Comparison of the Effects of Acetylsalicylic Acid, Ticlopidine and Cilostazol on Primary Hemostasis Using a Quantitative Bleeding Time Test Apparatus

1999 ◽  
Vol 29 (5) ◽  
pp. 269-276 ◽  
Author(s):  
Yoshiko Tamai ◽  
Hideki Takami ◽  
Rieko Nakahata ◽  
Fusako Ono ◽  
Akihiro Munakata
1998 ◽  
Vol 80 (07) ◽  
pp. 181-185 ◽  
Author(s):  
Hideki Takami ◽  
Rieko Nakahata ◽  
Yuka Nakui ◽  
Tomoaki Akagi ◽  
Akihiro Munakata ◽  
...  

SummaryWe have developed a new computerized system for measurement of quantitative bleeding time (QBT) to detect subtle abnormalities of primary hemostasis that are difficult to detect with the standard bleeding time determination. This new apparatus can simultaneously measure the bleeding time (BT; sec), amount of total blood loss (Tv; μl), maximum bleeding rate (Rmax; μl/sec) and bleeding pattern from the bleeding time incision. We have also developed a new holder for the Simplate that enables more consistent incisions and thus improves the reproducibility of the BT test.In this study, the newly developed QBT test was performed in 137 normal healthy volunteers and 10 patients having defined abnormalities of either primary or secondary hemostasis. Comparisons of the standard BT test and our QBT were made in 5 normal subjects and 7 thrombocytopenic patients. Additionally, 6 normal subjects were examined with both tests before and after administration of aspirin. Those results show that our QBT appears to be a more sensitive indicator of primary hemostasis than the standard BT method.


1996 ◽  
Vol 76 (03) ◽  
pp. 312-321 ◽  
Author(s):  
Diego Mezzano ◽  
Rodrigo Tagle ◽  
Olga Panes ◽  
Marcos Pérez ◽  
Patricio Downey ◽  
...  

SummarySeveral parameters of primary hemostasis and markers of activation of coagulation and fibrinolysis were measured in 48 patients with severe (creatinine clearance <20 ml/min) chronic renal failure (CRF) without dialysis and diseases or drugs affecting hemostasis. Bleeding time (BT) was prolonged in 25/48 patients, and was correlated with age of patients, severity of renal failure, hematocrit, impairment in platelet aggregation-secretion and decrease in platelet ATP content. Defects in von Willebrand factor played no role in the prolongation of the BT. Multivariate analysis showed that only platelet dysfunction and severity of renal disease were independent predictors of the BT in uremia. The platelet functional disorder was significantly correlated with a reduction in platelet ATP and ADP.High levels of plasma thrombin-antithrombin complexes (TAT), prothrombin fragment F1+2, fibrinogen and factor VIIc were observed in patients with CRF, as described in prethrombotic states. Plasmin-antiplasmin complexes (PAP), fibrinogen and fibrin degradation products (FgDP, FnDP) were significantly increased, and the activity of plasminogen activator inhibitor (PAI-1) was slightly reduced, denoting an activation of fibrinolysis.A negative correlation was found between platelet levels of ATP and ADP with plasma TAT, F1+2 and PAP. Furthermore, plasma PAI-1 activity was negatively correlated with the BT and was lower in patients with prolonged BT as compared with controls and patients with normal BT. These links between primary hemostasis and activation of coagulation and fibrinolysis suggest that increased intravascular generation of thrombin and/or plasmin is an important mediator of the defects in primary hemostasis, prolongation of the BT and, probably, bleeding in CRF.


Author(s):  
Л.А. Ляпина ◽  
Н.Ф. Мясоедов ◽  
Т.А. Шубина ◽  
Л.А. Андреева ◽  
Т.Ю. Оберган ◽  
...  

