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[Principal symptoms in hemostasis disorders].

In a retrospective study the results of laboratory investigations were correlated with actual or previous bleeding symptoms of 40 patients. In 22 patients, a defect of hemostasis was documented in the laboratory, whereas the bleeding disorder, suggested by severe hemorrhage, could not be classified in 3 additional patients. In the remaining 15 individuals, no abnormality could be detected by the available laboratory methods. In the group with a documented bleeding disorder, 13 of 22 patients had prolonged bleeding following dental extraction or other surgery of the oral cavity. Other bleeding symptoms were equally distributed among patients with and without a documented defect. 3 patients had a positive family history, i.e. relatives with a hemorrhagic tendency. In 6 patients, a correlation between bleeding and the ingestion of acetylsalicylic acid could be established, while in 4 it was probable. Hemorrhagic complications following oral surgery, particularly in combination with drugs known to interfere with platelet function and a positive family history, strongly suggest an abnormality of hemostasis. Among the 22 patients with a documented defect of hemostasis, only 6 were found who did not present at least one of these leading symptoms.

Blood Coagulation Disorders↗

[Effect of physical training on the clinical course and the status of blood coagulation hemostasis in patients with ischemic heart disease].

The effect of intensive rationed exercise on coagulation hemostasis was assessed in 92 males, including 10 normal subjects and 82 coronary patients. Twenty male coronary patients, treated with antianginal drugs, were taken as controls. There were no significant changes in coagulation hemostasis between normal subjects after an exercise course and coronary patients on antianginal treatment. Intensive rationed exercise normalized coagulation hemostasis in coronary patients, as evidenced by reduced thrombinemia owing to smaller concentrations of factors VIII and X and an increase in protein C content.

Adult↗

[Effect of minidoses of heparin on the blood coagulation and thrombocytic links of hemostasis in myocardial infarct in middle-aged and elderly patients].

A study was made of the effect of moderate (300-500 units/kg per day) and minimum (200-250 units/kg per day) heparin doses in intravenous drop administration on the coagulation and thrombocytic links of hemostasis in 26 elderly and advanced age patients with myocardial infarction. The patients were divided into 2 groups: streptodecase and heparin were administered to the patients of the 1st group and heparin only was administered to the patients of the 2nd group. No significant effect of streptodecase on the hemocoagulation link of hemostasis with a low risk of developing hemorrhagic complications was noted. In 72-96 h of treatment intravenous heparin administration resulted in a decrease in a level of blood antithrombin III causing a decrease in the efficacy of heparin therapy. Control over a level of blood antithrombin III in addition to routine tests (thrombin time, thromboelastogram) provided an opportunity for adequate anticoagulant therapy. A negative effect of heparin on the thrombocytic link of hemostasis with deterioration of disaggregation properties and an increase in aggregation was noted. Antiaggregation therapy in parallel with the start of heparin administration was found necessary.

Aged↗

Use of absorbable collagen for hemostasis in general surgical patients.

Absorbable collagen sheet hemostat was used to obtain hemostasis in 62 general surgical patients. It was unusually effective in controlling profuse capillary, venular, and arteriolar bleeding in 61 of the 62 patients, with a mean time to hemostasis of 2.2 minutes. Collagen hemostat was particularly effective in the gallbladder bed after cholecystectomy, at liver and pancreatic biopsy sites, and on the cut surface of the thyroid gland. Collagen hemostat was also effective in inducing hemostasis in three patients with altered coagulation parameters associated with liver disease and in another patient with von Willebrand's disease. The material was easy to handle when wet with blood and did not stick to gloves, surgical instruments, or sponges. The collagen sheet hemostat also conformed well to tissues. None of our 62 patients experienced foreign body reaction, infection, or allergic manifestations.

Adolescent↗

[State of microcirculation and cellular hemostasis in men with borderline arterial hypertension during thermoneutral "dry" water immersion].

