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Bleeding Time (bleeding + time)
Kinds of Bleeding Time Selected AbstractsHemostatic Defect in Baboons Autotransfused Treated Plasma to Simulate Shed BloodJOURNAL OF CARDIAC SURGERY, Issue 6 2006C. Robert Valeri M.D. This study was done to determine how autotransfusion of nontreated plasma and plasma treated with urokinase with and without aprotinin affected hemostasis in healthy baboons. Methods: A 500-mL volume of blood was collected from the baboon, a 250-mL volume of plasma was isolated, and the RBCs were reinfused. Three baboons were autotransfused untreated plasma. Four baboons received plasma that had been treated with 3000 IU/mL urokinase at +37°C for 30 minutes. Eight baboons received plasma that had been treated first with urokinase 3000 IU/mL at +37°C for 30 minutes and then with aprotinin (1000 KIU/mL). Bleeding time, fibrinogen degradation products (FDP), D-dimer, and alpha-2 antiplasmin levels were measured. Results: During the 4-hour period following autotransfusion of the urokinase-aprotinin-treated plasma, the levels of D-dimer and FDP were significantly higher and fibrinogen and alpha-2 antiplasmin levels were significantly lower than those levels seen after the autotransfusion of nontreated plasma. FDP and D-dimer levels showed significant positive correlations with prothrombin time (PT) and activated partial thromboplastin time (aPTT). A significant negative correlation was observed between thrombin time (TT) and fibrinogen level. A significant positive correlation was observed between bleeding time and D-dimer level and a significant negative correlation between the bleeding time and the fibrinogen level. Conclusions: The infusion of a volume of urokinase or urokinase-aprotinin treated autologous plasma equivalent to 15% of the blood volume was not associated with a bleeding diathesis in healthy baboons. [source] Hydrophilic Polymers with Potassium Salt and Microporous Polysaccharides for Use as Hemostatic AgentsDERMATOLOGIC SURGERY, Issue 12 2007JULIA HO MD BACKGROUND Postoperative bleeding can lead to complications such as hematoma, infection, dehiscence, and an unscheduled office visit. Topical hemostatic agents can be used to aid in hemostasis. OBJECTIVE The objective is to familiarize physicians with topical hemostatic agents,hydrophilic polymers with potassium salts (Urgent QR powder) and microporous polysaccharide hemispheres (Bleed-X). METHODS Two hemostatic agents, microporous polysaccharide hemospheres and hydrophilic polymers with potassium salt, are discussed. The literature is reviewed. RESULTS Numerous types of hemostatic agents exist. Topical hemostatic agents are safe, cost-effective, and efficient. CONCLUSION Microporous polysaccharide hemospheres and hydrophilic polymers with potassium salts can be an adjunct to hemostasis after cautery and ligation. Patients can apply hemostatic agents if they experience any bleeding leading to decreased office visits. Hemostatic agents used intraoperatively shorten bleeding time and enable the physician to use less cautery. Using hemostatic agents can lead to fewer hematomas, infections, and office visits. [source] Antiplatelet agents and bleeding time after endoscopic biopsy of the gastric antrum in Japanese patientsDIGESTIVE ENDOSCOPY, Issue 3 2010Takatsugu Yamamoto No abstract is available for this article. [source] MANAGEMENT OF ANTIPLATELET THERAPY FOR ENDOSCOPIC PROCEDURES: OPTIMAL CESSATION PERIOD OF ANTIPLATELET THERAPY FOR JAPANESEDIGESTIVE ENDOSCOPY, Issue 4 2007Yoshiko Tamai Although antiplatelet agents are widely used for the treatment and prevention of thrombotic diseases, only a few studies have reported the validity of the cessation period prior to endoscopic procedures. In 2002, the American Society for Gastrointestinal Endoscopy (ASGE) published a reference on the management of anticoagulation and antiplatelet therapy for endoscopic procedures, but it should be confirmed as appropriate for use in Asian patients. To evaluate the optimal cessation period of antiplatelet agents prior to endoscopic procedures for Japanese, we have studied: (i) the current clinically adopted cessation period of antiplatelet agents prior to invasive endoscopic procedures in Japan; (ii) the relationship between the cessation period of antiplatelet agents and complications around the invasive endoscopic procedures; (iii) colonic mucosal bleeding time after aspirin ingestion; and (iv) the time course of primary hemostasis after cessation of antiplatelet agents. We conclude that 3 days cessation period for aspirin, 5 days cessation for ticlopidine and 7 days cessation for aspirin + ticlopidine administration should be sufficient for Japanese. [source] Pharmacodynamics and pharmacokinetics of YM128, a GPIIb/IIIa antagonist prodrugDRUG DEVELOPMENT RESEARCH, Issue 3 2002Ken-ichi Suzuki Abstract We examined the biochemical properties of YM-57029 ({4-[4-(4-Carbamimidoylphenyl)-3-oxopiperazin-1-yl]piperidino}acetic acid monohydrochloride trihydrate) and the pharmacodynamics and pharmacokinetics of its prodrug, YM128 (Ethyl (Z)-(4-{4-[4-(N2 -hydroxycarbamimidoyl)phenyl]-3-oxopiperazin-1-yl}piperidino)acetate), an orally-active glycoprotein IIb/IIIa (GPIIb/IIIa) antagonist. YM-57029 strongly inhibited aggregation of human platelets induced by various agonists, with IC50 values ranging from 3.6 to 51 nM. YM-57029 specifically inhibited fibrinogen binding to purified GPIIb/IIIa about 1,000-fold more potently than Arg-Gly-Asp-Ser (RGDS). Moreover, YM-57029 effectively inhibited an Arg-Gly-Asp (RGD) peptide binding to platelets, suggesting that YM-57029 competed with the RGD sequence of ligand. YM-57029 or YM128 dose-dependently inhibited ex vivo platelet aggregation after iv bolus injection or oral administration to beagle dogs and cynomolgus monkeys. However, YM128 exerted more potent and prolonged inhibitory effects on platelet aggregation than YM-57029 after oral administration to cynomolgus monkeys. Furthermore, YM-57029 prolonged template bleeding time at a dose that inhibited ex vivo platelet aggregation during cumulative iv infusion to cynomolgus monkeys. Metabolic and pharmacokinetic studies showed that YM128 effectively converted into YM-57029 in liver microsomes from humans as well as dogs and monkeys, and that bioavailabilities of YM128 in dogs and monkeys were 32.3 and 22.2%, respectively. These results suggest that YM128, a prodrug of YM-57029, may be a valuable GPIIb/IIIa antagonist with good bioavailability in humans. Drug Dev. Res. 55:149,161, 2002. © 2002 Wiley-Liss, Inc. [source] Bernard Soulier syndrome in pregnancy: a systematic reviewHAEMOPHILIA, Issue 4 2010P. PEITSIDIS Summary., Bernard Soulier syndrome (BSS) is a rare disorder of platelets, inherited mainly as an autosomal recessive trait. It is characterised by qualitative and quantitative defects of the platelet membrane glycoprotein (GP) Ib-IX-V complex. The main clinical characteristics are thrombocytopenia, prolonged bleeding time and the presence of giant platelets. Data on the clinical course and outcome of pregnancy in women with Bernard Soulier syndrome is scattered in individual case reports. In this paper, we performed a systematic review of literature and identified 16 relevant articles; all case reports that included 30 pregnancies among 18 women. Primary postpartum haemorrhage was reported in 10 (33%) and secondary in 12 (40%) of pregnancies, requiring blood transfusion in 15 pregnancies. Two women had an emergency obstetric hysterectomy. Alloimmune thrombocytopenia was reported in 6 neonates, with one intrauterine death and one neonatal death. Bernard Soulier syndrome in pregnancy is associated with a high risk of serious bleeding for the mother and the neonate. A multidisciplinary team approach and individualised management plan for such women are required to minimise these risks. An international registry is recommended to obtain further knowledge in managing women with this rare disorder. [source] The role of the platelet function analyser (PFA-100TM) in the characterization of patients with von Willebrand's disease and its relationships with von Willebrand factor and the ABO blood groupHAEMOPHILIA, Issue 3 2003I. C. Nitu-Whalley Summary. Determination of the closure time (CT) with the platelet function analyser (PFA-100TM) is a useful screening test for von Willebrand's disease (VWD) but its role in the characterization of VWD is not well established. We studied the relationship between the prolongation of the CT with adenosine diphosphate (ADP) (CT-ADP) and epinephrine (CT-EPI) cartridges and the von Willebrand factor (VWF) in 53 patients with VWD. We found that a relatively small percentage of the prolongation of the CT-ADR and CT-ADP (16 and 29%, respectively) was determined by a reduction in VWF levels. The CT-ADP was significantly more prolonged in the presence of qualitative defects in VWF but could not discriminate between the VWD subtypes. The ABO blood group had no effect on the prolongation of the CT or the bleeding time. In conclusion, the PFA-100TM appears of little use in the characterization of severity and subtype of VWD. [source] Effect kinetics of desmopressin-induced platelet retention in healthy volunteers treated with aspirin or placeboHAEMOPHILIA, Issue 1 2000Lethagen Desmopressin is often used for haemostatic treatment in platelet dysfunction, but the effect kinetics of platelet responses and the mechanism of action are poorly known. This study aimed to determine the kinetics of platelet function responses induced by desmopressin in healthy volunteers treated with aspirin or placebo. Another aim was to correlate platelet responses to changes of von Willebrand factor (vWF) in plasma. We measured platelet function with a glass bead retention test, Ivy bleeding time, vWF:Ag and multimeric structure in plasma. Median baseline platelet retention was 12% (normal reference range 16,27%) during aspirin treatment and 18% during placebo. Median peak platelet retention after desmopressin was 33% during aspirin treatment and 34% during placebo. After about 3 h platelet function had returned to baseline. A second desmopressin dose after 3 h stimulated platelet retention to a similar extent as the first dose. There was no correlation between platelet responses and quantitative or qualitative changes of vWF in plasma. Platelet count did not change significantly. Thus, desmopressin's effect on platelet function