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In routine clinical practice, more than 80% of cases of thrombocytosis are considered reactive and are not associated with a clonal hematologic disorder ( Table 183-1 ). It is important to distinguish reactive thrombocytosis from essential thrombocythemia ( Fig. 183-3 ), because there is an increased risk of thrombosis associated with essential thrombocythemia but not with reactive thrombocytosis. The degree of thrombocytosis, platelet morphology, and platelet function tests are neither specific nor sensitive enough to distinguish essential from reactive thrombocytosis.

However, serum levels of both ferritin and C-reactive protein may help address the possibility of iron deficiency anemia and occult inflammatory process, respectively, as causes of possible reactive thrombocytosis. Essential thrombocythemia is characterized by normal C-reactive protein. A normal serum ferritin level excludes iron deficiency-associated reactive thrombocytosis, but a low level does not exclude the possibility of essential thrombocythemia. Howell-Jolly bodies on the peripheral blood smear suggest surgical or functional hyposplenism as a cause for reactive thrombocytosis ( Fig. 183-4 ). Serum TPO levels are generally not helpful in distinguishing essential thrombocythemia from either reactive thrombocytosis or other causes of primary thrombocytosis.

Causes of Platelet Count >500,000/uL
CAUSE     ADULT   %    Platelet Count > 1million/uL     CHILD    
Infection 22 % 31 % 31 %
Rebound thrombocytosis   19 % 3 % 15 %
Tissue damage (surgery) 18 % 14 % 15 %
Chronic inflammation 13 % 9 % 4 %
Malignancy 6 % 14 % 2 %
Renal disorders 5 % NS = not specified. 4 %
Hemolytic anemia 4 % NS 19 %
Postsplenectomy 2% 19% 1%
Blood loss NS 6% NS
Primary thrombocythemia 3% 14% 0%

Thrombocytosis - Essential

REF:  Ferri: Ferri's Clinical Advisor: Instant Diagnosis and Treatment, 2005 ed.

The peripheral smear in essential thrombocythemia is often unremarkable except for the abundance of platelets. However, some patients may display morphologic pleomorphism as well as giant platelets. Primary thrombocytosis may be ascribed to essential thrombocythemia only when bone marrow morphologic and cytogenetic findings do not suggest another chronic myeloid disorder. Bone marrow histology in essential thrombocythemia often reveals abnormal megakaryocyte clusters ( Fig. 183-5 ) that may or may not be accompanied by either increased overall cellularity or mild reticulin fibrosis.

A Philadelphia chromosome (or its molecular equivalent) establishes CML as the diagnosis and excludes essential thrombocythemia. A trilineage dysplasia suggests the myelodysplastic syndrome, and intense marrow cellularity with florid atypical megakaryocytic hyperplasia suggests "cellular phase" myeloid metaplasia.

Clinical Manifestations

Approximately 50% of patients with essential thrombocytosis may be asymptomatic at presentation. Vasomotor disturbances (headaches, lightheadedness, visual symptoms, palpitations, atypical chest pain, erythromelalgia, distal paresthesia) are the most frequent symptoms, occurring in 25 to 50% of patients. It is believed that these symptoms, especially erythromelalgia, are the result of small vessel platelet-endothelium interaction with associated inflammation and transient thrombotic occlusion. The life-threatening complications of essential thrombocythemia are thrombosis, hemorrhage, and transformation into myeloid metaplasia or acute myeloid leukemia (AML).

Arterial thrombosis (e.g., cerebrovascular or cardiovascular ischemia or infarcts, digital gangrene) is more frequent than venous thrombosis (pulmonary embolism, Budd-Chiari syndrome, portal vein thrombosis, deep vein thrombosis) in both essential thrombocythemia and polycythemia vera. The upper gastrointestinal system is the usual site of hemorrhage in essential thrombocythemia, and the risk of this complication is enhanced by the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Increased mucocutaneous bleeding is frequent and may be related to an acquired von Willebrand's (vW) defect .

Major thrombosis or hemorrhage occurs at presentation in approximately 15% and 5% of the patients, respectively; subsequent events during the first decade of the disease are approximately 20% and 5%, respectively. Leukemic transformation is rare (<5%) during the first 10 years but may be higher thereafter. Physical examination is often unremarkable, but approximately 25% of patients have palpable splenomegaly at diagnosis.

The key guide to long-term management of essential thrombocythemia is the patient's risk of thrombosis based on a history of prior thrombosis and age older than 60 years. The overall incidence of superficial or deep thrombosis in essential thrombocythemia is 20 to 40%, but major thrombosis (stroke, myocardial infarct, deep vein thrombosis, pulmonary embolism, digital arterial occlusion) occurs in only 10 to 20% of patients.

Cytoreductive (platelet-lowering) therapy reduces the risk of thrombosis in high-risk patients, in whom the platelet count may need to be reduced to 400,000/µL or lower. In other patients, the use of platelet-lowering agents is not supported. Only hydroxyurea has been shown prospectively to reduce the risk of thrombosis in essential thrombocythemia.


Goldman: Cecil Textbook of Medicine, 22nd ed., 2004