Platelet hemostasis, microcirculation, blood viscosity and lipid metabolism were examined in 18 men with borderline hypertension and 8 healthy men before, during and after 7-day immersion. The exposure to thermoneutral dry water immersion produced hypercoagulopathic changes of platelet hemostasis in the healthy and hypertensive subjects. Platelet hemostasis returned to the pretest level in the healthy subjects 2 days and in the hypertensive subjects only 5 days after exposure. Prior to immersion the hypertensive subjects showed signs of capillarotrophic insufficiency which increased after exposure. On immersion day 3 the hypertensive subjects exhibited a higher blood viscosity and a larger content of total lipids and free fatty acids. All the parameters returned to normal 2 days after immersion.

Blood Viscosity↗

Comparison of different methods for endoscopic hemostasis of bleeding canine esophageal varices.

Despite advances in the therapy of acute esophageal variceal hemorrhage, morbidity and mortality remain high. Continued severe variceal hemorrhage remains a major clinical problem in poor risk patients who cannot tolerate emergency surgery for hemostasis. Several endoscopic hemostatic methods might be effective for variceal hemostasis, but they have not been systematically evaluated. Using a reproducible canine model of esophageal varices, several hemostatic modalities were tested and compared to determine which were most effective in stopping variceal bleeding. Methods tested were endoscopic sclerotherapy, organ laser, neodymium-yttrium-aluminum-garnet laser, monopolar electro-coagulation, bipolar electrocoagulation, ferromagnetic tamponade, and endoscopic heater probe. Both neodymium-yttrium-aluminum-garnet laser and endoscopic sclerotherapy provided reliable hemostasis in acutely bleeding canine varices. Large heater probe controlled bleeding 50% of the time, and all the other methods stopped bleeding in less than half the trials. Rebleeding after balloon inflation proximal to the coagulated bleeding site did not occur with neodymium-yttrium-aluminum-garnet laser or endoscopic sclerotherapy-treated varices but did occur with the other methods. The principal differences between neodymium-yttrium-aluminum-garnet laser and endoscopic sclerotherapy were the ease of application of neodymium-yttrium-aluminum-garnet laser, the higher frequency of esophageal ulcers or erosions with neodymium-yttrium-aluminum-garnet laser, and the lack of variceal obliteration with neodymium-yttrium-aluminum-garnet laser.

Animals↗

[Infrared contact coagulation for hemostasis in liver and spleen].

With infrared contact coagulation (ICC) hemostasis of hepatic and splenic tissue is achieved by coagulation and mechanic compression of the bleeding surface. Thus, an eventual loss of energy due to a thick layer of blood can be avoided. After coagulation, the anti-adhesive effect of the cap of the ICC device prevents fresh bleeding. After experimental incisions on liver and spleen of various animal species hemostasis could be achieved quickly by application of ICC. Postoperative observation and histologic investigations were carried out until the 80th postoperative day. Hemostasis was observed in all cases, there were no signs of recidivant bleeding at relaparotomy. A slow absorption f necrotic tissue was observed. This could be a disadvantage regarding long term wound healing.

Animals↗

[Percutaneous administration of collagen (VasoSeal): an efficacious system of hemostasis after catheterization or interventional procedures using arterial approach].

INTRODUCTION: The widespread use of PTCA and complex percutaneous interventional techniques has significantly increased peripheral vascular complications prompting the development of innovative hemostatic closure devices. METHODS: To evaluate the efficacy and safety of a bovine collagen plug (VasoSeal), we sealed 362 consecutive femoral artery puncture sites in 324 patients (240 males) (mean age 57.9 +/- 11.3 years), who underwent interventional procedures or diagnostic catheterization during acute or chronic anticoagulant treatment. RESULTS: Complete hemostasis was achieved in 2.31 +/- 1.97 minutes in 342 cases (94.4%), with a mean activated clotting time at collagen deployment of 197 +/- 56". In 20 cases, mechanical arterial compression was needed in order to obtain vascular hemostasis (mean time: 44 +/- 13 min). We observed 1 arteriovenous fistula and 1 acute arterial thrombosis (collagen related at surgical inspection) which underwent successful surgical treatment. Minor complications without clinical sequelae were: small hematomas in 13 cases (3.8%), 4 groin abscesses (1.1%) and 4 cases of lymphangitis (1.1%). CONCLUSIONS: Percutaneous collagen application at the femoral artery puncture site allows quick and effective hemostasis with low incidence of peripheral vascular complications following interventional percutaneous procedures or catheterization during anticoagulant treatment.