lasts for about 3 h, but may be prolonged by a second dose immediately thereafter. These findings may have important clinical implications for patients with aspirin-induced platelet dysfunction undergoing surgery. [source] Hemostatic Defect in Baboons Autotransfused Treated Plasma to Simulate Shed BloodJOURNAL OF CARDIAC SURGERY, Issue 6 2006C. Robert Valeri M.D. This study was done to determine how autotransfusion of nontreated plasma and plasma treated with urokinase with and without aprotinin affected hemostasis in healthy baboons. Methods: A 500-mL volume of blood was collected from the baboon, a 250-mL volume of plasma was isolated, and the RBCs were reinfused. Three baboons were autotransfused untreated plasma. Four baboons received plasma that had been treated with 3000 IU/mL urokinase at +37°C for 30 minutes. Eight baboons received plasma that had been treated first with urokinase 3000 IU/mL at +37°C for 30 minutes and then with aprotinin (1000 KIU/mL). Bleeding time, fibrinogen degradation products (FDP), D-dimer, and alpha-2 antiplasmin levels were measured. Results: During the 4-hour period following autotransfusion of the urokinase-aprotinin-treated plasma, the levels of D-dimer and FDP were significantly higher and fibrinogen and alpha-2 antiplasmin levels were significantly lower than those levels seen after the autotransfusion of nontreated plasma. FDP and D-dimer levels showed significant positive correlations with prothrombin time (PT) and activated partial thromboplastin time (aPTT). A significant negative correlation was observed between thrombin time (TT) and fibrinogen level. A significant positive correlation was observed between bleeding time and D-dimer level and a significant negative correlation between the bleeding time and the fibrinogen level. Conclusions: The infusion of a volume of urokinase or urokinase-aprotinin treated autologous plasma equivalent to 15% of the blood volume was not associated with a bleeding diathesis in healthy baboons. [source] Effect of NSAID administration on creatinine clearance in healthy dogs undergoing anaesthesia and surgeryJOURNAL OF SMALL ANIMAL PRACTICE, Issue 12 2000S. F. Forsyth Thirty healthy male dogs were randomly assigned to receive carprofen (4 mg/kg intravenously), ketoprofen (2 mg/kg intravenously) or saline (0.2 ml/kg intravenously) at induction of anaesthesia for castration surgery. A routine castration was undertaken and a buccal mucosal bleeding time was assessed at the completion of surgery. Twenty-four hours after surgery a 24,hour endogenous creatinine clearance study was undertaken. Buccal mucosal bleeding time was not significantly different between the three groups. Creatinine clearance was significantly lower (P , 0.01) in the two groups of dogs that received a non-steroidal anti-inflammatory drug compared with that in the dogs that received sterile saline. There was no significant difference between the carprofen and ketoprofen groups with respect to creatinine clearance. [source] Targeted inhibition of the serotonin 5HT2A receptor improves coronary patency in an in vivo model of recurrent thrombosisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2010K. PRZYKLENK Summary.,Background: Release of serotonin and activation of serotonin 5HT2A receptors on platelet surfaces is a potent augmentative stimulus for platelet aggregation. However, earlier-generation serotonin receptor antagonists were not successfully exploited as antiplatelet agents, possibly owing to their lack of specificity for the 5HT2A receptor subtype. Objective: To assess whether targeted inhibition of the serotonin 5HT2A receptor attenuates recurrent thrombosis and improves coronary patency in an in vivo canine model mimicking unstable angina. Methods: In protocol 1, anesthetized dogs were pretreated with a novel, selective inverse agonist of the 5HT2A receptor (APD791) or saline. Recurrent coronary thrombosis was then initiated by coronary artery injury + stenosis, and coronary patency was monitored for 3 h. Protocol 2 was similar, except that: (i) treatment with APD791 or saline was begun 1 h after the onset of recurrent thrombosis; (ii) template bleeding time was measured; and (iii) blood samples were obtained for in vitro flow cytometric assessment of platelet responsiveness to serotonin. Results: APD791 attenuated recurrent thrombosis, irrespective of the time of treatment: in both protocols, flow,time area (index of coronary patency; normalized to baseline coronary flow) averaged 58,59% (P < 0.01) following administration of APD791 vs. 21,28% in saline controls. Moreover, the in vivo antithrombotic effect of APD791 was not accompanied by increased bleeding, but was associated with significant and selective inhibition of serotonin-mediated platelet activation. Conclusion: 5HT2A receptor inhibition with APD791, even when initiated after the onset of recurrent thrombosis, improves coronary patency in the in vivo canine model. [source] Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studiesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2008P. C. WONG Summary.,Background:,Apixaban is an oral, direct and highly selective factor Xa (FXa) inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases. Objective:,We