GPIIb-IIIa Antagonist-induced Reduction in Platelet Surface Factor V/Va Binding and Phosphatidylserine Expression in Whole Blood

2000 ◽  
Vol 84 (09) ◽  
pp. 492-498 ◽  
Author(s):  
Lori Krueger ◽  
A. L. Frelinger ◽  
Marc Barnard ◽  
Mary Mascelli ◽  
Marian Nakada ◽  
...  
Keyword(s):  
Unfractionated Heparin ◽  
Whole Blood ◽  
Venous Blood ◽  
Annexin V ◽  
Procoagulant Activity ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Factor V ◽  
Platelet Surface ◽  
Fibrinogen Binding

SummaryIn addition to inhibition of platelet aggregation, GPIIb-IIIa antagonists may reduce thrombotic events via other mechanisms. In a novel whole blood flow cytometric system, we investigated the effects of GPIIb-IIIa antagonists, in the presence or absence of thrombin inhibitors, on platelet surface-bound factor V/Va and platelet surface phospholipids. Diluted venous blood was incubated with either buffer or a GPIIb-IIIa antagonist (abciximab, tirofiban, or eptifibatide). Some samples were pre-incubated with clinically relevant concentrations of unfractionated heparin (UFH), a low molecular weight heparin, a direct thrombin inhibitor, or buffer only. Platelets were then activated and labeled with mAb V237 (factor V/Va-specific) or annexin V (binds phosphatidylserine), fixed, and analyzed by flow cytometry. In the absence of thrombin inhibitors, GPIIb-IIIa antagonists (especially abciximab) significantly reduced agonist-induced platelet procoagulant activity, as determined by reduced binding of V237 and annexin V. At high pharmacologic concentrations, unfractionated heparin and enoxaparin, but not hirudin, further reduced factor V/Va binding to the surface of activated platelets in the presence of GPIIb-IIIa antagonists. Agonist-induced platelet procoagulant activity was reduced in a patient with Glanzmann’s thrombasthenia. We conclude that GPIIb-IIIa antagonists reduce platelet procoagulant activity in whole blood and heparin and enoxaparin augment this reduction. Fibrinogen binding to GPIIb-IIIa is important in the generation of platelet procoagulant activity.

scholarly journals Bivalirudin Use in an Infant With Persistent Clotting on Unfractionated Heparin

2011 ◽  
Vol 16 (2) ◽  
pp. 108-112
Author(s):  
Katherine M. Malloy ◽  
Tara A. McCabe ◽  
Robert J. Kuhn
Keyword(s):  
Unfractionated Heparin ◽  
Pediatric Population ◽  
Coronary Intervention ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
First Year ◽  
Heparin Infusion ◽  
Percutaneous Coronary ◽  
First Year Of Life

ABSTRACT Bivalirudin is a direct thrombin inhibitor approved for use in adult patients with heparin-induced thrombocytopenia (HIT) undergoing percutaneous coronary intervention. Recently, its use in the pediatric population has increased due to its anti-thrombin-independent mechanism of action. As heparin products produce great inter- and intraindividual variability in pediatric patients, often due to decreased anti-thrombin concentrations in the first year of life, some practitioners have turned to direct thrombin inhibitors, such as bivalirudin, for more predictable pharmacokinetics and effects on bound and circulating thrombin. We report our experience using bivalirudin in a 2-month-old female with recurrent systemic thrombi despite continuous unfractionated heparin infusion. Due to the patient's inability to maintain therapeutic activated partial thromboplastin time (aPTT) values during heparin infusion, bivalirudin was initiated at 0.1 mg/kg/h and increased due to subtherapeutic aPTTs to a maximum of 0.58 mg/kg/h. Therapeutic aPTTs were achieved at the increased dose; however, the patient's worsening renal impairment with resultant drug accumulation and overwhelming sepsis on day 5 of therapy led to discontinuation of the infusion and the initiation of comfort measures.

