Autoimmune Haematological Disorders
Immune thrombocytopenia (ITP)
Presentation
ITP can occur at any age and is characterized by thrombocytopenia, with increased marrow megakaryocytes, and shortened platelet survival.
Presentation is usually with sudden onset of petechiae, particularly around the feet, and bleeding (nose, gums, bowel, urinary tract).
Can occur with:
infection (including HIV)
drugs (the list is very long!)
malignancy (lymphoma, adenocarcinoma)
common variable immunodeficiency
other autoimmune diseases (SLE, thyroid disease, autoimmune hepatitis).
Neonatal alloimmune thrombocytopenia may occur in mothers who are negative for the platelet antigen PLA1, who become sensitized in prior pregnancies where infants are PLA1 positive or by blood transfusion; other platelet antigen systems have also been involved.
Immuno pathology
Antibody-coated platelets are destroyed by the phagocytic cells in the peripheral blood.
Many platelet antigens have been shown to be targets for the autoimmune response, including GPIIb/IIIA, GPIb/IX and GP V (after chickenpox).
Detection of anti-platelet antibodies is difficult and few centres offer this routinely.
A wide variety of tests are used.
Diagnosis (see Box 9.1)
Diagnosis can usually be made clinically, with the assistance of a bone marrow examination.
Investigations are needed to rule out associated autoimmune disease (SLE), immunodeficiency, and malignancy.
Drug history should be reviewed.
Treatment
Treatment is complex and should be undertaken by a haematologist.
Any underlying cause should be treated or removed (drugs).
Therapy is determined by the severity of the thrombocytopenia: counts of <20×109/L usually lead to bleeding problems.
First-line therapy is either steroids or hdIVIg.
Thromopoetin receptor antagonists (romiplostim, a fusion protein analogue of thrombopoetin) are likely to replace IVIg and have been approved by NICE. Romiplostim is administered weekly as a subcutaneous injection.
Second-line therapies include cytotoxics, danazol, dapsone, and splenectomy.
Rituximab may be valuable in resistant cases (unlicensed indication).
If splenectomy is undertaken, the usual precautions should be taken (see Chapter 2, p.112).
Autoimmune haemolytic anaemia
Classification
Immune haemolytic anaemia is divided into two categories depending on the temperature at which haemolysis takes place.
Warm haemolytic anaemia:
idiopathic autoimmune (AIHA)
Cold haemolytic anaemia:
idiopathic cold agglutinin disease
cold agglutinins secondary to infection (Mycoplasma pneumoniae, EBV)
cold antibody disease (Donath-Landsteiner antibody, occurs in childhood or secondary to syphilis)—paroxysmal cold haemoglobinuria
cold antibody disease secondary to lymphoma (CHAD).
Other causes of haemolytic anaemia include:
drug-induced (which may be due to bystander immune-complex-mediated damage or direct binding of antigen (e.g. penicillin) to the red cell membrane causing the formation of an immunoreactive neo-antigen)
massive haemolysis may occur following mismatched blood transfusions (ABO incompatibility, preformed isoagglutinins)
as a result of rhesus incompatibility (rhesus haemolytic disease of the newborn); in association with ITP (Evans syndrome).
Presentation
Depends on the underlying cause.
Signs of anaemia ± jaundice will usually be the presentation.
Diagnosis (see Box 9.2)
The immunological process is identified by Coombs’ test, which identifies the presence of immunoglobulin and C3 on the red cell membrane.
Assays are done at different temperatures to identify warm or cold antibodies.
Panels of typed red cells can be used to identify the specificity of the antibody.
In the direct test, an anti-human IgG is used to demonstrate pre-bound IgG on the patient’s red cells.
In the indirect test, the patient’s serum is incubated with normal erythrocytes to demonstrate the presence of anti-red cell antibodies in the serum.
Pre-bound antibody can be eluted from the red cell for further studies.
Serum haptoglobins are decreased during active haemolysis and serum LDH is increased.
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