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 10
6
/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
patients treated with
32
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 dis

orders in
association with extreme thrombocytosis: An analysis of 129 cases. Am J Hematol
20:365, 1985 [PMID: 3865532]
Elliot MA
et al: Thrombosis and hemorrhage in polycythemia vera and
essential thrombocythaemia. Br J Haematol 128:275, 2005
Levine RL, Gilliland DG: JAK-
2 mutations and their relevance to
myeloproliferative disease. Curr Opin Hematol 14:43, 2007 [PMID: 17133099]
Reilly JT: Idiopathic myelofibrosis: Pathogenesis to treatment. Hematol
Oncol 24:56, 2006 [PMID: 16477581]
Spivak JL: Poly
cythemia vera: Myths, mechanisms, and management.
Blood 100:4272, 2002 [PMID: 12393615]
Vainchenker W
et al: A unique activating mutation in JAK2 (V617F) is at
the origin of polycythemia vera and allows a new classification of
myeloproliferative diseases
. Hematology (Am Soc Hematol Educ Program):195,
2005
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