Inherited Causes of Blood Clots « IHTC

Most hepatomas have a defect in prothrombin carboxylation, and can secrete under-carboxylated prothrombin or des-γ-carboxy-prothrombin (DCP), the function of which is unknown. We considered that the prothrombin-DCP axis might also be involved in growth control. Hepatocytes and hepatoma cells were treated with prothrombin and DNA synthesis and cytoskeletal changes were studied. Prothrombin inhibited DNA synthesis in hepatocytes on fibronectin, but not collagen matrix. Hepatoma cell lines were not inhibited. We found that hepatoma cell matrix conferred resistance to hepatocytes. Prothrombin decreased fibronectin but not collagen amounts, but only in the presence of hepatocytes and not hepatoma cells, indicating that it has a differential action on matrix proteins. It also caused changes in cell shape and actin depolymerization. In vivo, there was a decrease in plasma prothrombin activity after a partial hepatectomy (PH), concomitant with the peak of DNA synthesis in the hepatocytes at 24 h after PH. Injection of warfarin at the time of PH, further inhibited PT activity and enhanced this 24 h peak of DNA synthesis. Furthermore, repeated injection of prothrombin lowered the peak DNA synthesis after PH. The data support the hypothesis that prothrombin can act as a hepatocyte growth inhibitor, likely at the level of fibronectin loss and result in cytoskeletal changes. Hepatomas resist this action, possibly due to their different matrix proteins. This represents a novel mechanism for growth regulation and provides a possible biological significance for the tumor marker DCP.

Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity

Curnutte, M.D., Ph.D., Stuart J

Activated Partial Thromboplastin Time [APTT]

Thrombin promotes its own formation by the activation of the helper protein factor V, but it also inhibits its own formation.

Thrombin on its own is able to activate factor V into Va. The inactivation of this factor V takes extra steps and therefore is slower.

First thrombin has to bind to thrombomodulin (present on the endothelial surface of the vessel and therefore hardly in a wound) and then the thrombomodulin-thrombin complex activates a plasma proenzyme, protein C, into its active form APC that degrades factor Va.

Data Interpretation: Screening Tests - Answers

Drugs that are designed to inhibit thrombosis by selectively attacking one single enzyme may in practice work out completely different than expected.

direct thrombin inhibitor ..

Thrombin from human plasma lyophilized powder, …

N2 - Most hepatomas have a defect in prothrombin carboxylation, and can secrete under-carboxylated prothrombin or des-γ-carboxy-prothrombin (DCP), the function of which is unknown. We considered that the prothrombin-DCP axis might also be involved in growth control. Hepatocytes and hepatoma cells were treated with prothrombin and DNA synthesis and cytoskeletal changes were studied. Prothrombin inhibited DNA synthesis in hepatocytes on fibronectin, but not collagen matrix. Hepatoma cell lines were not inhibited. We found that hepatoma cell matrix conferred resistance to hepatocytes. Prothrombin decreased fibronectin but not collagen amounts, but only in the presence of hepatocytes and not hepatoma cells, indicating that it has a differential action on matrix proteins. It also caused changes in cell shape and actin depolymerization. In vivo, there was a decrease in plasma prothrombin activity after a partial hepatectomy (PH), concomitant with the peak of DNA synthesis in the hepatocytes at 24 h after PH. Injection of warfarin at the time of PH, further inhibited PT activity and enhanced this 24 h peak of DNA synthesis. Furthermore, repeated injection of prothrombin lowered the peak DNA synthesis after PH. The data support the hypothesis that prothrombin can act as a hepatocyte growth inhibitor, likely at the level of fibronectin loss and result in cytoskeletal changes. Hepatomas resist this action, possibly due to their different matrix proteins. This represents a novel mechanism for growth regulation and provides a possible biological significance for the tumor marker DCP.

Inhibition by warfarin enantiomers of prothrombin synthesis, protein carboxylation, and the regeneration of vitamin K from vitamin K epoxide

Prothrombin G20210A mutation - UpToDate

We now report that prothrombin is converted to α-thrombin by primary cultures of normal adult rat hepatocytes and α-thrombin is also a potent inhibitor of hepatocytes DNA synthesis.

Role of prothrombin complex concentrate in perioperative coagulation therapy

The Conversion of Prothrombin to Thrombin - The …

Thrombin generation is a unique way to test for changes in the hemostatic system and therefore is an ideal method to study anticoagulants and antithrombotics. We have supported, designed and performed many clinical studies for small and major pharmaceutical companies to study the effect of certain medication on the hemostatic system. This does not only relate to the known antithrombotics but also to medication not directly aimed for influencing the hemostatic system.

01/05/1974 · The Conversion of Prothrombin to Thrombin ..

29/01/2017 · F2 coagulation factor II, thrombin ..

Heparin makes antithrombin a much more potent thrombin inhibitor, it works on the drain side.

Thrombin comes in normally but goes out much faster. The result is less thrombin