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Review of the pH of hemostatic agents used in tissue displacement.

Newer hemostatic agents such as the tetrahydrozolines and oxymetazolines have a more acceptable pH and should be kinder to tooth structure and soft tissue than the conventional solutions. Although additional study is needed, it would seem prudent to be cautious in using low pH hemostatic agents and avoid the exposure to sensitive intraoral tissues-particularly delicate tissues--or tooth preparation close to the dental pulp.

Alum Compounds↗

Studies concerning the hsitotoxicity of isobutyl-2-cyanoacrylate tissue adhesive when employed as an oral hemostat.

An experimental study was implemented to determine the effectiveness of isobutyl-2-cyanoacrylate (bucrylate) as an oral hemostat, its influence on sequential wound healing, and its potential as a carcinogen. Segregated groups of equal numbers of male and female Long-Evans Hooded Rats underwent deep (socket) and superficial (surface) aerosol placement of bucrylate to maxillary molar extraction sites. Bucrylate proved to be an effective oral hemostat, rapidly retarding postextraction hemorrhage. Deep placement of the adhesive resulted in retarding of healing and lingering macrohistiocytic aggregates in wounds. Superficial placement of the material resulted in very little long-term macrohistiocytic response, and would healing showed little retardation. A neoplastic potential was not demonstrated for bucrylate.

Aerosols↗

Evaluation of hemostatic activity of desamino-D-arginine vasopressin (DDAVP) in uremic rats.

DDAVP, an analog of vasopressin, has been shown to have hemostatic activity. Although it has been used clinically to control bleeding, there have been very few attempts to characterize this agent in experimental animals. We describe a new animal model which is fast, reliable and inexpensive, and which may be used to screen novel analogs of the peptide. Under sodium pentobarbital anesthesia, rats were bilaterally nephrectomized and implanted with indwelling intravenous cannulae. The next day they were re-anesthetized, a standardized cut was made in the tail and the tail was allowed to bleed into warm isotonic saline (25 ml). After 10 min., the tail was removed from the saline and the blood loss was measured either by laser nephelometry or by colorimetric analysis. DDAVP was then injected intravenously and the rat was allowed to rest quietly for 30 min., after which time a second incision was made in the tail and blood loss again measured for 10 min. Unlike bleeding time which was highly variable, blood loss proved to be a reliable index of the hemostatic activity. Thus we were able to demonstrate that DDAVP reduced blood loss in the uremic rats, whereas it was without effect in intact rats.

Animals↗

Hemostatic alterations are unrelated to the stage of tumor in untreated malignant melanoma and breast carcinoma.

A study of hemostatic variables was carried out in 80 untreated patients with breast adenocarcinoma or malignant melanoma, chosen as examples of tumors that can be accurately staged for localization or spread. The most marked abnormalities were high levels of clotting factors V and VIII, plasminogen, von Willebrand factor and fibrogen-fibrin degradation products. These abnormalities occurred in both types of tumors, albeit slightly more markedly in melanomas, and were also present in localized tumors. Our data indicate that in tumors, abnormalities of the hemostatic system are an early phenomenon unrelated to the presence of widespread malignancy.

Adenocarcinoma↗

Osseous regeneration in the presence of four common hemostatic agents.

