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Influence of hemostatic factors on spontaneous abortion.

To assess the relationship between hemostatic factors and spontaneous abortion, 134 pregnant women presenting to the emergency department were recruited and followed through 22 weeks' gestation. Cases were women experiencing a spontaneous abortion and controls were women who maintained their pregnancy. Fibrinogen, factor VII antigen, activated protein C-sensitivity ratio (APC-SR), protein S, and plasmin-antiplasmin (PAP) were measured. Cases had lower mean levels of fibrinogen and factor VII antigen compared with controls (3.1 g/L vs. 3.7 g/L and 89% of normal vs. 109% of normal, respectively). Regression analyses found that women with fibrinogen levels below 3.0 g/L had a five-fold increased risk of spontaneous abortion (OR = 5.1, 95% CI: 1.8-14.4) and women with factor VII antigen levels below 94% of normal had a threefold increased risk of spontaneous abortion normal (OR = 3.3, 95% CI: 1.2-8.5). Similar mean levels of APC-SR, protein S, and PAP were found in the two groups.

Abortion, Spontaneous↗

[Evaluation of a hemostatic device with percutaneous collagen application (VasoSeal) compared to a mechanical compression system (Compressar) after transfemoral catheterization of patients suffering from arterial occlusive disease].

PURPOSE: Comparison of the efficacy of VasoSeal and a mechanical compression system (Compressar) for percutaneous hemostasis after femoral arterial catheterization of patients with arterial occlusive disease. MATERIALS AND METHODS: 60 patients underwent either diagnostic angiography or interventional procedures. The level of anticoagulation, blood pressure, and activation clotting time were recorded, and the time to hemostasis after sheath removal was measured. VasoSeal application was considered "successful" if the compression time was less than two minutes. On the subsequent day as well as 4 months later, color coded Doppler ultrasound was performed to register treatment success and potential (late) complications. RESULTS: 57 patients qualified for inclusion in this study. In 21 of the 26 patients who underwent the procedure with the VasoSeal, immediate hemostasis was achieved within 1.75 minutes. In all 31 patients who had the Compressar applied, hemostasis was successful with a mean compression time of 17.4 minutes. Thus, VasoSeal significantly reduced hemostasis time irrespective of anticoagulation status, but it had a much higher incidence of minor local complications (bleeding, hematoma) compared to the control group (34.6 % vs. 5.8 %). The technical success was lower with VasoSeal than with Compressar (81 % vs. 100 %). Both groups had no severe or late complications. CONCLUSION: According to our results, VasoSeal does not provide a suitable alternative compared to the effective, safe and cheap application of Compressar as a hemostatic device.

Adult↗

Evaluation of hemostatic and fibrinolytic alterations associated with daily administration of low-molecular-weight heparin for a 12-week period.

The PTCA procedure fails in 30-50% of patients due to late restinosis, meaning that this is a problem of 100,000-150,000 people per year in the USA alone. It has been found that heparin and low-molecular-weight heparin (LMWH) have an inhibitory effect on smooth muscle cell (SMC) proliferation and migration, the major causes of restinosis. However, little is known about the toxicity and side effects of these drugs when used for a long period as may be required for prophylaxis of PTCA restinosis. To investigate possible side effects, non-human primates received daily injections of 1 mg/kg s.c. LMWH (Mono-Embolex) over a 12-week period. The hemostatic system was monitored through measurement of ACT-celite, APTT, Heptest, TT(10U/mL), TFPI, Anti-IIa activity, Anti-Xa activity, ACA-Heparin, AT III, factor VIII R:Ag, fibrinogen, and thrombomodulin levels. Elisa tests for t-PA, PAI-1, u-PA, FgDP, TDP, and D-Di levels were used for measurements of fibrinolytic activity. Increased values of ACT, APTT, Heptest, TT, Anti-IIa, Anti-Xa, ACA-Heparin, and TFPI were observed four hours after LMWH injections. AT III, vWFAg, fibrinogen and thrombomodulin showed no change from the pre-study baseline. An accumulation effect was seen in the APTT and Heptest over the 12 weeks. After the first week the blood levels of Anti-IIa activity remained elevated at 20% inhibition rather than 0% 24 hrs after drug administration. This activity slowly decreased after discontinuation of drug. The Anti-Xa blood level activity remained elevated at 40% inhibition 24 hrs after drug administration 2 weeks into the study, and this activity was detectable even 2 weeks after cessation of drug administration. There was increasing activity of the fibrinolytic system with LMWH treatment. After two weeks t-PA increased two-fold to 6 ng/mL but returned to baseline at six weeks. There was a corresponding increase of the TDP but not a clear increase in D-Di and FgDP. The increase of u-PA was limited to the first days of LMWH treatment only. The PAI-1 activity increased gradually over the entire study period. No bleeding complications occurred throughout the study. The long-term administration of Mono-Embolex as projected for the use in the prophylaxis of restinosis following PTCA appears to be safe for patients.

