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[Bed-side management of post-operative bleeding in transurethral resection of the prostate--hemostatic trial with thrombin solution injected into the resected cavity of the prostate].

To control post-operative bleeding from the resected cavity in transurethral resection of the prostate (TUR-P), 20,000 units of thrombin dissolved in 5-20 ml of physiological saline was injected into the cavity in one shot with a new type of 3-way Foley catheter. The catheter has two holes close to the balloon, and the holes provide outlets through which the solution is directly injected into the cavity. Out of 23 patients between 58 and 87 years old, 11 were given thrombin and 12 were control cases. In each case, urine blood volume (ml/hr) was determined before (a) and after (b) injection. The hemostatic effect was assessed with a "hemostatic index" of b/a. There was a statistically significant difference in the hemostatic indices between thrombin group and the control. (p less than 0.02) This new hemostatic method proved to be a very useful easy bed-side technique to control bleeding even in sudden bleeding after TUR-P. No serious side effects were found during the course of this study.

Aged↗

Morphology of the hemostatic plug in human skin wounds: transformation of the plug.

The transformation of hemostatic plugs in human skin wounds was studied in vivo after bleeding had stopped. Standardized bleeding time incisions were made on the dorsal side of the forearm of four normal male volunteers. The wounds were excised by punch biopsy 10 minutes, 30 minutes, or 2 hours after they had been made and studied by light and electron microscopy. The wounds were filled with red blood cells, and a network of fibrin strands was found in the wound, particularly near transected vessels. Polymorphonuclear leukocytes were encountered within transected vessels and at 2 hours also in the wounds and in concentric rings around the vessels up to 0.5 mm. from the wound. On top of the wounds a superficial scab, consisting of red blood cells and presumably air-dried proteins, had formed. Hemostatic plugs were found at the ends of transected blood vessels. At 10 minutes the plugs consisted of largely degranulated platelets which showed strong interdigitation. Fibrin was still absent from the center of the plugs. At 30 minutes the platelets became less densely packed, and small fibrin fibers were deposited between the platelets in large peripheral areas of the plugs. At 2 hours some of the platelets had assumed rounded shapes with few interdigitations and larger spaces between them. Areas in the plug with platelets that had lost their integrity alternated with areas where platelets still had their cytoplasmic matrix and were interdigitated. Fibrin fibers were especially demonstrable between the degenerated platelet vesicles. This occurred everywhere in small hemostatic plugs and in the periphery of larger plugs. In one individual it was also observed in the center of large hemostatic plugs. In the other individuals fibrin was present centrally as amorphous dark staining material which was fibrillar in tangential sections.

Adult↗

Curvilinear relations between age and hemostatic parameters in Chinese.

The role of hemostatic factors in the pathogenesis of cardiovascular disease has gained much attention recently. Information about hemostatic factors, and their age patterns is sparse for orientals. With the data collected in the Cardiovascular Disease Risk Factor Two-township Study in Taiwan, this study shows that, in general, the older the age, the stronger the tendency toward thrombosis. With advancing age, prothrombin time, activated partial thromboplastin time, and antithrombin-III level decreased steadily; but mean values of fibrinogen, factor VIIc, and factor VIIIc increased. Gender differences in the age patterns of the above factors are carefully described. Curvilinear relations between hemostatic factors and age were demonstrated for adults aged 18 and above for all hemostatic factors studied. This curvilinearity should be taken into consideration when adjusting for the effect of age in data analysis to avoid residual confounding, particularly when the age range of the study subjects is wide.

Adolescent↗

Fluoxetine and hemostatic function: a pilot study.