Contribution of platelets to tumor aggressivity.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21156-e21156
Author(s):  
Judith Delage ◽  
Hong Li ◽  
He Lu ◽  
Lionel Cazin ◽  
Jeannette Soria ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Cancer Cells ◽  
Antithrombin Iii ◽  
Factor Xa ◽  
Procoagulant Activity ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Breast Cancer Cell Lines ◽  
Cancer Aggressiveness ◽  
Mcf 7

e21156 Background: The interaction between cancer and coagulation process has been shown since many years. The aim of our study is to understand the mechanisms implicated and to propose new therapeutic approaches. Methods: Two breast cancer cell lines were used: a very aggressive (MDA-MB231) and a much less aggressive (MCF-7). Platelet aggregation tests were done with washed platelets, normal or fibrin removed plasma and cancer cells (20 to 2.105 cells/ml). Procoagulant activity of cancer cells was studied. Aspirin, Apyrase (ADPase), a direct thrombin inhibitor (Hirudin), two Xa inhibitors (Fondaparinux, Rivaroxaban) were the inhibitors tested. Interaction between platelets and cancer cells was visualized by confocal microscopy. Angiogenic effect of supernatants from platelets-cancer cells co-incubation was investigated. Results: The data obtained show that a platelet aggregation is induced by cancer cells in the presence of a small amount of plasma. This aggregation depends on both the type and number of cancer cells. Aggressive MDA-MB231 cells have a more potent pro-aggregating activity than MCF-7. This aggregation appears to be due to thrombin generation since it is inhibited by Hirudin. Rivaroxaban, a direct inhibitor of factor Xa, inhibits platelets aggregation but not Fondaparinux, an indirect anti Xa inhibitor which binds to Antithrombin III. Aspirin and Apyrase have no effect. Moreover, the procoagulant activity of cancer cells with plasma is inhibited by Hirudin and Rivaroxaban but not by Fondaparinux. This suggests that the Fondaparinux-Antithrombin III complex cannot access to cell membrane-bound factor Xa. It may be due to its steric hindrance since thromboplastin induced coagulation is inhibited by Rivaroxaban but not by Fondaparinux. The confocal microscopic study shows that platelets protect tumor cells from immune attack via the formation from a protective envelope around cancer cells. Angiogenesis assays show that activation of platelets by cancer cells releases angiogenesis stimulating factors and cytokines. Conclusions: The present work confirms the crucial role of platelets in cancer aggressiveness and reveals that Rivaroxaban or Thrombin inhibitors could be efficient drugs to reduce cancer progression, metastasis and thrombosis.

scholarly journals Annexin V as a probe of aminophospholipid exposure and platelet membrane vesiculation: a flow cytometry study showing a role for free sulfhydryl groups

Blood ◽  
1993 ◽  
Vol 81 (10) ◽  
pp. 2554-2565 ◽  
Author(s):  
J Dachary-Prigent ◽  
JM Freyssinet ◽  
JM Pasquet ◽  
JC Carron ◽  
AT Nurden
Keyword(s):  
Flow Cytometry ◽  
Platelet Activation ◽  
Annexin V ◽  
Cytoskeletal Proteins ◽  
Procoagulant Activity ◽  
Ionophore A23187 ◽  
Calpain Activity ◽  
Platelet Surface ◽  
Reactive Agents ◽  
Platelet Secretion

Annexin V, a protein with a high affinity and a strict specificity for aminophospholipids at physiologic calcium concentrations, was used to probe platelet activation and the development of procoagulant activity. Platelet secretion was studied in parallel using VH10, a murine monoclonal antibody specific for GMP-140, an alpha-granule membrane glycoprotein. Both proteins were labeled with fluorescein isothiocyanate and platelet activation was assessed by flow cytometry. Microparticles, which are shed from the platelet surface and also support procoagulant activity, were distinguished from platelets according to their associated light scattering signal. The relative ability of different inducers to trigger exposure of the procoagulant surface and microparticle formation was: ionophore A23187 = thrombin plus collagen = collagen = thrombin. The density of aminophospholipid on microparticles was higher than on remnant platelets. Platelet activation by these agonists was accompanied by GMP-140 exposure, both on platelets and microparticles. Here, thrombin was the most efficient agonist. The mechanisms responsible for the above processes were investigated using E-64-d, a specific membrane-permeable inhibitor of Ca(2+)-activated protease (calpain); tetracaine, an activator of calpain; and N-ethylmaleimide and diamide, two sulfhydryl-reactive agents. These agents were added to platelets alone or before stimulation by agonists. Calpain activity was assessed by the hydrolysis of cytoskeletal proteins as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Results showed that calpain activity is not essential for aminophospholipid translocation or for secretion. In contrast, although sulfhydryl-reactive agents alone can trigger procoagulant activity, they inhibit microvesicle formation and platelet secretion induced by the above agonists, suggesting that different mechanisms account for these phenomena. The use of annexin V in flow cytometry is a rapid method to assess procoagulant activity in platelets and the loss of phospholipid asymmetry in cell membranes.