Animals↗

Comparison of the hemostatic effect of endoscopic injection with fibrin glue and hypertonic saline-epinephrine for peptic ulcer bleeding: a prospective randomized trial.

BACKGROUND AND STUDY AIMS: Although endoscopic injection therapy using various agents has been considered the least expensive and most effective technique in obtaining hemostasis in peptic ulcer bleeding, most of these agents induce tissue necrosis or degeneration. Theoretically the injection of fibrin glue (FG) to halt peptic ulcer bleeding may be safer than the use of other agents, but randomized clinical trials to compare the efficacy of FG and other agents are rare. The aim of this study was to compare the hemostatic efficacy between FG and hypertonic saline-epinephrine (HSE) in peptic ulcer bleeding. PATIENTS AND METHODS: From March 1992 to December 1993 we conducted a prospective randomized trial in 127 patients with peptic ulcer bleeding, in whom a visible vessel or active bleeding was identified. Patients were randomized into two groups, an FG group comprising 64 patients who received FG injections, and an HSE group, comprising 63 patients who received HSE injections. RESULTS: The two groups were comparable with regard to age, sex, bleeding focus and bleeding stigma. Permanent hemostasis using only endoscopic treatment was achieved in 59 cases (92.2 %) in the FG group and in 54 cases (85.7 %) in the HSE group. Rebleeding occurred in seven cases (10.9%) in the FG group and in 14 cases (22.2%) in the HSE group (P=0.087); emergency surgery was undertaken in four (6.3%) and seven cases (11.1%), respectively (P = 0.33); death occurred in one case (1.6%) and four cases (6.3%), respectively (P = 0.165). CONCLUSIONS: These results suggest that endoscopic injection of FG is an effective method in the control of peptic ulcer bleeding. However, even though there is a strong trend supporting the hypothesis that fibrin glue is superior to HSE, no statistically significant differences are noted. A trial involving larger numbers may produce a positive result.

Epinephrine↗

The healing process of experimentally produced bleeding lesions after hemostatic electrocoagulation with simultaneous instillation of water.

Fifty experimentally induced, standardized gastric bleeding lesions were successfully arrested in the dog using electrocoagulation with simultaneous instillation of water (EHT-coagulation). The contact pressure of the coagulating electrode was kept almost constant by means of a spring mechanism. The coagulated lesions healed without secondary enlargement of the coagulation effect and without complication. No secondary perforations were observed. Even when coagulation was carried out at an output power about 30% higher than the mimimum power necessary for reliable hemostatic coagulation, no complications were observed. Only with additional post bleeding arrest coagulation in excess of 10 seconds at this higher output, were two primary performations produced in 2 out of 12 cases. The non-perforated remaining 10 lesions healed without complication. With additional coagulation (at power output setting 6 for 20 seconds - 8 cases; at power setting 7 for 10 seconds - 6 cases), no perforations were observed and healing was without complications. Thus, in animal experiments, the therapeutic range for the arrest of bleeding using the electro-hydro-thermo-electrode is adequately large. The technique should be tested in clinical trials.