The iliac crest is a common site for bone procurement in oral and maxillofacial surgery. The goal of this study was to evaluate the potential for bone regeneration in the presence of four common hemostatic agents in a manner that parallels iliac bone procurement in humans. The agents evaluated were 1) Avitene (microfibrillar collagen; Medchem Products, Inc, Woburn, MA); 2) bone wax (beeswax with isopropyl palmitate; Ethicon, Inc, Somerville, NJ); 3) Gelfoam (absorbable gelatin sponge; The Upjohn Company, Kalamazoo, MI); and 4) Surgicel (oxidized regenerated cellulose; Johnson & Johnson Products, Inc, Patient Care Division, New Brunswick, NJ). Five surgical defects in each of four dogs were created for placement of the four materials; one defect served as an empty control site. The dogs were then allowed to heal over a 2-month period. Radiographic and histologic examination showed new bone formation in the presence of Avitene, Surgicel, and Gelfoam. Residual material incorporated in bone, without foreign-body response, was noted in the Avitene and Gelfoam sites. Bone wax, however, showed an intense foreign-body reaction, characterized by giant cells, plasma cells, fibrous granulation tissue, and lack of bone reformation. On the basis of these initial findings, it was concluded that Surgicel, Avitene, and Gelfoam may be adequate hemostatic agents for use in iliac bone procurement, whereas the use of bone wax appears to be contraindicated.

Animals↗

Radiological and histopathological examination of early tissue reactions to absorbable hemostatic agents in the rabbit brain.

Topical hemostatic agents are widely and safely used in neurosurgery. The purpose of this study was to compare and analyse the early tissue reactions to two hemostatic agents, oxidized regenerated cellulose and gelatin sponge, in rabbit brain by magnetic resonance imaging and histopathologic sections. Bilateral identical parenchymal lesions were made in the frontal regions of each hemisphere in 13 rabbits. Hemostasis was achieved using oxidized regenerated cellulose or gelatin sponge, one agent being used on each side. Cranial magnetic resonance imaging was performed 24 h postoperatively and there was no statistical difference in edema formation at the site of the lesions. Histopathologic examinations indicated that pericapillary edema and endothelial distortion were common in both groups but that there was additional tissue degeneration evident in the regions where gelatin sponge had been used. Oxidized regenerated cellulose seemed to cause greater tissue distortion in magnetic resonance images than gelatin sponge but in contrast, histological examination of lesions in which oxidized regenerated cellulose had been used revealed less tissue degeneration than histopathologic examinations of lesions in which gelatin sponge had been used.

Animals↗

Hemostatic markers and platelet aggregation factors as predictive markers for type of stroke and neurological disability following cerebral infarction.

We investigated the plasma levels of D-dimer, fibrinogen, beta-thromboglobulin (BTG) and platelet factor-4 (PF-4), indices of the occurrence of platelet activation in vivo, to find out their role in pathophysiology of ischemic stroke and whether or not such a role has any effect on the disability and the prognosis of stroke patients. A total of 76 patients with AIS aged from 26 to 85 (32 men, 44 women) and 30 cases as controls with similar age (18 men, 12 women) were included in the study. The plasma levels of D-dimer, BTG and PF-4 were measured by ELISA method using a special commercial kit. The cases were allocated into two groups as non-embolic (NEI) and cardioembolic stroke (CEI). The D-dimer levels in 76% of 42 patients in NEI group (p<0.05) and 85.2% of 34 patients in CEI group (p<0.05) were outside the confidence interval (CI) defined for the control group. The levels of BTG were elevated in 81% of 42 cases with NEI (p<0.05) and in 76% of 34 cases with CEI, with reference to CI of control group. The levels of PF-4 were significantly increased in 86% of cases with NEI (p<0.05) and in 88% of cases with CEI than controls (p<0.05). It was observed that the cases with high Rankin scores had higher levels of D-dimer (p<0.005), BTG (p<0.01) and PF-4 (p<0.01) than those with lower scores. There was a correlation between hemostatic markers, platelet activation and functional disability. D-dimer levels were an important marker that determined to degree of the activation of hemostatic system, especially in CEI subtype. The platelet aggregation had an important role in pathophysiology of ischemic stroke and this condition is significant in NEI subgroup and subjects with large infarcts and high disability scores.

Adult↗

Surgical complications from hemostatic puncture closure devices.