Administration, Cutaneous↗

Hemostasis abnormalities in patients with vascular dementia and Alzheimer's disease.

Since it has not been established to what extent abnormalities of hemostasis contribute to the occurrence and development of dementia, selected measurements of coagulation and fibrinolysis were obtained in elderly patients with Alzheimer's disease (n = 22) or vascular dementia (n = 29), compared with healthy individuals in the same age range (n = 61). Hemostasis abnormalities were more frequent and marked in vascular dementia, being expressed as significant increases of plasminogen activator inhibitor type 1, von Willebrand factor, D-dimer and activated factor VII. However, some hemostasis measurements (von Willebrand factor, activated factor VII) were abnormally high also in the patients with Alzheimer's disease, a condition in which vascular damage is not considered to play a major pathogenetic role. It could not be established in this study whether or not these hemostatic abnormalities play a casual role in the pathogenesis of dementia, or whether they are secondary to inflammation and chronic vascular disease. Nevertheless, their presence may contribute to aggravating vascular disease.

Aged↗

V2 receptor antagonism of DDAVP-induced release of hemostasis factors in conscious dogs.

The synthetic arginine vasopressin (AVP) analog 1-desamino-8-D-arginine vasopressin (DDAVP) is used in a variety of hemorrhagic disorders. The present experiments were designed to further characterize the mechanism of DDAVP-induced release of hemostasis factors. The [3H]AVP-labeled AVP receptor in canine renomedullary membranes exhibited an AVP V2 profile because the V2 receptor agonist DDAVP displayed similar subnanomolar affinities as the natural hormone AVP, whereas the two selective V1a compounds SR 49059 and d(CH2)5Tyr(Me)AVP as well as the selective V1b agonist D-Pal and oxytocin were much less potent. The rank order of the binding affinities of three V2 receptor antagonists was SR 121463 (a newly described selective V2 receptor antagonist) > OPC 31260 >> d(CH2)5D-Ile2,Ile4AVP. In conscious dogs, DDAVP (0.1-1 microg/kg I.V.) caused a dose-related increase (maximum, 43-52% at 30 min) in plasma levels of factor VIII (FVIII), von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA), but not in levels of plasminogen activator inhibitor-1. A DDAVP-induced hemostasis factor release was also observed in bilaterally nephrectomized dogs. Pretreatment with SR 121463 inhibited DDAVP-induced (1 microg/kg I.V.) increases in FVIII, vWF and t-PA plasma levels in a dose-dependent manner (ID50 = 14.0 +/- 4.0, 12.4 +/- 3.0 and 16.7 +/- 1.0 microg/kg I.V., respectively). OPC 31260 (300 microg/kg I.V.) revealed a lower activity than SR 121463, and d(CH2)5[D-Ile2,Ile4]AVP (30 microg/kg I.V.) was without effect on the DDAVP response. Pretreatment with SR 49059 (1 mg/kg I.V.) and SR 27417 (a platelet-activating factor receptor antagonist) (1 mg/kg I.V.) had no effect on the DDAVP-induced (1 microg/kg I.V.) increases in FVIII, vWF and t-PA plasma levels. The present results, therefore, strongly suggest that the effect of DDAVP on hemostasis factors occurs via a specific interaction with extrarenal V2 receptors.

