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

ComplicationsPerhaps 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...
Nội dung trích xuất từ tài liệu:
Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 10) Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 10) Complications Perhaps no other condition in clinical medicine has caused otherwise astutephysicians to intervene inappropriately more often than thrombocytosis,particularly if the platelet count is >1 x 106/µL. It is commonly believed that ahigh platelet count causes intravascular stasis and thrombosis; however, nocontrolled clinical study has ever established this association, and in patientsyounger than age 60, the incidence of thrombosis was not greater in patients withthrombocytosis than in age-matched controls. To the contrary, very high platelet counts are associated primarily withhemorrhage due to acquired von Willebrand disease. This is not meant to implythat an elevated platelet count cannot cause symptoms in a patient with ET, butrather 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 andrespond only to lowering of the platelet count, while other symptoms such aserythromelalgia respond simply to platelet cyclooxygenase 1 inhibitors such asaspirin or ibuprofen, without a reduction in platelet number. Still others mayrepresent an interaction between an atherosclerotic vascular system and a highplatelet count, and others may have no relationship to the platelet countwhatsoever. Recognition that PV can present with thrombocytosis as well as thediscovery 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 riskfactors requires no therapy. Indeed, before any therapy is initiated in a patient withthrombocytosis, the cause of symptoms must be clearly identified as due to theelevated platelet count. When the platelet count rises above 1 X 10 6/µL, asubstantial quantity of high-molecular-weight von Willebrand multimers areremoved from the circulation and destroyed by the platelets, resulting in anacquired form of von Willebrand disease. This can be identified by a reduction inristocetin cofactor activity. In this situation, aspirin could promote hemorrhage.Bleeding in this situation usually responds to ε-aminocaproic acid, which can begiven prophylactically before and after elective surgery. Plateletpheresis is at besta temporary and inefficient remedy that is rarely required. Importantly, ET 32patients treated with P or alkylating agents are at risk of developing acuteleukemia without any proof of benefit; combining either therapy with hydroxyureaincreases this risk. If platelet reduction is deemed necessary on the basis ofsymptoms refractory to salicylates alone, IFN-α, the quinazoline derivative,anagrelide, or hydroxyurea can be used to reduce the platelet count, but none ofthese is uniformly effective nor without significant side effects. Hydroxyurea andaspirin are more effective than anagrelide and aspirin for prevention of TIAs butnot more effective for the prevention of other types of arterial thrombosis andactually less effective for venous thrombosis. Normalizing the platelet count doesnot prevent either arterial or venous thrombosis. Risk of gastrointestinal bleedingis also higher when aspirin is combined with anagrelide. As more clinical experience is acquired, ET is more benign than previouslythought. Evolution to acute leukemia is more likely to be a consequence of therapythan of the disease itself. In managing patients with thrombocytosis, thephysicians first obligation is to do no harm. Further Readings Buss DH et al: The incidence of thrombotic and hemorrhagic disorders inassociation with extreme thrombocytosis: An analysis of 129 cases. Am J Hematol20:365, 1985 [PMID: 3865532] Elliot MA et al: Thrombosis and hemorrhage in polycythemia vera andessential thrombocythaemia. Br J Haematol 128:275, 2005 Levine RL, Gilliland DG: JAK-2 mutations and their relevance tomyeloproliferative disease. Curr Opin Hematol 14:43, 2007 [PMID: 17133099] Reilly JT: Idiopathic myelofibrosis: Pathogenesis to treatment. HematolOncol 24:56, 2006 [PMID: 16477581] Spivak JL: Polycythemia vera: Myths, mechanisms, and management.Blood 100:4272, 2002 [PMID: 12393615] Vainchenker W et al: A unique activating mutation in JAK2 (V617F) is atthe origin of polycythemia vera and allows a new classification ofmyeloproliferative diseases. Hematol ...