Chapter 44: Primary and Familial Thrombocythemia

INTRODUCTION

• The upper limit of a normal platelet count is usually between 350 × 10⁹/L and 450 × 10⁹/L depending on the clinical laboratory and specific method used.

• Table 44–1 presents the major causes of elevation of the platelet count above the normal limit.

ESSENTIAL THROMBOCYTHEMIA (CLONAL THROMBOCYTOSIS)

Pathophysiology

• Essential thrombocythemia is a clonal disorder of multipotential hematopoietic progenitor cell and is a chronic myeloproliferative disorder related to polycythemia vera and primary myelofibrosis.

• Approximately 50 percent of patients express a mutant form of the Janus (JAK)2 signaling kinase (JAK2 V617F) found in several myeloproliferative disorders (polycythemia vera, primary myelofibrosis, rare cases of myelodysplastic syndromes). The mutant allele is almost invariantly found in one copy per cell in patients with essential thrombocythemia, and leads in vitro and in vivo to hematopoietic growth factor hypersensitivity, a hallmark of the disease.

• A smaller fraction of patients display other mutations of JAK2, or of the thrombopoietin receptor, c-Mpl. Nearly one-half of patients fail to express one of these mutations, and usually display lower hemoglobin concentrations than patients with JAK2 V617F.

Clinical Features

• The criteria used for the diagnosis of essential thrombocythemia are shown in Table 44–2.

• Usually develops between ages 50 and 70. Sex distribution is slightly skewed toward women, especially in younger patients.

• Because platelet counts are now often done routinely, the disorder is being discovered in younger individuals and in patients who are asymptomatic.

• Rare familial cases have been reported.

• Constitutional or hypermetabolic symptoms are very uncommon.

• Mild splenomegaly is found in 40 to 50 percent of patients.

• Patients may have ecchymoses and bruising due to functional platelet deficiencies, or due to acquired von Willebrand disease if platelet counts are very high.

• Bleeding and thrombotic complications are major causes of morbidity and mortality. Table 44–3 summarizes the risks of thrombosis or bleeding.

• Bleeding is common and is characteristic of platelet or vascular disorders: mucosal, gastrointestinal, cutaneous, genitourinary, and postoperative.

• Use of aspirin may occasionally lead to serious bleeding complications, especially when platelet counts are above 1500 × 10⁹/L due to acquired von Willebrand disease.

• Thrombosis, more often arterial than venous, is ...