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PubMed2002

Hemostatic effects induced by Thalassophryne nattereri fish venom: a model of endothelium-mediated blood flow impairment.

Accidents by Thalassophryne nattereri fish venom are characterised by severe local symptoms and signs including pain of fast onset, oedema and necrosis with impaired muscle regeneration. These effects have been related to alterations in hemostatic mechanisms and cytolytic effects rather than to conventional inflammatory pathways. In this work we evaluated the effects induced by the venom on microcirculatory vessels, platelets and blood coagulation. Effects evoked by topical application of venom on cremaster muscle were visualised through intravital microscopy. Stasis was observed, concomitantly with the presence of thrombi in venules and focal transient constrictions in arterioles, all of which impaired the blood flow. Significant alterations on vessel walls took place few minutes after venom application, characterised by increment in thickness, probably by deposition of fibrin. Increase in vascular permeability was also observed in venules. Additionally, the action of the venom was locally restricted since no alteration on systemic blood coagulation was observed. Venom lacked a direct pro-coagulant activity, but exerted a strong cytolytic effect on platelets and endothelial cells in vitro. These data suggest that venom action on endothelium may contribute to blood stasis and to the formation of platelet and fibrin thrombi, with the consequent ischemia, contributing to the local effects of the venom.

Animals↗
PubMed2001

Hemostatic laparoscopic partial nephrectomy: initial experience with the radiofrequency coagulation-assisted technique.

OBJECTIVES: The techniques for hemostasis after renal tumor excision have limited the widespread application of laparoscopic partial nephrectomy (LPN). To improve hemostasis and aid visualization, we report our experience with a novel radiofrequency coagulation (RFC) technique for LPN. METHODS: Ten patients underwent RFC-assisted LPN. The demographic and perioperative data were tabulated. Patients were positioned as for laparoscopic nephrectomy, and laparoscopic ports were placed. The kidney within Gerota's fascia was mobilized, and the fat overlying the tumor was carefully removed for pathologic evaluation. Under laparoscopic guidance, a radiofrequency probe was percutaneously inserted into the lesion and deployed to coagulate the lesion and a margin of normal parenchyma. Laparoscopic scissors were used to excise the lesion; additional hemostatic maneuvers were used selectively. RESULTS: The mean renal tumor size was 2.1 cm (range 1.0 to 3.2). The median operative time was 170 minutes and the median blood loss was 125 mL. The RFC technique resulted in complete tissue coagulation within the treated volume, thereby facilitating intraoperative visualization, minimizing blood loss, and permitting rapid and controlled tumor resection. The renal architecture was preserved, allowing accurate diagnosis of renal cell carcinoma and angiomyolipoma in 9 and 1 cases, respectively. No perioperative complications occurred. CONCLUSIONS: The use of RFC is an effective method to facilitate LPN of both exophytic and endophytic masses. By coagulating a margin of normal parenchyma, the technique minimizes blood loss and improves visualization during LPN. We anticipate this technique will broaden the clinical application for LPN.

Adult↗
PubMed1989

Effects of two hemostatic agents on osseous healing.

The effects of Adaptic and Avitene on bone healing were evaluated histologically. The studied materials were placed in osseous defects created in rat tibias with a #8 round bur in a slow-speed handpiece. The materials were left in situ for experimental periods of 7, 14, 28, 60, 90, and 120 days. Histological evaluation of specimens from each of these periods demonstrated that Avitene was resorbed and did not impede bone healing. Adaptic was not resorbed at the end of the longest experimental period, 120 days. This material caused a foreign body reaction characterized by encapsulation of the Adaptic by fibrous connective tissues. Both Adaptic and Avitene were satisfactory hemostatic agents. The results of this study suggest that Adaptic should be used only in those situations where complete retrieval of the material from surgical sites can be assured.

Animals↗
PubMed1989

Hemostatic effects of air versus fluid in diabetic vitrectomy.

