Bleeding due to thrombocytopenia or abnormal platelet function is characterized by purpura and bleeding from mucous membranes. Bleeding is uncommon with platelet counts above 50 X 109/litre, and severe spontaneous bleeding is unusual with platelet counts above 20 X 109/litre.
This is caused by reduced platelet production in the bone marrow or excessive peripheral destruction of platelets. A bone marrow aspirate to assess whether the numbers of megakaryocytes are reduced or normal/increased is an essential part of the investigation.
Autoimmune thrombocytopenic purpura (AITP)
Thrombocytopenia is due to immune destruction of platelets. The sensitized platelets are removed by the reticuloendothelial system. There are two distinct clinical syndromes.
Acute AITP is usually seen in children, often following a viral infection. It has been suggested that the thrombocytopenia is due to the deposition of immune complexes on platelets, but the acute development of platelet autoantibodies is probably responsible for the shortened platelet survival.
Chronic AITP is characteristically seen in adult women. It is usually idiopathic but may occur in association with other autoimmune disorders such as SLE, thyroid disease and autoimmune haemolytic anaemia (Evans’ syndrome), in patients with chronic lymphocytic leukaemia and solid tumours and after viral infections with viruses such as HIV. Platelet autoantibodies are detected in about 60-70% of patients, and are presumed to be present, although not detectable, in the remaining patients.
Major haemorrhage is rare and is only seen in patients with severe thrombocytopenia. Easy bruising, purpura, epistaxis and menorrhagia are common. Physical examination is normal except for evidence of bleeding. Splenomegaly is rare.
The only blood count abnormality is thrombocytopenia. Normal or increased numbers of megakaryocytes are found in the bone marrow, which is otherwise normal. The detection of platelet autoantibodies is not essential for confirmation of the diagnosis, which often depends on exclusion of other causes of excessive destruction of platelets.
Acute AITP in children usually remits spontaneously. It is still not clear whether treatment in the acute phase with steroids or high-dose intravenous immunoglobulin is effective in minimizing the period of thrombocytopenia or in reducing the incidence of chronic AITP, which develops in 5-10% of children.
Spontaneous remissions are rare in chronic AITP. The main aims of treatment are to reduce the production of platelet autoantibodies and the removal of antibodycoated platelets. Initial treatment is with prednisolone, 40-60 mg daily in adults with cautious reduction of the dose after remission has occurred.
Twenty per cent of patients have a complete response and require no further treatment; 60% have a partial response, and half of these have little bleeding associated with mild or moderate thrombocytopenia (platelet count 30-100 X 1Q9/litre) and may require small doses of steroids, such as prednisolone 5-15 mg daily, or no further treatment. The other half of the partial responders eventually relapse and require splenectomy, as do the 20% of patients who failed to respond to steroids at all. Splenectomy should be avoided in young children because of the subsequent risk of severe pneumococcal infection. There is a 90% response rate to splenectomy, although about 30% of responders eventually relapse. Some of these refractory patients may respond to immunosuppressive drugs such as azathioprine, cyclophosphamide or vincristine or to danazol, which is a non-virilizing androgen. Intravenous infusion of high-dose immunoglobulin produces a rapid rise in the platelet count due to blockade of Fe receptors in the spleen. The increase in platelet count is usually transient but may be useful in patients with acute haemorrhage and in preparing patients with chronic AITP for surgery. Transfused platelets survive no longer than the patient’s own platelets but may sometimes be beneficial in patients with life-threatening bleeding. Other immune thrombocytopenias
DRUGS cause immune thrombocytopenia by the same mechanisms as described for drug-induced immune haemolytic anaemia. The same drugs may be responsible for immune haemolytic anaemia, thrombocytopenia or neutropenia in different patients; it is not known what determines the target cell in each case.
FETOMATERNAL ALLOIMMUNE THROMBOCYTOPENIA is due to fetomatemal incompatibility for plateletspecific antigens, usually for HPA-1a (human platelet alloantigen, previously called PIAl), and is the platelet equivalent of HDN. The mother is HPA-1a-negative and produces antibodies which destroy the HPA-1a-positive fetal platelets.
Thrombocytopenia is self-limiting after delivery, but platelet transfusions may be required to prevent or treat bleeding associated with severe thrombocytopenia; platelets may be prepared from HPA-1a-negative volunteers or the mother herself. Recently, it has been recognized that severe bleeding such as intracranial haemorrhage may occur in utero. Antenatal treatment of the mother with steroids and/or high-dose intravenous immunoglobulin or platelet transfusions given directly to the fetus by ultrasound-guided needling of the umbilical vessels have been effective in preventing haemorrhage in severely affected cases.
POST-TRANSFUSION PURPURA (PTP) is rare, occurring 2-12 days after a blood transfusion. PTP is associated with a platelet -specific alloantibody, usually anti- HPA-Ia in a HPA-1a-negative individual. PTP almost invariably occurs in females who have been previously immunized by pregnancy or blood transfusion. The cause of the platelet destruction is uncertain. PTP is self-limiting but high-dose intravenous immunoglobulin may limit the period of thrombocytopenia.
PLATELET FUNCTION DISORDERS
These are usually asociated with excessive bruising and bleeding and, in some of the acquired forms, with thrombosis. The platelet count is normal or increased and the bleeding time is prolonged. The rare inherited defects of platelet function require more detailed investigations such 3S platelet aggregation studies and factor VIII:C and VIII :vWF assays, if von Willebrand’s disease is suspected. Acquired forms of platelet dysfunction include:
• Myeloproliferative disorders
• Uraemia and liver disease
• Drugs, e.g. aspirin and dipyridamole
If there is serious bleeding or if the patient is about to undergo surgery, drugs with antiplatelet activity should be withdrawn and any underlying condition should be corrected if possible. In patients with renal failure, the haematocrit should be increased to greater than 0.30 litre litre'” and the use of desmopressin (DDAVP) may be helpful. Platelet transfusions may be required if these measures are unsuccessful.