BACKGROUND: Isolated case reports have appeared implicating fluoxetine as a cause of impaired hemostatic function. The authors attempted to investigate this phenomenon. METHOD: The hemostatic function of 10 patients with DSM-III-R major depression was investigated before and after a trial of treatment with fluoxetine. The tests included international normalized ratio, partial thromboplastin time, factors II, V, VII, VIII:C, IX, X, XI, XII, fibrinogen, thrombin time, bleeding time, euglobulin lysis time, protein kinase C, antithrombin, platelet counts, D dimer, lupus inhibitor, and platelet sensitivity studies to the following agonists: adenosine diphosphate, epinephrine, collagen, and arachidonic acid. Hemostatic data on a patient with a drug-related bleeding episode are not available. RESULTS: No significant difference was found in any of the parameters tested. CONCLUSION: This study failed to demonstrate any compromised hemostatic function associated with fluoxetine therapy. However, the possibility of a type II statistical error exists. It is possible that bleeding events may occur as an idiosyncratic reaction to fluoxetine treatment.

Adult↗

Markers of hemostatic activation in affected coronary arteries during angioplasty.

To characterize the extent of early activation of the hemostatic system following angioplasty, we obtained blood samples from the involved coronary artery of 11 stable angina patients during the procedure and measured sensitive markers of thrombin formation (fibrinopeptide A, prothrombin fragment 1.2, and soluble fibrin) and of platelet activation (beta-thromboglobulin). Levels of hemostatic markers in venous blood obtained from 14 young individuals with low pretest probability for coronary artery disease were not significantly different from levels in venous blood or intracoronary samples obtained prior to angioplasty. Also, there was no translesional (proximal and distal to the lesion) gradient in any of the hemostatic markers before or after angioplasty in samples obtained between 18 and 21 min from the onset of the first balloon inflation. Furthermore, no significant difference was noted between angioplasty and postangioplasty intracoronary concentrations. We conclude that intracoronary hemostatic activation does not occur in the majority of patients during and immediately following coronary angioplasty when high doses of heparin and aspirin are administered.

Adult↗

Treatment with a GnRH analogue: effects on hemostatic risk factors for thrombo-embolic disease.

OBJECTIVE: Steroid hormones, especially estrogens, are known to affect hemostatic risk factors for thromboembolism, cardiovascular disease, and stroke. We examined these risk factors during depression of the serum estradiol concentration by a GnRH analogue. DESIGN: Patients were treated with a GnRH analogue, goserelin (Zoladex), 3.6 mg/inj monthly, for a period of 6 months. Blood samples were collected during and after treatment and in a control group. In ten patients a blood sample was also drawn before treatment. Measurements were made of serum estradiol, and the plasma concentrations of tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI-1) antigen, antithrombin III (AT III) and protein C activity, factor VII (FVII) antigen, and fibrinogen. SETTING: Outpatient clinics at the Departments of Obstetrics and Gynecology at two university hospitals in southern Sweden. PARTICIPANTS: Twenty-seven women with endometriosis were consecutively included. A control group comprised 20 women with normal menstrual cycles. MAIN OUTCOME MEASURES: The concentrations of the hemostatic components during depression of the serum estradiol concentrations, as compared to those during normal ovulatory cycles. RESULTS: Serum estradiol concentrations during treatment were comparable to those of postmenopausal women (mean, 23.2 pmol/L), and both AT III and protein C activity were significantly increased (P < .005 and P < .02, respectively). As compared to controls, plasma concentrations of PAI-1 and t-PA of patients were significantly higher both during and after treatment. In the subgroup also studied prior to treatment, there were no differences in hemostatic components, when comparing pretreatment and posttreatment values. CONCLUSIONS: Treatment with this type of GnRH analogue for 6 months is safe with regard to its effect on hemostatic risk factors. The similar responses of t-PA and its inhibitor, PAI-1, to alterations in estrogen levels as well as inflammatory reactivity presumably constitute a balance mechanism preserving fibrinolytic defenses.

Adult↗

Hemostatic and metabolic variables in women with polycystic ovary syndrome.

