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Platelets are cell fragments that function in the clotting system. Thrombopoietin, primarily produced in the liver in response to decreased numbers of marrow megakaryocytes and circulating platelets, stimulates the bone marrow to synthesize platelets from megakaryocytes. Platelets circulate for 7 to 10 days. About ¹⁄₃ are always transiently sequestered in the spleen. The platelet count is normally 140,000 to 440,000/μL. However, the count can vary slightly according to menstrual cycle phase, decrease during near-term pregnancy (gestational thrombocytopenia), and increase in response to inflammatory cytokines (secondary, or reactive, thrombocytosis). Platelets are eventually destroyed, primarily by the spleen.

Platelet disorders include an abnormal increase in platelets (thrombocythemia, a myeloproliferative disorder; and thrombocytosis, a reactive phenomenon—see Myeloproliferative Disorders: Thrombocytosis), a decrease in platelets (thrombocytopenia), and platelet dysfunction. Any of these conditions, even conditions with increased platelets, may cause defective formation of hemostatic plugs and bleeding.

Etiology and Pathophysiology

Causes of thrombocytopenia (see Table 1: Thrombocytopenia and Platelet Dysfunction: Classification of Thrombocytopenia) include failed platelet production, increased splenic sequestration of platelets with normal platelet survival, increased platelet destruction or consumption, dilution of platelets, and a combination of these. Increased splenic sequestration is suggested by splenomegaly.

Table 1
Classification of Thrombocytopenia Cause Conditions Failed platelet production   Diminished or absent megakaryocytes in marrow Leukemia, aplastic anemia, paroxysmal nocturnal hemoglobinuria (some patients), myelosuppressive drugs Diminished platelet production despite the presence of megakaryocytes in marrow Alcohol-induced thrombocytopenia, thrombocytopenia in megaloblastic anemias, HIV-associated thrombocytopenia, some myelodysplastic syndromes Platelet sequestration in enlarged spleen Cirrhosis with congestive splenomegaly, myelofibrosis with myeloid metaplasia, Gaucher's disease Increased platelet destruction or use   Immunologic destruction Idiopathic thrombocytopenic purpura, HIV-associated thrombocytopenia, posttransfusion purpura, drug-induced thrombocytopenia, neonatal alloimmune thrombocytopenia, connective tissue disorders, lymphoproliferative disorders Nonimmunologic destruction Disseminated intravascular coagulation, thrombotic thrombocytopenic purpura–hemolytic-uremic syndrome, thrombocytopenia in acute respiratory distress syndrome Dilution Massive blood replacement or exchange transfusion (loss of platelet viability in stored blood)

The risk of bleeding is inversely proportional to the platelet count. When the platelet count is < 50,000/μL, minor bleeding occurs easily and the risk of major bleeding increases. Counts between 20,000 and 50,000/μL predispose to bleeding with trauma, even minor trauma; with counts < 20,000/μL, spontaneous bleeding may occur; with counts < 5000/μL, severe spontaneous bleeding is more likely. However, patients with counts < 10,000/μL may be asymptomatic for years.

Platelet dysfunction may stem from an intrinsic platelet defect or from an extrinsic factor that alters the function of normal platelets. Dysfunction may be hereditary or acquired. Hereditary disorders of platelet function consist of von Willebrand's disease, the most common hereditary hemorrhagic disease, and hereditary intrinsic platelet disorders, which are much less common. Acquired disorders of platelet function are commonly due to diseases as well as to aspirin Some Trade Names
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and other drugs.

Symptoms and Signs

Petechiae in Immune-Mediated Thrombocytopenic Purpura

Ecchymoses in Immune-Mediated Thrombocytopenic Purpura

Platelet disorders result in a typical pattern of bleeding: multiple petechiae in the skin, typically most evident on the lower legs; scattered small ecchymoses at sites of minor trauma; mucosal bleeding (epistaxis, bleeding in the GI and GU tracts, vaginal bleeding); and excessive bleeding after surgery. Heavy GI bleeding and bleeding into the CNS may be life threatening. However, massive bleeding into tissues (eg, deep visceral hematomas or hemarthroses) does not commonly occur and suggests a coagulation disorder (eg, hemophilia).

Diagnosis

Platelet disorders are suspected in patients with petechiae and mucosal bleeding. A CBC with platelet count, coagulation studies, and a peripheral blood smear are obtained. Excessive platelets and thrombocytopenia are diagnosed from the platelet count; coagulation studies are normal unless there is a simultaneous coagulopathy. If the CBC, platelet count, and INR are normal and PTT is normal or only slightly prolonged, then platelet dysfunction is suspected.

In patients with thrombocytopenia, the peripheral smear may suggest the cause (see Table 2: Thrombocytopenia and Platelet Dysfunction: Peripheral Blood Findings in Thrombocytopenic Disorders). If the smear shows abnormalities other than thrombocytopenia, such as nucleated RBCs or abnormal or immature WBCs, then bone marrow aspiration is indicated. Bone marrow aspiration reveals the number and appearance of megakaryocytes and is the definitive test for many diseases causing marrow failure. If the bone marrow is normal but the spleen is enlarged, increased splenic sequestration is the likely cause of thrombocytopenia; if the bone marrow is normal and the spleen is not enlarged, excess platelet destruction is the likely cause. Measurement of antiplatelet antibodies is not clinically useful. HIV testing is performed in patients at risk of HIV infection.

Table 2
Peripheral Blood Findings in Thrombocytopenic Disorders Findings Conditions Normal RBCs and WBCs Idiopathic thrombocytopenic purpura Gestational thrombocytopenia HIV-related thrombocytopenia Drug-induced thrombocytopenia Posttransfusion purpura RBC fragmentation Thrombotic thrombocytopenic purpura–hemolytic-uremic syndrome Preeclampsia with DIC Metastatic carcinoma WBC abnormalities Immature cells or increased mature lymphocytes in leukemia Markedly diminished granulocytes in aplastic anemia Hypersegmented polymorphonuclear leukocytes in megaloblastic anemias Frequent giant platelets (approaching the size of RBCs) Bernard-Soulier syndrome and other congenital thrombocytopenias RBC abnormalities, nucleated RBCs, and immature granulocytes Myelodysplasia RBC = red blood cell; WBC = white blood cell; DIC = disseminated intravascular coagulation.

In patients with platelet dysfunction, a hereditary cause is suspected if there is a lifelong history of easy bruising and bleeding after tooth extractions or surgery. In the case of a suspected hereditary cause, von Willebrand's antigen and factor activity studies are obtained. If a hereditary cause is not suspected, further tests are unnecessary.

Treatment

In patients with thrombocytopenia or platelet dysfunction, drugs that further impair platelet function should be avoided, particularly aspirin Some Trade Names
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and other NSAIDs. Patients may require platelet transfusion, but only in limited situations (see Transfusion Medicine: Platelets). Prophylactic transfusions are used sparingly because they may lose their effectiveness with repeated use due to the development of platelet alloantibodies. In platelet dysfunction or thrombocytopenia caused by decreased production, transfusions are reserved for active bleeding or severe thrombocytopenia (eg, platelet count < 10,000/μL). In thrombocytopenia caused by platelet destruction, transfusions are reserved for life-threatening or CNS bleeding.

Last full review/revision November 2005

Content last modified November 2005