Animals↗

Antitumor effect of oxycellulose as a hemostatic during operation.

Oxycellulose, a hemostatic agent used in operation showed antitumor effect in vitro on a murine hepatic cell carcinoma (MH 134), a murine fibrosarcoma (Meth A) and a murine colon carcinoma (Colon 26). The effect was also confirmed in vivo by the survival of mice inoculated with Meth A or MH 134. Eighty milligrams per mouse of this agent, however, showed a toxicity rather than an antitumor effect. The antitumor effect of oxycellulose on Meth A did not compare with that of etoposide or mitomycin C in vivo. The antitumor effect on MH 134 was equal to that of etoposide but not mitomycin C. Oxycellulose inhibited tritium thymidine uptake into Colon 26 cells to the same extent as 5-fluorouracil and mitomycin C and it caused 51Cr-labelled Colon 26 cells but not from 5-fluorouracil or mitomycin C. Oxycellulose decreased a larger number of viable tumor cells than 5-fluorouracil or mitomycin C when the tumor cells were incubated for 24 hours at 37 degrees C. DNA histogram with MH 134 cells showed oxycellulose decreased a ratio of tumor cells in S-phase. These results suggest that the antitumor effect of oxycellulose is cytocidal and phase-specific.

Animals↗

Tubeless percutaneous nephrolithotomy using hemostatic gelatin matrix.

We describe using hemostatic gelatin matrix (FloSeal; Baxter Inc., Irvine, CA) to provide hemostasis of the tract after percutaneous nephrolithotomy, thereby obviating a nephrostomy tube. For patients who are rendered stone free, a 7F, 11.5-mm occlusion balloon catheter, passed retrograde, is used to occlude the collecting system at the level of entry of the 30F Amplatz sheath. FloSeal is then injected through the partially retracted Amplatz sheath while withdrawing the applicator and the sheath in tandem. The guidewire is withdrawn per urethra until its tip resides in the renal pelvis. A 36-cm, 7F tail stent is passed retrograde, and the skin is closed with cyanoacrylate adhesive (Ethicon, Somerville, NJ). A Foley catheter is placed, to be removed the next morning; the patient can be discharged on postoperative day 1. The ureteral stent is removed in 5 to 7 days as an outpatient procedure.

Balloon Occlusion↗

Hemostatic evaluation in bleeding disorders from native blood. Clinical experience with the hemostatometer.

Primary hemostasis (PH), i.e., hemostatic platelet plug formation, and the subsequent coagulation were recorded and quantified from the same nonanticoagulated venous blood sample with the use of the Haemostatometer. In addition, platelet thrombus formation induced by interaction of flowing native blood with a collagen fiber under low shear rates (450 s-1) was simultaneously analyzed by this device. The effect of monoclonal antibodies (MoAbs) directed against von Willebrand's factor antigen (vWF:Ag), platelet glycoprotein Ib (GPIb) and the GPIIb/IIIa complex, and fibrinogen were studied. PH was significantly inhibited by MoAbs against vWF:Ag, GPIIb/IIIa, and fibrinogen but was unaffected by antibody against GPIb. Collagen-induced thrombosis was prevented by MoAbs against vWF:Ag and GPIb, slightly inhibited by antifibrinogen, and unaffected by blockage of platelet membrane GPIIb/IIIa. The effect of a single 600-mg dose of aspirin was monitored, and abnormal PH was still detectable five days later. From the 13 hemophiliacs tested, 7 showed significantly prolonged PH. In von Willebrand's disease, a characteristic defect of PH with significant inhibition or absence of collagen-platelet interaction was observed in all the 11 patients. PH was greatly prolonged in both of the two patients with storage pool deficiency. The technique detected improvement of platelet function, i.e., PH in all of six patients with bleeding disorders after replacement therapy or DDAVP infusion. The authors conclude that the Haemostatometer technique is a sensitive test for determining platelet dysfunction and monitoring efficacy of factor-replacement or DDAVP therapy.

