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[Microcirculatory hemostasis in children with insulin-dependent diabetes mellitus].

Study of microcirculatory hemostasis in children with insulin-dependent diabetes mellitus helped the authors to make new conclusions on metabolic changes underlying blood coagulation cellular factors, namely, the red cell and platelet levels. Fifty children aged 7 to 15, suffering from type I condition, were examined. Ten of these were examined during the compensation stage, 23 during decompensation without ketosis, and 17 with ketoacidosis. Twelve age-matched healthy children were controls. Noticeable disorders in the microcirculatory hemostasis system were revealed in diabetic children, these changes manifesting by changed functional activities of red cells and platelets. Reduced share of platelet deaggregation, increased red cell aggregation time, reduced thromboelastogram chronometric constant and reduction of its structural parameters may be considered as the early signs of these changes. The risk of microcirculatory hemostasis disturbances augments with the disease duration and progress.

Adolescent↗

Defects in hemostasis in P-selectin-deficient mice.

Recently, our laboratory showed that platelets, like leukocytes, roll on activated endothelium expressing P-selectin, thus suggesting a role for P-selectin in hemostasis (Frenette et at, Proc Natl Acad Sci USA 92:7450, 1995). We report here that the P-selectin--deficient mice show a 40% prolongation of the bleeding time on amputation of the tip of the tail. Moreover, defective hemostasis was observed in a local Shwartzman-like reaction induced by skin injections of lipopolysaccharide followed by tumor necrosis factor-alpha in the P-selectin--deficient mice. The hemorrhagic lesions, quantitated both macroscopically and microscopically, were twofold larger in the P-selectin--deficient mice. This was also confirmed by measuring the radioactivity in the skin using chromium-labeled red blood cells. Therefore, it is evident that P-selectin plays a role in hemostasis as suggested by its support of platelet rolling.

Animals↗

Repeated fasting and refeeding with 20:5, n-3 eicosapentaenoic acid (EPA): a novel approach for rapid fatty acid exchange and its effect on blood pressure, plasma lipids and hemostasis.

Twenty hypertensive subjects participated in three clinical trials of 13 days each, to examine the effects of Alsepa fish oil [20:5, n-3 eicosapentaenoic acid (EPA) 180 mg, and 22:6 n-3 docosahexaenoic acid (DHA) 120 mg] on n-3 for n-6 polyunsaturated fatty acids (PUFA) exchange on serum phospholipids, blood pressure (BP), triglycerides (TG) and primary hemostasis. After 13 days, plasma phospholipids showed an increase in sigma n-3 (EPA and DHA) from 2.0 to 5.9% (P < 0.01), and a decrease in sigma n-6 (arachidonic acid and linoleic acid) from 29.8 to 22.6% (P < 0.01). A concomitantly significant reduction in systolic BP (SBP) (158.7 +/- 23.8 mm Hg to 146.5 +/- 17.0 mm Hg, P = 0.04), and diastolic BP (DBP) (80.8 +/- 8.4 mm Hg to 72.9 +/- 14.9 mm Hg, P = 0.04) as well as a significant decrease in platelet adhesion and aggregation on extra cellular matrix measured as a percentage of surface coverage (11.9 +/- 4.8% to 4.2 +/- 3.2%, P = 0.0001) was observed. In addition, a significant reduction in baseline dependent TG was observed; the higher the baseline level TG, the more pronounced the reduction (average 159.2 +/- 74.6 mg% to 108.0 +/- 46.1 mg%, P = 0.001). No change was observed in total cholesterol, high and low density lipoprotein (HDL, LDL), platelet and fibrinogen. Repeated fasting and refeeding with fish oil facilitated plasma exchange of n-3 for n-6 PUFA, improved BP, clinical metabolic parameters and lowered platelet reactivity in the vessel wall (primary hemostasis). In severe and life-threatening situations, the beneficial effects of fish oil should be considered for rapid exchange of n-3 for n-6 PUFA. In this study we describe a novel approach for rapid fatty acid exchange by fasting/refeeding with fish oil supplementation, as well as improved BP, plasma lipids and primary hemostasis. Further research is required on the therapeutic use of fish oils and the physiological mechanisms involved in fatty acid exchange.

