Similarities between baboon and human blood clotting

Hampton, James W.; Matthews, Colin D.

doi:10.1152/jappl.1966.21.6.1713

Cited by 57 publications

(24 citation statements)

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“…Since the concentrations of protein C and prothrombin in the baboon are in the normal human range [16], we can speculate that a similar circulating level of APC is reached in human plasma at the site where thrombin is formed; we therefore chose 25 nM, which gave a convenient 70% inhibition of thrombin generation in normal controls. In ft-PRP we then sought the concentration that gave a similar inhibition.…”

Section: Discussionmentioning

confidence: 99%

Calibrated Automated Thrombin Generation in Frozen-Thawed Platelet-Rich Plasma to Detect Hypercoagulability

Régnault

Béguin

Lecompte

2003

Pathophysiol Haemos Thromb

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To enhance the practical applicability of the calibrated automated thrombogram (CAT) we investigated whether frozen-thawed platelet-rich plasma (ft-PRP) can be used to assess the function of the protein C inhibitory pathway, while preserving the natural phospholipid composition. Recalcified ft-PRP triggered with 0.5 pM recombinant human tissue factor shows a median thrombin potential of 1,779 nM·min, against 1,576 nM·min for fresh PRP. To obtain ∼70% inhibition, 6.7 nM activated protein C (APC) has to be added, instead of 25 nM in fresh PRP; so the relative APC resistance of PRP appears to depend upon the presence of intact platelets. Factor VIII, added to normal ft-PRP to obtain a concentration of 3.3 U/ml, increases the thrombin potential in the presence of APC 1.5-fold, from 524 to 808 nM·min, in keeping with previously published increases in thrombotic risk in patients with high factor VIII levels. We conclude that thrombography in ft-PRP, with and without added APC, can be used to assess known risk factors for thrombosis, which allows the design of large clinical studies aimed at proving the relationship between thrombin potential and clinical outcome.

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Section: Discussionmentioning

confidence: 99%

Calibrated Automated Thrombin Generation in Frozen-Thawed Platelet-Rich Plasma to Detect Hypercoagulability

Régnault

Béguin

Lecompte

2003

Pathophysiol Haemos Thromb

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“…19 To study the role of PDGF in more relevant arterial injury models, baboons were chosen because they exhibit a vascular anatomy and homeostatic mechanisms similar to those found in humans. 20,21 Experimental arterial injury was produced by 2 methods that simulate therapeutic procedures used in humans, namely, surgical carotid artery endarterectomy and balloon catheter dilatation of the femoral artery. Using these models, the effects of alpha and beta PDGFR antagonism on vascular lesion formation was evaluated.…”

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confidence: 99%

The Role of Alpha and Beta Platelet-Derived Growth Factor Receptor in the Vascular Response to Injury in Nonhuman Primates

Giese

Marijianowski²,

McCook³

et al. 1999

ATVB

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Abstract-Restenosis remains a significant clinical problem associated with mechanical interventional procedures for arterial revascularization or repair, including coronary angioplasty and stenting. Studies with rodents have established that platelet-derived growth factor (PDGF), a potent chemotactic and mitogenic agent for vascular smooth muscle cells, is a key mediator of lesion formation after vascular injury. To further explore this hypothesis in a more clinically relevant model, neutralizing monoclonal antibodies (mAbs) were used to examine the effect of selective inhibition of alpha or beta PDGF receptor (PDGFR) on neointima formation in nonhuman primates. Carotid arteries were injured by surgical endarterectomy and femoral arteries by balloon catheter dilatation. Immunostaining revealed that both injuries induced cell proliferation and the upregulation of beta PDGFR but not alpha PDGFR. By 7 days after injury, beta PDGFR staining was limited to the luminal region of the media, the small areas of neointima, and the adventitia. Nearly all bromodeoxyuridine-positive cells were found in these regions as well. After 30 days, a concentric neointima that stained strongly for beta PDGFR had formed in the carotid and femoral arteries. Treatment of baboons with anti-beta PDGFR mAb 2A1E2 for 6 days after injury reduced the carotid artery and femoral artery lesion sizes by 37% (PϽ0.05) and 48% (PϽ0.005), respectively, when measured at 30 days. Under the same conditions, treatment with anti-alpha PDGFR mAb 2H7C5 had no effect. These findings suggest that PDGF mediates neointima formation through the beta PDGFR, and that antagonism of this pathway may be a promising therapeutic strategy for reducing clinical restenosis.

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“…4 ' s Although it is difficult to establish equivalent thrombogenicity among humans and other species, available evidence suggests that the baboon is a good animal for simulating arterial thrombotic processes in humans.…”

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confidence: 99%

Platelet interactions with Dacron vascular grafts. A model of acute thrombosis in baboons.

Hanson¹,

Kotzé²,

Savage³

et al. 1985

Arteriosclerosis

128

139

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We have developed a model of acute Dacron graft thrombosis in baboons in order to assess platelet alterations secondary to arterial thrombus formation. In this model, thrombus formation was initiated by Dacron vascular grafts inserted as extension segments into chronic arteriovenous Silastic shunts. Following platelet labeling with 111In-oxine, platelet deposition was measured for 1 hour following blood contact under arterial flow conditions using a scintillation camera. Graft platelet activity rapidly increased 40- to 50-fold, plateauing by 1 hour. All grafts produced equivalent reductions in circulating platelet count and blood 111In-platelet radioactivity, demonstrating that the labeled cells were functionally equivalent to the total platelet population. After graft placement, the remaining platelets survived normally. Acute platelet deposition was equivalent on grafts placed 1, 24, 48, and 72 hours following injection of the labeled cells, indicating that a variable delay between platelet labeling and graft imaging was without detectable consequence. Platelet destruction by the graft produced a tenfold increase in plasma levels of platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) but did not modify either the alpha-granule (PF4, beta TG) or dense granule (ADP, ATP) contents of circulating platelets.

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Similarities between baboon and human blood clotting

Cited by 57 publications

References 0 publications

Calibrated Automated Thrombin Generation in Frozen-Thawed Platelet-Rich Plasma to Detect Hypercoagulability

Calibrated Automated Thrombin Generation in Frozen-Thawed Platelet-Rich Plasma to Detect Hypercoagulability

The Role of Alpha and Beta Platelet-Derived Growth Factor Receptor in the Vascular Response to Injury in Nonhuman Primates

Platelet interactions with Dacron vascular grafts. A model of acute thrombosis in baboons.

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