scholarly journals Epinephrine induces platelet fibrinogen receptor expression, fibrinogen binding, and aggregation in whole blood in the absence of other excitatory agonists

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 150-158
Author(s):  
SJ Shattil ◽  
A Budzynski ◽  
MC Scrutton
Keyword(s):  
Monoclonal Antibody ◽  
Whole Blood ◽  
Platelet Activating Factor ◽  
Synergistic Interaction ◽  
Receptor Expression ◽  
Thrombin Inhibitors ◽  
Early Event ◽  
Fibrinogen Receptor ◽  
Fibrinogen Binding ◽  
Adrenergic Antagonist

The exposure of fibrinogen receptors is an early event in agonist- induced platelet activation. Previous measurements of fibrinogen binding or aggregation in platelet-rich plasma or washed platelets have failed to define whether the initial response to epinephrine results solely from a direct effect of this agonist. To address this problem, we have measured fibrinogen receptor exposure on platelets in whole blood by using flow cytometry and a fluorescein isothiocyanate-labeled monoclonal antibody specific for the activated fibrinogen receptor (FITC-PAC1). We also measured platelet-bound fibrinogen with an antifibrinogen monoclonal antibody (FITC-9F9) as well as platelet aggregation in whole blood. In blood anticoagulated with citrate and in the presence of a cyclooxygenase inhibitor, epinephrine (0.1 to 100 mumol/L) caused significant FITC-PAC1 binding (P less than .001) that was maximal at 10 mumol/L epinephrine. The maximal epinephrine response was one third of that observed with 10 mumol/L adenosine diphosphate (ADP) and was eliminated by yohimbine, an alpha 2-adrenergic antagonist. Incubation of the blood with apyrase or phosphoenolpyruvate plus pyruvate kinase to remove extracellular ADP resulted in a 40% to 50% reduction in the epinephrine response. Despite this, FITC-PAC1 binding was still significant at epinephrine greater than or equal to 1 mumol/L (P less than .05). No reduction in epinephrine-induced FITC- PAC1 binding was observed in the presence of ATP alpha S, an ADP receptor antagonist; cinanserin, a serotonin antagonist; or WEB-2086, a platelet activating factor antagonist. Furthermore, addition of the thrombin inhibitors hirudin or leupeptin to citrated blood had no effect on the extent of the epinephrine response. Blood anticoagulated with hirudin also demonstrated an epinephrine response, even in the presence of apyrase. Similar results were obtained when FITC-9F9 was used to detect fibrinogen binding or when aggregation was assessed by a decrease in the number of single platelets. We conclude that epinephrine itself can induce fibrinogen receptor exposure, fibrinogen binding, and aggregation. This primary response is independent of synergistic interaction of epinephrine with traces of ADP, serotonin, platelet activating factor, or thrombin. However, such synergistic interaction with ADP present in whole blood may enhance the responses induced by epinephrine.

Platelet Hyporeactivity in Very Low Birth Weight Neonates

1997 ◽  
Vol 77 (05) ◽  
pp. 1002-1007 ◽  
Author(s):  
Damodara Rajasekhar ◽  
Marc R Barnard ◽  
Francis J Bednarek ◽  
Alan D Michelson
Keyword(s):  
Flow Cytometry ◽  
Binding Site ◽  
Whole Blood ◽  
Very Low Birth Weight ◽  
Thromboxane A2 ◽  
Platelet Surface ◽  
Activated Platelets ◽  
Fibrinogen Binding ◽  
Platelet Binding ◽  
Thromboxane A2 Analogue

