Expression of coagulant activity in human platelets: Release of membranous vesicles providing platelet factor 1 and platelet factor 3

Sandberg, Helena; Bode, Arthur P.; Dombrose, Frederick A.; Hoechli, Mathias; Lentz, Barry R.

doi:10.1016/0049-3848(85)90122-7

Cited by 114 publications

(64 citation statements)

References 36 publications

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“…The second phase of the rise in prothrombinase activity occurs over a C6PS concentration range of 10 -100 M, consistent with this being due to binding of C6PS to FX a (8). 2 We conclude that C6PS binding to factor X a still has a significant role in fully activating factor X a even when it is already partially activated by binding to FV a .…”

Section: Activation Of Meizothrombin To Thrombin In the Presence Of Fmentioning

confidence: 57%

“…Binding is accompanied by conformational changes in FX a that alter protein function (8). 2 Four C6PS molecules also bind to bovine FV a to induce conformational and functional changes (10). We present here compelling evidence that PS binding to these two proteins regulates their assembly into an active complex and thus regulates the functioning of the prothrombinase complex.…”

mentioning

confidence: 71%

“…It has become clear only very recently that PS regulates the structure and function of factors X a and V a (8, 10). 2 Here we explore further the extent of this regulation.Factor V exists in plasma as an inactive, single chain glycoprotein with a molecular mass of 330 kDa. The active form of factor V, FV a , has a central domain removed to yield a heterodimer composed of two chains, a heavy chain (M r ϭ 94,000 in the bovine species; 105,000 in human) and a heterogeneous light chain (M r ϭ 74,000 in FV a1 or 71,000 in FV a2 ).…”

mentioning

confidence: 99%

“…It has become clear only very recently that PS regulates the structure and function of factors X a and V a (8, 10). 2 Here we explore further the extent of this regulation.…”

mentioning

confidence: 99%

“…This activation requires assembly of an enzyme complex, called prothrombinase (1), which consists of blood coagulation factors X a (a serine protease) and V a (a cofactor), Ca 2ϩ , and membranous vesicles derived from stimulated platelets (2). Several studies (3)(4)(5) have suggested that phosphatidylserine (PS) 1 might play a specific role in prothrombin activation.…”

mentioning

confidence: 99%

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Soluble Phosphatidylserine Triggers Assembly in Solution of a Prothrombin-activating Complex in the Absence of a Membrane Surface

Majumder

Weinreb

Zhai

et al. 2002

Journal of Biological Chemistry

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Factor X a (FX a ) binding to factor V a (FV a ) on plateletderived membranes containing surface-exposed phosphatidylserine (PS) forms the "prothrombinase complex" that is essential for efficient thrombin generation during blood coagulation. There are two naturally occurring isoforms of FV a , FV a1 and FV a2 . These two isoforms differ by a 3-kDa polysaccharide chain ( ). The ability of soluble PS to trigger formation of a soluble prothrombinase complex suggests that exposure of PS molecules during platelet activation is likely the key event responsible for the assembly of an active membrane-bound complex.The final step in the blood coagulation cascade involves the activation of prothrombin to thrombin, which is the central enzyme of the coagulation system. This activation requires assembly of an enzyme complex, called prothrombinase (1), which consists of blood coagulation factors X a (a serine protease) and V a (a cofactor), Ca 2ϩ , and membranous vesicles derived from stimulated platelets (2). Several studies (3-5) have suggested that phosphatidylserine (PS) 1 might play a specific role in prothrombin activation. PS is asymmetrically distributed to the cytoplasmic surface of resting platelet membranes (6) but is exposed when human platelets are activated (7). It has become clear only very recently that PS regulates the structure and function of factors X a and V a (8, 10). 2 Here we explore further the extent of this regulation.Factor V exists in plasma as an inactive, single chain glycoprotein with a molecular mass of 330 kDa. The active form of factor V, FV a , has a central domain removed to yield a heterodimer composed of two chains, a heavy chain (M r ϭ 94,000 in the bovine species; 105,000 in human) and a heterogeneous light chain (M r ϭ 74,000 in FV a1 or 71,000 in FV a2 ). The heavy and light chains form a tight complex in the presence of a calcium ion (11). The heterogeneity in the light chain is seen in both the bovine and human molecules. In the human form, it appears to arise from glycosylation of Asn 2181 at the C-terminal end of the light chain (12). Prothrombinase complexes assembled from the two molecular species derived from human plasma are observed to have somewhat different cofactor activities (13,14). This has been attributed to substantially different affinities for binding to membranes (13). However, our lab has reported that the two forms of both bovine and human FV a bind to membranes with only ϳ3-fold different affinities (12,14). This suggests that differences in the ability to support prothrombinase activity must reflect either different binding between factors FX a and FV a1 versus FV a2 or different intrinsic activities of the FX a ⅐FV a1 and FX a ⅐FV a2 complexes. Although our results have favored the former possibility (14), it has been difficult to prove this unambiguously because it is difficult to measure precisely the interaction between FX a and FV a on a membrane surface (15).The presence of FV a in a reaction mixture is critical to obtaining a maximal and physiologicall...

