* This is the Professional Version. *
Overview of Platelet Disorders
Platelets are cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes, which in turn shed platelets from their cytoplasm. Thrombopoietin is produced in the liver at a constant rate and its circulating level is determined by the extent to which circulating platelets are cleared, and possibly by bone marrow megakaryocytes. Platelets circulate for 7 to 10 days. About one third 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 by apoptosis, a process independent of the spleen.
Platelet disorders include
Any of these conditions, even those in which platelets are increased, may cause defective formation of hemostatic plugs and bleeding.
The risk of bleeding is inversely proportional to the platelet count and platelet function (see Table: Platelet Count and Bleeding Risk). When platelet function is reduced (eg, as a result of uremia or aspirin use), the risk of bleeding increases.
Platelet Count and Bleeding Risk
Essential thrombocythemia is a myeloproliferative disorder (see Essential Thrombocythemia) involving overproduction of platelets because of a clonal abnormality of a hematopoietic stem cell. A markedly elevated platelet count is typically associated with thrombosis, but some patients develop bleeding.
Reactive thrombocytosis (see Reactive Thrombocytosis (Secondary Thrombocythemia)) is platelet overproduction in response to another disorder. There are many causes, including acute infection, chronic inflammatory disorders (eg, RA, inflammatory bowel disease, TB, sarcoidosis), iron deficiency, and certain cancers. Reactive thrombocytosis is not typically associated with an increased risk of thrombosis.
Causes of thrombocytopenia can be classified by mechanism (see Table: Classification of Thrombocytopenia) and include decreased platelet production, increased splenic sequestration of platelets with normal platelet survival, increased platelet destruction or consumption (both immunologic and nonimmunologic causes), dilution of platelets, and a combination of these mechanisms.
Increased splenic sequestration is suggested by splenomegaly.
A large number of drugs may cause thrombocytopenia (see Thrombocytopenia: Other Causes : Drug-induced immunologic destruction), typically by triggering immunologic destruction.
Overall, the most common specific causes of thrombocytopenia include
Drug-induced thrombocytopenia due to immune-mediated platelet destruction (commonly, heparin, trimethoprim/sulfamethoxazole)
Drug-induced thrombocytopenia due to dose-dependent bone marrow suppression (eg, chemotherapeutic agents)
Thrombocytopenia accompanying systemic infection
Immune thrombocytopenia (ITP, formerly called immune thrombocytopenic purpura)
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 disease, the most common hereditary hemorrhagic disease, and hereditary intrinsic platelet disorders (see Hereditary Intrinsic Platelet Disorders), which are much less common. Acquired disorders of platelet function (see Acquired Platelet Dysfunction) are commonly due to diseases (eg, renal failure) as well as to aspirin and other drugs.
Classification of Thrombocytopenia
Platelet disorders result in a typical pattern of bleeding:
Heavy GI bleeding and bleeding into the CNS may be life threatening. However, bleeding into tissues (eg, deep visceral hematomas or hemarthroses) rarely occurs with thrombocytopenia, which causes immediate, superficial bleeding following an injury. Bleeding into the tissues (often delayed for up to a day after trauma) suggests a coagulation disorder (eg, hemophilia).
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 based on the platelet count; coagulation studies are normal unless there is a simultaneous coagulopathy. In patients with a normal CBC, platelet count, INR, and PTT, platelet dysfunction is suspected.
In patients with thrombocytopenia, the peripheral smear may suggest the cause (see Table: Peripheral Blood Findings in Thrombocytopenic Disorders). If the smear shows abnormalities other than thrombocytopenia, such as nucleated RBCs or abnormal or immature WBCs, bone marrow aspiration is indicated. Bone marrow aspiration reveals the number and appearance of megakaryocytes and is the definitive test for many disorders causing bone marrow failure. However, normal number and appearance of megakaryocytes does not always indicate normal platelet production. For example, in patients with immune thrombocytopenia, platelet production may be decreased despite the normal appearance and increased number of megakaryocytes. 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 done in patients at risk of HIV infection. Bone marrow examination is rarely required in patients who present with typical features of ITP.
Peripheral Blood Findings in Thrombocytopenic Disorders
In patients with platelet dysfunction, a drug cause is suspected if symptoms began only after the patient started taking a potentially causative drug (eg clopidogrel, ticagrelor). Platelet dysfunction caused by drugs may be severe, but specialized tests are rarely needed. A hereditary cause is suspected if there is a lifelong history of easy bruising; bleeding after tooth extractions, surgery, childbirth, or circumcision; or heavy menstruation. In the case of a suspected hereditary cause, von Willebrand factor (VWF) antigen and VWF activity studies are routinely done. In some patients, platelet aggregation tests may identify a defect in how the platelet responds to various platelet agonists (adenosine diphosphate [ADP], collagen, thrombin) and thereby demonstrate the type of platelet defect. Platelet dysfunction caused by systemic disorders is typically mild and of minor clinical importance. In these patients, the causative systemic disorder is the clinical concern, and hematologic tests are unnecessary.
In patients with thrombocytopenia or platelet dysfunction, drugs that further impair platelet function, particularly aspirin and other NSAIDs, should not be given. Patients who are already taking such drugs should consider alternative drugs, such as acetaminophen, or simply stop using them.
Patients may require platelet transfusion, but transfusions are given only in limited situations (see Blood Products : 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 patients with active bleeding, severe thrombocytopenia (eg, platelet count < 10,000/μL), or in need of invasive procedures. In thrombocytopenia caused by platelet destruction, transfusions are reserved for life-threatening or CNS bleeding.
* This is the Professional Version. *