Effects of Abciximab on the Architecture of Platelet-Rich Clots in Patients With Acute Myocardial Infarction Undergoing Primary Coronary Intervention

Collet, Jean‐Philippe; Montalescot, G.; Lesty, Claude; Mishal, Zohar; Soria, Jeannette; Choussat, R.; Drobinski, G; Soria, Claudine; Pinton, Philippe; Barragan, Paul; Thomas, Daniel

doi:10.1161/01.cir.103.19.2328

Cited by 67 publications

(34 citation statements)

References 13 publications

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“…[63][64][65][66] This is attributed to the tightly contracted fibrin network; however, it may also result from crosslinking of additional a 2 AP to fibrin as a result of the high local concentration of FXIII-A. It has recently been shown that supplementing blood of thrombocytopenic patients with FXIII, thrombin activatable fibrinolysis inhibitor, or fibrinogen increases clot strength and decreases lysis.…”

Section: Discussionmentioning

confidence: 99%

Functional factor XIII-A is exposed on the stimulated platelet surface

Mitchell

Lionikiene

Fraser

et al. 2014

Blood

105

141

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Key Points• Factor XIII-A is exposed in protruding caps on the activated platelet surface.• Platelet FXIII-A exerts antifibrinolytic function by cross-linking a 2 AP to fibrin.Factor XIII (FXIII) stabilizes thrombi against fibrinolysis by cross-linking a 2-antiplasmin (a 2 AP) to fibrin. Cellular FXIII (FXIII-A) is abundant in platelets, but the extracellular functions of this pool are unclear because it is not released by classical secretion mechanisms. We examined the function of platelet FXIII-A using Chandler model thrombi formed from FXIIIdepleted plasma. Platelets stabilized FXIII-depleted thrombi in a transglutaminase-dependent manner. FXIII-A activity on activated platelets was unstable and was rapidly lost over 1 hour. Inhibiting platelet activation abrogated the ability of platelets to stabilize thrombi. Incorporating a neutralizing antibody to a 2 AP into FXIII-depleted thrombi revealed that the stabilizing effect of platelet FXIII-A on lysis was a 2 AP dependent. Platelet FXIII-A activity and antigen were associated with the cytoplasm and membrane fraction of unstimulated platelets, and these fractions were functional in stabilizing FXIII-depleted thrombi against lysis. Fluorescence confocal microscopy and flow cytometry revealed exposure of FXIII-A on activated membranes, with maximal signal detected with thrombin and collagen stimulation. FXIII-A was evident in protruding caps on the surface of phosphatidylserine-positive platelets. Our data show a functional role for platelet FXIII-A through exposure on the activated platelet membrane where it exerts antifibrinolytic function by cross-linking a 2 AP to fibrin. (Blood. 2014;124(26):3982-3990) IntroductionFactor XIII (FXIII) plays an essential role in normal hemostasis where it contributes to the regulation of fibrinolysis, 1-3 the maintenance of pregnancy, 4 wound healing, and angiogenesis. 5 The function of FXIII in hemostasis is further emphasized in its deficiency, which results in hemorrhage 6,7 and slow wound healing. 4,7 FXIII circulates in plasma as a heterotetramer (FXIII-A 2 B 2 ) where the catalytic A (FXIII-A 2 ) subunits are almost exclusively in complex with the inhibitory carrier B (FXIII-B 2 ) subunits. 8 FXIII is activated by the combined action of thrombin and Ca 21 to form the active transglutaminase (TG) FXIIIa. 9,10 FXIIIa confers stability to the fibrin matrix by cross-linking fibrin, substantially altering its rheologic properties.11,12 TG catalyzes formation of covalent e-(g-glutamyl) lysyl bonds 13 in which the lysine e-amino group is cross-linked to the glutamine g-carboxymide group. 14The cross-linking of g-chains confers a degree of rigidity to the fibrin network, which is further stabilized by the cross-linking of a-chains 15 to generate high-molecular-weight polymers. 10,16 FXIIIa also cross-links inhibitors of fibrinolysis to fibrin, further increasing its insolubility and resistance to plasmin. These inhibitors include a 2 -antiplasmin (a 2 AP), 17 thrombin activatable fibrinolysis inhibitor, 18 and plasminogen ac...