Adult↗

[Disorder of the thrombocytic-vascular component of hemostasis in thyrotoxicosis].

Hemocoagulation and the platelet-vascular hemostasis mechanism were investigated in 79 patients suffering from thyrotoxicosis of different severity by clinical observations and laboratory studies. Along with hemocoagulation defects, there were revealed thrombocytopenia, reduction of the platelet adhesive-aggregation activity and of the vascular wall resistance. The extent of these disturbances depended on the severity of thyrotoxicosis. In the authors opinion, affection of the platelet-vascular hemostasis component, combined with hemocoagulation disturbances played an important role in the development mechanism of increased hemorrhagic tendency of the tissues and hemorrhagic diathesis in thyrotoxicosis. The necessity of complex treatment of patients with thyrotoxicosis with prescription of agents normalizing hemocoagulation and the platelet-vascular hemostasis mechanism is founded.

Blood Coagulation Disorders↗

Does endoscopic hemostasis effect the reduction of mortality in patients with hemorrhage from the digestive tract?

BACKGROUND/AIMS: Endoscopy is the method of choice for localizing the sites of hemorrhage and transendoscopic hemostatic procedures in patients with hemorrhage from the digestive tract. The aim of the study was to establish the efficacy of endoscopic hemostasis and to analyze the mortality of patients with upper digestive tract hemorrhage. METHODOLOGY: The retrospective analysis included those patients who had undergone urgent endoscopic examination of the upper digestive tract and hemostatic interventions with injection sclerotherapy, laser photocoagulation or electrocoagulation of the hemorrhaging spot in the period between January 1994 and May 1995. RESULTS: 1000 patients were examined, 638 men and 362 women. In only 312 patients (31.2%) the examination revealed signs of acute or recent hemorrhage. Hemostatic interventions were performed in 275 (27.5%) cases. During hospitalization at the medical wards, 14 (9/275, 5.1%) patients died. In 9 patients (9/275, 3%) with acute hemorrhage, endoscopic hemostasis did not prove successful, therefore after several unsuccessfully repeated endoscopic interventions (21 in all), the patients were treated operatively. During the postoperative period, 4 patients died due to complications. CONCLUSIONS: Despite the development of endoscopic instruments and improved methods of hemostasis, mortality due to hemorrhage from the digestive tract has not dramatically decreased. Numerous demanding endoscopic procedures are usually carried out in older patients which also suffer from other diseases. These diseases represent the risk factors for eventual surgical treatment and the ensuing complications.

Adolescent↗

[Endoscopic hemostasis for esophagogastric bleeding: technical assessment and recent advances].

The method and its technical issues of endoscopic hemostasis for the upper gastro-intestinal bleeding were reviewed. Precise diagnosis of bleeding point by endoscopic observation has become almost perfect with the technological progress of endoscopy. For large veins such as esophagogastric varices, endoscopic sclerotherapy has achieved great success. For small protruded vessels such as small arteries, mechanical method like clipping or band-ligation has advantage. Chemical or physical coagulation is also very useful for hemostasis of small vessels. Combination of two or three methods is sometimes effective in complicated patients. Endoscopic hemostasis is now golden standard for gastrointestinal hemorrhage.

Endoscopy, Gastrointestinal↗

Alterations in hemostasis associated with hyperthermia in a canine model.