Adult↗

The hemostatic effect of conjugated water-soluble estrogens in rats.

Estrogenic steroids have been used as hemostatic agents in various surgical procedures in humans. Their use to reduce bleeding has been based mainly on clinical observation. The present study was carried out to test experimentally whether intravenously administered Premarin reduces capillary bleeding. Skin-graft donor sites in rats served as the standard capillary bleeding source in this controlled double-blind experiment, in which Premarin was found to appreciably reduce capillary bleeding.

Animals↗

The effectiveness of a fibrinogen-thrombin-collagen-based hemostatic agent in an experimental arterial bleeding model.

The hemostyptic agent used in this study is a recently developed material that consists of a collagen fleece containing fibrinogen, thrombin, and aprotinin integrated into its surface (FTCH) with excellent topical hemostyptic properties. The potential use of this substance for cardiovascular surgery was evaluated in a canine arterial bleeding model, which allowed comparison of the new agent with previously used pure collagen (CHF) as well as study of the hemostyptic under elevated blood pressure conditions. The results revealed that FTCH induced reliable hemostasis in 10-mm injuries of the canine hypogastric artery up to a systolic blood pressure of 260 mmHg, whereas bleeding control by CHF alone was impossible. To assess the long-term reliability of FTCH, the dogs were re-explored at intervals of 14 and 31 days after operation. At relaparotomy, the arteries were patent and there was no evidence of recurrent bleeding, thrombosis formation, or aneurysmatic changes. Histologic examinations showed well-healed vascular lesions covered by cell-depleted collagen tissue and a partially resorped hemostyptic. FTCH will not replace adequate surgical techniques but could be useful as a quickly available and easily applicable hemostatic means in otherwise uncontrollable diffuse or acute bleeding in cardiovascular surgery.

Animals↗

Management of middle meningeal and superficial temporal artery hemorrhage from total temporomandibular joint replacement surgery with a gelatin-based hemostatic agent.

Complications associated with temporomandibular joint (TMJ) replacement surgery may include injury to nerves, blood vessels, and otologic structures. Vascular injuries can be associated with trauma to the carotid artery and its terminal branches, the superficial temporal artery, and the internal maxillary artery. Suggested management to control hemorrhage has included uniand bipolar electrocautery, laser ablation, local anesthetics with vasoconstrictors, direct pressure, embolization, and ligation. In this case report, the iatrogenic injury to both the middle meningeal and superficial temporal arteries during total TMJ replacement surgery controlled by using a gelatin-based hemostatic agent is discussed.

Adult↗

Hemostatic and fibrinolytic parameters in survivors of myocardial infarction: a low plasma level of plasmin-alpha2-antiplasmin complex is an independent predictor of coronary re-events.

Abnormalities of coagulation or fibrinolysis play a role in the pathogenesis of coronary artery disease (CAD). Elevated plasma levels of fibrinogen, von Willebrand factor antigen, plasminogen activator inhibitor-1 and tissue-type plasminogen activator were reported to be predictive for reinfarction and death in patients with CAD. We investigated the risk for coronary re-events associated with 18 hemostatic and fibrinolytic parameters in a prospective study including 200 survivors of myocardial infarction (MI). During a 2-year follow-up, 37 patients suffered one of the following predefined re-events: fatal MI (n = 2), non-fatal MI (n = 5), percutaneous transluminal coronary angioplasty (n = 17) or coronary artery bypass grafting (n = 13). Low plasmin-alpha2-antiplasmin complex (PAP) plasma levels were associated with an up to fivefold (95% confidence interval, 1.6-15.3) increase in relative risk. The association between decreasing PAP levels and coronary re-events remained significant (P = 0.004) after correction for possible confounders using multiple logistic regression analysis. Our data indicate low PAP plasma levels to be associated with subsequent coronary events in patients with a history of MI.

