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PubMed1977

The hemostatic effects of orally administered Yunnan Bai Yao in rats and rabbits.

The effects of orally administered Yunnan Bai Yao were studied on the bleeding time in rats and the blood clotting time in rabbits. Significant decreases were seen in both the bleeding and clotting times, observed over a 4 h period following administration. These effects were seen as early as 1/2 h and were still present at 4 h. Graded doses of Yunnan Bai Yao produced dose-related decreases in blood clotting times in the rabbits. The findings suggest that some active principle, able to affect the hemostatic mechanism, is absorbed after oral administration of the herbal preparation.

Administration, Oral↗
PubMed1990

Hemostatic protein-polymer sheath: new method to enhance hemostasis at percutaneous biopsy.

Serious hemorrhagic complications have been reported with percutaneous biopsy, albeit infrequently. A hemostatic protein-polymer sheath (PPS) designed to limit the risk of bleeding was evaluated by performing liver biopsies on pigs given anticoagulants. After administration of anesthesia and laparotomy, biopsies were performed under direct vision with a cutting biopsy needle (a) alone, (b) fitted with the PPS, or (c) fitted with a thrombin-coated PPS. Dry sponges were applied and subsequently weighted to quantitate blood loss. At all levels of anticoagulation, use of the PPS enhanced hemostasis; the thrombin coating supplemented effectiveness. The PPS appears to be a simple and effective method of achieving hemostasis at high-risk percutaneous biopsy.

Animals↗
PubMed2005

[Fibrinogen. An old hemostatic protein with a new function: non-invasive marker of subclinical atherosclerosis].

The formation of a fibrin clot is one of the key events in atherothrombotic vascular diseases, such as myocardial infarction, ischemic stroke and peripheral arterial disease. Fibrin is formed from a circulating precursor, fibrinogen, by the action of thrombin. Both genetic and environmental factors are important determinants of the circulating fibrinogen levels. Epidemiologic studies have demonstrated a role for this hemostatic protein in the prediction of cardiovascular disease. As an acute-phase reactant, fibrinogen is also a marker of inflammation. Likewise, recent studies from our group have shown that increased fibrinogen levels represent a marker of subclinical atherosclerosis, likely to be useful in the identification of asymptomatic subjects at risk for cardiovascular disease.

Arteriosclerosis↗
PubMedDate not supplied

Hemostatic and fibrinolytic response to nasal desmopressin in hemodialysis patients.

OBJECTIVE: To evaluate the effect of desmopressin (DDAVP) on hemostatic parameters during dialysis and in the interval between dialysis sessions. SUBJECTS AND METHODS: Fifteen patients dialyzed twice weekly at least for 1 year and 15 healthy volunteers serving as a control group were enrolled in the study. Bleeding time, platelet count, prothrombin time, activated partial thromboplastin time, tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), euglobulin clot lysis time, protein C, protein S, fibrinogen, D-dimer, factor V, VII, VIII, IX, X and von Willebrand factor (VWF) values were studied at the beginning, at 2 and 4 h of dialysis with and without administration of DDAVP at a dose level of 2 microg/kg intranasally. RESULTS: After dialysis, bleeding time shortened, PAI-1 and fibrinogen levels were lower, while VWF and D-dimer levels were higher. After DDAVP administration, bleeding time, PAI-1 levels were significantly lower (p <0.01), while tPA, factor VIII and VWF levels increased significantly (p <0.001). CONCLUSION: The findings indicate that DDAVP can be used for patients on dialysis with serious bleeding.

Administration, Intranasal↗
PubMed1991

Effect of local hemostatics on platelet aggregation.

The platelets play an important role in the normal hemostasis, and it is known that both natural and synthetic macromolecules may induce platelet activation and aggregation. Thus, the purpose of the present study was to investigate the platelet aggregating effect of five different local hemostatics. Platelet aggregation was assessed by aggregometry. Unwoven fleece of bovine collagen polymer in fibrillar form induced aggregation in combination with small amounts of platelet agonists; ADP and adrenaline. Ordinary, nonabsorbable bone wax also induced aggregation in combination with the agonists, but larger concentrations of agonists were needed. Bioerodible polyorthoester with physical properties such as bone wax, oxidized cellulose and gelatin sponge did not promote platelet aggregation.

Adenosine Diphosphate↗
PubMed1987

In vitro effect of a microfibrillar collagen hemostat on platelets.

Microscopic particles of microfibrillar collagen hemostat (MCH) have been shown to pass through a 40-micron blood transfusion filter. This study indicates that MCH passing through the filter retains a significant portion of its ability to aggregate platelets in vitro and the aggregating ability is dose related. The extent of platelet aggregation in the presence of the MCH filtrate or an ADP standard was measured photometrically and log dose-response curves constructed from the data. An ED50 of 3.6 micrograms protein/ml platelet-rich plasma (PRP) was calculated at a protein concentration of 7.6 mg/ml in the MCH filtrate and an ED50 of 5.9 micrograms protein/ml PRP at 12 mg/ml protein in the MCH filtrate. The platelet aggregating ability of the MCH filtrates corresponded to 18.8 and 39.6% of the maximum response produced by adenosine-5'-diphosphate. These findings support the view that blood contaminated with MCH should not be returned to a patient's circulation.