BACKGROUND: For securing immediate hemostasis following percutaneous arterial catheterization, the Food and Drug Administration has approved three hemostatic puncture closure devices. We reviewed our institutional experience with one device (Angio-Seal). METHODS: A retrospective, single-center, nonrandomized observational study was made of all vascular complications following femoral cardiac catheterization. RESULTS: An immediate mechanical failure of the device was experienced in 34 (8%) patients. Surgical repair was required in 1.6% (7 of 425) of patients following Angio-Seal versus 0.3% (5 of 1662) following routine manual compression (P = 0.004). In 5 patients, the device caused either complete occlusion or stenosis of the femoral artery. The polymer anchor embolized in 1 patient and was retrieved with a balloon catheter at surgery. CONCLUSION: During the first year of utilization of a percutaneous hemostatic closure device following cardiac catheterization, we observed a marked increase in arterial occlusive complications requiring surgical repair. Surgeons must be familiar with the design of these devices to achieve precise repair of surgical complications.

Arterial Occlusive Diseases↗

Smear layer instability caused by hemostatic agents.

The effect of hemostatic agents, other than a 15.5% Fe2(SO4)3 solution, on prepared tooth structure is unknown. The purpose of this study was to (1) compare the effect of six commonly used hemostatic solutions and two nondental astringents on the dentinal smear layer and (2) determine whether different responses caused by product and/or time could be established. Standardized dentinal smear layers were exposed to eight astringent solutions for 30, 120, and 300 seconds (n = 6). A total of 144 SEM photographs at x2400 magnification were ranked according to predetermined criteria for five categories of smear layer removal and etching of underlying tooth structure. There were significant differences (p < 0.001) caused by the solution, exposure time, and their interaction. Greatest smear layer removal was observed with 21.3% AlCl3-6 hydrate, 8% racemic epinephrine HCl, and 15.5% Fe2(SO4)3 solutions at longer exposures. These caused significantly more removal than did almost pH neutral tetrahydrozoline or oxymetazoline (p < 0.05).

Acid Etching, Dental↗

Changes on hemostatic parameters induced by 17beta-estradiol, ethinylestradiol, and the 17beta-aminoestrogen pentolame in the male Wistar rat.

Oral contraceptives containing estrogens increases the incidence of thromboembolic events. In contrast, administration of 17beta-aminoestrogens prolonged blood clotting time (BCT) in rodents. We studied the effect of estradiol (E(2)), ethinylestradiol (EE) and pentolame on some screening hemostatic tests. BCT was evaluated 24, 48, 72 and 96 h post-treatment. Rats received subcutaneously (s.c.) for five consecutive days E(2) (0.1-1000 microg), EE (1-1000 microg), pentolame (0.1-1000 microg), or vehicle (propyleneglycol 0.3 ml). At 48 h post-treatment E(2) (1000 microg) diminished BCT (32%, P<0.01), in contrast pentolame (1000 microg) augmented BCT by 41% (P<0.01). After 72 h, E(2) showed procoagulant effects with 10, 100 and 1000 microg doses (-45, -30, and -21%, respectively). Significant effects on BCT of EE were observed 72 h after with 1000 microg (-12%, P<0.05). Animals were treated s.c. for two consecutive days with E(2) (3mg/100g), pentolame (4 mg), or vehicle (0.1 ml). BCT, bleeding time (BT), platelet aggregation (PA), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen concentration were determined. E(2) produced a significant diminution on BCT (-20%) after 72 h whereas pentolame increased BCT from 24 to 96 h (62%, maximal response at 48 h). APTT and PT coagulation times of the groups treated with E(2) and pentolame were lengthened (33 and 29%; 16 and 24%, respectively; P<0.05). Fibrinogen concentration increased (115%, P<0.01) only in the pentolame-treated group. Pentolame and E(2) produced any effects on BT and PA compared with control groups, indicating that platelet function was not modified. Our results indicate that E(2), EE and pentolame affects the plasmatic phase of the hemostatic mechanism.