Adult↗

Hemostatic effect of glue-lipiodol mixture plugged in the needle tract after renal biopsies in a high-risk, anticoagulated rabbit model.

RATIONALE AND OBJECTIVES: To investigate the hemostatic effect of a glue-lipiodol mixture plugged immediately into the needle tract after renal biopsy of high-risk, anticoagulated rabbits by use of a large-core gun biopsy needle and the subsequent pathological changes of the biopsy tract. METHODS: Twenty-five rabbits weighing 2 kg were divided into five groups (five rabbits each) according to time of sacrifice at 0, 2, 4, 6, and 8 days after biopsy. After anesthesia was induced, both kidneys were exposed and a bolus of 100 U/kg heparin was administered intravenously. Blood sampling was done twice, once before and once after heparinization, and activated partial thromboplastin times were measured for each. Then renal biopsies were performed in 25 pairs of kidneys by using an 18-gauge automated biopsy gun. The glue-lipiodol mixture was not injected into the first biopsy sites (control). Immediately after the second biopsies were done, 0.5 mL of the glue-lipiodol mixture at a 1:3 ratio was plugged into the needle tract through the outer cannula while withdrawing it slowly. Bleeding times of the two biopsies of each pair of kidneys were measured. All rabbits were humanely killed at their previously scheduled times, and histopathological findings were evaluated for the presence of inflammation, necrosis, foreign body reaction, and fibrosis around the biopsy tract. All parameters were classified into four categories according to the degree of severity, from 0 to + + +. RESULTS: Twenty-five cases (100%) of the controls bled after the biopsies were performed. Four of them (16%) showed immediate, massive, pulsatile bleeding. In contrast, only 11 of 25 cases (44%) bled at the second biopsy (plugged) sites and only two of them (8%) showed pulsatile bleeding. Mean bleeding times were 228 seconds in controls and 26 seconds in the glue-lipiodol mixture-plugged sites (P < 0.000). Histopathological examination of the needle tract in the plugged group revealed mild inflammation in the 0- to 2-day groups and moderate inflammation and mild necrosis in the 4- and 6-day groups. In the 8-day group, inflammation was diminished and only mild fibrosis was noted. There was no foreign body reaction in any of the specimens of the plugged group. CONCLUSIONS: We conclude that a glue-lipiodol mixture, when used as a plug material for the renal biopsy tract, is an efficacious method of bleeding control that is associated with a low incidence of pathological alterations in an anticoagulated rabbit model, thus demonstrating its future potential for clinical application.

Animals↗

Application of a granular mineral-based hemostatic agent (QuikClot) to reduce blood loss after grade V liver injury in swine.

BACKGROUND: Uncontrolled hemorrhage is a leading cause of death in cases of trauma. Many products currently are under development to control traumatic bleeding. One such Food and Drug Administration (FDA)-approved product is QuikClot. This study determined the efficacy of QuikClot, a hemostatic agent, in reducing blood loss and mortality in a standardized model of severe liver injury as well as the consequences of its use. METHODS: Swine received either QuikClot or gauze treatment after induction of grade V liver injuries. Hemostasis, blood loss, resuscitation volume, 60-minute survival, and peak tissue temperatures were measured. RESULTS: Hemostasis was improved with QuikClot (p < 0.05), and resuscitation volume was consequently reduced (p < 0.05). Posttreatment blood loss was reduced (p < 0.01) with QuikClot (1,397 mL), as compared with gauze (5,338 mL). The survival rate was seven of eight in the QuikClot group and one of eight in the gauze group (p < 0.01). Peak temperature at the tissue interface was increased (p < 0.01) with QuikClot (93.3 +/- 10.5 degrees C), as compared with gauze (37.5 +/- 6.5 degrees C). QuikClot use was associated with both macro- and microscopic tissue damage caused by the exothermic reaction. CONCLUSION: QuikClot provides hemostasis and decreased mortality in this model of severe liver injury. The beneficial aspects of QuikClot treatment must, however, be balanced against the tissue-damaging effects of the exothermic reaction.