Animals↗

[Importance of endoscopic hemostasis in peptic ulcer hemorrhage in a teaching hospital].

INTRODUCTION: The results of endoscopic treatment for bleeding peptic ulcers in a teaching hospital are little reported. Most studies are published by a limited number of specialized authors with a reported success rate of 76-83%. The aim of this study is to evaluate the success rate in a teaching hospital. PATIENTS AND METHOD: We retrospectively studied 150 patients hospitalized in our service between 1994 and 1995. They comprised 59 females (median age 80.5 [24-93] years) and 91 males (median age 61.5 [26-98]). 49% were aged 70 or over. 39 patients (29%) had a past history of peptic ulcer disease, the others being admitted for an initial episode of bleeding ulcer. Biopsies for urease test were obtained in 84 patients. In this group the prevalence of Helicobacter pylori infection was respectively 88% and 58% in subjects with a history of ulcer disease and in those with an initial episode of bleeding ulcer. 46% and 54% respectively had taken nonsteroidal anti-inflammatory drugs during the previous weeks. Neither of these two risk factors was present in 9 patients without a previous history of ulcer disease; they were present in none of those with a history. RESULTS: All patients underwent emergency esogastroduodenoscopy; 48 underwent endoscopic hemostasis. 12 gastroenterologists were involved in these procedures. The definitive success rate is 81%. The success rate for a first hemostasis for a posterior bulbar ulcer is 41% vs 88% for the other localizations, a difference which is statistically significant (p = 0.002). Endoscopic hemostasis showed a higher failure rate where the bleeding stigmata was a spurting vessel (44% vs 18%) but this was not significant (p = 0.18). CONCLUSION: Endoscopic treatment for bleeding peptic ulcer is effective in a teaching hospital. The technique shows a higher failure rate for posterior bulbar ulcers. In view of the risk of recurrence, patients should be kept in hospital after a first procedure.

Adult↗

Retransfusion of suctioned blood during cardiopulmonary bypass impairs hemostasis.

In a previous study we observed extensive clotting and fibrinolysis in blood from the thoracic cavities during cardiopulmonary bypass. We hypothesized that retransfusion of this suctioned blood could impair hemostasis. In this prospective clinical study we investigated the effect of suctioned blood retransfusion on systemic blood activation and on postoperative hemostasis. During coronary artery bypass grafting in 40 patients, suctioned blood was collected separately. It then was retransfused to the patient at the end of the operation (n = 19), or it was retained (n = 21). During the study, 12 consecutive patients, randomized in two groups of 6, were analyzed for biochemical parameters indicating blood activation and clotting. The immediate and significant increase in circulating concentrations of thrombin-antithrombin III complex, tissue-type plasminogen activator, fibrin degradation products, and free plasma hemoglobin demonstrated the effect of suctioned blood retransfusion. Moreover, the increased concentrations of thrombin-antithrombin III complex and fibrin degradation products indicated renewed systemic clotting and fibrinolysis as a direct result of the retransfusion of suctioned blood. Concentrations of all indicators mentioned remained significantly lower in the retainment group. The clinical data showed that retainment of suctioned blood resulted in significantly decreased postoperative blood loss (822 mL in the retransfusion group versus 611 mL in the retainment group; p < 0.05) and similar or even reduced consumption of blood products (513 versus 414 mL red blood cell concentrate and 384 versus 150 mL single-donor plasma; both not significant). We conclude that retransfusion of highly activated suctioned blood during cardiopulmonary bypass exacerbates wound bleeding.

Blood Transfusion, Autologous↗

Historical review: more than two decades understanding the genetic architecture of hemostasis and thrombosis.