evaluated the in vitro properties of apixaban and its in vivo activities in rabbit models of thrombosis and hemostasis. Methods:,Studies were conducted in arteriovenous-shunt thrombosis (AVST), venous thrombosis (VT), electrically mediated carotid arterial thrombosis (ECAT) and cuticle bleeding time (BT) models. Results:,In vitro, apixaban is potent and selective, with a Ki of 0.08 nm for human FXa. It exhibited species difference in FXa inhibition [FXa Ki (nm): 0.16, rabbit; 1.3, rat; 1.7, dog] and anticoagulation [EC2× (,m, concentration required to double the prothrombin time): 3.6, human; 2.3, rabbit; 7.9, rat; 6.7, dog]. Apixaban at 10 ,m did not alter human and rabbit platelet aggregation to ADP, ,-thrombin, and collagen. In vivo, the values for antithrombotic ED50 (dose that reduced thrombus weight or increased blood flow by 50% of the control) in AVST, VT and ECAT and the values for BT ED3× (dose that increased BT by 3-fold) were 0.27 ± 0.03, 0.11 ± 0.03, 0.07 ± 0.02 and > 3 mg kg,1 h,1 i.v. for apixaban, 0.05 ± 0.01, 0.05 ± 0.01, 0.27 ± 0.08 and > 3 mg kg,1 h,1 i.v. for the indirect FXa inhibitor fondaparinux, and 0.53 ± 0.04, 0.27 ± 0.01, 0.08 ± 0.01 and 0.70 ± 0.07 mg kg,1 day,1 p.o. for the oral anticoagulant warfarin, respectively. Conclusions:,In summary, apixaban was effective in the prevention of experimental thrombosis at doses that preserve hemostasis in rabbits. [source] Recombinant activated factor VII efficacy and safety in a model of bleeding and thrombosis in hypothermic rabbits: a blind studyJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2007A. GODIER Summary.,Background:,Recombinant activated factor VII (rFVIIa) is increasingly used to secure hemostasis in hemorrhagic situations in trauma and surgical patients. Hypothermia is often observed in these clinical settings. Objective:,To study the efficacy and safety of rFVIIa in hypothermia in a rabbit model of bleeding and thrombosis. Methods:,Sixty-nine rabbits were anesthetized, ventilated and monitored for blood pressure, temperature and carotid flow. The Folts model was used: a stenosis (75%) and an injury were carried out on the carotid artery, inducing thrombosis. Blood flow decreased as thrombus size increased until the pressure gradient was such that the thrombus was released and local arterial blood flow was suddenly restored. This is known as a cyclic flow reduction (CFR). After counting baseline CFRs during a 20-min period (P1), rabbits were randomized blindly to one of four groups: normothermic (NT) placebo or rFVIIa (150 ,g kg,1), hypothermic (HT) (34 °C) placebo or rFVIIa. Then CFRs were recorded over a second period (P2). At the end of the experiment, a hepato-splenic section was performed and the amount of blood loss was recorded. After each period, the following were measured: ear immersion bleeding time (BT), hemoglobin, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen. Results:,Hypothermia increased BT and blood loss. These effects were reversed by rFVIIa. In NT rabbits, rFVIIa shortened BT but did not reduce blood loss. rFVIIa-treated rabbits bled similarly regardless of temperature. The incidence of CFRs was higher in treated than placebo animals regardless of temperature. rFVIIa decreased PT and aPTT without modifying platelet count or fibrinogen level. Conclusion:,Hemostatic efficacy of rFVIIa was maintained in hypothermia. However, the number of CFRs was higher in the rFVIIa-treated group than in the placebo groups, whether for NT or HT rabbits. [source] Effects of factor XI deficiency on ferric chloride-induced vena cava thrombosis in miceJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2006X. WANG Summary.,Background:,Increased plasma levels of coagulation factor (F) XI are a risk factor for venous thrombosis. Objective:,To further explore the relationship between FXI and venous thrombosis, we evaluated FXI-deficient and wild-type mice in a ferric chloride (FeCl3)-induced vena cava thrombosis model. Methods and Results:,Thrombosis was induced by 3-min topical application of filter papers containing increasing concentrations of FeCl3 and the thrombus was measured at 30 min. In contrast to wild-type mice, FXI-deficient mice failed to form a thrombus with 5% FeCl3, and were partially protected against 7.5% and 10% FeCl3, respectively. The protective effect was substantially stronger than a high dose of heparin (1000 units kg,1, i.v.), clopidogrel (30 mg kg,1, p.o.) or argatroban (30 mg kg,1, i.p.). These antithrombotic agents resulted in off-scale bleeding in a tail bleeding time assay, whereas the bleeding time of FXI-deficient mice was unchanged compared to wild-type mice. In addition to its known effect on the coagulation cascade, enhanced clot lysis was demonstrated in FXI-deficient mouse and human plasma compared to those supplemented with FXIa. Conclusion:,Given the strong antithrombotic efficacy (possibly contributed by strong anticoagulant activity associated with increased fibrinolytic activity) and mild bleeding diathesis associated with FXI deficiency, therapeutic inhibition of FXI may be a reasonable therapeutic strategy to treat or prevent venous thrombosis. [source] Are the bleeding time and PFA-100® useful in the initial screening of patients with mucocutaneous bleedings of hereditary nature?