SummaryVery few studies have examined platelet function in very low birth weight (VLBW) preterm neonates, because of the relatively large volumes of blood required. In this study, platelet function in clinically stable VLBW neonates was examined by whole blood flow cytometry, which requires only 5 |jl1 of whole blood per assay. The following monoclonal antibodies were used: S12 (P-selectin-specific, reflecting a granule secretion), PAC1 (directed against the fibrinogen binding site exposed on the GPIIb-IIIa complex of activated platelets), F26 (directed against a conformational change in fibrinogen bound to the GPIIb-IIIa complex), and 6D1 (directed against the von Willebrand factor binding site on the GPIb-IX-V complex). VLBW neonates, like normal adults, did not have circulating activated platelets, as determined by the lack of binding of SI2, PAC1, and F26 in the absence of an added agonist. VLBW neonatal platelets were markedly less reactive than adult platelets to thrombin, ADP/epinephrine, and U46619 (a stable thromboxane A2 analogue), as determined by the extent of increase in the platelet binding of SI2, PAC1, and F26, and the extent of decrease in the platelet binding of 6D1. In summary, compared to adults, the platelets of VLBW neonates are markedly hyporeactive to thrombin, ADP/epinephrine and a thromboxane A2 analogue in the physiologic milieu of whole blood, as determined by: 1) the increase in platelet surface P-selectin; 2) the exposure of the fibrinogen binding site on the GPIIb-IIIa complex; 3) fibrinogen binding; and 4) the decrease in platelet surface GPIb. This platelet hyporeactivity may be a factor in the propensity of VLBW neonates to intraventricular hemorrhage. In addition to its previously defined use as a test of platelet hyperreactivity, the present study suggests that whole blood flow cytometry may be useful in the clinical assessment of platelet hyporeactivity.

The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2469-2478 ◽  
Author(s):  
Dagmar Dörmann ◽  
Kenneth J. Clemetson ◽  
Beate E. Kehrel
Keyword(s):  
Binding Site ◽  
Critical Role ◽  
Good Evidence ◽  
Procoagulant Activity ◽  
Platelet Glycoprotein ◽  
Platelet Surface ◽  
Fibrinogen Binding ◽  
Thrombin Activation ◽  
Thrombotic Diseases ◽  
Von Willebrand

Abstract The role of the platelet glycoprotein (GP) Ib-V-IX receptor in thrombin activation of platelets has remained controversial although good evidence suggests that blocking this receptor affects platelet responses to this agonist. The mechanism of expression of procoagulant activity in response to platelet agonists is also still obscure. Here, the binding site for thrombin on GPIb is shown to have a key role in the exposure of negatively charged phospholipids on the platelet surface and thrombin generation, in response to thrombin, which also requires protease-activated receptor-1, GPIIb-IIIa, and platelet-platelet contact. Von Willebrand factor binding to GPIb is not essential to initiate development of platelet procoagulant activity. Inhibition of fibrinogen binding to GPIIb-IIIa also failed to block platelet procoagulant activity. Both heparin and low molecular weight heparin block thrombin-induced platelet procoagulant activity, which may account for part of their clinical efficacy. This study demonstrates a new, critical role for platelet GPIb in hemostasis, showing that platelet activation and coagulation are tightly interwoven, which may have implications for alternative therapies for thrombotic diseases.

Microfluidic and Flow Cytometric Studies Support a Role for Monocytes and Coated Platelets in the Prothrombotic State in Heparin-Induced Thrombocytopenia (HIT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 539-539
Author(s):  
Valerie Tutwiler ◽  
Hyun Sook Ahn ◽  
Douglas B. Cines ◽  
Rodney M. Camire ◽  
Mortimer Poncz ◽  
...  
Keyword(s):  
Whole Blood ◽  
Platelet Adhesion ◽  
Conflicts Of Interest ◽  
Thrombus Formation ◽  
Passive Immunization ◽  
Annexin V ◽  
Thrombin Inhibitor ◽  
Prothrombotic State ◽  
Flow Cytometric ◽  
Activated State