OBJECTIVE: To study whether a previously demonstrated increased morbidity in cardiovascular disease (CVD) and diabetes mellitus in women with polycystic ovary syndrome (PCOS) is associated with certain hemostatic variables that are known to be markers for CVD. DESIGN: The study was a trans-sectional follow-up study from a cohort of women with PCOS. SETTING: The women with PCOS were recruited from hospital clinics and referents were randomized from a population study of women from the same area. PARTICIPANTS: The investigation involved 28 women aged 43 to 62 years diagnosed to have PCOS on ovarian histopathology at wedge resection 25 to 34 years previously and 56 referents who were matched by age and body mass index. MAIN OUTCOME MEASURES: In connection with a clinical investigation, the hemostatic variables fibrinogen, von Willebrand factor antigen, factor VII procoagulant activity, factor VII antigen, and plasminogen activator inhibitor as well as the metabolic variables serum insulin and serum triglycerides were assayed. RESULTS: There was a strong positive correlation between serum concentrations of triglyceride, basal insulin, and abdominal obesity on the one hand, and plasminogen activator inhibitor, fibrinogen, and von Willebrand factor on the other, among women with PCOS as well as among referents. There were significantly higher mean concentrations of fibrinogen and factor VII:Ag among referents, but the mean values of most hemostatic variables studied showed no differences between the groups. CONCLUSION: Women with an altered metabolic profile were also found to have affected hemostatic factors, but PCOS in itself did not seem to influence them.

Adult↗

Assessment of the hemostatic effectiveness of human platelets treated with aminomethyltrimethyl psoralen and UV A light using a rabbit ear bleeding time technique.

The photochemical aminomethyltrimethyl psoralen (AMT), in conjunction with UV A light (UVA), has been shown to inactivate human immunodeficiency virus-1 and model viruses in platelet suspensions under conditions that have only a minimal effect on in vitro platelet properties. A rabbit ear bleeding time technique was used to assess the hemostatic effectiveness of human platelet suspensions treated with AMT/UVA. New Zealand White rabbits were made thrombocytopenic by a combination of irradiation and heterologous antirabbit platelet antiserum. Reticuloendothelial function in these rabbits was suppressed by the intravenous administration of ethyl palmitate. The hemostatic function of 1- and 5-day-old human platelet suspensions (14.5% plasma) that had been treated on day 1 with 40 micrograms/mL AMT and 24 kJ/m2 UVA (1 x UVA) was evaluated by measuring microvascular bleeding times after a standard incision. Comparable bleeding times were observed after infusion with both control and AMT/UVA-treated platelets stored for either 1 or 5 days. With the transfusion of AMT/1 x UVA-treated platelets stored for 5 days, the mean (+/- SD) bleeding time was 156.3 +/- 39.2 seconds (n = 10). With untreated platelets (no AMT/no UVA), stored for 5 days, the mean bleeding time was 189.2 +/- 36.4 seconds (n = 10). Neither AMT nor 1 x UVA treatment alone influenced the observed bleeding times. In contrast, the hemostatic effectiveness of human platelet suspensions was diminished if they were exposed to three times the standard UVA dose (72 kJ/m2) on day 1 and stored for 4 more days, regardless of whether AMT was present, with the mean bleeding time increasing to 442.2 +/- 122.6 seconds (n = 15, AMT present) or 396.0 +/- 45.9 seconds (n = 10, AMT absent). These results are consistent with data obtained from in vitro studies and indicate that virucidal AMT/1 x UVA treatment does not influence platelet hemostatic function. However, the final conditions to achieve these results must be carefully controlled.

Animals↗

Family history of coronary heart disease and hemostatic variables in middle-aged adults. Atherosclerosis Risk in Communities Investigators and Family Heart Study Research Group.

Individuals with a family history of coronary heart disease (CHD) may be predisposed to atherothrombosis. To investigate this hypothesis, a family CHD risk score was computed for approximately 13,000 men and women aged 45 to 64; hemostatic variables (fibrinogen, factor VIIc, factor VIIIc, von Willebrand factor, antithrombin III. protein C) were also measured in plasma. After adjustment for age and ethnicity, there was a statistically significant, positive association between the family risk score and four of the six hemostatic variables (fibrinogen, factor VIIc, factor VIIIc, von Willebrand factor) in women and all six hemostatic variables in men. In general, these associations were weak and substantially attenuated after adjustment for constitutional, lifestyle, and biochemical covariates. These results indicate that mean levels of selected hemostatic variables, like traditional CHD risk factors, are higher in individuals with a family history of heart disease.

