Thrombosis in thrombocythemic Ph‐ myeloproliferations is associated with higher platelet count prior to the event: results of analyses of prothrombotic risk factors from a registry of patients treated with anagrelide

Abstract

Controversies still exist regarding definition of the thrombotic risks in Ph-(BCR/ABL1-) myeloproliferative disorders with thrombocythemia (MPD-T). Platelet counts at diagnosis are currently not taken as a risk factor of thrombosis. In our cohort of 1179 patients with MPD-T, prospectively registered for anagrelide treatment, we found that the median platelet count prior to the thrombotic event was significantly higher than at time points without any ensuing thrombosis (453 vs. 400 9 10 9 /L, P < 0.001), albeit higher platelet counts at diagnosis tended to be connected with fewer thrombotic events (in contrast to WBC counts at diagnosis). The JAK2 V617F mutation predicted both arterial and venous events, while age >65 yr, hypertension, diabetes mellitus, smoking, elevated triglyceride and homocysteine levels predicted arterial events only. For venous events, the specific thrombophilic risk factors (factor V 'Leiden' and others), antiphospholipid antibodies, and elevated factor VIII levels played a major role. During anagrelide treatment (AE aspirin), we documented a decrease in both venous (6.7-fold) and arterial events (1.8-fold), while bleeding (mostly minor events) increased twofold compared to history. Our results suggest that keeping platelet counts at low levels may be a meaningful therapeutic measure to prevent thrombosis, although their counts at diagnosis lack any prognostic value.

Predictive factors of thrombosis for patients with essential thrombocythaemia: A single center study

“…8 The systematic review and meta-analysis of 2,436 patients with ET shows that JAK2 positivity correlated with a clear increase in the odds of thrombosis (OR = 1.83) 9 , and this was also observed by others. [10][11][12] Our findings are in line with the results of Schwartz et al, 13 who have proven, on the basis of an analyzed cohort of 1,179 thrombocythemic Ph-myeloptroliferations, that JAK2 mutation affected significantly the incidence of thrombosis (both arterial and venous). The JAK2 mutation has been included recently into the major criteria for ET 14,15 , and is also considered as a major prothrombotic risk factor in the International Prognostic Score in Essential Thrombocythemia (IPSET) risk factor study in WHO-defined ET.…”

“…FVLeiden mutation and protein C deficiency, were connected with thrombotic venous events. 13 In conclusion, our results strongly suggest that changes of mean platelet volume can serve as an additional and simple test in prothrombotic state assessment in ET patients, but this needs to be confirmed in a larger population. The presence of JAK2 mutation and leukocytosis has been proven to be a strong predictor for thromboembolic events in ET patients.…”

“…It is in agreement with the results of other authors. 11,13 Out of five ET patients presenting APCR the factor V Leiden heterozygous mutation has been confirmed in 2, and the remaining three had acquired APCR. Both ET patients with FVL mutation experienced thrombotic events.…”

Influence of platelet and white blood cell counts on major thrombosis – analysis from a patient registry in essential thrombocythemia

“…However, the calculated cutoff for median WBC counts for an increased risk for thrombosis was 8.48 G/L and therefore lower than the definition for CR according to the ELN criteria with <10 G/L (22). A very recent analysis of the Czech part of the registry revealed a higher platelet count prior to a thrombotic event compared to time points without an event (454 G/L vs. 400 G/L) despite a lack of any prognostic value of platelet counts at diagnosis (23). In our cohort, the clinical impact of median platelet counts during the course of the disease and median platelet counts to a greater or lesser extent directly prior to a thrombotic event was comparable (data not shown).…”

A phase III randomized, multicentre, double blind, active controlled trial to compare the efficacy and safety of two different anagrelide formulations in patients with essential thrombocythaemia – the TEAM‐ET 2·0 trial

“…Notably, the trial was designed to test non‐inferiority of the two formulations rather than superiority. The primary endpoint of the trial, platelet counts during the maintenance period, was chosen because high platelet counts are associated with a higher risk to develop thrombosis in ET patients (Piccin et al , ; Buxhofer‐Ausch et al , ; Schwarz et al , ).…”