The potential hemostatic effect of an intravitreal air bubble after diabetic vitrectomy was studied in an animal model and in a randomized clinical trial. One day after vitrectomy with induced intraoperative hemorrhage, vitreous cavity hemorrhage was present in 60% of air-filled rabbit eyes compared with 27% of fluid-filled eyes. The prevalence and extent of hemorrhage was equal in the two groups on postoperative days 3 and 7. In a clinical trial of 51 eyes undergoing diabetic vitrectomy, 70% of eyes randomized to air-filled vitreous cavity after vitrectomy had vitreous cavity hemorrhage on postoperative day 1 compared with 50% of fluid-filled eyes. At 1 week, the incidence of hemorrhage was 78% for air and 61% for fluid. The 6-month visual and anatomic results were similar in both groups. These findings suggest that an intravitreal air bubble neither improves hemostasis nor reduces the visual outcome after diabetic vitrectomy.

Adult↗
PubMed1997

Tissue reaction to three subcutaneously implanted local hemostatic agents.

Soft tissue response to three subcutaneously implanted local hemostatic agents; oxidised regenerated cellulose (Surgicel), gelatin sponge (Spongostan) and collagen sponge (Hemostagen) were evaluated histopathologically 7, 14, 21, 30 and 45 days following their implantation in rats. The results showed that all materials were well tolerated by soft tissues. These materials neither seemed to impair nor contribute to wound healing.

Animals↗
PubMed1985

Hemostatic abnormalities in renal disease.

Numerous hemostatic abnormalities have been associated with acute and chronic renal disease. The most common abnormalities are defective platelet aggregation, decreased platelet adhesiveness, decreased platelet factor-3 availability, and prolongation of the bleeding time. Among the above platelet function tests, the bleeding time is the single test that most closely correlates with clinical bleeding. The nature of the platelet defect in uremia is still not well understood. The pathophysiologic mechanisms which have been implicated include platelet inhibition by plasma metabolites, eg, urea, guanidinosuccinic acid, phenolic acid; increased vessel wall prostacyclin; abnormal platelet arachidonic acid metabolism; increased levels of parathyroid hormone (PTH); defective binding of the Factor VIII complex to platelets or defective binding of platelets to vessel wall subendothelium by the Factor VIII complex; decreased platelet-vessel wall-interaction due to severe anemia; platelet storage pool deficiency; defective fibrinogen binding to platelets. Dialysis remains the mainstay of the prevention and treatment of uremic bleeding although it is not always immediately effective. The availability of cryoprecipitate and DDAVP offers an alternative and effective treatment for the temporary reversal of uremic bleeding in patients who require urgent invasive procedures.

Bleeding Time↗
PubMed1981

The importance of local hemostatic procedures in dental extractions and oral mucosal bleeding of hemophiliac patients.

Deficient coagulation factor replacement therapy is often indispensable for dental extractions and oral mucosal bleeding in hemophiliac patients. High concentrates are often infused in large amounts of volume, until complete hemostasis is achieved. Considering the various side effects of replacement therapy the volume infused should be reduced to a minimum. Several aspects associated with replacement therapy for the control of oral bleeding are studied. Our conclusion is that local hemostatic procedures are even more important than replacement therapy. The use of surgical packs and band retainers proved to be of benefit in this study.

Adolescent↗
PubMed1997

Hemostatic efficacy of a fibrin sealant-based topical agent in a femoral artery injury model: a randomized, blinded, placebo-controlled study.