Use of hyperthermia in the treatment of cancer and viral infection has received renewed interest. However, the in vivo relationship between hyperthermia and direct versus indirect effects upon hemostasis are incompletely defined, although we do know that disseminated intravascular coagulation (DIC) is a common sequel to heat stroke. The purpose of the present study was to more precisely define the relationship between hyperthermia and derangements of hemostasis, thereby providing a guideline for the development of safe hyperthermia treatment regimens. The present investigation examined the in vivo effects of high-grade whole-body hyperthermia (WBH) (42.5 degrees C, 90 min) on hemostasis in a canine model. Induction of hyperthermia via extracorporeal circulation of heated blood (ECC-WBH) caused thrombocytopenia, increased plasma fibrin degradation products (FDPs), prolonged clotting times, increased serum liver enzymes, and evidence of spontaneous bleeding. However, when WBH was induced by peritoneal lavage (PL-WBH), transient thrombocytopenia was the only significant alteration. Temporal correlation between hemostatic alterations and elevations in serum alanine aminotransferase (ALT) levels in the ECC-WBH treatment group suggested that liver injury is responsible, at least in part, for the coagulopathy associated with high-grade hyperthermia and that in the absence of liver injury, identical degrees of hyperthermia cause only incidental decreases in platelet numbers.

Animals↗

Relative risks of reported serious injury and death associated with hemostasis devices by gender.

PURPOSE: To assess relative risks by gender of reported serious injuries and deaths associated with the use of hemostasis devices, stratified by year of report, type of injury, and type of device. METHODS: Reports from the Food and Drug Administration's Medical Device Reporting system and National Center for Health Statistics data on use of cardiac catheterization were used to estimate relative risks of reported serious injuries and deaths by gender. RESULTS: Estimated risks of reported serious injuries and deaths associated with hemostasis devices were two to three times greater in females than in males for hemorrhage and hematoma (p < 0.0001), but there was no significant difference in risks by gender for infection. CONCLUSIONS: Cardiac catheterization is sometimes associated with serious injuries and deaths. Among patients who receive hemostasis devices, the risk of these events are disproportionately greater in women.

Angioplasty, Balloon, Coronary↗

Evaluation of endoscopic hemostasis using an improved clipping apparatus.

Endoscopic clipping hemostasis (ECH) is an effective method to control bleeding. However, ordinary clipping apparatuses have not been widely adopted because of several disadvantages. Accordingly, we developed an improved ECH apparatus that can be used during a general endoscopic examination without requiring an assistant. It is not only easy to operate but also ensures safe and effective hemostasis. The ECH apparatus was employed in 80 patients between February 1983 and August 1987 at the Sakura National Hospital. Fifty-one of the patients had upper gastrointestinal bleeding; in 29, preventive clipping was performed after polypectomy. Permanent hemostasis was maintained in 43 (84.3%) of the patients with upper gastrointestinal bleeding, and no bleeding was recognized in any of the 29 patients treated with prophylactic clipping following polypectomy.

Endoscopes↗

Prompt and safe femoral hemostasis with a collagen device after intracoronary implantation of Palmaz-Schatz stents.

We report the safety and efficacy of sealing the femoral puncture site with percutaneously applied collagen after Palmaz-Schatz stent implantation in 100 consecutive patients. Patients were anticoagulated with continuous heparin infusion, overlapping oral anticoagulants, and antiplatelet therapy by dextran, aspirin, and dipyridamole. At the time of sheath removal and collagen application, the mean activated partial thromboplastin time and prothrombin time values expressed as international normalized ratio were 3.2 +/- 2.1 and 1.6 +/- 0.7, respectively. The hemostasis time ranged from 1 to 8 minutes (mean 2.18 +/- 2.08 minutes). Only two (2%) patients had major puncture-site bleeding (not seal related in one case) that required surgery and blood transfusions. Small (< 6 cm) and medium (6 to 10 cm) hematomas observed in 12 (12%) and 2 (2%) patients, respectively, resolved spontaneously without sequelae. Local infection developed in 2 (2%) patients, who were successfully treated with antibiotics without clinical consequences. Subacute stent thrombosis was observed in only 1 (1%) patient. Repeat catheterization through the same femoral artery was performed at 6-month follow-up in 55 patients without difficulty or vascular complications. These findings suggest that percutaneous collagen application after coronary stenting is a secure method of achieving prompt and effective femoral hemostasis with a low incidence of major vascular bleeding complications despite intense anticoagulation. Stable hemostasis may allow continued full-dose anticoagulation, reducing the risk of stent subacute thrombosis.