Abstract Abstract 539 HIT is an immune thrombocytopenia associated with a high risk of developing thrombosis. A passive immunization murine model of this disorder has provided important insights into the underlying pathogenesis of this disease, but is limited by its inability to study human cells and limited ability to define the contribution of various hematopoeitic and vascular cells to the prothrombotic state. We used a microfluidic system in conjunction with flow cytometry to further our understanding of the prothrombotic nature of HIT. Platelet adhesion and aggregation was studied in whole blood labeled with Calcein AM, perfused through a microfluidic channel (BioFlux 200 system, Fluxion) coated with von Willebrand factor (vWf) at shear stress of 20 dyne/cm2 at 37°C. A 40–60% increase in platelet adhesion (relative area covered by platelets) with up to a 4 fold increase in average aggregate size was seen in the presence of the pathogenic HIT-like monoclonal antibody (moAb) KKO (50 μg/ml) in conjunction with PF4 (10 μg/ml) when compared to control samples with PF4 only or with PF4 plus a non-pathogenic anti-PF4 moAb RTO (p <0.01). Monocyte-depletion decreased platelet aggregation by 20 – 40% relative to whole blood or after monocyte-repletion (P<0.0001). In HIT, thrombin plays a key role in the formation of platelet aggregates. Addition of thrombin inhibitor PPACK to the whole blood stimulated by KKO and PF4 decreased thrombus formation in the microfluidic chamber by 40% (p<0.001). Coated platelets are prothrombotic and characterized by phosphatidylserine (PS) exposure and binding of FVa and FXa. This activated state requires dual stimulation via thrombin and ITAM receptors. Flow cytometric studies of annexin V and FXa binding showed extensive induction of coated platelets in whole blood by KKO plus PF4 in contrast to PF4 or PF4 plus RTO (annexin V: p<0.0001; Factor Xa p<0.01). These new studies, focused on human blood, support our finding in the passive murine HIT model as to the importance of monocytes to thrombus formation and suggest that the prothrombotic nature of HIT may also be promoted by the generation of coated platelets. Identification of coated platelets may also lead to new diagnostic tests and new therapeutic interventions in HIT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Contact-induced neutrophil activation by platelets in human cell suspensions and whole blood

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1238-1246 ◽  
Author(s):  
A Ruf ◽  
RF Schlenk ◽  
A Maras ◽  
E Morgenstern ◽  
H Patscheke
Keyword(s):  
Whole Blood ◽  
Light Transmission ◽  
Light And Electron Microscopy ◽  
Adenosine Diphosphate ◽  
Polymorphonuclear Neutrophils ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Platelet Surface ◽  
Enhanced Chemiluminescence ◽  
Fibrinogen Binding

Platelet-dependent activation of polymorphonuclear neutrophils (PMNL) was investigated with a lumi-aggregometer in heparinized whole blood and platelet-PMNL suspensions. The lumi-aggregometer allowed us to simultaneously monitor increases in impedance or light transmission as consequences of platelet aggregation and luminol-enhanced chemiluminescence (CL) as a measure of the oxidative burst in PMNL. Aggregation and platelet-PMNL contacts were also checked by light and electron microscopy. In whole blood, adenosine diphosphate (ADP) and the thromboxane A2 mimetic U 46619 induced the aggregation (increase in impedance) and the CL, which were both suppressed by EDTA, arginyl- glycyl-aspartyl-serine (RGDS) peptide, and the absence of stirring. In contrast, FMLP caused only CL that was unaffected by EDTA, RGDS peptide, and nonstirring. Similar observations were obtained with mixed suspensions containing washed platelets and PMNL at their physiologic concentrations. ADP, U 46619, and thrombin induced both aggregation (increase in light transmission) and CL, whereas FMLP caused CL but only very weak aggregation. Exogenous fibrinogen strongly enhanced the effects of ADP and U 46619. Iloprost, EDTA, RGDS peptide, red blood cell (RBC) ghosts, and nonstirring inhibited the effects induced by the platelet agonists, but were ineffective on the CL induced by FMLP. Treatment of platelets with aspirin did not affect the CL of PMNL induced by platelets. Microscopic examination, the requirements of stirring, Ca2+, and fibrinogen, and the inhibitory effects of RGDS peptide and RBC ghosts show that stimulated platelets activate PMNL in a contact-dependent manner that depends on fibrinogen binding. This was confirmed by the immunochemical demonstration of fibrinogen (but not of fibronectin) in the contact spaces between activated platelets and PMNL. Because supernatants and lysates of resting or thrombin- stimulated platelets did not induce the CL of PMNL, soluble agonists did not appear to be involved. Nonstimulated washed platelets also caused CL of PMNL that required stirring and Ca2+ and was inhibited by RBC ghosts. No CL occurred in unstimulated stirred whole blood, suggesting that a preactivation of platelets during the preparation may be responsible for the effects of unstimulated washed platelets. The results show that platelets provide a strong stimulus for PMNL that requires intercellular contact. Fibrinogen exposure on the platelet surface seems to be necessary for the activation of PMNL by stimulated platelets.

