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February 1, 1998Journal of Clinical InvestigationOpen Access

Activated human protein C prevents thrombin-induced thromboembolism in mice. Evidence that activated protein c reduces intravascular fibrin accumulation through the inhibition of additional thrombin generation.

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Key result

Activated human protein C administered intravenously before thrombin challenge reduced mortality by over 85% in a mouse model of acute intravascular fibrin deposition.

Why the study?

Does activated protein C prevent mortality in a mouse model of thrombin-induced thromboembolism?

Population

Male CD-1 mice weighing 20-25 g

Comparison

Human activated protein C administered… vs Vehicle/saline administered intravenously 2…

Design

Preclinical, Pathologist unaware of the treatment administered to the animals

Follow-up

15 minutes

Authors

PGPaolo GreseleSMStefania MomiMBMauro Berrettini

Discussion

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Overview

Hypothesis-generating for activated protein C in thromboembolism; should not yet change clinical practice pending human trials.

Structured PICO

Does activated protein C prevent mortality in a mouse model of thrombin-induced thromboembolism?

P
Population
Male CD-1 mice weighing 20-25 g subjected to a model of acute thrombin-induced pulmonary thromboembolism.
I
Intervention
Human activated protein C (APC) administered intravenously as a bolus (doses up to 2 mg/kg) 2 minutes before thrombin challenge (1,250 U/kg)
C
Comparator
Vehicle/saline administered intravenously 2 minutes before thrombin challenge
O
Outcome
Mortality (death or prolonged paralysis of the hind limbs within 15 minutes)hard clinical

Main Result

Effect estimate: >85% reduction

Absolute Event Rate: 12% vs 80%

p-value: p=<0.008

Activated protein C prevents thrombin-induced thromboembolism and death in mice by inhibiting endogenous thrombin generation, thereby facilitating endogenous fibrinolysis.

Limitations

  • Animal model may not fully translate to human pathology
  • Short observation period of 15 minutes

Cite This Study

Gresele et al. (1998) studied Thrombin-induced thromboembolism. Activated human protein C (APC) vs. Vehicle/saline was evaluated on Mortality (>85% reduction, p=<0.008). Activated human protein C administered intravenously before thrombin challenge reduced mortality by over 85% in a mouse model of acute intravascular fibrin deposition.

synapsesocial.com/papers/6a93eb2d5e7ae87f038f985ehttps://doi.org/10.1172/jci575
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Inhibition of platelet-dependent thrombus formation by human activated protein C in a primate model1989 · 13 citations
  2. 2The profibrinolytic effect of activated protein C in clots formed from plasma is TAFI-dependent1996 · 292 citations
  3. 3Cross-linking of alpha 2-plasmin inhibitor to fibrin by fibrin-stabilizing factor.1980 · 401 citations
  4. 4Alteration of fibrin network by activated protein C1994 · 3 citations
  5. 5Thrombin-mediated activation of factor XI results in a thrombin-activatable fibrinolysis inhibitor-dependent inhibition of fibrinolysis.1997 · 234 citations