Administration, Cutaneous↗

Hemostasis and mechanism of action of selective antimetastatic drugs in mice bearing Lewis lung carcinoma.

The selective antimetastatic agents p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK), 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) and (+/-)1,2-di(3,5-dioxopiperazin-1-yl)propane (ICRF-159) have been shown to markedly depress the formation of spontaneous hematogenous metastases in mice bearing s.c. Lewis lung carcinoma, with a mechanism unrelated to cytotoxicity for tumor cells. The effects on hemostasis of DM-COOK, DTIC and ICRF-159 have thus been examined in comparison with those of a purely cytotoxic agent, cyclophosphamide, in mice bearing i.m. Lewis lung carcinoma. The parameters considered are the number of platelets and their aggregability, prothrombin and partial thromboplastin times, plasma fibrinogen concentration and tumor cell procoagulant activity. Slight variations are caused by drug treatment in tumor-bearing mice as compared with untreated tumor-bearing controls; the pattern of effects of the selective antimetastatic agents does not differ from that of the reference cytotoxic compound used, cyclophosphamide. These data thus indicate that the effects on hemostasis of the drugs examined can contribute only marginally to their antimetastatic action, since more pronounced effects on hemostasis have been shown to be required to significantly affect metastasis formation.

Animals↗

Comparative effects of a contraceptive vaginal ring delivering a nonandrogenic progestin and continuous ethinyl estradiol and a combined oral contraceptive containing levonorgestrel on hemostasis variables.

OBJECTIVE: This study aimed to compare the effects on hemostasis variables of a contraceptive vaginal ring with those of an oral contraceptive. STUDY DESIGN: Twenty-three and 22 healthy premenopausal women were randomized to the contraceptive vaginal ring (150 microg Nestorone and 15 microg ethinyl estradiol) or Stediril 30 during 3 cycles. Analysis of covariance was performed with baseline values as covariate. RESULTS: The contraceptive vaginal ring changed most hemostasis variables similarly but raised (95% confidence intervals of percent treatment differences) Factor VIIt (28% to 49%), extrinsic activated protein C resistance (14% to 65%), and sex hormone-binding globulin (117% to 210%) and lowered Protein S (-32% to -16%) and the global activated partial thromboplastin time-based activated protein C resistance (-12% to -2%) more than the oral contraceptive. CONCLUSION: The contraceptive vaginal ring affected some measured hemostasis variables and sex hormone-binding globulin differently from the oral contraceptive, most likely because of difference in androgenicity of the progestins. The results suggest that the contraindications for oral contraceptive use would also apply to the tested contraceptive vaginal ring.

Activated Protein C Resistance↗

A prospective study on the effects on hemostasis of two oral contraceptives containing drospirenone in combination with either 30 or 20 microg ethinyl estradiol and a reference containing desogestrel and 30 microg ethinyl estradiol.