Adenosine Diphosphate↗
PubMed2006

Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk.

OBJECTIVE: We undertook a linkage disequilibrium (LD)-based genetic approach to investigate the hypothesis that common sequence variants in 5 thrombosis genes influence plasma hemostatic protein levels or risk of cardiovascular disease (CVD). METHODS AND RESULTS: In a reference panel, we characterized LD structure at the fibrinogen gene cluster (fibrinogen-beta[FGB], FGA, and FGG), factor VII (F7), and tissue plasminogen activator (PLAT) loci. Forty-one tag single nucleotide polymorphisms (SNPs) were genotyped in 1811 unrelated Framingham Heart Study participants. There were significant associations of 9 FGB SNPs with fibrinogen level (minimum P=0.002) and of 7 F7 SNPs and factor VII level (minimum P<0.0001). SNPs at the PLAT locus were not associated with PLAT level. In stepwise analysis, a single FGB variant explained 1% of the residual variance in fibrinogen level, and 2 F7 SNPs together explained 10% of the residual variance in factor VII level. Two PLAT haplotypes were associated with CVD (multivariable-adjusted global P=0.0004). CONCLUSIONS: A comprehensive survey of common sequence variation demonstrates that cis-regulatory SNPs explain a modest proportion of the residual variance in circulating fibrinogen and factor VII level and PLAT haplotypes increase the risk of CVD. Additional studies are warranted to confirm the association of PLAT sequence variation and risk of CVD.

Aged↗
PubMed2000

Relationship of fibrinogen levels and hemostatic abnormalities with organ damage in hypertension.

Elevated plasma levels of fibrinogen and activated coagulation pathways are risk factors of cardiovascular disease in the general population. In a cross-sectional study of a case series, we investigated the relationship between fibrinogen and hemostatic markers with target-organ damage (TOD) in patients with arterial hypertension. Prothrombin time, partial thromboplastin time, fibrinogen, fibrin D-dimer, prothrombin fragment 1+2 (F1+2), and antithrombin III were measured in 352 untreated patients with mild to moderate essential hypertension and 92 normotensive controls. Staging of TOD was assessed according to W.H.O. guidelines by clinical evaluation and laboratory tests including measurements of creatinine clearance, proteinuria, ophthalmoscopy, electrocardiography, echocardiography, and ultrasound examination of major arteries. F1+2 concentrations were significantly greater in hypertensive patients than normotensive controls and were positively correlated with blood pressure. Age, blood pressure levels, duration of hypertension, smoking, HDL-cholesterol, triglycerides, and plasma fibrinogen, fibrin D-dimer, and F1+2 levels were significantly related to the presence and severity of TOD in univariate analysis. Plasma fibrinogen and D-dimer levels were related to organ damage independent of age, blood pressure, duration of hypertension, and smoking status. Separate analysis indicated significant association of fibrinogen and D-dimer levels with cardiac, cerebrovascular, peripheral vascular, and renal damage. In conclusion, elevated plasma levels of fibrinogen and a prothrombotic state are associated with the presence and severity of TOD in patients with essential hypertension and may contribute to the development of atherosclerotic disease in these patients.

Aged↗
PubMed1988

Fibrin glue: a review of its preparation, efficacy, and adverse effects as a topical hemostat.

Fibrin glue is composed of two separate solutions of fibrinogen and thrombin. When mixed together, these agents mimic the last stages of the clotting cascade to form a fibrin clot. Fibrin glue is available in Europe but is not commercially available in the U.S.; therefore, investigators have extemporaneously compounded their own fibrin glue. Fibrinogen can be obtained from pooled, single-donor, and autologous blood donors and is usually isolated by the process of cryoprecipitation. The thrombin component is generally derived from commercial bovine sources. Some investigators have added calcium chloride and/or antifibrinolytics (i.e., aminocaproic acid, aprotinin) to their preparations. Fibrin glue can be applied using a double-barrel syringe or by spray application. Although fibrin glue has been used in a variety of surgical procedures, it has been especially useful in heparinized patients undergoing cardiovascular procedures requiring extracorporeal circulation, as it does not require an intact hemostatic system to be effective. Fibrin glue also has been evaluated in presealing woven or knitted Dacron vascular grafts. The major drawback to its use is the risk of transmitted serological disease from pooled and single-donor blood donors. The safest preparations use the patient's own blood to prepare fibrin glue. Overall, fibrin glue is a useful adjunct to other methods to control bleeding in selected surgical patients.

Administration, Topical↗
PubMed2000

Changes of hemostatic molecular markers after gynecological surgery.

