Kallikrein Activates Prothrombin

Stief, T.

doi:10.1177/1076029607308036

Cited by 29 publications

(21 citation statements)

References 17 publications

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“…Thrombin generation seems to depend not only on the extrinsic but also on the intrinsic pathway. 10 Small amounts of thrombin generated by contact-activation 11 or cold-activation of plasma activate factor V or factor VIII, accelerating both extrinsic and intrinsic coagulation [12][13][14] and activating platelets. [15][16][17] The phenomenon of cold-activation of plasma has been known for some decades, [18][19][20][21] but the exact thrombin amount generated in cold-activated recalcified plasma was not quantified.…”

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confidence: 99%

Intrinsic Hemostasis Activation by Freezing and Thawing of Plasma

Stief

Otto

Renz

2007

Clin Appl Thromb Hemost

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Low-grade contact activation of hemostasis is clinically relevant. Freezing/thawing of plasma was studied in the intrinsic coagulation activity assay. Normal plasmas were frozen at −80°C or −20°C and thawed at 37°C or 23°C. These plasmas and unfrozen samples were activated by SiO2 -CaCl2. Freezing/thawing of normal plasma induced about 100-fold more thrombin activity at 5 minutes coagulation reaction time than the respective unfrozen samples. Freezing at −80°C induces more artificial changes than freezing at −20°C. In 9 of 10 plasmas of patients receiving coumarin, nearly no additional thrombin is generated within a 12-minute coagulation reaction time. Minor procoagulant changes of plasma might be dangerous in patients with insufficient liver function, who might not tolerate a therapy with fresh frozen plasma, which behaves as a procoagulant because of its matrix changes. The intrinsic coagulation activity assay allows the measurement of low-grade contact activation of frozen/thawed plasma.

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confidence: 99%

Intrinsic Hemostasis Activation by Freezing and Thawing of Plasma

Stief

Otto

Renz

2007

Clin Appl Thromb Hemost

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“…Cleavage of UFH into LMWH of about 6000 Da might prevent this folding into a molecule with multiple polynegative niches. The contact activator UFH via kallikrein [11] might generate spurious amounts of thrombin that, via activation of pro-accelerin to accelerin (activated factor V), self-amplifies its generation in the EXCA.…”

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confidence: 99%

The anticoagulant capacity of plasmatic unfractionated heparin decreases at 23°C

Stief

2007

Blood Coagulation &Amp; Fibrinolysis

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Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are important clinical anticoagulants. As polynegative molecules they are potential triggers of the contact phase of coagulation. An incubation temperature lower than the physiological 37 degrees C favours intrinsic haemostasis activation by the polynegative molecule SiO2. The efficiency of UFH and LMWH after a plasmatic preincubation at 37 or at 23 degrees C is therefore studied. Samples (150 mul) of unfrozen pooled normal plasma supplemented with 0, 0.01, 0.1, or 1 IU/ml heparin or dalteparin in 5-ml polystyrole tubes were incubated for 10-70 min at 37 or at 23 degrees C. The extrinsic coagulation activity assay (EXCA) was then performed. Preincubation at 37 degrees C of 0.1 IU/ml plasmatic UFH does not result in any thrombin generation in EXCA-1, whereas preincubation at 23 degrees C results in a thrombin generation of about 0.1 IU/ml thrombin. Plasmatic UFH (0.01 IU/ml) at 23 degrees C acts nearly half as efficiently as 0.01 IU/ml plasmatic LMWH. Polynegatively charged niches particularly in the larger UFH molecule might trigger the contact system of haemostasis, especially at 23 degrees C. In contrast, the anticoagulant capacity of LMWH does not change significantly with temperature.

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“…Procoagulant microparticles released by tumor cells contain TF but could also potentiate intrinsic blood activation pathway supplying additional amount of negatively charged surface, which finally results in increased amount of active kallikrein [28]. Moreover, it has been evidenced recently that kallikrein can activate prothrombin directly [29].…”

Section: Discussionmentioning

confidence: 99%

Direct analysis reveals an absence of γ-carboxyglutamic acid in cancer procoagulant from human tissues

Kaplińska

Mielicki

2009

Blood Coagulation &Amp; Fibrinolysis

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Additional carboxylation of glutamic acid by vitamin K-dependent gamma-carboxylase is a common posttranslational modification of many proteins, including some of blood clotting factors. Vitamin K-antagonists, such as warfarin, are often included in the therapy of malignant disease, decreasing the blood coagulation potential. Cancer procoagulant, a direct blood coagulation factor X activator from malignant tissue, is considered as a vitamin K-dependent protein, so it could serve as one of possible targets for the therapy with warfarin. However, there is still no experimental data demonstrating directly the presence of gamma-carboxyglutamic acid (Gla) in a cancer procoagulant molecule. The presence of Gla in cancer procoagulant isolated from human amnion-chorion membranes and from human malignant melanoma WM 115 cell line was analyzed directly, using specific anti-Gla monoclonal antibodies. There was no detectable amount of Gla in cancer procoagulant isolated from fetal or malignant tissue. Cancer procoagulant from human tissues does not contain Gla-rich domain. The finding indicates that cancer procoagulant is rather a poor target for warfarin therapy of malignant disease.

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Kallikrein Activates Prothrombin

Cited by 29 publications

References 17 publications

Intrinsic Hemostasis Activation by Freezing and Thawing of Plasma

Intrinsic Hemostasis Activation by Freezing and Thawing of Plasma

The anticoagulant capacity of plasmatic unfractionated heparin decreases at 23°C

Direct analysis reveals an absence of γ-carboxyglutamic acid in cancer procoagulant from human tissues

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