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Section: Discussionmentioning

confidence: 99%

Functional factor XIII-A is exposed on the stimulated platelet surface

Mitchell

Lionikiene

Fraser

et al. 2014

Blood

105

141

View full text Add to dashboard Cite

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“…In our study, GP IIb/IIIa receptor antagonists were used more frequently in TIMI 0-1 and 2 groups. It is known that intravenous administration of these antagonists not only blocks the final common pathway for platelet aggregation and prevents aggregation regardless of the initial activating stimulus, but could also enable lysis of an acutely formed platelet thrombus [19,20]. Although proximal and distal mechanical protection devices and thrombectomy catheters may also prevent from distal embolization, their effects on myocardial perfusion and clinical outcome in patients with AMI remain unclear and controversial [21].…”

Section: Discussionmentioning

confidence: 99%

Post-procedural TIMI flow grade 2 is not associated with improved prognosis in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary revascularization (PL-ACS registry)

et al. 2016

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Background: The impact of final Thrombolysis in Myocardial Infarction (TIMI) flow in the infarct-related artery (IRA) on outcomes in non-ST-segment elevation myocardial infarction (NSTEMI) patients treated with percutaneous coronary intervention (PCI) is unknown.This study aimed to evaluate the impact of post-procedural TIMI flow in IRA on outcomes in NSTEMI patients undergoing percutaneous coronary revascularization. 3.26%; 2: 61, 2.20%; 3: 2,616, 94.54%). Methods: We analyzed 2,767 patients with first NSTEMI from the Polish Registry of Acute Coronary Syndromes (PL-ACS) who underwent PCI. The patients were divided according to Results:The following mortality values were obtained in TIMI 0-1, 2, and 3 groups, respectively: in-hospital, 12.22%, 13.11%, 1.72% (p < 0.0001); 1-month, 13.33%, 13.11%, 3.44% (p < 0.0001); 12-month, 15.56%, 16.39%, 6.50% (p < 0.0001); 36-month, 25.56%, 21.31%, 13.91% (p = 0.0007) . Mortality rates in patients with final TIMI 0-1 and 2 were not significantly different. Optimal TIMI 3 was independently associated with baseline TIMI 2-3 (OR ±

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“…However, none was found to promptly and effectively restore the coronary flow. 10) Recently, administration of a platelet glycoprotein IIb/IIIa antagonist, abciximab, was reported to be able to enhance the fibrinolytic effect, change the thrombus architecture, and increase the coronary flow in vitro 11) and platelet activation was considered an underlying mechanism in patients with an acute myocardial infarction. Using quantitative myocardial contrast echocardiographic study, tirofiban also improved microvascular flow and reduced the infarct area after coronary occlusion/reperfusion in open-chest dogs.…”

Section: Discussionmentioning

confidence: 99%

Restoration of Normal Coronary Flow With Tirofiban by Intracoronary Administration for No-reflow Phenomenon After Stent Deployment

et al. 2005

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SUMMARYNo-reflow phenomenon is frequently observed during percutaneous coronary intervention in patients with acute coronary syndrome. It may jeopardize hemodynamic status or result in ischemic chest pain in these patients. Currently, there is no adequate solution for this problem. We report our experience with an acute coronary syndrome patient who developed no-reflow phenomenon associated with ST segment elevation and shock after percuteneous coronary balloon dilatation and stent deployment. Intracoronary administration of tirofiban immediately restored the coronary flow of the target vessel, and the disastrous condition reversed. Our experience suggests that intracoronary administration of tirofiban can be considered as an option in case of no-reflow phenomenon during percutaneous coronary intervention. (Int Heart J 2005; 46: 139-145)

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Effects of Abciximab on the Architecture of Platelet-Rich Clots in Patients With Acute Myocardial Infarction Undergoing Primary Coronary Intervention

Abstract: Abciximab dramatically reduces platelet aggregate size and increases the fibrin accessibility of ex vivo PRC in AMI patients. These modifications could participate in the better coronary artery patency observed with abciximab.

Cited by 67 publications

References 13 publications

Functional factor XIII-A is exposed on the stimulated platelet surface

Functional factor XIII-A is exposed on the stimulated platelet surface

Post-procedural TIMI flow grade 2 is not associated with improved prognosis in patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary revascularization (PL-ACS registry)

Restoration of Normal Coronary Flow With Tirofiban by Intracoronary Administration for No-reflow Phenomenon After Stent Deployment

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