Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 10)

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Complications Perhaps no other condition in clinical medicine has caused otherwise astute physicians to intervene inappropriately more often than thrombocytosis, particularly if the platelet count is 1 x 106/µL. It is commonly believed that a high platelet count causes intravascular stasis and thrombosis; however, no controlled clinical study has ever established this association, and in patients younger than age 60, the incidence of thrombosis was not greater in patients with thrombocytosis than in age-matched controls. To the contrary, very high platelet counts are associated primarily with hemorrhage due to acquired von Willebrand disease. This is not meant to imply that an...

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Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 10) Complications Perhaps no other condition in clinical medicine has caused otherwise astute physicians to intervene inappropriately more often than thrombocytosis, particularly if the platelet count is >1 x 106/µL. It is commonly believed that a high platelet count causes intravascular stasis and thrombosis; however, no controlled clinical study has ever established this association, and in patients younger than age 60, the incidence of thrombosis was not greater in patients with thrombocytosis than in age-matched controls. To the contrary, very high platelet counts are associated primarily with hemorrhage due to acquired von Willebrand disease. This is not meant to imply that an elevated platelet count cannot cause symptoms in a patient with ET, but rather that the focus should be on the patient, not the platelet count. For example,
some of the most dramatic neurologic problems in ET are migraine-related and respond only to lowering of the platelet count, while other symptoms such as erythromelalgia respond simply to platelet cyclooxygenase 1 inhibitors such as aspirin or ibuprofen, without a reduction in platelet number. Still others may represent an interaction between an atherosclerotic vascular system and a high platelet count, and others may have no relationship to the platelet count whatsoever. Recognition that PV can present with thrombocytosis as well as the discovery of previously unrecognized causes of hypercoagulability (Chap. 111) make the older literature on the complications of thrombocytosis unreliable. Essential Thrombocytosis: Treatment Survival of patients with ET is not different than for the general population. An elevated platelet count in an asymptomatic patient without cardiovascular risk factors requires no therapy. Indeed, before any therapy is initiated in a patient with thrombocytosis, the cause of symptoms must be clearly identified as due to the elevated platelet count. When the platelet count rises above 1 X 10 6/µL, a substantial quantity of high-molecular-weight von Willebrand multimers are removed from the circulation and destroyed by the platelets, resulting in an acquired form of von Willebrand disease. This can be identified by a reduction in ristocetin cofactor activity. In this situation, aspirin could promote hemorrhage. Bleeding in this situation usually responds to ε-aminocaproic acid, which can be given prophylactically before and after elective surgery. Plateletpheresis is at best
a temporary and inefficient remedy that is rarely required. Importantly, ET 32 patients treated with P or alkylating agents are at risk of developing acute leukemia without any proof of benefit; combining either therapy with hydroxyurea increases this risk. If platelet reduction is deemed necessary on the basis of symptoms refractory to salicylates alone, IFN-α, the quinazoline derivative, anagrelide, or hydroxyurea can be used to reduce the platelet count, but none of these is uniformly effective nor without significant side effects. Hydroxyurea and aspirin are more effective than anagrelide and aspirin for prevention of TIAs but not more effective for the prevention of other types of arterial thrombosis and actually less effective for venous thrombosis. Normalizing the platelet count does not prevent either arterial or venous thrombosis. Risk of gastrointestinal bleeding is also higher when aspirin is combined with anagrelide. As more clinical experience is acquired, ET is more benign than previously thought. Evolution to acute leukemia is more likely to be a consequence of therapy than of the disease itself. In managing patients with thrombocytosis, the physician's first obligation is to do no harm. Further Readings Buss DH et al: The incidence of thrombotic and hemorrhagic disorders in association with extreme thrombocytosis: An analysis of 129 cases. Am J Hematol
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