Blood Coagulation↗

Can advanced hemostatic parameters detect disseminated intravascular coagulation more accurately in patients with cirrhosis of the liver?

BACKGROUND: Laboratory diagnosis of disseminated intravascular coagulation (DIC) is difficult in patients with cirrhosis of the liver due to the complicated hemostatic changes of DIC. More recently, newer molecular hemostatic markers have been used to improve the diagnosis of DIC. This study evaluated the ability of the more advanced hemostatic tests to diagnose DIC in patients with cirrhosis of the liver. METHODS: A series of hemostatic tests and parameters including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), factor VIII assay, antithrombin (AT) activity, fibrinogen, plasminogen, protamine sulfate test (PST), fibrin (ogen) degradation product (FDP), D-dimer, thrombin-antithrombin complex (TAT) (measured by modified antithrombin, ATM), euglobulin lysis test (ELT) and platelet count were performed in 51 patients with cirrhosis of the liver. A diagnosis of DIC was made according to the following parameters and criteria: a) platelets less than 80 x 10(9)/l; b) PT greater than 1.5, c) APTT greater than 1.3; d) TT greater than 24 sec; e) AT less than 60%; f) ATM greater than 14.7 ng/ml (normal, mean +/- 3 SD); g) fibrinogen less than 1.50 g/l; h) positive PST; i) D-dimer greater than 1.0 microgram/ml; j) FDP greater than 20 micrograms/ml; k) ELT less than 150 min; l) plasminogen less than 50%. DIC was diagnosed if six or more of the above items were present, and at least two of them were item (a) to (h), and at least two were item (g) to (l). RESULTS: Although eight patients had results that fitted the diagnostic criteria of DIC by using the more advanced tests, only two of them were diagnosed with DIC by conventional testing. The concentration of factor VIII in these eight patients did not markedly decrease. CONCLUSIONS: New tests are not necessary to improve the diagnosis of DIC in patients with cirrhosis of the liver.

Adult↗

Hemostatic effects of oral contraceptives in women who developed deep-vein thrombosis while using oral contraceptives.

OBJECTIVE: Comparison of the effect of oral contraceptives on hemostatic variables in venous thrombosis patients (thrombosis while using oral contraceptives) with the effect in healthy control subjects. Our aim was to assess whether some of these effects were more pronounced in women who had suffered thrombosis, i.e., whether these were "hemostatic hyperresponders". STUDY DESIGN: A population-based case-control study, the Leiden Thrombophilia Study. MATERIALS AND METHODS: We investigated 99 pre-menopausal women, age 15-49 years, who had used oral contraceptives at the time of a first, objectively confirmed episode of deep-vein thrombosis. They were not pregnant, nor in puerperium, nor had had a recent miscarriage, and were not using injectable progestogens, nor suffering from inherited coagulation defects. The median time between occurrence of deep-vein thrombosis and venepuncture was 18 months, and 30 of the 99 women were still using oral contraceptives, while 69 had discontinued oral contraceptive use. In addition, a group of 153 control women (54 of them were oral contraceptive users and 99 were non-users) were studied. The following hemostatic variables were measured: APTT, factor VII, factor VIII, factor XII, fibrinogen, prothrombin, total antithrombin, normalised activated protein C sensitivity ratio (n-APC-sr), protein C, protein S and free protein S. RESULTS: We found marked and significant effects of oral contraceptive use on the levels of several clotting factors, with an increase in factor VII, factor XII, protein C and a decrease in antithrombin, n-APC-sr and protein S. Less marked effects that were non-significant or only significant in either patients or controls, were an increase in factor VIII, fibrinogen and prothrombin and a decrease in the APTT and free protein S. In the former thrombosis patients several of these effects of oral contraceptives were more pronounced than in healthy women: specifically on factor VII, antithrombin, n-APC-sr and protein C. CONCLUSIONS: Our results of the effects of oral contraceptives generally confirm previous reports in healthy volunteers. Our data also show that in former deep-vein thrombosis patients these effects are more pronounced. Apparently some women become "high hemostatic responders" when exposed to oral contraceptives, and they may be the women most vulnerable to its thrombogenic effects.