From the beginning of the millennium and the development of genome-wide analyses, the technical advances and remarkable increase in research sample sizes have led to an escalating number of discoveries revealing genetic determinants of levels of the main factors regulating hemostasis and thrombosis and demonstrating a clear polygenic complex regulation of most coagulation factors. These discoveries have been useful to understand the biology underlying hemostasis regulation and to understand risk of associated thrombotic disease, such as venous thromboembolism, coronary artery disease, and ischemic stroke. In this historical review, we outline the main discoveries in genetic studies of coagulation factors (fibrinogen and its alternatively spliced &#x3b3;' isoform, D-dimer, factor [F]V, FVII, FVIII, von Willebrand factor, and FXI), the main natural anticoagulants (protein C, protein S, and antithrombin), components of fibrinolysis (tissue plasminogen activator and plasminogen activator inhibitor-1), and global coagulation tests (prothrombin time and activated partial thromboplastin time). We explore the clinical implications of these discoveries and suggest new avenues for future investigation.

Humans↗

Fibrin glue achieves hemostasis in patients with coagulation disorders.

Fibrin glue (FG), made with highly concentrated human fibrinogen and clotting factors, was used to achieve parenchymal organ hemostasis in patients with disordered coagulation secondary to massive transfusion, chronic disease, and disseminated intravascular coagulation; it was effective in controlling liver hemorrhage in seven patients and in the performance of a splenorrhaphy in one other patient. The coagulation profile was grossly abnormal in all patients, and the mean +/- SD intraoperative blood loss was 5.1 +/- 4.2 L; patients received 14 +/- 10 U of blood perioperatively. The amount of FG required to achieve hemostasis varied directly with the extent of injury and intraoperative blood loss (r = .84), and all patients with a blood loss greater than 4 L required at least 25 mL of FG to stop bleeding. Two patients died postoperatively secondary to cardiac arrest and adult respiratory distress syndrome. Because FG does not depend on adequate platelet or clotting factor levels to be effective, it is especially useful in patients with parenchymal organ hemorrhage and disordered coagulation.

Adult↗

Rapid hemostasis of arterial puncture sites with collagen in patients undergoing diagnostic and interventional cardiac catheterization.

Despite the continuous reduction of sheath sizes in diagnostic and interventional cardiac catheterizations and the discontinuation of coumadin use after coronary stent implantation, a challenging role remains for hemostatic devices in the sealing femoral puncture sites. Since the introduction of the vascular hemostatic device (VHD) in 1991 and the hemostatic puncture closing device (HPCD) in 1992, numerous studies investigating these devices have been published. The deployment success rates reported in 2,292 patients for VHD is 97%, ranging from 88 to 100%. For HPCD, the mean deployment success rate resulting from 622 published patients leads to an identical result of 97%, ranging between 91 and 100%. For time to hemostasis, data have been analyzed according to the four different clinical situations, depending on level of anticoagulation (none or full) and the time of sheath removal (immediate or delayed). In randomized studies, when compared with the manual control groups, both devices revealed a statistically significant reduction in time to hemostasis: 12 to 16 minutes less for diagnostic catheterization and 14 to 30 minutes less for PTCA. As for minor local complications, no clinically relevant differences seem to exist. None of these devices has been proven to reduce major local complications. Prospective trials addressing early mobilization after percutaneous transluminal coronary angioplasty and the cost effectiveness of arterial closure devices in defined subgroups are warranted.

Angioplasty, Balloon, Coronary↗

Cell adhesion and regulatory molecules involved in tumor formation, hemostasis, and wound healing.

