An abnormal pattern of multiple platelet function abnormalities and increased thromboxane generation in patients with primary thrombocytosis and thrombotic complications

Abstract

Platelet aggregation (PA) induced by ADP, collagen and epinephrine, plasma levels of β‐thromboglobulin (βTG) and thromboxane B2 (TXB2) and serum TXB2 generation were studied in 11 patients with primary thrombocytosis (7 with essential thrombocythaemia and 4 with polycythaemia vera) and compared with 16 healthy subjects. 5 patients suffered from peripheral vascular ischaemia and another 3 had venous thrombosis, but none had bleeding complications. The patients showed an abnormal pattern of platelet function and of thromboxane generation distinct from the healthy subjects in three aspects, a) Shape change was 5–26 times greater, the lag‐time of collagen PA was 2.3‐2.9 times longer and the extent of epinephrine PA was nil or very low. ADP‐or collagen‐induced PA was also reduced (p<0.02). b) Plasma TXB2 generation (corrected to a normal platelet concentration) stimulated by the three PA inducers was within the range of the healthy subjects in spite of the reduced extent of PA. c) Plasma βTG level and serum TXB2 generation (both corrected to a normal platelet concentration) were 2.9‐7.1 times higher (p < 0.001) indicating enhanced in vivo platelet activation and possibly increased thrombin generation. These abnormalities were not detected in another 4 patients with secondary thrombocytosis. The abnormal pattern of platelet function and thromboxane generation can be a useful laboratory method in the evaluation of patients with primary thrombocytosis. It might also explain the thrombotic complications which occurred in 8 of the patients in a manner such that increased or normal TXB2 generation overcomes the reduced extent of PA. In this respect, the pronounced serum TXB2 synthesis might be a marker of intravascular thrombosis.

Thrombocytosis in 715 Dogs (2011–2015)

“…Thrombocytosis is often an incidental finding in animals, whereas in people, thrombocytosis is associated with increased risk for hemorrhage or thrombosis, and is used as a prognostic factor in certain disease states . Increased platelet mass is proposed to cause shearing within the vasculature, leading to platelet hypersensitivity .…”

“…16,17 Thrombocytosis is often an incidental finding in animals, whereas in people, thrombocytosis is associated with increased risk for hemorrhage or thrombosis, and is used as a prognostic factor in certain disease states. 18,19 Increased platelet mass is proposed to cause shearing within the vasculature, leading to platelet hypersensitivity. 20 Such platelets are easily activated, and their aggregation can lead to microischemic events or depletion of von Willebrand factor multimers, increasing the risk for bleeding or thrombosis.…”

Thromboelastographic evaluation in dogs with hyperadrenocorticism

“…Thrombocytosis in dogs with HAC, as demonstrated in our study, raises questions about its clinical significance and potential association with thrombotic complications. In human medicine, thrombocytosis is considered a prognostic factor for hemorrhage or thrombosis in certain disease states [24,25]. By extending this knowledge to veterinary medicine, our findings highlight the need for future investigations to establish the correlation between platelet dynamics, as indicated by thrombocytosis and the MA value, and the occurrence of thrombotic events in dogs with HAC.…”

A spotlight on the management of complications associated with myeloproliferative neoplasms: a clinician’s perspective

“…Demonstrating increased thromboxane A2 metabolites, a key feature of platelet activation, in the urine of MPN patients was part of the basis for the ECLAP trial assessing the effect of aspirin in reducing thrombosis risk [54]. Increased levels of platelet activation products in the plasma have also been demonstrated [55].…”