Animals↗

Hemostatic efficacy of two advanced dressings in an aortic hemorrhage model in Swine.

BACKGROUND: An effective hemostatic agent capable of stopping severe arterial bleeding and sustaining hemostasis over a prolonged time is required. The U.S. Army recently distributed fibrin sealant (under an Investigational New Drug-approved protocol) and chitosan dressings among deployed medics for treating severe external hemorrhage on the battlefield. The purpose of this study was to evaluate the efficacy of these dressings, as compared with the standard gauze army field dressing, to provide initial and sustained hemostasis up to 96 hours in a lethal uncontrolled arterial hemorrhage model. METHODS: Anesthetized pigs were splenectomized and chronically instrumented for fluid/drug administration and continuous monitoring of vital signs. An infrarenal aortotomy was created using a 4.4-mm aortic hole punch and free bleeding was allowed for 5 seconds. While bleeding profusely, a dressing was applied and pressed into the wound for 4 minutes (occluding the distal flow) and then released. If hemostasis was not obtained, the dressing was replaced with a new one (maximum, two dressings per experiment) with another 4-minute compression. If hemostasis was achieved, the abdomen was closed; the animal was then recovered and monitored up to 96 hours. Initial hemostasis, duration of hemostasis, survival time, blood loss, and other variables were measured. RESULTS: Application of army field dressing (gauze) did not stop the arterial hemorrhage and led to exsanguination of all the pigs (n = 6) within 10 to 15 minutes of the injury. Chitosan dressing produced initial hemostasis in five of seven pigs. However, the dressings failed to maintain hemostasis for more than 1.6 hours (range, 28-102 minutes), resulting in secondary bleeding and death of the animals. Fibrin sealant dressing produced initial hemostasis in all the pigs (n = 6) and maintained hemostasis in five cases, with one failure at 2.2 hours. These pigs resumed normal activities and lived for the 96-hour experiment duration. Computed tomographic images and histologic sections of the aortas from surviving fibrin sealant dressing-treated animals showed formation of pseudoaneurysms and early granulation tissue at the aortotomy site. The posttreatment blood loss, duration of hemostasis, and survival time were significantly different in the fibrin sealant dressing group than the chitosan dressing and army field dressing groups. CONCLUSION: Both chitosan dressing and fibrin sealant dressing stopped initial arterial bleeding that could not be controlled by the standard army field dressing. However, although the fibrin sealant dressing secured hemostasis for up to 4 days, the chitosan dressing consistently failed within 2 hours after application. There may be a risk of rebleeding for high-pressure arterial wounds treated with chitosan dressings, particularly in situations where definitive care is delayed substantially.

Analysis of Variance↗

Recombinant factor VIIa (NovoSeven) as a hemostatic agent after surgery for congenital heart disease.

BACKGROUND: Postoperative bleeding and blood product requirements can be substantial in children undergoing open-heart surgery, and reexploration is required in 1% of cases. Recombinant activated factor VII (rFVIIa, NovoSeven, NovoNordisk, Denmark) is a hemostatic agent approved for the treatment of hemophilic patients with inhibitors to factor VIII or factor IX. It has also been used with success in other conditions. We present our experience with rFVIIa treatment for uncontrolled bleeding after open-heart surgery in five pediatric patients. METHODS: The study group consisted of five patients after open-heart surgery with excessive blood loss. The patients were treated with rFVIIa after failure of conventional treatment to control the bleeding. Blood loss, blood product consumption, and coagulation test results were recorded before and after rFVIIa administration. RESULTS: In all cases, blood loss decreased considerably after rFVIIa administration (mean 7.8 ml x kg(-1) x h(-1)), almost eliminating the need for additional blood products, and the prolonged prothrombin time normalized. In two patients with thrombocytopathy, rFVIIa helped to discriminate surgical bleeding from bleeding caused by a defect in hemostasis. No side effects of rFVIIa treatment were noted. CONCLUSIONS: These cases support the impression that RFVIIa is efficient and safe in correcting hemostasis in children after cardiopulmonary bypass when other means fail. However, the data are still limited, and more extensive research is needed.