PURPOSE: The efficacy of currently available topical hemostatic agents requires the formation of fibrin generated from circulating blood. Fibrin sealant, which is prepared from high concentrations of thrombin and fibrinogen, has been used in liquid form to promote hemostasis during vascular surgery. In a blinded, randomized, placebo-controlled fashion, we evaluated a dry dressing of purified, viral-inactivated human fibrinogen and human thrombin in a large animal model of arterial injury. METHODS: Dressings were prepared by application of a layer of lyophilized human fibrin sealant or immunoglobulin G (IgG, control) to a silicone backing material. Six anesthetized female Yorkshire pigs (16 to 27 kg) received bilateral, 4 mm longitudinal femoral arteriotomies after surgical exposure of the arteries. The arteriotomies were not closed. In each animal a fibrin sealant dressing was applied to one artery and a control dressing to the other. Each dressing was secured on the arteriotomy by a mechanical device. After application of the dressings, blood flow was restored to each limb for 1 hour. The compressive device was released for 5 seconds at intervals of 15 minutes to assess hemostasis. Blood flow was measured distal to each arteriotomy with a dual-channel flowmeter to adjust equal bilateral compression. RESULTS: Blood loss (mean +/- SEM) was significantly less from the arteriotomy treated with the fibrin-based dressing compared with the control dressing (4.9 +/- 4.0 ml versus 82.3 +/- 11.1 ml; p = 0.0005). Complete hemostasis was achieved at the first 15-minute interval in five of six arteriotomies treated with fibrin sealant and in none of the six control arteriotomies during 1 hour of assessment (p = 0.03). Blood flow through each femoral artery at baseline was the same in both treatment and control arteries (fibrin sealant, 114.2 +/- 17.4 ml/min; control, 106.7 +/- 16.5 ml/min; p = 0.24) and was not significantly different throughout the experiment. CONCLUSIONS: Fibrin-based dressings provide effective hemostasis in a large animal model of arterial injury. Further development of these dressings will address optimal formulation and configuration for clinical use. Our results suggest that fibrin-based dressings will be effective in promotion of hemostasis in arterial bleeding, without compromising blood flow.

Animals↗
PubMedDate not supplied

Use of fibrin sealant as a hemostatic agent after liver biopsy in swine.

PURPOSE: To determine whether fibrin sealant injected into the tract created by liver biopsy can be used to decrease postprocedural bleeding. An innovative delivery system was used to deploy the fibrin sealant. MATERIALS AND METHODS: Fibrin sealant is a hemostatic agent consisting of a suspension of fibrinogen and thrombin. A delivery system was devised whereby fibrin sealant could be injected into the tract created by liver biopsy. Thirty swine were randomized into three groups: control (n = 10), heparin (n = 10), and warfarin (n = 10). Each swine underwent laparotomy and was randomized to undergo three to five open liver biopsies with either a 14-gauge cutting needle in conjunction with the fibrin sealant device or a standard 14-gauge cutting needle alone. Forty-seven biopsy procedures were performed with the device; 64 biopsy procedures were performed without the device. Immediate blood loss per biopsy (mL) was estimated based on the size of the blood stain on a sponge. Specimens were assessed for sample size. RESULTS: Immediate blood loss with and without the device, respectively, was: control, 0.1 mL, 5.4 mL; heparin, 0 mL, 7 mL; warfarin, 0.1 mL, 9.3 mL. These differences were significant (P < .01) for each group of swine. In 43 of 47 biopsies (91%), the device functioned without difficulty. There was no difference in sample size when the device was used. CONCLUSIONS: The fibrin sealant device is effective in reducing bleeding after open liver biopsy in anticoagulated and nonanticoagulated swine. The promising results suggest that a trial of percutaneous liver biopsy in swine should be considered.

Animals↗
PubMed1997

A pump-prime aprotinin dose in cardiac surgery: appraisal of its effects on the hemostatic system.

OBJECTIVES: To examine pump-prime aprotinin action on coagulation and fibrinolysis in patients undergoing primary coronary revascularization. DESIGN: A prospective randomized study. SETTING: A university hospital. PARTICIPANTS: Forty-three patients were randomly assigned to either group A, 21 patients treated with 2 x 10(6) kallikrein inhibitor units (KIU) of aprotinin in the cardiopulmonary bypass (CPB) prime, or group B, 22 patients, untreated. INTERVENTIONS: Patients, scheduled for elective coronary surgery, were treated with 2 x 10(6) KIU of aprotinin in the CPB prime. Markers of coagulation and fibrinolysis were evaluated. MEASUREMENTS AND MAIN RESULTS: Surgical times, number of reopenings, and allogeneic blood requirements were collected for each patient. Blood samples were obtained before and after surgery for assessing coagulation (prothrombin time [PT], activated partial thromboplastin time [aPTT], ethanol test, factor VII, antithrombin III [AT III], thrombin-antithrombin III complex [TAT], fragment 1.2 of prothrombin [F1.2]) and fibrinolysis (fibrin degradation products [FOP], plasmin-antiplasmin complexes [PAP], D-dimers) markers variations. In group A surgical times were faster, there were fewer reopenings (0 v 3), and fewer blood transfusions (1 patient v 4 patients). The two groups did not differ for PT, aPTT, and fibrinogen measurements. Postoperative FDP (measurable in more patients of group B at the end of the operation), PAP, and D-dimers postoperatory levels (less increased in aprotinin group) show the antifibrinolytic properties of the drug. Regarding the coagulation markers, factor VII decreased, whereas TAT and F1.2 increased, all to a lesser extent in the aprotinin group compared with the untreated patients, at the end of operation. CONCLUSION: Pump-prime aprotinin minimized, even if not completely inhibited, the activation of coagulation and fibrinolysis during CPB, possibly ensuring a less complicated and safer postoperative recovery. It seemed to allow the maintenance of a correct balance of hemostatic systems, avoiding the risk of thrombotic phenomena.

