https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(06)68263-9.pdf

Seven haemostatic gene polymorphisms in coronary disease : meta-analysis of 66 155 cases and 91 307 controls

Bleeding, Blood Transfusion, and Increased Mortality After Percutaneous Coronary Intervention: Implications for Contemporary Practice

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1538-7836.2007.02500.x

The central role of thrombin in hemostasis.

Perioperative bleeding is a major challenge particularly because of increasing clinical use of potent antithrombotic drugs. Understanding current concepts of coagulation is important in determining the preoperative bleeding risk of patients, and in managing hemostatic therapy perioperatively. The serine protease thrombin plays pivotal roles in the activation of additional serine protease zymogens (inactive enzymatic precursors), cofactors, and cell-surface receptors. Thrombin generation is closely regulated to locally achieve rapid hemostasis after injury without causing uncontrolled systemic thrombosis. During surgery, there are major disturbances in coagulation and inflammatory systems because of hemorrhage/hemodilution, blood transfusion, and surgical stresses. Postoperative bleeding often requires allogeneic blood transfusions, which support thrombin generation and hemostasis. However, procoagulant activity and inflammation are increased postoperatively; thus, antithrombotic therapy may be required to prevent perioperative thrombotic complications. There have been significant advances in the management of perioperative hemostasis and thrombosis because of the introduction of novel hemostatic and antithrombotic drugs. However, a limitation of current treatment is that conventional clotting tests do not reflect the entire physiological processes of coagulation making optimal pharmacologic therapy difficult. Understanding the in vivo regulatory mechanisms and pharmacologic modulation of thrombin generation may help control bleeding without potentially increasing prothrombotic risks. In this review, we focus on the regulatory mechanisms of hemostasis and thrombin generation using multiple, simplified models of coagulation.

Blood coagulation: hemostasis and thrombin regulation.

Fluid resuscitation after massive hemorrhage in major surgery and trauma may result in extensive hemodilution and coagulopathy, which is of a multifactorial nature. Although coagulopathy is often perceived as hemorrhagic, extensive hemodilution affects procoagulants as well as anticoagulant, profibrinolytic, and antifibrinolytic elements, leading to a complex coagulation disorder. Reduced thrombin activation is partially compensated by lower inhibitory activities of antithrombin and other protease inhibitors, whereas plasma fibrinogen is rapidly decreased proportional to the extent of hemodilution. Adequate fibrinogen levels are essential in managing dilutional coagulopathy. After extensive hemodilution, fibrin clots are more prone to fibrinolysis because major antifibrinolytic proteins are decreased.Fresh frozen plasma, platelet concentrate, and cryoprecipitate are considered the mainstay hemostatic therapies. Purified factor concentrates of plasma origin and from recombinant synthesis are increasingly used for a rapid restoration of targeted factors. Future clinical studies are necessary to establish the specific indication, dosing, and safety of novel hemostatic interventions.

/pdf/pathophysiology-and-treatment-of-coagulopathy-in-massive-1d8tco7mf6.pdf

Pathophysiology and Treatment of Coagulopathy in Massive Hemorrhage and Hemodilution

Stable Suppression of a Novel Oncogene, AHI-1, in Human Cutaneous T-Cell Leukemia Cells Normalizes Its Transforming Activity In Vitro and In Vivo and Aberrant Expression of AHI-1 Is Also Present in Leukemic Sezary Cells from Patients with Sezary Syndrome.

Youwen Zhou

Papers

Stable Suppression of a Novel Oncogene, AHI-1, in Human Cutaneous T-Cell Leukemia Cells Normalizes Its Transforming Activity In Vitro and In Vivo and Aberrant Expression of AHI-1 Is Also Present in Leukemic Sezary Cells from Patients with Sezary Syndrome.