Введение. Препараты разной структуры - углеводной, пептидной, белковой оказывают значительный противосвертывающий эффект в кровотоке с одновременным улучшением углеводного обмена. Цель - изучение в сравнительном аспекте влияния препаратов разной структуры (пептида, производного диоксикумарина и ацетилсалициловой кислоты -АСК) на свертывание крови, изменение углеводного обмена при интрагастральном способе их введении крысам. Методика. Использовались стандартные коагулологические методы и способы определения уровня глюкозы крови крыс. Каждый из препаратов (пептид Lys-Arg-Arg-Lys-Pro-Gly-Pro, варфарин и АСК) вводили лабораторным крысам Wistar интрагастрально в эффективной дозе (100 мкг/кг - пептид и варфарин и 1 мг/кг - АСК) в течение 7 сут на фоне развития метаболического синдрома, индуцируемого высококалорийной диетой (ВКД). Определения производили через 20 и 168 ч после последнего введения препаратов при продолжающемся постоянном кормлении крыс ВКД. Результаты. Установлено, что как через 20 ч, так и через 168 ч после последнего введения пептида и АСК агрегация тромбоцитов имела тенденцию к снижению и составляла 72-76% (через 20 ч) и 81-66,7% (через 168 ч); фибринолиз статистически значимо повышался при действии пептида на 61-180%, АСК - на 15-41%, варфарина - на 14-34%; активированное частичное тромбопластиновое время значимо удлинялось под влиянием пептида и варфарина на 24-52 и 31-52% соответственно; свертывание крови по тесту протромбинового времени снижалось только под влиянием варфарина (на 12.3%); уровень глюкозы крови нормализовался под влиянием всех использованых препаратов и составлял 4,9-6,5 ммоль/л против 8.1-8.8 ммоль/л при метаболическом синдроме. Заключение. При сравнении действия пептида, варфарина и АСК установлены гипокоагуляционные и гипогликемические эффекты в разной степени. Максимальным антикоагулянтным и фибринолитическим действием обладал пептид; варфарин проявлял антикоагулянтное действие только по тесту протромбиновое время, ацетилсалициловая кислота обладала антитромбоцитарным и фибриндеполимеризационным действием. Drugs with different structure, carbohydrates, peptides, and proteins, can produce a significant anticoagulation effect and simultaneously improve carbohydrate metabolism. The aim of this study was to compare effects of drugs with different structure, a peptide, a dioxicoumarin derivative, and acetylsalicylic acid (ASA), on coagulation and changes of carbohydrate metabolism in intragastric administration to rats. Methods. Standard methods for studying coagulation and measuring blood glucose in rats were used. Each of the study drugs (Lys-Arg-Arg-Lys-Pro-Gly-Pro peptide, warfarin, and ASA) was administered to Wistar rats intragastrically at an effective dose (100 mcg/kg for the peptide and warfarin and 1 mg/kg for ASA) for 7 days during the development of metabolic syndrome (MS) induced by a high-calorie diet (HCD). Measurements were performed at 20 and 168 h after the last administration of the drugs with continuing HCD. Results. Both at 20 and 168 h after the last administration of the peptide and ASA, platelet aggregation showed a tendency to a decrease and was 72-76% (at 20 h) and 81-66.7% (at 168 h); fibrinolysis significantly increased under the action of the peptide, ASA, and warfarin by 61-180%, 15-41%, and 14-34%, respectively. Activated partial thromboplastin time significantly increased under the action of the peptide and warfarin by 24-52% and 31-52%, respectively; blood clotting as estimated in the prothrombin time test decreased only under the action of warfarin by 12.3%; blood glucose returned to a normal level under the action of each of the three study drugs and was 4.9-6.5 mmol/l vs. 8.1-8.8 mmol/l in MS. Conclusion. The peptide, warfarin, and ASA produced different degrees of the anticoagulation and hypoglycemic effects. The peptide had the strongest anticoagulation and fibrinolytic effects, warfarin produced an anticoagulant effect only according to the prothrombin time test, and acetylsalicylic acid exerted both antiplatelet and fibrin-depolymerizing effects.


1998 ◽  
Vol 160 (4) ◽  
pp. 1599-1600
Author(s):  
P. Peterson ◽  
T.E. Hayes ◽  
C.F. Arkin ◽  
E.G. Bovill ◽  
R.B. Fairweather ◽  
...  

1998 ◽  
Vol 79 (04) ◽  
pp. 843-847 ◽  
Author(s):  
Petteri Kauhanen ◽  
Petri Kovanen ◽  
Timo Reunala ◽  
Riitta Lassila

SummaryWe studied the effects of stimulated skin mast cells on bleeding time and thrombin generation which was measured using prothrombin fragment F 1+2 (F 1+2) and thrombin-antithrombin-III-complex (TAT). In 10 patients with urticaria pigmentosa (chronic cutaneous mast cell accumulation) the mean bleeding time was significantly prolonged in wounds made on urticaria pigmentosa lesions vs. normal skin (460 ± 34 vs. 342 ± 27 s, p = 0.005). In 10 atopic subjects skin incisions were made on prick-tested sites 30, 60, 120 and 240 min after administration of an allergen (acute mast cell stimulation), histamine or vehicle. The mean bleeding time was significantly prolonged at all time points, being maximal at 120 min (60% prolonged) in wounds made on allergen-stimulated skin areas (p <0.01) compared with histamine or vehicle sites. Administration of allergen or histamine lowered the TAT concentration in the bleeding-time blood. Furthermore, TAT and F 1+2 levels in the bleeding-time blood were lower at 60, 120 and 240 min after allergen or histamine application in comparison with samples collected at 30 min. We conclude that skin mast cells can regulate primary hemostasis by prolonging bleeding time and by inhibiting thrombin generation.


1999 ◽  
Vol 82 (10) ◽  
pp. 1250-1254 ◽  
Author(s):  
Olga Panes ◽  
Blanca Muñoz ◽  
Edgar Pais ◽  
Rodrigo Tagle ◽  
Fernando González ◽  
...  

