Changes in distribution of platelet membrane glycoproteins in patients with myeloproliferative disorders

Abstract

Glycoproteins have been discovered to be important to platelet function both in normal and pathological states. We have studied membrane glycoprotein patterns in 16 patients with various myeloproliferative disorders. There was an abnormal ratio of glycoprotein I:glycoprotein IV in patients with myeloproliferative disease compared with controls. There was no discernible correlation between glycoprotein pattern and aggregation response or platelet count, but patients with megathrombocytes had higher values for glycoprotein IV than those without megathrombocytes. These experiments suggest that patients with myeloproliferative disorders may have alterations in membrane glycoproteins that could alter platelet function.

Hemostatic disorders in a JAK2V617F-driven mouse model of myeloproliferative neoplasm

“…These observations call for several comments: (1) Only a few JAK2 V617F platelets attached to collagen, and they were unable to form thrombi when using whole blood at arterial shear rates; because the appearance of the moderate GPVI deficiency and of the vasodilatation is markedly delayed with respect to the defect in thrombus formation (day 60 vs day 13), their responsibility in the inability of platelets to form thrombi on collagen can be ruled out. (2) Controversial data have been reported regarding GP expression at the platelet surface in PV, ET, 13,[24][25][26] and PMF 13 patients; however, we found only a mild GPVI deficiency in JAK2 V617F KI mice. Such a defect has been previously reported in PV and ET patients 27 and is unlikely to affect adhesion and activation in thrombus formation according to a previous report indicating that a 20% expression of GPVI is sufficient to permit platelet activation by collagen.…”

Profile of blood coagulation and fibrinolysis in chronic myeloproliferative disorders.

“…This has generally been attributed to platelet dysfunction by extensive work performed on platelet function and its constituents. Platelet dysfunction includes defective response of platelets to various aggregating agents (Inceman and Tangun 1972; Zucker and Mielke 1972; Berger et al 1973; Adams et al 1974;Stathakis et al 1974;Papayannis et al 1974), the presence of spontaneous platelet aggregation (Barbui et al 1973;Preston et al 1974) or circulating platelet aggregates (Wu 1978), decreased amounts of platelet adenine nucleotides (Nishimura et al 1979), variations in platelet coagulant activities (Walsh et al 1977; , elevated plasma f3-thromboglobulin and platelet factor IV (Boughton et al 1978; , abnormality of platelet prostaglandin synthesis (Keenan et al 1977; Okuma and Uchino 1979), changes in distribution of platelet membrane glycoproteins (Bolin et al 1977), and variations in platelet factor VIII-related antigen (VIIIR : Ag) (Takahashi and Shibata 1980).…”

Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery.

“…In contrast, the definition of acquired disorders of platelet membrane glycoproteins has been less clear (2)(3)(4)(5)(6)(7). Changes ofsurface glycoproteins may occur in circulating platelets that could increase the risk for bleeding or thrombosis: plasma membrane microparticles can be lost, causing a decreased concentration of intrinsic plasma membrane glycoproteins (8)(9)(10)(11)(12); the microparticles themselves may accumulate in the plasma; a-granule membrane proteins can become exposed on the platelet surface following secretion (13)(14)(15); and large, contact-promoting a-granule secreted proteins can rebind to the cell surface (16)(17)(18)(19)(20)(21).…”