PURPOSE: In this open-label, randomized study, we assessed the effects on hemostasis of two combined oral contraceptives containing drospirenone (DRSP) as progestogen component. METHODS: Three milligrams of DRSP, a progestogen with antimineralocorticoid activity, was combined with either 30 or 20 microg ethinyl estradiol (EE) (DRSP/30EE; DRSP/20EE) and compared with a preparation containing 150 microg desogestrel (DSG) and 30 microg ethinyl estradiol (DSG/30EE). A total of 75 healthy female volunteers aged 18-35 years were enrolled. The hemostasis variables were measured in the medication-free precycle (baseline); in the first, third and sixth treatment cycle; and in the follow-up phase. The target variables for comparison were the relative changes from baseline to Cycle 6. RESULTS: Data of 25 volunteers in each group were valid for the per-protocol evaluation. Most changes in hemostasis variables were similar in the three treatment groups. All procoagulatory variables and the anticoagulatory variable protein C antigen increased slightly, while protein S antigen and activity decreased. For fibrinogen and protein S activity, the changes were statistically significant: less pronounced with DRSP/20EE compared to DSG/30EE at Cycle 6. There were no statistically significant differences in the changes of antifibrinolytic variables, the global clotting tests and D-dimer. All pairwise comparisons of DRSP/30EE vs. DSG/30EE yielded nonsignificant results; however, there was a trend of a lower impact of DRSP/20EE on nearly all hemostatic parameters compared to the 30EE products. All three study treatments were safe and well tolerated by the volunteers and provided adequate contraceptive reliability. CONCLUSION: The changes in the hemostatic variables for DRSP/20EE were less pronounced compared to DSG/30EE and DRSP/30EE. The results were in accordance with previous reports on effects of similar OCs.

Adolescent↗

Improved hemostasis during laparoscopic partial nephrectomy using gelatin matrix thrombin sealant.

OBJECTIVES: To evaluate whether using a biologic hemostatic sealant facilitates hemostasis during laparoscopic partial nephrectomy. Secure and durable parenchymal hemostasis is a critical requirement during laparoscopic partial nephrectomy. METHODS: Since September 1999, laparoscopic partial nephrectomy has been performed in more than 300 patients by a single surgeon, duplicating open surgical principles. Recently, from patient 225 onward, we modified our technique by incorporating topical application of a gelatin matrix thrombin sealant (FloSeal) to cover the partial nephrectomy bed before sutured renorrhaphy over a Surgicel bolster. The impact of FloSeal on reducing hemorrhagic complications was evaluated by comparing two sequential groups of patients: group 1 consisted of 68 patients in whom FloSeal was not used (patients 156 to 224) and group 2 consisted of 63 patients in whom it was used (patients 225 to 288). RESULTS: Groups 1 (no FloSeal) and 2 (FloSeal) were comparable in tumor size, number of central tumors, and performance of pelvicaliceal suture repair (84% versus 92%; P = 0.16). Intraoperative variables were also comparable in terms of mean warm ischemia time (36.1 versus 37.2 minutes; P = 0.55), blood loss (150 versus 106 mL; P = 0.36), operative time, and hospital stay. However, the FloSeal group had significantly fewer overall complications (37% versus 16%; P = 0.008) and tended toward a lower rate of hemorrhagic complications (12% versus 3%), although this did not achieve statistical significance (P = 0.08). CONCLUSIONS: The results of this study have shown that adjunctive use of gelatin matrix thrombin sealant substantially enhances parenchymal hemostasis and has decreased our procedural and hemorrhagic complications to levels comparable with contemporary open partial nephrectomy series. This gelatin matrix-thrombin tissue sealant is now a routine part of laparoscopic partial nephrectomy at our institution.

Gelatin Sponge, Absorbable↗

Improved clinical effectiveness with a collagen vascular hemostasis device for shortened immobilization time following diagnostic angiography and percutaneous transluminal coronary angioplasty.

This study prospectively compared immobilization time followed by use of a vascular hemostasis device (VasoSeal) versus manual compression to achieve hemostasis at the arterial puncture after angiography and percutaneous transluminal coronary angioplasty (PTCA). The trial shows that use of a vascular hemostasis device results in earlier mobilization, even in highly anticoagulated PTCA patients compared with manual compression, with no statistically significant complications.

Adolescent↗

Central venous catheter placement in patients with disorders of hemostasis.