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2004M. Cattaneo No abstract is available for this article. [source] Synthetic selective inhibitors of coagulation factor Xa strongly inhibit thrombin generation without affecting initial thrombin forming time necessary for platelet activation in hemostasisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2004M. Ieko Summary., DX-9065a and JTV-803, synthetic selective inhibitors of activated factor X (FXa), have recently been demonstrated as strongly effective antithrombotic agents in animal thrombosis models, yet with a low risk of bleeding. The aim of the present study was to elucidate these characteristics. Using a chromogenic assay with purified coagulation factors, 73.9% of thrombin generation was suppressed by the addition of DX-9065a (0.20 µm) and 75.7% by JTV-803 (0.18 µm). Inhibition by argatroban (0.19 µm) was less (36.0%) and initial thrombin forming time (T50), the time required to generate 50% thrombin activity in vitro, which is considered important for platelet aggregation in hemostasis, was significantly prolonged by argatroban. In contrast, DX-9065a and JTV-803 had no apparent influence on T50, suggesting that initial thrombin was formed immediately, as in the control. We also investigated platelet aggregation in defibrinated plasma induced by tissue factor, to clarify whether initial thrombin contributes to hemostasis. Aggregation was not affected by the addition of either FXa inhibitor, whereas it was significantly reduced by argatroban. Our results suggest that initial thrombin, which is formed despite the presence of a FXa inhibitor, can activate platelets. We concluded that DX-9065a and JTV-803 are able to inhibit thrombin generation significantly without affecting the formation of initial thrombin for platelet activation, which may contribute to hemostasis through the preservation of normal bleeding time. [source] Safety of plasmin in the setting of concomitant aspirin and heparin administration in an animal model of bleedingJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2003S. Sadeghi Summary., Plasmin is a direct thrombolytic which has been shown to have a strikingly favorable benefit to risk profile in comparison with plasminogen activators, notably tissue plasminogen activator (t-PA). As heparin is known to increase the risk of hemorrhage when co-administered with a plasminogen activator, we asked whether adjunct antithrombotic agents such as aspirin and heparin would affect the safety of plasmin. Three groups of rabbits were administered plasmin at a dose (4 mg kg,1) designed to induce significant decreases in antiplasmin, fibrinogen and factor (F)VIII, to about 25, 40 and 40%, respectively, of baseline values, but not cause prolongation of the ear puncture bleeding time. In a blinded and randomized trial, the results show that an intravenous aspirin bolus plus heparin administered as a bolus followed by a maintenance continuous infusion did not significantly prolong the bleeding time during plasmin infusion. These data indicate that in the rabbit, concomitant use of aspirin plus heparin does not affect the safety of a therapeutic dose of plasmin. [source] Lineage-specific overexpression of the P2Y1 receptor induces platelet hyper-reactivity in transgenic miceJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2003B. Hechler Summary., In order to investigate the role of the platelet P2Y1 receptor in several aspects of platelet activation and thrombosis, transgenic (TG) mice overexpressing this receptor specifically in the megakaryocytic/platelet lineage were generated using the promoter of the tissue-specific platelet factor 4 gene. Studies of the saturation binding of [33P]2MeSADP in the presence or absence of the selective P2Y1 antagonist MRS2179 indicated that wild-type (WT) mouse platelets bore 150 ± 31 P2Y1 receptors and TG platelets 276 ± 34, representing an 84% increase in P2Y1 receptor density. This led to a well defined phenotype of platelet hyper-reactivity in vitro, as shown by increased aggregations in response to adenosine 5,-diphosphate (ADP) and low concentration of collagen in TG as compared with WT platelets. Moreover, overexpression of the P2Y1 receptor enabled ADP to induce granule secretion, unlike in WT platelets, which suggests that the level of P2Y1 expression is critical for this event. Our results further suggest that the weak responses of normal platelets to ADP are due to a limited number of P2Y1 receptors rather than to activation of a specific transduction pathway. TG mice displayed a shortened bleeding time and an increased sensitivity to in vivo platelet aggregation induced by infusion of a mixture of collagen and epinephrine. Overall, these findings emphasize the importance of the P2Y1 receptor in hemostasis and thrombosis and suggest that variable expression levels of this receptor on platelets might play a role in thrombotic states in human, which remains to be assessed. [source] Etomidate and thiopental inhibit platelet function in patients undergoing infrainguinal vascular surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2001A. Gries Background: Postoperative