Amino Alcohols↗

Is veno-occlusive disease a specific syndrome or the exacerbation of physiopathologic hemostatic changes in hematopoietic stem cell transplantation (HSCT)?

The objective of the present study was to analyze whether veno-occlusive disease (VOD) is based on specific findings or whether this syndrome is the exacerbation of changes in hemostatic parameters that develop following hematopoietic stem cell transplantation (HSCT). 40 patients undergoing HSCT were enrolled (6 allogeneic bone marrow transplantation and 34 peripheral stem cell rescue-2 allogeneic, 32 autologous). Measurements of hemostatic parameters (endothelial, hypercoagulability and fibrinolytic markers) were obtained prior to chemotherapy and weekly thereafter for 3 weeks. The incidence of VOD was 15%. HSCT showed a state of moderate hypercoagulability (increase of thrombin-antithrombin complex and fibrinogen, and decrease of Factor VII, Protein C, and antithrombin-III), probably as a consequence of marked endothelial damage (increase of von Willebrand Factor and tissue plasminogen activator). All these alterations create a potentially prothrombotic state, more pronounced in VOD. The decreasing incidence of VOD and the moderate disease in all patients suggest that increasing improvements in transplant strategies have reduced the risk and severity of a syndrome that at the beginning of the transplantation era was a leading cause of morbidity/mortality.

Adolescent↗

Effects of all-trans-retinoic acid and arsenic trioxide on the hemostatic disturbance associated with acute promyelocytic leukemia.

To study the in vivo effect of all-trans-retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) on the expression of tissue factor (TF) and the other hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from acute promyelocytic leukemia (APL) patients. The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription-polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA), TF antigen of APL cell lysate, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As(2)O(3) therapy. The plasma level of P-selectin, TF, thrombin-antithrombin complex (TAT), soluble fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), plasmin-antiplasmin complex, tissue plasminogen activator (t-PA) activity, urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and D-dimer (D-D) significantly increased. Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG) activity, alpha(2)-plasminogen inhibitor activity (alpha(2)-PI), and plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The protein C activity (PC:A) and protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As(2)O(3) therapy downregulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, significantly inhibited coagulation activation, corrected secondary hyperfibrinolysis and the other hemostatic abnormalities, and thus greatly improved the bleeding symptom in early stage of the treatment.

Adolescent↗

Hemostatic capability of rapidly curable glues from gelatin, poly(L-glutamic acid), and carbodiimide.

The hemostatic capability of rapidly curable glues composed of gelatin and poly(L-glutamic acid) (PLGA) was compared with that of the conventional fibrin glue. The hydrogels produced from mixed gelatin and PLGA aqueous solution within several seconds by addition of water-soluble carbodiimide (WSC) was applied to the dog spleen injured by needle pricking. The WSC-catalyzed gelatin-PLGA glues exhibited higher hemostatic capability than the fibrin glue. The total amount of bleeding from the injured spleen until hemostasis when the gelatin-PLGA hydrogel glues were applied was significantly smaller than that of the fibrin glue application. The gelatin-PLGA glue application enhanced the success rate of complete hemostasis to a significantly greater extent than the fibrin glue, while the frequency of glue applications until achieving complete hemostasis decreased. The gelatin PLGA hydrogels strongly adhered to the surface of dog spleen, whereas the fibrin hydrogel was easily detached from the spleen surface. It was concluded that this strong adhesion mechanically suppressed the bleeding, leading to enhanced hemostasis by the rapidly curable gelatin-PLGA glues.

Animals↗

In vivo evaluation of a new type I collagen hemostatic plug for high-risk, large-core biopsies.