Adult↗
PubMed1999

Dental extractions in patients maintained on continued oral anticoagulant: comparison of local hemostatic modalities.

OBJECTIVE: The purpose of this study was to evaluate postoperative bleeding in patients treated with oral anticoagulant drugs who underwent dental extractions without interruption of the treatment and to compare the effect of 3 different hemostatic modalities. STUDY DESIGN: A total of 150 patients who underwent dental extractions were divided into 3 groups. Local hemostasis was carried out as follows: group 1 (119 extractions), with gelatin sponge and sutures; group 2 (117 extractions), with gelatin sponge, sutures, and mouthwash with tranexamic acid; group 3 (123 extractions), with fibrin glue, gelatin sponge, and sutures. RESULTS: Of 150 patients, 13 (8.6%) presented with postoperative bleeding: 3 patients from group 1, 6 patients from group 2, and 4 patients from group 3. CONCLUSIONS: Dental extractions can be performed without interruption in patients treated with oral anticoagulant. Local hemostasis with gelatin sponge and sutures is sufficient.

Administration, Oral↗
PubMed2004

Recombinant-activated factor VII as hemostatic therapy in eight cases of severe hemorrhage from esophageal varices.

BACKGROUND AND AIMS: There are several treatment options for gastroesophageal variceal hemorrhage. In severe cases, bleeding persists and is associated with a dismal outcome. The coagulation disorders might be correlated with risk of bleeding in patients with portal hypertension. The administration of activated recombinant factor VII corrects prothrombin time transiently in nonbleeding patients with cirrhosis as well as in bleeding ones. The aim of this study was to assess the hemostatic efficacy of activated recombinant factor VII in bleeding esophageal varices. METHODS: Between May 2001 and September 2002, 112 patients with cirrhosis and an episode of acute esophageal variceal bleeding were admitted. On an open basis with a single intravenous dose of 4.8 mg of recombinant factor VII, we treated 8 patients experiencing severe and active hemorrhage from esophageal varices unresponsive to pharmacologic therapy, endoscopic therapy, or balloon tamponade. RESULTS: Eight (7%) of 112 patients met entry criteria. Hemostasis was achieved in all the cases after recombinant activated factor VII therapy. Rebleeding and mortality rates were 25% and 50% (2 and 4 patients), respectively. CONCLUSIONS: In our experience, recombinant activated factor VII achieves hemostasis in bleeding esophageal varices unresponsive to standard treatment.

Aged↗
PubMedDate not supplied

Hemostatic effects of phospholipid vesicles carrying fibrinogen gamma chain dodecapeptide in vitro and in vivo.

We studied prototypes of platelet substitutes that bear on their surface a dodecapeptide, HHLGGAKQAGDV (H12). The peptide is a fibrinogen gamma chain carboxy-terminal sequence (gamma400-411) and recognizes specifically the active form of glycoprotein (GP) IIb/IIIa on the surface of activated platelets. We conjugated H12 to the end of poly(ethylene glycol) chains on the surface of a phospholipid vesicle with an average diameter of 220 nm to prepare H12-PEG-vesicles. The half-life of the H12-PEG-vesicles was significantly prolonged by PEG modification, and the ability of H12 on the surface of the vesicle to recognize GPIIb/IIIa was maintained even though the surface was modified with PEG chains. The H12-PEG-veiscles enhanced the in vitro thrombus formation of platelets that were adhering to a collagen-immobilized plate, when thrombocytopenia-imitation blood was passed over the plate. Based on the flow cytometric analyses of PAC-1 binding and P-selectin expression, the H12-PEG-vesicles were shown not to cause platelet activation. Furthermore, the H12-PEG-vesicles dose-dependently shortened the tail bleeding time of thrombocytopenic rats. It was confirmed that the H12-PEG-vesicles had a hemostatic effect and may be a suitable candidate for an alternative to human platelet concentrates transfused into thrombocytopenic patients.