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Section: Activation Of Meizothrombin To Thrombin In the Presence Of Fmentioning

confidence: 57%

mentioning

confidence: 71%

mentioning

confidence: 99%

“…It has become clear only very recently that PS regulates the structure and function of factors X a and V a (8, 10). 2 Here we explore further the extent of this regulation.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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Soluble Phosphatidylserine Triggers Assembly in Solution of a Prothrombin-activating Complex in the Absence of a Membrane Surface

Majumder

Weinreb

Zhai

et al. 2002

Journal of Biological Chemistry

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Assessment of material-induced procoagulant activity by a modified Russell viper venom coagulation time test

Gemmell

1998

J. Biomed. Mater. Res.

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Platelet activation is an inevitable consequence of blood-material interactions. The ability of those activated platelets and platelet-derived microparticles to enhance coagulation reactions leading to thrombin/fibrin formation has not been well studied despite its potential significance. Activated platelets and platelet-derived microparticles are known to dramatically enhance the catalytic efficiencies of the tenase and prothrombinase complexes. In this paper, a modified Russell viper venom coagulation time test is used to quantitate material-induced procoagulant activity due to the generation of activated phospholipid surfaces. In our test system, polyethylene and Silastic tubes were filled with heparinized whole blood and left to gently flow back and forth at 37 degrees C. After 1 h, the blood within the tubes was gravity drained and the plasma fraction assayed for procoagulant activity. The clotting times were determined by a Coag-A-Mate X2 instrument after the automated addition of Russell viper venom (to activate factors V and X) and calcium ions. Appreciable procoagulant activity was generated during whole blood contact within polyethylene and Silastic tubes although significantly greater activity was generated by the latter surface. As previously reported, platelet-derived microparticles also were detected by flow cytometry. Filtration of the plasma after material contact through a 0.1 microm filter led to substantial gains in clotting times and to near complete removal of microparticles, indicating that the material-induced microparticles likely were responsible for the procoagulant activity.

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Phospholipid Scramblase: When Phospholipid Asymmetry Goes Away

Bevers¹,

Williamson²

2011

Transmembrane Dynamics of Lipids

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Expression of coagulant activity in human platelets: Release of membranous vesicles providing platelet factor 1 and platelet factor 3

Cited by 114 publications

References 36 publications

Soluble Phosphatidylserine Triggers Assembly in Solution of a Prothrombin-activating Complex in the Absence of a Membrane Surface

Soluble Phosphatidylserine Triggers Assembly in Solution of a Prothrombin-activating Complex in the Absence of a Membrane Surface

Assessment of material-induced procoagulant activity by a modified Russell viper venom coagulation time test

Phospholipid Scramblase: When Phospholipid Asymmetry Goes Away

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