PURPOSE: To evaluate in a swine model the hemostatic properties of a new, expansile type I collagen plug for use in high-risk renal biopsies. MATERIALS AND METHODS: Highly purified bovine type I collagen was formed into porous cylindrical plugs and compressed radially to fit into a 5-F delivery system. On hydration these collagen plugs demonstrated radial expansion with approximately 1,600% volumetric expansion ratio. Direct exposure of both kidneys was performed in a 25-kg swine, and a bolus of 3,000 U of heparin was administered to create a coagulopathic state. A 14-gauge Temno coaxial biopsy gun was utilized in performing nine pairs of renal biopsies. The first biopsy of each biopsy pair represented the control biopsy (without collagen plug placement), whereas the second biopsy of each pair represented the plugged biopsy. The presence and duration of hemorrhage from each biopsy site was monitored visually. RESULTS: The biopsy sites without collagen plug showed immediate hemorrhage in nine of nine cases (100%), and in two of nine cases (22%) pulsatile bleeding was noted. With the use of the collagen plug, seven of nine (78%) sites showed immediate hemorrhage, but in no case was pulsatile bleeding noted. Mean bleeding duration was 156 seconds for the control biopsies versus 73 seconds for the biopsy sites plugged with collagen (P = .03, Mann-Whitney rank sum test). Bleeding duration was less than 1 minute in only one of nine (11%) control biopsies compared to six of nine (67%) collagen plug biopsies. CONCLUSIONS: A recently developed, expansile collagen hemostatic plug significantly decreases the duration of hemorrhage at renal biopsy sites in an anticoagulated swine model.

Animals↗

Hemostatic effects of SF6 after diabetic vitrectomy for vitreous hemorrhage.

PURPOSE: To investigate the hemostatic effects of SF6 gas in preventing postoperative vitreous hemorrhage in diabetic vitrectomy. METHODS: A prospective, randomized study of 33 diabetic eyes with vitreous hemorrhage, treated by vitrectomy. In 17 of our cases SF6 20% was injected into the eye at the end of the operation, while in 16 cases BSS remained in the vitreous cavity. RESULTS: The incidence of vitreous hemorrhage recurrence was 17.6% for the SF6 group and 12.5% for the BSS group (statistically not significant). Progression of lens opacities was observed in 23.5% of the SF6 group, and in 18.8% of the BSS group (statistically not significant, with a higher incidence in the SF6 group). CONCLUSIONS: SF6 gas did not show hemostatic effects in the cases studied. Furthermore, it may have contributed to cataract progression. Therefore we suggest that the use of SF6 is not recommended as a treatment modality in preventing new vitreous hemorrhage after diabetic vitrectomy.

Adult↗

Titanium hemostatic clip tailoring method to overcome vessel caliber discrepancy in interposition saphenous vein graft for carotid artery resection.

CONCLUSION: This method makes it possible to perform the ISVG simply and within a short time and, therefore, is very useful for shortening the duration to block circulation. OBJECTIVE: Complete excision of a malignant tumor which invades carotid artery walls essentially requires the resection and reconstruction of the carotid artery. In most cases, an interposition graft using a saphenous vein has been performed; however, the discrepancy in vessel caliber between the common carotid artery and the saphenous vein can complicate the surgical technique. We have introduced and evaluated a new titanium hemostatic clip tailoring method to overcome the vessel caliber discrepancy in interposition saphenous vein graft (ISVG) for carotid artery resection in the treatment of head and neck cancers. MATERIAL AND METHODS: After carotid artery resection, the calibers of the proximal common carotid artery and the vein were compared, and the size of the orifice of the common carotid artery was gradually reduced to a little larger than or the same as that of the vein using a titanium hemostatic clip. Subsequently, the common carotid artery was connected to the vein by means of anastomosis. The same method was also applied to the distal anastomosis site. Thereafter, the vessels were connected through the anastomosis, and circulation was restored by releasing a vascular clamp. Then, the redundant portion on the outside of the carotid artery was sutured by means of the blanket-edge suture method, using 6-0 Prolene. RESULTS: We employed this method in two patients with recurrent squamous cell carcinoma and neuroblastoma, respectively. The ISVG of these patients was found to maintain good patency at follow-up angiography after 1 year, and no specific vascular complications were observed.

