Ultrastructure of activated mouse platelets: A qualitative scanning electron microscopy study

Pretorius, Etheresia; Oberholzer, Hester Magdalena; Smit, E. V.D.M.

doi:10.1002/jemt.20569

Cited by 1 publication

(1 citation statement)

References 19 publications

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“…Human prothrombin and the thrombin B chain have 81.4% and 88.8% amino acid identity with murine prothrombin and thrombin, respectively, and highly-conserved substitutions in non-identical residues. 25 Human and mouse thrombin bind and cleave human and mouse fibrinogen 26 , activate platelets to form aggregates with pseudopodia 27 , bind murine thrombomodulin, and support activated protein C generation 28,29 . To assess the ability of human (pro)thrombin to support thrombin generation in murine plasma, murine plasma was spiked with vehicle or murine or human prothrombin to 200% (final, endogenous plus spiked human prothrombin) and thrombin generation was measured by calibrated automated thrombography in the absence and presence of 200 nM murine thrombomodulin.…”

Section: Resultsmentioning

confidence: 99%

Elevated Prothrombin Promotes Venous, but Not Arterial, Thrombosis in Mice

Aleman

Walton

Byrnes

et al. 2013

ATVB

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Objective Individuals with elevated prothrombin, including those with the prothrombin G20210A mutation, have increased risk of venous thrombosis. Although these individuals do not have increased circulating prothrombotic biomarkers, their plasma demonstrates increased tissue factor-dependent thrombin generation in vitro. The objectives of this study were to determine the pathologic role of elevated prothrombin in venous and arterial thrombosis in vivo, and distinguish thrombogenic mechanisms in these vessels. Approach and results Prothrombin was infused into mice to raise circulating levels. Venous thrombosis was induced by electrolytic stimulus to the femoral vein or inferior vena cava ligation. Arterial thrombosis was induced by electrolytic stimulus or ferric chloride application to the carotid artery. Mice infused with prothrombin demonstrated increased tissue factor-triggered thrombin generation measured ex vivo, but did not have increased circulating prothrombotic biomarkers in the absence of vessel injury. Following venous injury, elevated prothrombin increased thrombin generation and the fibrin accumulation rate and total amount of fibrin ~3-fold, producing extended thrombi with increased mass. However, elevated prothrombin did not accelerate platelet accumulation, increase the fibrin accumulation rate, or shorten the vessel occlusion time following arterial injury. Conclusions These findings reconcile previously discordant findings regarding thrombin generation in hyperprothrombinemic individuals measured ex vivo and in vitro, and show elevated prothrombin promotes venous, but not arterial, thrombosis in vivo.

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