Polymorphonuclear leukocyte activation and hemostasis in patients with essential thrombocythemia and polycythemia vera

Abstract

Thrombohemorrhagic complications are a major cause of morbidity and mortality in patients with essential thrombocythemia (ET) and polycythemia vera (PV). The pathogenesis of these complications is not completely clarified. Several studies have described abnormalities of red blood cells and platelets in these patients. However, no studies are available on changes in the polymorphonuclear leukocytes (PMNs), which can play an important role in the activation of the hemostatic system. In patients with ET (n = 37) and PV (n = 34), a series of PMN activation parameters (PMN membrane CD11b and leukocyte alkaline phosphatase [LAP] antigen expression, cellular elastase content, plasma elastase, and myeloperoxidase levels) was evaluated simultaneously with the levels of plasma markers of endothelial damage (thrombomodulin and von Willebrand factor antigen) and hypercoagulation (thrombin-antithrombin complex, prothrombin fragment 1 + 2, and D-dimer). The results show the occurrence of PMN activation in both groups of patients compared with a control group of healthy subjects. An increase in CD11b and LAP expression by PMN membrane was observed, together with a significant increase in cellular elastase content, plasma elastase, and myeloperoxidase levels. In addition, patients had high plasma levels of endothelial and hypercoagulation markers compared with controls. For the first time, these data show that in ET and PV, 2 hematologic conditions that place patients at increased risk for thrombosis, an in vivo leukocyte activation occurs and is associated with laboratory signs of endothelium and coagulation system activation.

The JAK2V617F mutation and thrombosis

“…Activated neutrophils and monocytes can promote thrombosis by releasing granules and forming aggregates with platelets, which, in turn, can trigger monocyte tissue factor expression, pro‐inflammatory cytokines and mediators of cell damage. Several studies have shown enhanced neutrophil activation, increased formation of neutrophil‐platelet aggregates, and increased markers of endothelial damage in PV and ET patients compared to controls (Falanga et al , 2000; Jensen et al , 2000). Greater mean percentages of neutrophil‐aggregates have been described in patients with a history of microvascular or thrombotic events (Jensen et al , 2001).…”

“…Other markers of haemostatic activation, including prothrombin fragment 1 + 2 (F1 + 2) and thrombin‐antithrombin (TAT) complexes have previously been shown to be increased in MPD compared to controls (Falanga et al , 2000). Recently investigators have addressed these (and other markers) in relation to JAK2 status.…”

Leukocytosis in polycythemia vera and splenomegaly in essential thrombocythemia are independent risk factors for hemorrhage

“…Consistent with findings from previous studies, we found that leukocytosis was an independent risk factor for bleeding overall as well as specifically for patients with PV and patients with ET. Leukocytes may directly participate in the interaction between platelet and vascular endothelium . Evangelista et al .…”

Pregnancy complications predict thrombotic events in young women with essential thrombocythemia

“…These diseases have many clinical features including a predisposition to vascular events, and progression to myelofibrosis and acute myeloid leukemia. Thrombosis is the main cause of morbidity and mortality: blood rheology, possibly relating to leukocyte adhesion, platelet activation and platelet‐leukocyte aggregates , is believed to have a leading role in the development of these complications.…”