Adolescent↗

The hemostatic agent ethamsylate promotes platelet/leukocyte aggregate formation in a model of vascular injury.

The hemostatic agent ethamsylate enhances membrane expression of P-selectin in human platelets, but whether this promotes platelet-leukocyte aggregate formation is unknown. Here we investigated this point by flow cytometry determination of human platelet-leukocyte aggregates under basal conditions and after whole-blood perfusion through a damaged rabbit aorta segment. Actions of ethamsylate on adhesive molecules of platelets and leukocytes were investigated in parallel. Under basal conditions, ethamsylate was unable to modify whole-blood platelet-leukocyte aggregation, but following whole-blood perfusion through a damaged vessel, ethamsylate produced a modest, but significant increase in platelet-leukocyte aggregates (48+/-21 and 45+/-26% above control levels at ethamsylate 20 and 40 microm respectively). In isolated leukocyte plasma membranes, 14C-ethamsylate specifically bound up to an amount of 660 pmol/mg protein. Moreover, at concentrations > or =1 microm, ethamsylate induced an important (100-200%) and significant increase in the P-selectin glycoprotein ligand 1 (PSGL-1) fluorescence signal in isolated leukocytes and was unable to significantly modify the percentage of CD11b-positive cells. However, no significant changes in aggregate formation were found when ethamsylate was incubated with isolated leukocytes and blood was reconstituted and perfused. In isolated platelet cell membranes, anti-P-selectin antibody and the anti-integrin RGD-containing pentapeptide (GRDGS) were unable to displace 14C-ethamsylate binding. In conclusion, ethamsylate specifically binds to plasma membranes of leukocytes, enhances membrane PSGL-1 expression and promotes leukocyte-platelet aggregation in whole-blood perfused through a damaged vascular segment. These results together with the previously observed enhancement of platelet P-selectin membrane expression [Thromb. Res. (2002)107:329-335] confirms and extends the view that ethamsylate acts on the first step of hemostasis, by improving platelet homo- and heterotypic adhesiveness.

Animals↗

The plasma hemostatic proteome: thrombin generation in healthy individuals.

BACKGROUND AND OBJECTIVES: The range of plasma concentrations of hemostatic analytes in the population is wide. In this study these components of blood coagulation phenotype are integrated in an attempt to predict clinical risk. METHODS: We modeled tissue factor (TF)-induced thrombin generation in the control population (N = 473) from the Leiden Thrombophilia Study utilizing a numerical simulation model. Hypothetical thrombin generation curves were established by modeling pro- and anticoagulant factor levels for each individual. These curves were evaluated using parameters which describe the initiation, propagation and termination phases of thrombin generation, i.e. time to 10 nm thrombin (approximate clot time), total thrombin and the maximum rates and levels of thrombin generated. RESULTS AND CONCLUSIONS: The time to 10 nm thrombin varied over a 3-fold range (2.9-9.5 min), maximum levels varied over a approximately 4-fold range (200-800 nm), maximum rates varied approximately 4.8-fold (90-435 nm min(-1)) and total thrombin varied approximately 4.5-fold (39-177 microm s(-1)) within this control population. Thrombin generation curves, defined by the clotting factor concentrations, were distinguished by sex, age, alcohol consumption, body mass index (BMI) and oral contraceptive (OC) use (OC > sex > BMI > age). Our results show that the capacity for thrombin generation in response to a TF challenge may represent a method to identify an individual's propensity for developing thrombosis.

Adult↗