Animals↗
PubMed1999

Pharmacokinetics and hemostatic effects of saruplase in patients with acute myocardial infarction: comparison of infusion, single-bolus, and split-bolus administration.

Saruplase, or unglycosylated, single-chain urokinase-type plasminogen activator (scu-PA) selectively activates fibrin-bound plasminogen, and is subsequently converted to its two-chain derivative tcu-PA (urokinase) by plasmin. The efficacy of a 20 mg IV bolus followed by an infusion of 60 mg over 1 hour (standard regimen) has been demonstrated in acute myocardial infarction (AMI). The Bolus Administration of Saruplase in Europe (BASE) study compared the efficacy of standard therapy, single bolus (80 mg), and split bolus (2 x 40 mg at 30-minute intervals) in AMI. In a substudy of BASE, the pharmacokinetics of total u-PA activity (amidolytic activity after plasmin treatment), high molecular weight (HMW) u-PA antigen, and tcu-PA activity were compared in patients receiving standard therapy (n = 4), single bolus (n = 4), or split bolus (n = 5). Total u-PA activity and HMW u-PA antigen were similar. The maximum concentration (C(max,), mean +/- SD) of total u-PA activity was 2.2 +/- 0.3 microg/mL after standard therapy, 16.3 +/- 3.9 microg/mL after single bolus, and 8.2 +/- 1.6 ug/mL after split bolus. The area under the concentration versus time curve (AUC) values of total u-PA activity were 1.7 +/- 0.1 microg/mL*h (standard therapy), 4.0 +/- 0.9 microg/mL*h (bolus), and 3.0 +/- 0.7 microg/mL*h (split bolus). The dominant initial half-lives (t(1/2) alpha) were 7.1 +/- 1.1 minutes (standard), 8.8 +/- 0.8 minutes (bolus), and 5.1 +/- 2.1 minutes (split bolus). Maximum plasma concentrations of of tcu-PA activity were observed at 5.2 +/- 7 minutes (standard), 21 +/- 10 minutes (bolus), and 42 +/- 2 minutes (split bolus). C(max) was lowest after standard therapy (0.6 +/- 0.3 microg/mL), highest after bolus (4.2 +/- 2.2 microg/mL), and approximately twice as high as standard therapy after split bolus (1. 3 +/- 0.8 microg/mL). After standard therapy the mean fibrinogen concentration decreased gradually from approximately 300 mg/dL to 70 mg/dL at 90 and 120 minutes. After a single bolus the fibrinogen concentration decreased below the limit of quantification within 30 minutes and remained there for at least 120 minutes. Directly after the second 40 mg dose of the split bolus, the fibrinogen levels had an accelerated and more pronounced decrease to approximately 65 mg/dL at 90 and 120 minutes. A single bolus results in very high early total u-PA activity, which accelerates the appearance of tcu-PA activity and fibrinogen consumption. The pharmacokinetics and hemostatic effects of the split-bolus regimen are more comparable with those of standard therapy.

Adolescent↗
PubMed1997

In vitro evaluation of the hemostatic effectiveness of non viable platelet preparations: studies with frozen-thawed, sonicated or lyophilized platelets.

OBJECTIVES: Because of the limited life span of platelets in regular storage systems, we were interested in investigating the effects on hemostasis of nonliving platelet derivatives. METHODS: We evaluated the effects of different platelet preparations on primary hemostasis in a well-established perfusion model. Studies were carried out with blood anticoagulated with low molecular weight heparin. Similar amounts of frozen-thawed, sonicated or lyophilized platelets were added to normal blood or to blood which had been experimentally depleted of platelets. Platelet interaction with the subendothelium and fibrin deposition were morphometrically evaluated. RESULTS: Addition of nonviable platelet preparations to thrombocytopenic blood always promoted a statistically significant increase in the deposition of fibrin on the subendothelium, but only lyophilized platelets retained some ability to interact with the subendothelium. Flow cytometry studies demonstrated the presence of GPIb, GPIIIa and P-selectin on lyophilized platelets. CONCLUSIONS: Preparations containing nonviable platelets may still retain some hemostatic properties.

