Pre eclampsia occurs in 5 to 7 % percent of pregnancies.
Superimposed HELLP syndrome develops in 4 to 12 percent of women with pre eclampsia or eclampsia.
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HELLP The pathogenesis of HELLP is not well understood. Findings are attributed to abnormal vascular tone,
vasospasm and coagulation defects. No common precipitating factor has been found. Some insult that leads to microvascular endothelial
damage and intravascular platelet activation. Platelet activation, causing vasospasm, platelet
agglutination and aggregation, and further endothelial damage.
Fibrin forms networks in the small bld vsl. Liver appears to be the main site of this process This cascade is only terminated with delivery.
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HELLP MAHA. Elevated liver enzyme levels are thought to be
secondary to obstruction of hepatic blood flow by fibrin deposits in the sinusoids.
This obstruction leads to periportal necrosis and, in severe cases, intrahepatic haemorrhage, subcapsular hematoma or hepatic rupture.
The thrombocytopenia has been attributed to increased consumption and/or destruction of platelets.
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HELLP
PT, APTT, Fbrinogen usually normal DIC is also seen in about 20% of all women with HELLP
syndrome Fibrinogen <3g/l in this setting suspect DIC
Infections Malaria – anaemia is often only mild
*can be severe esp.with falciparum infections
*Blackwater fever rare but serious complication, seen in endemic areas & in those who have repeated attacks. Pptd by antimalarial drugs.
*Diagnosis by demonstrating the parasite.
*Antigen tests
Infections Clostridium welchii – due to direct action of toxin
*mostly post abortal or puerperal infections
*Intra vascular spherocytic anaemia, retic count not very high
Drugs Due to direct toxic effects in normal subjects
*Sulphasalazine
Haemolysis in subjects with metabolic abnormality G6PD def*Primaquine, Nitrofurantoin
Due to a immune mechanism*Quinine, Penicillin, Sulphonamides
Toxins – Snake bite
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Paroxysmal Nocturnal Haemoglobinuria
Acquired chronic intra vascular haemolysis May have thrombosis and pancytopenia Nonmalignant clonal expansion of one or several hematopoietic stem cells that have acquired
a somatic mutation of PIGA Affected stem cells are deficient in glycosyl
phosphatidylinositol–anchored proteins (GPI-APs)
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Urine haemosiderin HAM test Flow cytometry for GPI –AP LDH
Transfusion Iron replacement
14 year old boy
C/O - fever, yellow discolourationof eyes and abdominal pain – 2 weeks
O/E – Pale ++ , Icteric +, Spleen – 1cm
What are the first line investigations?