Abortion, Spontaneous↗

Evaluation of a novel hemostatic device in an ovine parenchymal organ bleeding model of normal and impaired hemostasis.

Bleeding is a problem encountered by many surgeons, often complicated by the presence of coagulopathy or anticoagulant. The hemostatic effectiveness of CoStasis Surgical Hemostat (with bovine collagen, bovine thrombin, and autologous plasma) was evaluated and compared to a collagen sponge and to two investigational fibrin-sealant preparations under conditions of normal and impaired coagulation. A liver resection and controlled incisions in spleens and kidneys were made in sheep. Time to complete hemostasis and total blood loss were measured. Tissue response was evaluated at 7, 30, 60, and 75 days. CoStasis-treated sites demonstrated significantly shorter time to hemostasis (all surgical sites combined) compared with fibrin sealant (investigational fibrin sealant 1) (p= .005) or collagen sponge (p=0.013). In anticoagulated animals, CoStasis and fibrin sealant (investigational fibrin sealant 2) had comparable mean times to hemostasis, and CoStasis-treated sites exhibited lowered average blood loss compared to investigational fibrin-sealant-2 treated sites. CoStasis-treated sites demonstrated higher levels of tissue repair (lower inflammation, more extensive tissue repair, and less residual implant) compared to fibrin-sealant- or collagen-sponge-treated sites in Phases I and II. These findings demonstrate that CoStasis is a highly effective hemostatic agent for control of bleeding from parenchymal organs. Furthermore, under conditions of compromised coagulation, treatment with CoStasis demonstrates a reduction in average blood loss when compared to treatment with fibrin sealant.

Animals↗

Hemostatic and healing studies of sodium amylose succinate (IP760).

Acute and chronic studies were performed in the canine model to evaluate a new topical hemostatic agent in terms of initial hemostatic capability and tissue/material interaction during the healing process. IP760, a porous amylose succinate material, was applied to large splenic surface wounds in six acute and twelve chronic animals. Microfibrillar collagen (Avitene) was used in twelve chronic animals for comparison. While the hemostatic capabilities of the two agents were comparable, marked differences were noted in the healing response. In the IP760-treated wound sites the acute inflammatory response, granulation tissue infiltration with fibrosis and healing occurred earlier and in a more homogeneous manner than in the Avitene-treated wound sites. Healing of the IP760-treated wounds occurred concomitantly with the development of granulation tissue and fibrosis and the rapid resorption of the IP760.

Administration, Topical↗

Development of a recombinant human collagen-type III based hemostat.

Animal-tissue-derived collagen, containing mostly type I collagen with a minor amount of type III collagen, has been widely used in the production of hemostats for many decades, although it has been known for a long time that type III collagen is more likely to induce platelet aggregation in vitro. Because it is hard to purify type III from animal tissue, it has not been possible to correlate this finding with in vivo data. In this report, it is demonstrated that recombinant human collagen III fibrils are more capable of inducing platelet aggregation in vitro than those comprised of bovine collagen I, in agreement with previously published data on tissue-derived type III collagen. When formed into three-dimensional matrices, the use of type III collagen results in formulations with better mechanical integrity, larger surface area, and higher hemostatic activity in a rabbit spleen injury model as compared with commercially available hemostats formed from bovine type I collagen.

Animals↗

Serological analysis of patients treated with a new surgical hemostat containing bovine proteins and autologous plasma.