platelet hyperaggregability following general anesthesia has been reported in patients undergoing major vascular surgery. In contrast, since anesthetic agents inhibited platelet function both in vitro and in vivo, an increased risk for postoperative bleedings due to prolonged platelet dysfunction has been discussed. Nevertheless, data describing platelet-affecting properties of induction agents such as etomidate and thiopental in patients undergoing major vascular surgery are lacking. Methods: Platelet function was determined at 0, 2, 20, and 200 ,g/ml thiopental and at 0, 0.2, 2, 20 ,g/ml etomidate in vitro in blood samples drawn from 16 patients suffering from severe occlusive arterial disease. In addition, 30 patients undergoing vascular surgery were investigated before (PRE) and after anesthesia induction (T0) either with etomidate (ETO group, n=16) or thiopental (THIO group, n=14), and 2 h after the beginning of surgery (T2). Platelet function was determined according to platelet aggregation, in vitro bleeding time, and flow cytometric measurements. Results:In vitro, P-selectin expression was inhibited by etomidate at 2 and 20 ,g/ml (,28% and ,38%, respectively) and also by thiopental at 200 ,g/ml (,27%). In patients undergoing vascular surgery, anesthesia induction in the ETO group resulted in a 31% prolongation of the in vitro bleeding time and an inhibition of ADP- and collagen-induced platelet aggregation (,30% and ,17%, respectively) and of P-selectin expression (,25%) at T0. In the THIO group, only ADP-induced platelet aggregation was affected (,16%). At T2, all parameters had reached PRE level again in both groups. Furthermore, in comparison with the THIO group, operation time was significantly prolonged and transfusion volume was significantly increased in the ETO group. In addition, platelet count and hematocrit significantly decreased at T2, whereas levels of tPA, PAI-1, fibrinogen and antithrombin III and partial thromboplastin time remained unchanged in both groups during the study period. Conclusions: In the present study, etomidate and, to a minor extent, thiopental offered significant platelet inhibitory properties. Anesthetic-induced platelet inhibition may lead to higher transfusion rates and prolonged operation times. Therefore, anesthetic-related platelet inhibitory properties should be considered when searching for the anesthetic agent of choice, especially in patients with compromised hemostasis and co-existing bleeding disorders. [source] Presentation and pattern of symptoms in 382 patients with Glanzmann thrombasthenia in IranAMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2004G. Toogeh Abstract Glanzmann thrombasthenia (GT) is a rare autosomal recessive disease characterized by prolonged bleeding time with normal platelet count and morphology. It is caused by the quantitative or qualitative deficiency of the platelet glycoprotein IIb,IIIa. In 382 Iranian patients with GT diagnosed at a single center during the period 1969,2001, consanguinity between parents was 86.6%, in accord with the high frequency of intrafamilial marriages in Iran. Almost all patients had had abnormal mucocutaneous bleeding (epistaxis and gum bleeding); at follow-up, 4/5 of the patients had been transfused at least once to control hemorrhagic episodes. As expected, almost all the patients had a normal platelet count while the leukocyte count was increased in 19.3%. Among women, an unexpected low rate of pregnancies was observed. Am. J. Hematol. 77:198,199, 2004. © 2004 Wiley-Liss, Inc. [source] Antiinflammatory and Anticoagulant Effects of Transgenic Expression of Human Thrombomodulin in MiceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010S. Crikis Thrombomodulin (TBM) is an important vascular anticoagulant that has species specific effects. When expressed as a transgene in pigs, human (h)TBM might abrogate thrombotic manifestations of acute vascular rejection (AVR) that occur when GalT-KO and/or complement regulator transgenic pig organs are transplanted to primates. hTBM transgenic mice were generated and characterized to determine whether this approach might show benefit without the development of deleterious hemorrhagic phenotypes. hTBM mice are viable and are not subject to spontaneous hemorrhage, although they have a prolonged bleeding time. They are resistant to intravenous collagen-induced pulmonary thromboembolism, stasis-induced venous thrombosis and pulmonary embolism. Cardiac grafts from hTBM mice to rats treated with cyclosporine in a model of AVR have prolonged survival compared to controls. hTBM reduced the inflammatory reaction in the vein wall in the stasis-induced thrombosis and mouse-to-rat xenograft models and reduced HMGB1 levels in LPS-treated mice. These results indicate that transgenic expression of hTBM has anticoagulant and antiinflammatory effects that are graft-protective in murine models. [source] Plasma Exchange Before Surgery for Left Ventricular Assist Device ImplantationARTIFICIAL ORGANS, Issue 6 2008Rajko Radovancevic Abstract:, Left ventricular assist device (LVAD) implantation in end-stage heart failure patients is frequently associated with hemorrhagic complications requiring reoperation. The preoperative