Anastomosis, Surgical↗

Effect of hemostatics used during operations for digestive organ on cancer cells present in the peritoneal cavity.

We investigated effects of hemostatics used during operations for digestive organ on cancer cells present in the peritoneal cavity using BALB/c mice inoculated with Meth A tumor cells (fibrosarcoma) intraperitoneally (i.p.) and C3H/He mice inoculated with MH134 tumor cell (hepatic cell carcinoma) i.p. Microfibrillar collagen hemostat (Avitene) or fibrinogen preparation (Beriplast P) did not affect survivals of those tumor-bearing mice. Gelatin sponge (Spongel)prolonged survivals of MH134 tumor-bearing mice. Liquid form gelatin used instead of Spongel displayed in vitro antitumor effect on MH134 tumor cells at the concentration of 15 mg/ml. Radioactive sodium chromate-labeled MH134 and Meth A tumor cells were not lysed when they were incubated with 15 mg/ml of liquid form gelatin for 24 hours. On the other hand, the tritium thymidine (3H-TdR) uptake by MH134 or RL male 1 tumor cells was suppressed when they were incubated with 15 mg/ml of liquid form gelatin for 24 hours. Proliferation of Meth A tumor cells were not affected by the treatment. Effect of liquid form gelatin on phytohemagglutinin (PHA)-stimulated spleen cells as a benign counter-part of RL male 1 tumor cells (T cell lymphoma) was examined. Liquid form gelatin (15 mg/ml) did not suppress 3H-TdR uptake by PHA-stimulated spleen cells.

Animals↗

Hemostatic effects of stress hormone infusion.

BACKGROUND: Surgery causes changes in hemostasis, leading to a hypercoagulable state. This postoperative increase in hemostatic function is attenuated in patients receiving regional anesthesia compared with those receiving general anesthesia. Regional anesthesia also decreases the neuroendocrine response to surgery compared with general anesthesia, and this effect is hypothesized to be responsible for the differences in hemostatis. To test the hypothesis that neuroendocrine hormones cause changes in hemostasis, we infused stress hormones into normal volunteers and measured hemostatic function. METHODS: After drug screening, 12 normal volunteers were studied. On two admissions, volunteers randomly received either stress hormone (epinephrine, cortisol, or glucagon) or placebo infusion for 24 h. During infusion, patients remained at bed rest and received controlled meals. Blood was obtained from indwelling venous catheters before infusion and 2, 8, and 24 h after the start of infusion. Blood was analyzed for neuroendocrine hormone concentrations, glucose, complete blood count, coagulation proteins, platelet reactivity, and activity of the fibrinolytic system. RESULTS: In the stress hormone group, concentrations of epinephrine, norepinephrine, cortisol, glucagon, and insulin were increased during the infusion period compared with those in the placebo group. Glucose concentrations and white blood cell counts were increased in the stress hormone group compared with those in the placebo group. Circulating fibrinogen concentrations increased 30% and ex vivo collagen-induced platelet reactivity increased 123% (aggregation) and 103% (dense granule release) in the stress hormone infusion group, whereas there was no change in the placebo group. Fibrinolytic proteins were similar in both groups, demonstrating a decrease in plasminogen activator inhibitor-1 activity at 8 and 24 h (196% in the hormone group vs. 199% in the placebo group). CONCLUSIONS: Infusion of stress hormones to concentrations found during surgery is safely tolerated and causes metabolic changes observed with surgery. Stress hormone infusion increases ex vivo platelet reactivity and fibrinogen concentrations that resemble changes seen postoperatively but does not recreate the postoperative decrease in fibrinolytic activity. Differences in neuroendocrine response between types of anesthesia may explain some postoperative changes in platelet function and acute phase reactivity, but additional uncharacterized factors are responsible for the differences in fibrinolysis.

Adolescent↗