All the following conditons cause thrombocytopenia EXCEPT-
TEXTBOOK OF PATHOLOGY HARSHMOHAN 6TH EDITION PG NO 332&333 THROMBOCYTOPENIAS Thrombocytopenia is defined as a reduction in the peripheral blood platelet count below the lower limit of normal i.e. below 150,000/ml. Thrombocytopenia is associated with abnormal bleeding that includes spontaneous skin purpura and mucosal haemorrhages as well as prolonged bleeding after trauma. However, spontaneous haemorrhagic tendency becomes clinically evident only after severe depletion of the platelet count to level below 20,000/ml. SECTION II Haematology and Lymphoreticular Tissues Thrombocytopenia may result from 4 main groups of causes: 1. Impaired platelet production. 2. Accelerated platelet destruction. 3. Splenic sequestration. 4. Dilutional loss. A list of causes of thrombocytopenia is given in Table 13.2. Three of the common and impoant causes-- drug-induced thrombocytopenia, idiopathic thrombocytopenic purpura (ITP), and thrombotic thrombocytopenic purpura (TTP), are discussed below. Drug-induced Thrombocytopenia Many commonly used drugs cause thrombocytopenia by depressing megakaryocyte production. In most cases, an immune mechanism by formation of drug-antibody complexes is implicated in which the platelet is damaged as an 'innocent bystander'. Drug-induced thrombocytopenia is associated with many commonly used drugs and includes: chemotherapeutic agents (alkylating agents, anthracyclines, TABLE 13.2: Causes of Thrombocytopenia. I. II. IMPAIRED PLATELET PRODUCTION 1. Generalised bone marrow failure e.g. Aplastic anaemia, leukaemia, myelofibrosis, megaloblastic anaemia, marrow infiltrations (carcinomas, lymphomas, multiple myeloma, storage diseases). 2. Selective suppression of platelet production e.g. Drugs (quinine, quinidine, sulfonamides, PAS, rifampicin, anticancer drugs, thiazide diuretics), (heparin, diclofenac, acyclovir), alcohol intake. ACCELERATED PLATELET DESTRUCTION 1. Immunologic thrombocytopenias e.g. ITP (acute and chronic), neonatal and post-transfusion (isoimmune), drug-induced, secondary immune 'thrombocytopenia (post-infection, SLE, AIDS, CLL, lymphoma). 2. Increased consumption e.g. DIC, TTP, giant haemangiomas, microangiopathic haemolytic anaemia. III. SPLENIC SEQUESTRATION Splenomegaly IV. DILUTIONAL LOSS Massive transfusion of old stored blood to bleeding patients. antimetabolites), ceain antibiotics (sulfonamides, PAS, rifampicin, penicillins), drugs used in cardiovascular diseases (digitoxin, thiazide diuretics), diclofenac, acyclovir, heparin and excessive consumption of ethanol. Clinically, the patient presents with acute purpura. The platelet count is markedly lowered, often below 10,000/ml and the bone marrow shows normal or increased number of megakaryocytes. The immediate treatment is to stop or replace the suspected drug with instruction to the patient to avoid taking the offending drug in future. Occasional patients may require temporary suppo with glucocoicoids, plasmapheresis or platelet transfusions. Heparin-induced Thrombocytopenia Thrombocytopenia due to administration of heparin is distinct from that caused by other drugs in following ways: i) Thrombocytopenia is generally not so severe to fall to level below 20,000/ml. ii) Unlike drug-induced thrombocytopenia, heparin-induced thrombocytopenia is not associated with bleeding but instead these patients are more prone to develop thrombosis. The underlying mechanism of heparin-induced thrombocytopenia is formation of antibody against platelet factor 4 (PF-4)-heparin complex. This specific antibody activates the endothelial cells and initiates thrombus formation. It occurs in a small propoion of cases after the patient has received heparin for 5-10 days. Diagnosis is made by a combination of laboratory and clinical features with 4 Ts: thrombocytopenia, thrombosis, time of fall of platelet count, absence of other causes of thrombocytopenia. Immune Thrombocytopenic Purpura (ITP) Idiopathic thrombocytopenic purpura or immune thrombocytopenic purpura (ITP), is characterised by immunologic destruction of platelets and normal or increased megakaryocytes in the bone marrow. PATHOGENESIS. On the basis of duration of illness, ITP is classified into acute and chronic forms, both of which have different pathogenesis. Acute ITP. This is a self-limited disorder, seen most frequently in children following recovery from a viral illness (e.g. hepatitis C, infectious mononucleosis, CMV infection, HIV infection) or an upper respiratory illness. The onset of acute ITP is sudden and severe thrombocytopenia but recovery occurs within a few weeks to 6 months. The mechanism of acute ITP is by formation of immune complexes containing viral antigens, and by formation of antibodies against viral antigens which crossreact with platelets and lead to their immunologic destruction. Chronic ITP. Chronic ITP occurs more commonly in adults, paicularly in women of child-bearing age (20-40 years). The disorder develops insidiously and persists for several years. Though chronic ITP is idiopathic, similar immunologic thrombocytopenia may be seen in association with SLE, AIDS and autoimmune thyroiditis. The pathogenesis of chronic ITPis explained by formation of anti-platelet autoantibodies, usually by platelet-associated IgG humoral antibodies synthesised mainly in the spleen. These antibodies are directed against target antigens on the platelet glycoproteins, Gp IIb-IIIa and Gp Ib-IX complex. Some of the antibodies directed against platelet surface also interfere in their function. The mechanism of platelet destruction is similar to that seen in autoimmune haemolytic anaemias. Sensitised platelets are destroyed mainly in the spleen and rendered susceptible to phagocytosis by cells of the reticuloendothelial system.<\p>
Giant hemangioma
Infectious mononucleosis
HIV infection
Iron deficiency anemia
Haematology