coagulopathic profile includes prolonged prothrombin time (PT), partial thromboplastin time (PTT), and bleeding time; platelet dysfunction; decreased coagulation factor activity; and increased inflammatory markers. We compare outcomes in LVAD patients treated with preoperative plasma exchange with concurrent, nonrandomized control patients. We reviewed data from 68 consecutive elective patients who received LVADs at our institution. Thirty-five received LVADs after preoperative plasma exchange (replacement of one plasma volume of fresh frozen plasma), and 33 received LVADs without plasma exchange. Groups were comparable in age, sex, body weight, New York Heart Association class, intra-aortic balloon pump insertion, cardiac index, pulmonary capillary wedge pressure, creatinine, total bilirubin, hemoglobin levels, PT, international normalized ratio, PTT, and platelet count. Early mortality was lower in the plasma exchange group (0% [0/35] vs. 18% [6/33], P = 0.026), and postoperative chest tube drainage decreased by 33% (P = not significant). Blood transfusion requirements were similar.Perioperative mortality decreased in patients treated with plasma exchange before LVAD implantation. [source] Variables influencing Platelet Function Analyzer-100TM closure times in healthy individualsBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2005Hannelore Haubelt Summary We investigated the relationship between platelet function analyzer (PFA-100TM) closure times (CT) and bleeding time (BT), platelet aggregation (PA) induced by ADP, arachidonic acid, and collagen, blood cell counts, and von Willebrand factor (VWF) in 120 well-characterised healthy individuals. Pre-analytical and analytical conditions were standardised comprehensively. In a substantial number of cases the differences between duplicate measurements exceeded 15%. The reference range (5th and 95th percentiles) for CT with the collagen/epinephrine (CEPI) and the collagen/ADP (CADP) cartridge was 93,223 s and 64,117 s respectively. Re-examination of 11 individuals with CEPI-CT above the 95th percentile revealed considerable batch-to-batch variation of CEPI-CT. Males had significantly longer CADP than females (P = 0·002). CEPI and CADP-CT measured pm were significantly longer than corresponding values determined am (P = 0·003 and P < 0·0001 respectively). Blood group O was associated with greater CEPI and CADP-CT and lower VWF levels compared with non-O blood groups (P = 0·008, P = 0·0003 and P < 0·0001 respectively). Linear regression analysis revealed association between CEPI-CT, CADP-CT and VWF (P < 0·0001), but no relationship was found between CT and BT or between CT and PA. We conclude that VWF plasma levels modulate PFA-100TM CT to a greater extent than platelet function. Establishment of reliable reference ranges and careful standardisation of pre-analytical and analytical conditions is a prerequisite for obtaining reliable PFA-100TM results. Duplicate measurements are necessary. [source] A Val193Met mutation in GPIIIa results in a GPIIb/IIIa receptor with a constitutively high affinity for a small ligandBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2001John Fullard We have identified a patient designated as (GTa) with Glanzmann's Thrombasthenia (GT) diagnosed on the basis of a prolonged bleeding time and failure of the patient's platelets to aggregate. The number of glycoprotein (GP)IIb/IIIa receptors on the platelet surface was 37% of normal and those receptors displayed a defect in soluble fibrinogen binding. Nevertheless, GTa platelets showed increased adhesion to solid-phase fibrinogen and binding affinity for the RGD-mimetic 3H-SC52012, a non-peptide GPIIb/IIIa antagonist. Dithiothreitol (DTT) and ADP enhanced the affinity for [3H]-SC52012 in normal platelets, but had little effect in GTa platelets. These findings suggested that GTa platelets were locked in an altered affinity state. Genetic analysis showed that GTa was a compound heterozygote for the GPIIIa gene. One allele showed a deletion at the 3, end of exon 3 resulting in a premature stop codon. The second GPIIIa allele had a G to A transition at nucleotide 577, resulting in a Val193Met substitution. HEK 293T cells transfected with mutant GPIIb/IIIaV193M bound [3H]-SC52012 with a higher affinity than wild-type GPIIb/IIIa, and this was not increased by DTT. The mutant receptor distinguishes between platelet adhesion and aggregation, and demonstrates the phenotype that may be expected when platelet aggregation alone is inhibited. [source] Biological properties of a specific G,q/11 inhibitor, YM-254890, on platelet functions and thrombus formation under high-shear stressBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2006Toshio Uemura 1The effects of YM-254890, a specific G,q/11 inhibitor, on platelet functions, thrombus formation under high-shear rate condition and femoral artery thrombosis in cynomolgus monkeys were investigated. 2YM-254890 concentration dependently inhibited ADP-induced intracellular Ca2+ elevation, with an IC50 value of 0.92±0.28 ,M. 3P-selectin expression induced by ADP or thrombin receptor agonist peptide (TRAP) was strongly inhibited by YM-254890, with IC50 values of 0.51±0.02 and 0.16±0.08 ,M, respectively. 