A 60-year-old woman consults a physician because of weakness, headaches, dizziness, and tingling in her hands and feet. Physical examination demonstrates multiple areas of bruising on the back of her forearms and shins. On specific questioning, she reports having had five nosebleeds in the past two months, which she had attributed to “dry air”. Blood studies are drawn which show a platelet count of 1.2 × 106/µL, a red cell count of 5.1 ×106/µL, and a white count of 10,500/µL with a normal differential count. Review of the peripheral smear demonstrates many abnormally large platelets, platelet aggregates, and megakaryocyte fragments. No abnormal red or white blood cells are seen. Philadelphia chromosome studies are negative. Which of the following is the most likely diagnosis?
A. Chronic myelogenous leukemia
C. Polycythemia vera
D. Primary thrombocythemia
E. Secondary thrombocythemia
The correct answer is D. Primary thrombocythemia.
The most likely diagnosis is primary (essential) thrombocythemia. The condition is due to a clonal abnormality of a multipotent hematopoietic cell that produces megakaryocytic hyperplasia with resultant increased platelet count. Since the platelets are often abnormal, either a thrombotic or a hemorrhagic tendency may be seen. The platelet count may be as low as 500,000/µL or greater than 1,000,000/µL. The clinical presentation and laboratory findings illustrated in the question stem are typical. The other choices listed commonly must be excluded before a diagnosis of primary thrombocythemia is confirmed.
Chronic myelogenous leukemia (choice A) can be a cause of increased platelet count, but the absence of either a Philadelphia chromosome or a markedly increased white count argues against this possibility.
Myelofibrosis (choice B) can also cause thrombocythemia, but would likely show some abnormally shaped (often tear drops) red cells.
Polycythemia vera (choice C) can also cause thrombocythemia, but would be associated with an increased red cell mass.
Secondary thrombocythemia (choice E) is a reactive process that may occur in a variety of settings including chronic inflammatory disorders, acute infection, hemorrhage or hemolysis, tumors, iron deficiency, or splenectomy. Abnormal platelet forms are not usually seen on smears from these patients and platelet function tests are usually normal.