Transient thrombocytopenia is a common complication of infection, especially viral, and hemorrhage.

Cyclic thrombocytopenia is an uncommon disorder that may be constitutional or acquired. Constitutional cyclic thrombocytopenia is discussed in Chapter 4. Acquired cyclic thrombocytopenia is associated with antiplatelet antibody production, immunodeficiency, the menstrual cycle, myeloproliferative neoplasms, myelodysplastic syndromes, and malignant lymphoma (Table 9.1) (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11).It may be accompanied by periodic fluctuations in other cell counts and in the number of bone marrow megakaryocytes.

Persistent thrombocytopenia may be constitutional or acquired. Constitutional thrombocytopenia is discussed in Chapter 4. Acquired thrombocytopenia may be attributable to bone marrow-related causes or peripheral blood-related causes (Table 9.2) (12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22).

The bone marrow-related causes for include gold therapy, amegakaryocytic thrombocytopenic purpura, myelodysplastic syndrome, acute leukemia, and replacement of hematopoietic tissue by fibrous tissue, bone, malignant lymphoma, or metastatic malignancy. Autoantibodies to the thrombopoietin receptor have been reported in a patient with systemic sclerosis.

The peripheral blood-related causes may be categorized as increased platelet loss, consumption, destruction, or sequestration. Etiologies include cocaine use, drug- and immune-mediated thrombocytopenic purpura, hemorrhage, disseminated intravascular coagulation, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, phagocytosis by histiocytes (as in hemophagocytic syndrome) or neutrophils, and excessive platelet sequestration in the spleen as a result of splenomegaly. Drug-related thrombocytopenia is frequently attributable to heparin therapy but can rarely be seen with glycoprotein IIb’IIIa inhibitors.

The peripheral blood sometimes shows an increased mean platelet volume caused by the release of newly formed large platelets. The remaining complete blood cell count parameters are variable, depending on the etiology of the thrombocytopenia.

The bone marrow aspirate smears and histologic sections may show either increased, adequate, or decreased numbers of megakaryocytes. The megakaryocytes may be immature and’or mature. Compared with mature cells, immature megakaryocytes are relatively small, show fewer nuclear lobations, and possess less cytoplasm with more basophilia. The presence of increased megakaryocytes, including many immature forms, suggests peripheral platelet destruction or loss rather than failure of production. Conversely, a reduced number of megakaryocytes suggests failure of platelet production as the primary cause of thrombocytopenia. Abnormal megakaryocyte morphology suggests the possibility of a clonal hematopoietic disorder with ineffective and’or reduced platelet production.

Pseudothrombocytopenia is an artifactual decrease in the platelet count. It is caused by various conditions (Table 9.3) (23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46). Of these, the most common by far is ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia (EDTA-psTP), a condition of no clinical significance in which platelets clump on exposure to EDTA (Fig. 9.1).
Most patients are healthy; some have associated laboratory test abnormalities, drug exposure, or diseases (Table 9.4).