Animals↗
PubMed2003

Cellular mechanisms of the hemostatic effects of desmopressin (DDAVP).

The synthetic analog of vasopressin desmopressin (DDAVP) is widely used for the treatment of patients with von Willebrand disease (VWD), hemophilia A, several platelet disorders, and uremic bleeding. DDAVP induces an increase in plasma levels of von Willebrand factor (VWF), coagulation factor VIII (FVIII), and tissue plasminogen activator (t-PA). It also has a vasodilatory action. In spite of its extensive clinical use, its cellular mechanism of action remains incompletely understood. Its effect on VWF and t-PA as well as its vasodilatory effect are likely explained by a direct action on the endothelium, via activation of endothelial vasopressin V2R receptor and cAMP-mediated signaling. This leads to exocytosis from Weibel Palade bodies where both VWF and t-PA are stored, as well as to nitric oxide (NO) production via activation of endothelial NO synthase. The mechanism of action of DDAVP on FVIII plasma levels remains to be elucidated. The hemostatic effect of DDAVP likely involves additional cellular effects that remain to be discovered.

Deamino Arginine Vasopressin↗
PubMed2006

Glanzmann's thrombasthenia treatment: a prospective observational registry on the use of recombinant human activated factor VII and other hemostatic agents.

Glanzmann's thrombasthenia (GT) is a rare congenital bleeding disorder caused by deficiency or dysfunction of platelet surface glycoprotein (GP) IIb/IIIa receptor. Platelet transfusion is the standard treatment for bleeding that remains non-responsive to conservative measures, and for surgical coverage. Platelet transfusions, however, may result in the development of antibodies to GPIIb/IIIa and/or human leukocyte antigen (HLA), rendering further transfusions ineffective. Recombinant human activated factor VII (rFVIIa; NovoSeven/Niastase [Canada], Novo Nordisk, Bagsvaerd, Denmark) has documented efficacy in GT patients, and is approved in the European Union for the treatment of GT patients with platelet antibodies and platelet refractoriness. However, there are insufficient data to determine the optimal rFVIIa regimen (eg, for major surgery) or to allow thorough safety evaluation (eg, thrombotic risk). A post-marketing, prospective, observational, multinational registry has been developed to collect data on the efficacy and safety of rFVIIa in the treatment and prevention of bleeding in GT patients with platelet antibodies or platelet refractoriness. Patients treated with other hemostatic agents or rFVIIa to avoid the development of antibodies against GPIIb/IIIa will also be reported. Standardized data will be collected using a customized internet-based (www.glanzmann-reg.org) data collection tool. Data collection will begin in 2005 and continue for up to 6 years. Patients of all ages from any country are eligible for inclusion.

Autoantibodies↗
PubMed2006

Ultra-early hemostatic therapy for acute intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the least treatable form of stroke, and causes high mortality, severe disability, and a staggering economic burden. ICH accounts for 15% of stroke cases in the United States and Europe, and up to 30% in Asian populations. Computed tomography-based studies suggest that ICH growth within the first few hours of onset is common, and the principal cause of early neurological deterioration. Hematoma volume is also a well-established predictor of 30-day mortality. Intervention with ultra-early hemostatic therapy could minimize or prevent this early dynamic bleeding process, and might improve outcome. Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) is approved for the treatment of bleeding in patients with hemophilia and inhibitors, but it may also promote hemostasis in patients with normal coagulation by acting locally at the bleeding site without activation of systemic coagulation. In a randomized, double-blind, placebo-controlled trial of 399 ICH patients treated with a single dose of 40, 80, or 160 microg/kg of rFVIIa or placebo within 4 hours of onset, subsequent hematoma growth was reduced by approximately 50% with rFVIIa. This was associated with a significant reduction (38%) in mortality, and improved functional outcomes among survivors. A phase III trial comparing 20 and 80 microg/kg rFVIIa with placebo is now in progress to confirm these results.

Aprotinin↗