BACKGROUND: Patients requiring central venous access frequently have disorders of hemostasis. The aim of this study was to identify factors predictive of bleeding complications after central venous catheterization in this group of patients. METHODS: A retrospective analysis of all central venous catheters placed over a 2-year period (1997 to 1999) at our institution were performed. The age, sex, clinical diagnosis, most recent platelet count, prothrombin international normalized ratio (INR), activated partial thromboplastin time (aPTT), catheter type, the number of passes to complete the procedure, and bleeding complications were retrieved from the medical records. RESULTS: In a 2-year period, 2,010 central venous catheters were placed in 1,825 patients. Three hundred and thirty placements were in patients with disorders of hemostasis. In 88 of the 330 patients, the underlying coagulopathy was not corrected before catheter placement. In these patients, there were 3 bleeding complications requiring placement of a purse string suture at the catheter entry site. In the remaining 242 patients, there was 1 bleeding complication. Of the variables analyzed, only a low platelet count (<50 x 10(9)/L) was significantly associated with bleeding complications. CONCLUSION: Central venous access procedures can be safely performed in patients with underlying disorders of hemostasis. Even patients with low platelet counts have infrequent (3 of 88) bleeding complications, and these problems are easily managed.

Blood Coagulation Disorders↗

Histologic and immunohistochemical features in biopsy sites in which bovine collagen matrix was used for hemostasis.

BACKGROUND: Bovine collagen matrix (Helistat and Helatene), which is used primarily for hemostasis, decreases wound contracture in skin biopsy sites and promotes wound granulation. OBJECTIVE: Our purpose was to evaluate excision specimens of previous biopsy sites to determine whether there are histologic differences between cases in which bovine collagen matrix was used for hemostasis and those in which it was not used. METHODS: Thirty-two diagnostic punch biopsies were done with hemostasis obtained with bovine collagen matrix in 24 biopsies and by pressure alone in eight. The biopsy sites were reexcised at various time intervals, and the histologic and immunohistochemical features were evaluated and compared. RESULTS: In specimens in which collagen matrix was used, migration of stromal and epithelial cells along the bovine collagen matrix was evident by 2 days and had progressed rapidly by 4 days. Around and within the matrix hyaluronic acid increased during the first 8 to 10 days. Initially stromal cells stained with CD34 and reticulum fibers were present at 8 to 10 days. AT 12 to 15 days, factor XIIIa+ stromal cells were present within the matrix, and host collagen fibers were present and well-oriented within the degenerating matrix. Biopsy specimens allowed to heal without the matrix showed a delayed and an uneven increase in hyaluronic acid. Furthermore, the granulation tissue within the dermis showed no organization with a persistent acute inflammatory infiltrate and increased muscle actin-positive stromal cells as scar formation proceeded. CONCLUSION: Bovine collagen products appear to provide a matrix that promotes thrombosis. The collagen matrix also promotes migration and attachment of stomal and epithelial cells, thereby organizing and accelerating wound healing.

Actins↗

Hemostasis of punctured blood vessels using high-intensity focused ultrasound.

The hemorrhagic complications of vascular injury can be significant. We report on the use of high-intensity focused ultrasound (HIFU) to stop the hemorrhage of punctured blood vessels in pigs. Two HIFU transducers with frequencies of 3.5 and 2.0 MHz, each equipped with a water-filled conical housing, were used. Major blood vessels (femoral artery and vein, axillary artery, carotid artery and jugular vein), 2-10 mm in diameter, of anesthetized pigs were exposed surgically and punctured with 14- and 18-gauge needles to produce moderate to profuse bleeding. Complete hemostasis was achieved in less than 3 min of HIFU treatment in most blood vessels, and all vessels were patent after the treatment. Both HIFU frequencies were effective in producing hemostasis. Gross examination of the HIFU-treated vessels showed a consistent hardening of the soft tissue surrounding the blood vessels, providing a seal for the puncture hole. Microscopic examination of the vessels showed a remarkably localized HIFU treatment, resulting in coagulation of the adventitia, and an extensive fibrin network around the vessels and in the puncture hole. The vessel walls exhibited focal swelling, without evidence of irreversible injury. HIFU may provide a useful method for achieving hemostasis of punctured and traumatized blood vessels in a variety of clinical settings.

Animals↗