BACKGROUND: Dynamic changes in cell adhesion and migration are fundamental properties of the cells that are important in hemostasis, vascularization, and wound repair. Changes in cell adhesion and migration are very important in the formation of tumors, and invasion and metastasis by neoplasms. METHODS: Using immunolocalization and immunopurification techniques, expression of integrin molecules involved in cell adhesion has been characterized during tumor development and wound healing. The ability of cytokines to regulate expression and antibody and peptide inhibitors to inhibit function of integrins has been explored to better understand the role of integrins in pathogenesis. RESULTS: Increased suprabasilar expression of the integrins alpha 6 beta 4, alpha 2 beta 1, and alpha 3 beta 1 accompanies development of squamous cell neoplasms of the head and neck. Integrin alpha II beta 3 is an integrin receptor which is important in platelet aggregation in hemostasis and formation of tumor metastases. Increased expression of integrin alpha v beta 3 has been identified in angiogenesis in response to growth factors and tumor angiogenic factors. Cytokine TGF-beta and arachadonic acid metabolite 12(S)-HETE are important signals in regulation of integrins and affect cell aggregation and migration in these processes. Ligands and inhibitors for some of these receptors have been identified which will be useful in determining their role during tumor development and progression. CONCLUSION: Recent advances in understanding the functions of the integrin cell adhesion molecules may soon add new diagnostic methods and therapies to the armamentarium of the head and neck oncologic, microvascular, plastic, and reconstructive surgeon. Therapies directed at controlling integrin cell-adhesion molecule expression and function are being explored to improve scar formation, bone synthesis, inhibition of vascular occlusion, and inhibition of tumor invasion and metastasis.

Antigens, Surface↗

Hemostasis and fibrinolysis in severe liver failure and their relation to hemorrhage.

In a study of severe, decompensated liver failure, we tried to find a correlation between hemorrhage and parameters of hemostasis and fibrinolysis. Three groups of patients were studied: alcoholic cirrhosis; nonalcoholic cirrhosis, and acute liver failure without known prior liver disease. The two cirrhotic groups did not differ significantly from each other in coagulation or in fibrinolytic parameters, although liver function was more impaired in nonalcoholic cirrhosis. The levels of clotting factors, antithrombin III, prekallikrein, plasminogen and alpha 2-antiplasmin were significantly lower in the third group. Mean values of fibrinolytic activity (fibrin plate method) were slightly reduced as compared to normal in all three groups. Tissue plasminogen activator-related antigen tended to be elevated especially in alcoholic cirrhosis. The free fast-acting plasminogen activator inhibitor showed extremely high and extremely low levels in some patients among all three groups. Nonvariceal, capillary-type bleeding, including mucosal bleeding, hematomas and bleeding from puncture sites correlated with low thrombotest and normotest levels (p less than 0.01), low fibrinogen concentration (p less than 0.05) and with a high quotient of fibrinolytic activity (square root of lysis area) and normotest (p less than 0.001). The ratio between fibrin formation and dissolution appears to be an important parameter of hemorrhagic tendency in liver disease. Variceal bleeding appeared not to be related to impairment of hemostasis or fibrinolysis.

Acute Disease↗

Effects of oxaprozin alone or in combination with aspirin on hemostasis and plasma protein binding.

Oxaprozin, a new nonsteroidal antiinflammatory agent, was studied alone and in combination with aspirin for its effects on hemostasis and protein binding in 10 healthy adults. When both oxaprozin and aspirin were given separately for seven days and in combination for five days, both drugs prolonged bleeding time and inhibited collagen- and epinephrine-induced platelet aggregation to a similar degree. The effects of the combination of oxaprozin and aspirin were not additive. The data from the protein binding study showed that oxaprozin was more than 99 per cent bound to plasma proteins. Aspirin displaced oxaprozin from its binding sites. As a result, the rate of plasma clearance of oxaprozin significantly increased from 20 to 26 ml/min/kg (P less than 0.05), and the plasma half-life decreased from 45 to 40 hours. Platelet count and the humoral clotting mechanism were not affected by either drug alone or in combination. There was no clinical evidence of bleeding. One subject who received oxaprozin for 12 days and, in addition, aspirin for the last five days developed a rash that subsided after both drugs were discontinued; one subject treated with aspirin experienced tinnitus. These data suggest that oxaprozin, like aspirin and other nonsteroidal antiinflammatory drugs, should be used with caution when administered to patients who have suffered trauma, who undergo surgery, or who have known defects in hemostasis.

Adult↗