Summary Background: A defect in platelet function is the main determinant of the prolonged bleeding time in chronic renal failure (CRF). We previously reported a significant correlation between platelet abnormalities and elevated plasma markers of plasmin and thrombin generation. Our aim was to explore the effect of inhibiting both plasmin action with tranexamic acid (TA) and thrombin production with low molecular weight heparin (LMWH), on the bleeding time (BT) and platelet function in patients with CRF. Methods: 37 patients with CRF (mean creatinine 8.6 ± 4.4 mg/dl) under conservative treatment, with prolonged BT, entered this study and received TA during 6 days, with (n = 24) and without LMWH (n = 13). BT, platelet aggregation/secretion, platelet granule contents, von Willebrand factor and parameters of coagulation and fibrinolysis were recorded before and at the end of treatment. Results: The BT was shortened in 26/37 (67%) patients. This effect was associated with significant improvement of platelet aggregation and secretion, with decrease to a normal range of fibrin/fibrinogen degradation products, mild increase in plasmin-antiplasmin complexes and pronounced reduction of circulating plasminogen. No differences were seen among patients with or without LMWH. No serious side effects or complications were observed. Interpretation: These findings indicate that the activation of fibrinolysis plays a significant role in the defect of primary hemostasis in patients with CRF. Inhibition of plasmin activity with TA shortens the BT and improves platelet function in the majority of patients with severe disease.


1961 ◽  
Vol 14 (4) ◽  
pp. 381-384 ◽  
Author(s):  
M. L. N. Willoughby ◽  
M. J. Allington
Keyword(s):  

Author(s):  
Richard C. Becker ◽  
Frederick A. Spencer

Platelet antagonists play an important role in both primary and secondary prevention of atherothrombotic events. Despite their proven benefit, individual response (and protection) varies considerably, emphasizing the importance of developing monitoring tools (tested prospectively in clinical trials) that can better determine the degree of platelet inhibition that is both safe and effective. Platelet function studies were developed originally for the evaluation of patients with unexplained bleeding and have contributed greatly to the understanding, diagnosis, and management of hereditary abnormalities such as von Willebrand disease and Glanzmann’s thrombasthenia (platelet glycoprotein [GP] IIb/IIIa receptor deficiency). Although conventional platelet function studies (turbidimetric aggregometry) have technical limitations that preclude their routine use for gauging antithrombotic therapy, they may provide guidance when hemorrhagic complications arise and in determining pretreatment risk in individuals suspected of having an intrinsic platelet abnormality. The bleeding time, considered an indicator of primary hemostasis (platelet plug formation), is defined as the time between making a small standardized skin incision and the precise moment when bleeding stops. The test is performed with a template, through which the medial surface of the forearm is incised under 40 mmHg standard pressure. A normal bleeding time is between 6 and 10 minutes. Although considered a “standardized” test of platelet function, the bleeding time can be influenced by a variety of factors, including platelet count, qualitative abnormalities, and features intrinsic to the blood vessel wall (George and Shattil, 1991). Platelet adhesion is the initiating step in primary hemostasis. Although platelet binding is an important component of this process, there are many others, including blood flow rate, endothelial cell function, adhesive proteins, and the subendothelial matrix. The original test used for assessing adhesion, platelet retention, was based on adherence to glass bead columns. The current laboratory evaluation of platelet function is based predominantly on turbidimetric platelet aggregometry (also known as light transmission aggregometry). This test is performed by preparing platelet-rich plasma (with platelet-poor plasma as a control) and eliciting an aggregation response with adenosine diphosphate, epinephrine, collagen, arachidonic acid, and ristocetin (Born, 1962).


2006 ◽  
Vol 95 (02) ◽  
pp. 224-228 ◽  
Author(s):  
Markus Hinder ◽  
Annke Frick ◽  
Ronald Rosenburg ◽  
Galina Hesse ◽  
Marie-Laure Ozoux ◽  
...  

SummaryThe pharmacokinetics, pharmacodynamics and safety of the direct factor Xa inhibitor, otamixaban, with and without concomitant acetylsalicylic acid (ASA) were investigated in healthy volunteers. The study was a double-blind, placebo-controlled 3-way crossover study. Sixty-eight male volunteers in total were randomised to otamixaban, ASA, or otamixaban with ASA. ASA (300 mg once a day) was started2 days before and continued on the day of the otamixaban 6-hour IV infusion (0.3 and 0.5 mg/kg). Pharmacokinetic and pharmacodynamic parameters (coagulation markers, platelet function tests and skin bleeding time) were determined. Drug interaction was assessed by the ratios of geometric means and 90 confidence intervals (90% CI)of the parameter estimates.Pharmacokinetic parameters of otamixaban remain ed unchanged with ASA. Ratios of geometric means (90% CI) were for Ceoi 96.54 (91.21–102.19) and 95. 04 (90. 10–100. 24) and for AUC 98. 0 (93. 92–102. 25) and 95. 90 (92. 61–99. 31), for 0. 3 and 0. 5 mg/kg, respectively. No drug interaction was observed between otamixaban andASA on the coagulation and platelet function parameters. Neither otamixaban nor ASA had an effect on skin bleeding time; their co-administration led toa slight prolongation of skin bleeding time above the normal range without any clinically relevant bleeding. This study demonstrated that the desired effects of otamixaban and ASA, namely anticoagulation and platelet inhibition, respectively, are maintained during co-administration of both drugs.


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