Effects of recombinant factor VIIa on platelet function and clot structure in blood with deficient prothrombin conversion

Carr, Marcus E.; Martin, Erika J.; Kuhn, Janice; Seremetis, Stephanie

doi:10.1055/s-0037-1613465

Cited by 24 publications

(1 citation statement)

References 24 publications

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“…FXa mediates TF/FVIIa-dependent arterial (22) or platelet- (23,24) thrombus formation (24). In fact, TF (25), FVIIa (26) or FIIa (27) is able to induce platelet activation/aggregation consistent with the observation that recombinant FVIIa (rFVIIa) is of thrombogenicity (28). Treatment with anti-TF Ab attenuates thrombus formation (29,30) and leukocyte activation/proliferation (31), indicating the participation of TF in thrombogenesis.…”

Section: Role Of Tf-initiated Blood Coagulation In Thrombosissupporting

confidence: 70%

Role of Tissue Factor in Thrombosis. Coagulation-Inflammation-Thrombosis circuit

Chu¹

2006

Front Biosci

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Tissue factor (TF) plays a role in thrombogenesis. TF initiates blood coagulation resulting in the generation of protease coagulant mediators (FVIIa, FXa, and FIIa) and fibrin production. TF hypercoagulablility directly contributes to thrombus formation resulting from the major events of fibrin deposition and FIIa-induced platelet activation/aggregation. In addition, blood coagulation indirectly promotes thrombogenicity via the coagulation-inflammation cycle in which TF plays a diverging and converging role. As the consequence of coagulation-dependent inflammation in which protease-activated receptor (PAR) mediates the coagulant signaling to elicit cytokines, selectins, and growth factors, such inflammation facilitates thrombosis by platelet aggregation and leukocyte recruitment. As TF hypercoagulability concerned, anti-thrombotic strategies involve the prevention by anticoagulation and PAR antagonism. Anticoagulants block the direct and indirect thrombotic contributions, while PAR antagonists arrest coagulation-dependent inflammation. With respect to both thrombosis and inflammation being cardiovascular risk factors, such strategies offer diverse benefits to cardioprotection.

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Section: Role Of Tf-initiated Blood Coagulation In Thrombosissupporting

confidence: 70%

Role of Tissue Factor in Thrombosis. Coagulation-Inflammation-Thrombosis circuit

Chu¹

2006

Front Biosci

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Tissue factor upregulation drives a thrombosis–inflammation circuit in relation to cardiovascular complications

Chu

2006

Cell Biochem. Funct.

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The extrinsic coagulation is recognized as an 'inducible' signalling cascade resulting from tissue factor (TF) upregulation by exposure to clotting zymogen FVII upon inflammation or tissue injury. Following the substantial initiation, an array of proteolytic activation generates mediating signals (active serine proteases: FVIIa, FXa and FIIa) that lead to hypercoagulation with fibrin overproduction manifesting thrombosis. In addition, TF upregulation plays a central role in driving a thrombosis-inflammation circuit. Coagulant mediators (FVIIa, FXa and FIIa) and endproduct (fibrin) are proinflammatory, eliciting tissue necrosis factor, interleukins, adhesion molecules and many other intracellular signals in different cell types. Such resulting inflammation could ensure 'fibrin' thrombosis via feedback upregulation of TF. Alternatively, the resulting inflammation triggers platelet/leukocyte/polymononuclear cell activation thus contributing to 'cellular' thrombosis. TF is very vulnerable to upregulation resulting in hypercoagulability and subsequent thrombosis and inflammation, either of which presents cardiovascular risks. The prevention and intervention of TF hypercoagulability are of importance in cardioprotection. Blockade of inflammation reception and its intracellular signalling prevents TF expression from upregulation. Natural (activated protein C, tissue factor pathway inhibitor, or antithrombin III) or pharmacological anticoagulants readily offset the extrinsic hypercoagulation mainly through FVIIa, FXa or FIIa inhibition. Therefore, anticoagulants turn off the thrombosis-inflammation circuit, offering not only antithrombotic but anti-inflammatory significance in the prevention of cardiovascular complications.

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Advances in Haematological Pharmacotherapy in 21st Century

Ghosh¹,

Ghosh²

2010

Indian J Hematol Blood Transfus

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Last quarter of twentieth century and the first 10 years of 21st century has seen phenomenal development in haematological pharmacotherapy. Tailor made chemotherapeutic agents, vast array of monoclonal antibodies, epigenetic modifiers, growth factors for red cells white cells and platelets, peptidomimetics as growth factors, newer thrombin inhibitors, safer plasma derived protein molecules, recombinant molecules, newer immunomodulators, enzyme replacement therapy and above all a plethora of targetted molecules targeting innumerable pathways involved in cell division, growth, proliferation and apoptosis has given immense number of clinically usable molecules in the hand of modern haematologists to treat diverse hitherto untreatable haematological disorders effectively. In addition many old molecules are finding newer uses in diverse fields, thalidomide as an antiangiogenic molecule is a prime example of this genre. Present overview has tried to capture this rapidly evolving area in a broad canvas without going into details of indications and contraindications of the use of various drugs.

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Effects of recombinant factor VIIa on platelet function and clot structure in blood with deficient prothrombin conversion

Cited by 24 publications

References 24 publications

Role of Tissue Factor in Thrombosis. Coagulation-Inflammation-Thrombosis circuit

Role of Tissue Factor in Thrombosis. Coagulation-Inflammation-Thrombosis circuit

Tissue factor upregulation drives a thrombosis–inflammation circuit in relation to cardiovascular complications

Advances in Haematological Pharmacotherapy in 21st Century

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