A randomized, controlled clinical study of the management of diffuse bleeding with CoStasis surgical hemostat, a new hemostat containing bovine thrombin and collagen with the patient's own plasma, included patients undergoing cardiac, hepatic, iliac, and general surgery. Sera from 92 patients treated with CoStasis and 84 control patients were collected preoperatively and at a post surgical follow-up of 8 weeks. Among the control group, 57 patients were treated with Instat collagen sponge in noncardiac indications. Results showed that antibody responses in the CoStasis clinical study were similar to the reported literature for all antigens screened and were not associated with any adverse reactions. The bovine thrombin preparations in CoStasis and other commercially available thrombins were compared with the use of SDS-PAGE and Western blot analyses. Within this clinical study, CoStasis was shown to be a safe and effective hemostatic product containing bovine thrombin and bovine collagen and no pooled human blood products.

Animals↗

Development of a resorbable macroporous cellulosic material used as hemostatic in an osseous environment.

The control of bleeding is a frequently encountered therapeutic problem, particularly during dental surgery. The most efficient substances used to resolve this problem are not risk-free because of their animal or human origins, so cellulosic materials are potentially of interest. The aim of this study was to develop a resorbable macroporous cellulosic material for use as a resorbable hemostatic agent in bone sites. The degradation and the cytocompatibility of the cellulosic material versus controls were evaluated and its behaviour in vivo was studied. An original process using calcium carbonate powder as inverse matrix was used to develop a macroporous material. In order to predegrade the cellulosic material for hemostatic use, oxidation was performed with periodate. A dialdehyde component unstable at physiological pH was thus obtained. The material was found to have cytotoxicity, biocompatibility, and resorption properties similar to control but its hemostatic power was higher.

Absorbable Implants↗

Vitamin K administration to elderly patients with osteoporosis induces no hemostatic activation, even in those with suspected vitamin K deficiency.

The administration of menaquinone-4 (MK-4), one of subclasses of vitamin K2, significantly reduces bone loss in postmenopausal osteoporotic women. However, concerns have been raised about whether vitamin K administration alters the hemostatic balance by inducing a thrombotic tendency. We investigated were whether the administration of vitamin K in the form of MK-4 induced a thrombotic tendency in 29 elderly patients with osteoporosis (5 men, 24 women; age range 78.7+/-5.1 years). Patients were administered 45 mg/day (three times a day, 30 min after each meal) of MK-4 for 12 weeks. Blood samples were obtained from the patients at 0, 4 and 12 weeks after the start of MK-4 administration. A number of hemostatic parameters remained stable under the markedly increased plasma levels of MK-4. However, in patients with suspected vitamin K deficiency, whose plasma levels of vitamin K or factor VII were low, vitamin-K-dependent clotting factors such as factor VII and prothrombin were gradually increased after administration of MK-4. No changes in the sensitive molecular markers such as TAT and F1+2, which reflect the amount of thrombin generated in the blood stream, were observed, even in those patients with suspected vitamin K deficiency. These results indicate that MK-4 can be administered safely, with regard to maintaining the hemostatic balance, to osteoporotic patients receiving no anticoagulant therapy.

Aged↗

Gelatin-thrombin-based hemostatic sealant for intraoperative bleeding in vascular surgery.

Vascular surgical procedures may be prolonged because of intraoperative bleeding that is not easily controlled by cautery or suture ligation. This trial compared the ability of a new hemostat, FloSealTM Matrix (FM), with a known hemostat, Gelfoam(R) plus thrombin (GT), to control intraoperative bleeding. Patients undergoing vascular surgery procedures at four institutions were entered in the trial. After a bleeding site was identified, patients were randomized to one of the study agents: (1) FM, a cross-linked gelatin of bovine origin combined with thrombin, or (2) GT. The assigned agent was applied and the site observed for bleeding at 1, 2, 3, 6, and 10 min. The primary end point was cessation of bleeding within 10 min for the first identified site treated. Secondary end points were cessation of bleeding within 10 min for all sites and time to cessation of bleeding. Patients were assessed for morbidity at 30 days and 6-8 weeks after the operation. Analysis was performed on an intent-to-treat basis for analysis of hemostasis at 10 min and on protocol-valid patients for analysis of time to hemostasis. From our results we concluded that for patients undergoing vascular surgery procedures, the new topical hemostat, FloSeal Matrix, provides more rapid and effective hemostasis than Gelfoam plus thrombin.

Aged↗