Haemolysis and Acquired Haemolytic Anaemia Flashcards

Question

Autoimmune Haemolytic Anaemia: Types

Answer 1

Warm Autoimmune Haemolytic Anaemia Cold Autoimmune Haemolytic Anaemia

Answer 2

Red cell coated with immunoglobulin and/or complement: – Usually IgG and C3, rarely IgA Immunoglobulin recognized by Fc receptor on macrophages in reticuloendothelial (RE) system: – Loss of membrane leads to spherocytes – Shortened red cell lifespan ``` Clinical picture: – Any age, sex – Haemolytic anaemia – varying severity • Remit and relapse – Splenomegaly ```

Answer 3

1. Idiopathic (70% of cases) ``` 2.Secondary – Autoimmune diseases (SLE etc.) – Lymphoproliferative disorders: *Lymphoma *Chronic lymphocytic anaemia – Viral infections (EBV) – Drugs: Methyldopa etc. ```

Answer 4

Pallor Jaundice: - Mild - Fluctuating Dark urine +- Splenomegaly

Answer 5

Full blood count – Normocytic/macrocytic anaemia – Leucocytosis Peripheral smear – Spherocytes, polychromasia, nucleated red cells Features of EXTRAVASCULAR haemolysis Direct Coombs (DAT) positive – IgG and/or complement, IgA (rare) – Antibodies detected at 37°C

Answer 6

Remove/treat the underlying cause Corticosteroids Intravenous immunoglobulin (IVIG/Polygam®) Splenectomy Immmunosuppression – If steroids and/ or splenectomy have failed Folic acid is given in severe cases Blood transfusion – Least incompatible – If the specificity of the autoantibody is known, use donor blood that lacks the relevant antigen(s)

Answer 7

Antibody usually IgM and binds to red cells at 4°C - Highly effective fixing complement - INTRAVASCULAR AND EXTRAVASCULAR haemolysis Antibody attaches to red cells in the peripheral circulation – Blood temperature is cooled – Antibody elute of cell at warmer parts and only complement is usually detected

Answer 8

Chronic haemolytic anaemia: – Aggravated by cold – Mild jaundice and splenomegaly may be present Acrocyanosis (purplish skin discoloration) – Tip of the nose, ears, fingers and toes – Agglutination of red cells in small vessels

Answer 9

Full blood count – Normochromic/macrocytic anaemia – Leucocytosis Peripheral smear – Haemagglutination – Spherocytosis is less marked DAT – Complement (C3d) only on the red cell surface High titre of “cold” autoantibodies to red cells

Answer 10

Keep the patient WARM – Warmed fluids Treating the underlying cause Splenectomy doesn’t help – Unless massive splenomegaly Medication – Immunosuppression Steroids are not helpful

Answer 11

Antibody produced when red cells of one individual reacts with red cell of another

Answer 12

Transfusion of ABO-incompatible blood Rh disease of the new-born Allogeneic transplantation

Answer 13

Full blood count and peripheral smear – Anaemia – Features of haemolysis-INTRA- AND/OR EXTRAVASCULAR Direct antiglobulin test (Direct Coombs test) – Positive Antibody identification and quantification

Answer 14

Drug-red cell membrane complex Drug-protein-antibody complex True autoimmune haemolytic anaemia (Rare) Haemolytic anaemia disappears once drug is stopped

Answer 15

Antibody directed against a drug-red cell membrane complex Only massive doses Often antibiotics – E.g. penicillin and ampicillin

Answer 16

Drug-protein-antibody complex Deposition of complement – E.g. quinidine, rifampicin

Answer 17

True autoimmune haemolytic anaemia Role of drug uncertain -E.g. methyldopa

Answer 18

Causes haemolysis in a variety of ways: 1. Precipitates an acute haemolytic crisis in G6PD deficiency 2. Causes microangiopathic haemolytic anaemia • E.g. meningococcal or pneumococcal septicaemia 3. Malaria causes haemolysis by extravascular destruction of parasitized red cells as well as by direct intravascular lysis -Blackwater fever is an acute intravascular haemolysis accompanied by acute renal failure caused by Falciparum malaria 4. Clostridium perfringens septicaemia can cause intravascular haemolysis with marked microspherocytosis

Answer 19

Physical damage to red cells due to: - Microangiopathic haemolytic anaemia (MAHA) - Abnormal surfaces - Mechanical trauma

Answer 20

– Red cells passing through abnormally small vessels • Caused by deposition of fibrin strands or platelet aggregates

Answer 21

Physical damage to red cells on abnormal surfaces – e.g. artificial heart valves or arterial grafts – Arteriovenous malformations

Answer 22

March haemoglobinuria

Answer 23

Thrombotic microangiopathy Pathological lesion on tissue biopsy – Platelet-fibrin rich thrombus

Answer 24

1.Primary thrombotic microangiopathy (TMA) syndromes: Thrombotic thrombocytopenic purpura (TTP) Haemolytic Uremic Syndrome (HUS) - Atypical HUS or Complement-mediated TMA - Shiga toxin-mediated HUS (ST-HUS) Drug-induced TMA 2.Systemic disorders that may present with MAHA and thrombocytopenia: Disseminated intravascular coagulation (DIC) Systemic infection (Sepsis) : May be bacterial, viral, rickettsial, or fungal Systemic malignancy Pregnancy-related syndromes HELLP syndrome, pre-eclampsia, etc. Severe hypertension Systemic rheumatic diseases: E.g. Vasculitis, antiphospholipid syndrome, etc. Haematopoietic stem cell or organ transplants Renal vascular disorders

Answer 25

Acquired TTP – Severe ADAMTS13 deficiency (<10% ativity) – Due to an ADAMTS13 antibody (autoimmune condition) Hereditary TTP – Inherited ADAMTS13 mutation HIV associated TTP – Exact pathogenesis uncertain EMERGENCY REQUIRE URGENT TREATMENT AND REFERRAL

Answer 26

Clinically Suspicion Laboratory Suspicion

Answer 27

MAHA – Anaemia – Fever Platelet consumption – Petechiae Evidence of organ damage – Neurological symptoms – Cardiac symptoms – Gastrointestinal symptoms

Answer 28

MAHA – Red cell fragments (Schistocytes) – Raised LDH +++ Platelet consumption – Thrombocytopenia-Usually very low Evidence of organ damage – Renal dysfunction

Answer 29

IMPORTANT! Consider TTP in all patients with MAHA and thrombocytopenia - Especially if no alternative Check peripheral smear, consult haematologist Urgent referral to haematologist if TTP is suspected – Infusion with Fresh Frozen Plasma – Plasma exchange needed Immunosuppression

Answer 30

Disseminated Intravascular Coagulopathy(DIC) Pregnancy-Related Syndromes

Answer 31

Fibrin-rich microthrombi Consumption of coagulation factors – Leads to bleeding Occasional red cell fragments Thrombocytopenia less prominent Abnormal coagulation screen

Answer 32

Patient pregnant RED CELL FRAGMENTS on peripheral smear HELLP syndrome – Haemolysis – Elevated Liver enzymes – Low Platelets Pre-eclampsia – Neurological syndromes – Proteinuria – Hypertension

Answer 33

Drugs Wilson's Disease Chemical Poisoning Severe Burns * Wilson’s disease * Chemical poisoning * Severe burns

Answer 34

E.g. dapsone and Salazopyrin® High doses causes oxidative intravascular haemolysis with Heinz body formation in normal subjects

Answer 35

Acute haemolytic anaemia High levels of copper in the blood

Answer 36

E.g. with lead, chlorate or arsine

Answer 37

Damage to red cells Acanthocytosis or spherocytosis