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?