4YM-254890 had no effect on the binding of fibrinogen to purified GPIIb/IIIa, but strongly inhibited binding to TRAP-stimulated washed platelets. 5YM-254890 completely inhibited platelet shape change induced by ADP, but not that induced by collagen, TRAP, arachidonic acid, U46619 or A23187. 6YM-254890 attenuated ADP-, collagen-, TRAP-, arachidonic acid- and U46619-induced platelet aggregation with IC50 values of <1 ,M, whereas it had no effect on phorbol 12-myristate 13-acetate-, ristocetin-, thapsigargin- or A23187-induced platelet aggregation. 7High-shear stress-induced platelet aggregation and platelet-rich thrombus formation on a collagen surface under high-shear flow conditions were concentration dependently inhibited by YM-254890. 8The antithrombotic effect of YM-254890 was evaluated in a model of cyclic flow reductions in the femoral artery of cynomolgus monkeys. The intravenous bolus injection of YM-254890 dose dependently inhibited recurrent thrombosis without affecting systemic blood pressure or prolonging template bleeding time. 9YM-254890 is a useful tool for investigating G,q/11 -coupled receptor signaling and the physiological roles of G,q/11. British Journal of Pharmacology (2006) 148, 61,69. doi:10.1038/sj.bjp.0706711 [source] Pharmacological Profile and Therapeutic Potential of BM-573, a Combined Thromboxane Receptor Antagonist and Synthase InhibitorCARDIOVASCULAR THERAPEUTICS, Issue 1 2005Alexandre Ghuysen ABSTRACT BM-573 (N-terbutyl-N,-[2-(4,-methylphenylamino)-5-nitro-benzenesulfonyl]urea), a torsemide derivative, is a novel non-carboxylic dual TXA2 synthase inhibitor and receptor antagonist. The pharmacological profile of the drug is characterized by a higher affinity for the thromboxane receptor than that of SQ-29548, one of the most powerful antagonists described to date, by a complete prevention of human platelet aggregation induced by arachidonic acid at a lower dose than either torsemide or sulotroban, and by a significantly prolonged closure time measured by the platelet function analyser (PFA-100®). Moreover, at the concentrations of 1 and 10 ,M, BM-573 completely prevented production of TXB2 by human platelets activated by 0.6 mM of arachidonic acid. BM-573 prevents rat fundus contraction induced by U-46619 but not by prostacyclin or other prostaglandins. Despite possessing a chemical structure very similar to that of a diuretic torsemide, BM-573 has no diuretic activity. BM-573 does not prolong bleeding time and, unlike some of the other sulfonylureas, has no effect on blood glucose levels. In vivo, BM-573 appears to have antiplatelet and antithrombotic activities since it reduced thrombus weight and prolonged the time to abdominal aorta occlusion induced by ferric chloride. BM-573 also relaxed rat aorta and guinea pig trachea precontracted with U-46619. In pigs, BM-573 completely antagonized pulmonary hypertensive effects of U-46619 and reduced the early phase of pulmonary hypertension in models of endotoxic shock and pulmonary embolism. Finally, BM-573 protected pigs from myocardial infarction induced by coronary thrombosis. These results suggest that BM-573 should be viewed as a promising therapeutic agent in the treatment of pulmonary hypertension and syndromes associated with platelet activation. [source] What is vinculin needed for in platelets?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2010J. V. MITSIOS Summary.,Background: Vinculin links integrins to the cell cytoskeleton by virtue of its binding to proteins such as talin and F-actin. It has been implicated in the transmission of mechanical forces from the extracellular matrix to the cytoskeleton of migrating cells. Vinculin's function in platelets is unknown. Objective: To determine whether vinculin is required for the functions of platelets and their major integrin, ,IIb,3. Methods: The murine vinculin gene (Vcl) was deleted in the megakaryocyte/platelet lineage by breeding Vcl fl/fl mice with Pf4,Cre mice. Platelet and integrin functions were studied in vivo and ex vivo. Results: Vinculin was undetectable in platelets from Vcl fl/fl Cre+ mice, as determined by immunoblotting and fluorescence microscopy. Vinculin-deficient megakaryocytes exhibited increased membrane tethers in response to mechanical pulling on ,IIb,3 with laser tweezers, suggesting that vinculin helps to maintain membrane cytoskeleton integrity. Surprisingly, vinculin-deficient platelets displayed normal agonist-induced fibrinogen binding to ,IIb,3, aggregation, spreading, actin polymerization/organization, clot retraction and the ability to form a procoagulant surface. Furthermore, vinculin-deficient platelets adhered to immobilized fibrinogen or collagen normally, under both static and flow conditions. Tail bleeding times were prolonged in 59% of vinculin-deficient mice. However, these mice exhibited no spontaneous bleeding and they formed occlusive platelet thrombi comparable to those in wild-type littermates in response to carotid artery injury with FeCl3. Conclusion: Despite promoting membrane cytoskeleton integrity when mechanical force is applied to ,IIb,3, vinculin is not required for the traditional functions of ,IIb,3 or the platelet actin cytoskeleton. [source] | ||||||||||||||||||||||