The haematocrit and platelet target in polycythemia vera

Abstract

Summary Polycythemia vera (PV) is a chronic myeloproliferative disorder whose major morbidity and mortality are thrombohaemorragic events and progression to acute leukaemia or myelofibrosis. Whether the haematocrit and platelet count predict such complications remains unclear. The European Collaboration on Low‐dose Aspirin in Polycythemia Vera prospective study included 1638 PV patients. A total of 164 deaths (10%), 145 (8·85%) major thrombosis and 226 (13·8%) total thrombosis were encountered during 4393 person‐years follow‐up (median 2·8 years). In time‐dependent multivariable analysis, a haematocrit in the evaluable range of 40–55% was neither associated with the occurrence of thrombotic events, mortality nor with haematological progression in the studied population. The haematocrit of patients in the highest and lowest deciles at baseline was maintained within a narrow interval of haematocrit values ranging from 40% to 47% throughout follow‐up. High platelet count was associated with a lower progression rate to acute leukaemia/myelofibrosis, whereas it had no significant relationship with thrombotic events or mortality. Our findings do not suggest that the range of haematocrit (<55%) and platelet counts (<600 × 109/l) we encountered in our population had an impact on the outcome of PV patients treated by current therapeutic strategies.

Thrombocytosis and Thrombosis

“…Also, in the ECLAP prospective study, which enrolled 1638 PV patients with a median follow-up of 2.8 years and registered 226 thrombotic events, platelet count was not associated with thrombosis; major thrombosis occurred in 8.3% and 9.3% of patients whose baseline platelet count was greater, or lower, than 400 × 10 9 /L, respectively. 34 Incidentally, in that analysis, hematocrit in the range of 40% to 55% was not associated with occurrence of thrombosis. Finally, against a direct relationship between increased platelet count and thrombosis stand the results of MRC-PT1 trial, which randomly allocated 809 patients with high-risk ET to receive either hydroxyurea (HU) or anagrelide, in addition to low-dose aspirin.…”

“…Finally, uncertainties about the role of thrombocytosis in pathogenesis of thrombotic events are well reflected in the variable opinions about need, or opportunity, to control platelet counts in patients with PV that were manifested by expert hematologists from North America, 36 and also in the wide range of platelet count observed in the ECLAP study as opposite to the relatively narrow levels at which hematocrit was maintained. 34 Taken as a whole, these data weaken the intuitive role of increased platelet counts in the pathogenesis of thrombosis in CMPD, but they do not undermine the significance of several other lines of evidence for a contribution of platelets to thrombotic risk. In case of erythromelalgia in patients with ET, histopathology showed dermal arteriolar involvement, with arterial thrombi stained strongly for von Willebrand factor and weakly for fibrin.…”

Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic algorithms

“…94 At times, the distinction between PV and JAK2V617F-positive ET/PMF might not be clear cut but the therapeutic relevance of being precise in this regard is dubious. 95 We therefore recommend, in such instances, strict adherence to the 2008 WHO criteria for making a working diagnosis and close monitoring of the patient to capture any substantial changes that might warrant revision of diagnosis. Similarly, the possibility of CML mimicking either ET or PMF should always be entertained, especially in the absence of JAK2V617F.…”

How to manage children and young adults with myeloproliferative neoplasms

“…35 Moreover, in the ECLAP (European Collaborative Low-dose Aspirin in Polycythemia) Study, multivariate analysis considering all the confounders failed to show any correlation between HCT values in the range from 40 to 50% and incidences of thrombosis. 36 This uncertainty prompted Italian investigators to activate a prospective, multicenter, randomized clinical study (CYTO-PV) addressing the issue of the optimal target of cytoreduction in PV (EudraCT 2007-006694-91). While waiting for the results of this trial, my practice is to follow ELN recommendations and to perform phlebotomy withdrawing 250 to 500 ml of blood daily or every other day until a HCT value between 40 and 45% is obtained.…”