Tissue factor/factor VIIa pathway mediates coagulation activation in induced-heat stroke in the baboon

Abderrezak Bouchama, Falah Al-Mohanna, Lina Assad, Engin Baturcam, Abdelmoneim Eldali, Tarek Owaidah, Mohammed Dehbi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objective: Excessive activation of coagulation, which can culminate in overt disseminated intravascular coagulation, is a prominent feature of heat stroke. However, neither the mechanism that initiates the coagulation activation nor its pathogenic role is known. We examined whether the tissue factor/factor VIIa complex initiates the coagulation activation in heat stroke and, if so, whether upstream inhibition of coagulation activation through its neutralization may minimize cellular injury and organ dysfunction. We also examined whether coagulation inhibition influences heat stroke-induced fibrinolytic and inflammatory responses. Design: Randomized controlled study. Setting: Comparative Medicine Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Subjects: Baboons (Papio Hamadryas). Interventions: Twelve anesthetized baboons assigned randomly to recombinant nematode anticoagulant protein c2, a powerful inhibitor of tissue factor/factor VIIa-dependent coagulation (n = 6), or a control group (n = 6) were heat-stressed in a prewarmed neonatal incubator at 44-47°C until systolic blood pressure fell <90 mm Hg, signaling the onset of severe heat stroke. Recombinant nematode anticoagulant protein c2 was administered as a single intravenous dose of 30 μg/kg body weight at onset of heat stroke. The control group received an equivalent volume of sterile saline intravenously. Measurements and Main Results: Heat stroke was associated with coagulation activation and fibrin formation as evidenced by the increased plasma thrombin-antithrombin complexes, endogenous thrombin potential, and D-dimer levels. Recombinant nematode anticoagulant protein c2 induced significant inhibition of thrombin generation and fibrin formation. Inhibition of coagulation in recombinant nematode anticoagulant protein c2-treated animals did not influence either fibrinolysis (assessed by tissue plasminogen activator, plasmin-α2-antiplasmin complexes, and plasminogen activator inhibitor) or the release of pro-and anti-inflammatory cytokines. No difference in markers of cell injury and organ dysfunction was observed between recombinant nematode anticoagulant protein c2-treated and control groups. Conclusions: Tissue factor/factor VIIa-dependent pathway initiates coagulation activation in induced-heat stroke in the baboon without an effect on fibrinolysis and inflammation. The findings suggest also that coagulation activation is not a prerequisite of cell injury and organ dysfunction.

Original languageEnglish
Pages (from-to)1229-1236
Number of pages8
JournalCritical Care Medicine
Volume40
Issue number4
DOIs
Publication statusPublished - 1 Apr 2012
Externally publishedYes

Fingerprint

Heat Stroke
Factor VIIa
Papio
Thromboplastin
Fibrinolysis
Fibrin
Thrombin
Control Groups
Wounds and Injuries
Papio hamadryas
Blood Pressure
Plasminogen Inactivators
Incubators
Antifibrinolytic Agents
Saudi Arabia
Disseminated Intravascular Coagulation
Fibrinolysin
Tissue Plasminogen Activator
Anti-Inflammatory Agents
Hot Temperature

Keywords

  • disseminated intravascular coagulation
  • fibrinolysis
  • heat stress
  • hyperthermia
  • inflammation

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Tissue factor/factor VIIa pathway mediates coagulation activation in induced-heat stroke in the baboon. / Bouchama, Abderrezak; Al-Mohanna, Falah; Assad, Lina; Baturcam, Engin; Eldali, Abdelmoneim; Owaidah, Tarek; Dehbi, Mohammed.

In: Critical Care Medicine, Vol. 40, No. 4, 01.04.2012, p. 1229-1236.

Research output: Contribution to journalArticle

Bouchama, Abderrezak ; Al-Mohanna, Falah ; Assad, Lina ; Baturcam, Engin ; Eldali, Abdelmoneim ; Owaidah, Tarek ; Dehbi, Mohammed. / Tissue factor/factor VIIa pathway mediates coagulation activation in induced-heat stroke in the baboon. In: Critical Care Medicine. 2012 ; Vol. 40, No. 4. pp. 1229-1236.
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AU - Eldali, Abdelmoneim

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AU - Dehbi, Mohammed

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N2 - Objective: Excessive activation of coagulation, which can culminate in overt disseminated intravascular coagulation, is a prominent feature of heat stroke. However, neither the mechanism that initiates the coagulation activation nor its pathogenic role is known. We examined whether the tissue factor/factor VIIa complex initiates the coagulation activation in heat stroke and, if so, whether upstream inhibition of coagulation activation through its neutralization may minimize cellular injury and organ dysfunction. We also examined whether coagulation inhibition influences heat stroke-induced fibrinolytic and inflammatory responses. Design: Randomized controlled study. Setting: Comparative Medicine Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Subjects: Baboons (Papio Hamadryas). Interventions: Twelve anesthetized baboons assigned randomly to recombinant nematode anticoagulant protein c2, a powerful inhibitor of tissue factor/factor VIIa-dependent coagulation (n = 6), or a control group (n = 6) were heat-stressed in a prewarmed neonatal incubator at 44-47°C until systolic blood pressure fell <90 mm Hg, signaling the onset of severe heat stroke. Recombinant nematode anticoagulant protein c2 was administered as a single intravenous dose of 30 μg/kg body weight at onset of heat stroke. The control group received an equivalent volume of sterile saline intravenously. Measurements and Main Results: Heat stroke was associated with coagulation activation and fibrin formation as evidenced by the increased plasma thrombin-antithrombin complexes, endogenous thrombin potential, and D-dimer levels. Recombinant nematode anticoagulant protein c2 induced significant inhibition of thrombin generation and fibrin formation. Inhibition of coagulation in recombinant nematode anticoagulant protein c2-treated animals did not influence either fibrinolysis (assessed by tissue plasminogen activator, plasmin-α2-antiplasmin complexes, and plasminogen activator inhibitor) or the release of pro-and anti-inflammatory cytokines. No difference in markers of cell injury and organ dysfunction was observed between recombinant nematode anticoagulant protein c2-treated and control groups. Conclusions: Tissue factor/factor VIIa-dependent pathway initiates coagulation activation in induced-heat stroke in the baboon without an effect on fibrinolysis and inflammation. The findings suggest also that coagulation activation is not a prerequisite of cell injury and organ dysfunction.

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