Evaluation of the Contribution of Platelets to Clot Strength by Thromboelastography in Rabbits: The Role of Tissue Factor and Cytochalasin D

Nielsen, Vance G.; Geary, Brian T.; Baird, Manuel S.

doi:10.1213/00000539-200007000-00007

Cited by 77 publications

(30 citation statements)

References 12 publications

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“…Samples with platelet inhibition contained 340 ll of whole blood to which 10 ll of cytochalasin D (5 lM concentration) was added; this mixture was mixed the fluid in the cup up and down onto the pin thrice. This concentration of cytochalasin D reliably inhibits platelet activity in rabbit blood as assessed by thromboelastography [8]. Thirty seconds later, 10 ll of TF was added to the platelet-inhibited sample and mixed as before.…”

Section: Methodsmentioning

confidence: 99%

“…); and total thrombus generation (TTG, dynes/cm 2 ), the final viscoelastic resistance observed after clot formation. Lastly, the contribution of platelets and plasma to clot strength was determined by the difference in TTG values between platelet-intact and platelet-inhibited samples, similar to previously described methodology [8].…”

Section: Methodsmentioning

confidence: 99%

“…To this end, a novel, sedated New Zealand White (NZW) rabbit model of C. atrox venom administration and thromboelastographic assessment of coagulation was established [7], with the time course of loss of whole-blood coagulation function following exposure to a few concentrations of venom determined. The rabbit was chosen for this investigation as this model provides thromboelastographic coagulation kinetic data very similar to that of human beings, with similar contributions to clot strength from platelets and plasma proteins as discerned by platelet inhibition with cytochalasin D [8,9]. Further, the ultrastructure of human and rabbit plasma thrombi has remarkably similar ultrastructure as determined by scanning electron microscopy [10].…”

mentioning

confidence: 99%

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Crotalus atrox Venom Exposed to Carbon Monoxide Has Decreased Fibrinogenolytic Activity In Vivo in Rabbits

Nielsen

2017

Basic Clin Pharma Tox

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Envenomation by haemotoxic enzymes remains a significant source of human morbidity and mortality worldwide, with administration of long-acting or multiple doses of antivenom first-line therapy. However, coagulopathy can still occur and recur. Of interest, it has been recently demonstrated that direct, isolated exposure of snake venom enzymes with fibrinogenolytic activity to carbon monoxide (CO) abrogates venom-mediated loss of coagulation in human plasma. These observations of CO inhibition of venom fibrinogenolytic activity were subsequently repeated in rabbit whole blood. This study sought to translate these findings in an in vivo rabbit model of envenomation with fibrinogenolytic Crotalus atrox venom. Sedated rabbits were intravenously administered C. atrox venom (400 μg/kg) pre-exposed to 0 or 1000 μM carbon monoxide-releasing molecule-2 (CORM-2) in vitro. Arterial whole-blood samples demonstrated that compared to pre-envenomation values, the CORM-2-naïve venom significantly prolonged the onset of coagulation, decreased the velocity of clot growth and decreased clot strength as determined by thromboelastography an hour after venom injection. In contrast, CORM-2 pre-exposure prevented or attenuated C. atrox venom effects on coagulation kinetics. Future studies to determine whether rabbits injected with such venom subcutaneously/intramuscularly can have consequent coagulopathy abrogated by injection of carbon monoxide-releasing molecules into the 'bite site' are justified.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Crotalus atrox Venom Exposed to Carbon Monoxide Has Decreased Fibrinogenolytic Activity In Vivo in Rabbits

Nielsen

2017

Basic Clin Pharma Tox

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“…INTEM Ò and EXTEM Ò (TEM International GmbH) (ellagic acid and tissue factor activation, respectively) represent assays in which the intrinsic or the extrinsic coagulation pathways are triggered respectively. FIBTEM Ò (TEM International GmbH) (tissue factor activation) assay is used to assess clot formation with the inhibition of platelets by Cytochalasin D [18] and is strongly related to the fibrinogen concentration. Standard parameters such as clotting time (CT, s), clot formation time (CFT, s), alfaangle (a), maximum velocity (MaxVel, mm min )1 ), maximum clot firmness (MCF, mm) and the area under curve (AUC) were evaluated.…”