scholarly journals Platelet phosphatidylserine exposure and procoagulant activity in clotting whole blood – different effects of collagen, TRAP and calcium ionophore A23187

2003 ◽  
Vol 89 (01) ◽  
pp. 132-141 ◽  
Author(s):  
Mats Rånby ◽  
Tomas Lindahl ◽  
Sofia Ramström
Keyword(s):  
Whole Blood ◽  
Calcium Ionophore ◽  
Annexin V ◽  
Calcium Ionophore A23187 ◽  
Procoagulant Activity ◽  
Phospholipid Vesicles ◽  
Ionophore A23187 ◽  
Clotting Time ◽  
Phosphatidylserine Exposure ◽  
Free Plasma

SummaryWe have studied the effects of different platelet agonists on phosphatidylserine (PS) exposure and clotting times in blood without anticoagulants. Similar reductions in clotting time were obtained for collagen, TRAP-6 or calcium ionophore A23187 (50 μmol/L), in spite of huge differences in PS expression [6.7 ± 2.4%, 2.3 ± 0.5% and 99.9 ± 0.1%, respectively (mean ± SD, n = 5)]. Furthermore, the clotting times were much longer for samples with A23187 exposing the same amounts of PS as samples with collagen or TRAP-6. Annexin V reversed the clotting time reduction, but could not prevent coagulation. Addition of phospholipid vesicles containing 20% PS neither affected the clotting times nor induced clotting in recalcified, platelet-free plasma.We conclude that platelet PS exposure is necessary, but not sufficient, for the coagulation amplification observed when platelets are stimulated via physiological receptors in a whole blood environment.

scholarly journals Complement proteins C5b-9 stimulate procoagulant activity through platelet prothrombinase

Blood ◽  
1986 ◽  
Vol 68 (4) ◽  
pp. 875-880 ◽  
Author(s):  
T Wiedmer ◽  
CT Esmon ◽  
PJ Sims
Keyword(s):  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Procoagulant Activity ◽  
Ionophore A23187 ◽  
Factor V ◽  
Platelet Factor ◽  
Platelet Surface ◽  
Prothrombinase Complex ◽  
Factor Va ◽  
Exogenous Factors

Abstract The capacity of platelets treated with nonlytic concentrations of the C5b-9 proteins to catalyze prothrombin activation and thereby trigger clot formation has been investigated. When suspended in the presence of exogenous factors Xa and Va, gel-filtered platelets treated with purified C5b-9 proteins catalyzed prothrombin to thrombin conversion at rates up to tenfold above controls, and exceeded by up to fourfold the prothrombinase activity observed for thrombin-stimulated platelets. In the absence of added factor Va, C5b-9 assembly on the platelet surface significantly shortened the lag period before prothrombinase expression that was observed for untreated platelets and increased the maximum catalytic rate of thrombin formation. A comparison with other platelet stimuli revealed that the C5b-9-induced activation of platelet prothrombinase closely paralleled the effects mediated by calcium ionophore A23187. Our data suggest that the C5b-9 proteins promote the release of platelet factor V and the assembly of the prothrombinase complex, thereby potentiating the effects of thrombin on the activation of prothrombinase. Membrane assembly of the C5b-9 proteins was also observed to markedly accelerate the rate of platelet-catalyzed plasma clotting, suggesting a direct link between C5b-9-mediated prothrombinase activation and procoagulant activity accompanying immunologic damage to the platelet.

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