Section: Thromboelastometry In the Whole Bloodmentioning

confidence: 99%

Whole blood rotation thromboelastometry (ROTEM^®) in nine severe factor V deficient patients and evaluation of the role of intraplatelets factor V

et al. 2011

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Severe factor V (FV) deficiency (parahaemophilia) is a rare congenital hemorrhagic disorder characterized by very low or undetectable plasma FV levels and bleeding phenotype ranging from mild to severe. We evaluated whole blood (WB) rotation thromboelastometry (ROTEM) in parahaemophilia patients and the contribution of intraplatelets FV, if any, to clot formation. Standard ROTEM(®) assays were performed in WB from nine parahaemophilia patients and 50 healthy controls. In addition, platelets poor plasma from one parahaemophilia patient (PPP-Pt) or normal subjects (PPP-N) was reconstituted with washed platelets obtained either from one patient with parahaemophilia (Plts-Pt) or normal subjects (Plts-N) and ROTEM assays were performed in platelets rich plasma (PRP) samples. There was a prolongation of the WB clotting time (CT) in all assays in patients as compared with controls. However, maximum clot firmness (MCF) was similar in patients and controls. ROTEM in PPP-Pt showed both a prolongation of CT and a reduction of MCF as compared with PPP-N. The addition of either Plts-Pt or Plts-N to PPP-Pt resulted in similar increase in MCF and a decrease of CT which was more evident for PPP-Pt + Plts-N than PPP-Pt + Plts-Pt. In contrast, the addition of Plts-Pt or Plts-N to PPP-N had superimposable effects on both CT and MCF. In parahaemophilia patients, WB ROTEM(®) presents mainly with prolongation of CT and no relevant effect on MCF. Residual intraplatelets FV in parahaemophilia contributes significantly to thrombin generation as shown in artificially reconstituted PRP models.

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“…Alternatively, cytochalasin D [16,21,22] has been proposed as a tool to eliminate platelet in¯uence on MA by inhibition of platelet cytoskeletal reorganization [23]. There are few data comparing the effects of cytochalasin D and abciximab on MA in TEG, but none that examines whether a combination of these substances would have additional, synergistic effects and thereby enhance the diagnostic signi®cance of TEG tracings.…”

Section: Introductionmentioning

confidence: 99%

Different effects of abciximab and cytochalasin D on clot strength in thrombelastography

Lang

Toller

Gütl

et al. 2004

Journal of Thrombosis and Haemostasis

119

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Maximum amplitude (MA) in thrombelastography (TEG) consists of a plasmatic and a platelet component. To assess the magnitude of the plasmatic component, pharmacological approaches have been proposed to eliminate the platelet component. We evaluated the individual and combined effects of abciximab and cytochalasin D on the MA of TEG. Whole blood, platelet-rich plasma (PRP) and homologous platelet-poor plasma (PPP) from 20 healthy volunteers were spiked with abciximab or cytochalasin D or a combination of both and TEGs performed. Abciximab and cytochalasin D decreased MA in all samples. MA of whole blood (18.6 +/- 3.1 mm) and PRP (33.7 +/- 3.5 mm) spiked with abciximab or cytochalasin D alone (15.0 +/- 2.9 mm and 25.0 +/- 4.0 mm) were significantly higher when compared with abciximab and cytochalasin D combined (10.4 +/- 3.0 and 20.2 +/- 3.5 mm). While MA of PRP and homologous PPP were significantly (P < 0.001) different after individual administration of abciximab and cytochalasin D, combination of both abolished this difference (20.2 +/- 3.5 mm and 20.4 +/- 3.7 mm, P = 0.372). In whole blood of critically ill patients or patients undergoing major surgery there was also a significant difference of MA between abciximab alone and in combination with cytochalasin D (16.5 +/- 11.3 mm and 11.3 +/- 7.7 mm, P < 0.001). This indicates that in contrast to individual administration of abciximab or cytochalasin D, a combination of both compounds eliminates the platelet-specific effect on MA of TEG tracings.

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Evaluation of the Contribution of Platelets to Clot Strength by Thromboelastography in Rabbits: The Role of Tissue Factor and Cytochalasin D

Cited by 77 publications

References 12 publications

Crotalus atrox Venom Exposed to Carbon Monoxide Has Decreased Fibrinogenolytic Activity In Vivo in Rabbits

Crotalus atrox Venom Exposed to Carbon Monoxide Has Decreased Fibrinogenolytic Activity In Vivo in Rabbits

Whole blood rotation thromboelastometry (ROTEM^®) in nine severe factor V deficient patients and evaluation of the role of intraplatelets factor V

Different effects of abciximab and cytochalasin D on clot strength in thrombelastography

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Evaluation of the Contribution of Platelets to Clot Strength by Thromboelastography in Rabbits: The Role of Tissue Factor and Cytochalasin D

Cited by 77 publications

References 12 publications

Crotalus atrox Venom Exposed to Carbon Monoxide Has Decreased Fibrinogenolytic Activity In Vivo in Rabbits

Crotalus atrox Venom Exposed to Carbon Monoxide Has Decreased Fibrinogenolytic Activity In Vivo in Rabbits

Whole blood rotation thromboelastometry (ROTEM®) in nine severe factor V deficient patients and evaluation of the role of intraplatelets factor V

Different effects of abciximab and cytochalasin D on clot strength in thrombelastography

Contact Info

Product

Resources

About

Whole blood rotation thromboelastometry (ROTEM^®) in nine severe factor V deficient patients and evaluation of the role of intraplatelets factor V