The authors evaluated the hemostatic abnormalities occurring in the postoperative period of eight patients with malignant tumors and compared them with those occurring in the postoperative period of eight patients with benign tumors. Two of the patients with malignant tumor presented pulmonary embolism after operation. Plasma fibrinogen and fibrin degradation product levels in patients with malignant tumors were already high before operation and further increased significantly after operation. The plasma levels of D-dimer, thrombin-antithrombin complex, and free-tissue factor pathway inhibitor were increased in both groups after operation, but they were higher in patients with malignant tumors than in patients with benign tumors. The plasma levels of protein C and antithrombin were significantly decreased in both groups after operation. but they were significantly lower in patients with malignant tumors than in those with benign tumors. The decreased activity of protein C or antithrombin may be not only a risk factor of thrombotic disease, such as pulmonary embolism, but also the cause of thrombosis. In patients with malignant tumors, the operation time was significantly longer than that in patients with benign tumors. This long operative period might cause vascular endothelial cell injury which is reflected by the plasma levels of free-tissue factor pathway inhibitor, antithrombin, and protein C.

Adult↗
PubMed2003

Atherosclerotic and hemostatic abnormalities in patients undergoing hemodialysis.

Vascular events caused by atherosclerosis are the major cause of death in patients undergoing hemodialysis (HD). The relationship between the tests of atherosclerosis and hemostasis in 84 patients with HD was examined. Abnormal test results indicting the occurrence of atherosclerosis were found in 66% by the Fontaine score, in 33% by ankle blood pressures, and in 79% by aortic calcification index (ACI). When HD was prolonged, the mean Fontaine score and ACI were further increased. Particularly, the ACI tended to correlate with HD duration. The ankle-brachial index (ABI) was decreased in patients with HD duration of more than 10 years. Before HD, the plasma levels of fibrinogen, plasmin-plasmin inhibitor complex (PIC), thrombomodulin (TM), and D-dimer were increased, while the plasma levels of protein C (PC), antithrombin (AT), thrombin-antithrombin complex (TAT), and tissue plasminogen activator (tPA)-plasminogen activator inhibitor-I (PAI-I) complex (tPA-PAI-1 complex) were decreased. With prolonged HD, the plasma levels of AT and PC were decreased, while those of D-dimer were increased. The plasma levels of TAT and TPA-PAI-1 complex were significantly increased and those of PIC, soluble fibrin (SF) and D-dimer tended to be high in patients with less than 0.7 of ABI. The plasma levels of D-dimer, TPA-PAI-1 complex, TAT, PIC, and SF tended to be high in patients with more than 0.5 in ABI. These findings suggest that patients undergoing HD have progressive atherosclerosis and that this is associated with some hemostatic abnormalities.

Aged↗
PubMed2006

Challenges in the therapeutic use of a "so-called" universal hemostatic agent: recombinant factor VIIa.

Recombinant factor VIIa (rFVIIa) was developed in the early 1990s to provide "bypassing" hemostatic therapy for hemophilia A and B patients with inhibitors. More recently, it has been licensed for use in patients with inherited deficiency of factor VII. Since it was licensed for use in hemophilia with inhibitors in the US, Europe, and other countries for these specific indications, it has been used selectively but in a wide array of clinical settings for uncontrolled hemorrhage in individuals without an inherited bleeding disorder. Many of these uses have been described in the medical literature as case reports or small, uncontrolled series. Several randomized clinical trials (RCT) for these "off-label" medical uses have been published in recent months and will serve as the focus of this review. In particular, a review of an RCT for spontaneous intracranial hemorrhage that has demonstrated clinical efficacy in reducing both mortality and volume of central nervous system hemorrhage will be offered. A brief discussion of hypothesized physiologic mechanisms of supraphysiologic doses of rFVIIa will introduce the clinical discussion of these broad off-label uses. Since rFVIIa is a very expensive therapy, possible strategies for optimizing its use in the these settings will be presented.

Factor VII↗
PubMed2004

Heparin-level-based anticoagulation management during cardiopulmonary bypass: a pilot investigation on the effects of a half-dose aprotinin protocol on postoperative blood loss and hemostatic activation and inflammatory response.

UNLABELLED: Cardiac surgery involving cardiopulmonary bypass (CPB) leads to activation of the hemostatic/inflammatory system. We compared the influence of a half-dose aprotinin regimen on postoperative blood loss and the activation of the hemostatic/inflammatory system during CPB, when used during a heparin-level-based heparin management for cardiac surgery. Two-hundred patients (n = 100 in each group) were enrolled in this randomized prospective study. In Group I only heparin was given according to the results of the Hepcon HMS Plus. In Group II aprotinin was added with a bolus of 1 x 10(6) kallikrein inhibiting units (KIU) for the patient immediately before initiation of CPB, 1 x 10(6) KIU in the priming solution of the CPB, and a continuous infusion of 250,000 KIU/h during CPB. Postoperative blood loss was determined after 12 h. Heparin and antithrombin activity were evaluated by an anti-Xa assay and measurement of antithrombin III activity. Hemostatic activation was evaluated by adenosine diphosphate-stimulated platelet aggregometry and by measurements of the generation/release of beta-thromboglobulin (beta-TG), soluble P-selectin (sPS), thrombin (TAT), prothrombin 1 and 2 fragments (PTF1+2), factor XIIa (FXIIa), plasmin (PAP), and D-dimers. Inflammatory response was evaluated by measuring complement factors 5b-9 (C5b-9), interleukin (IL)-6, and neutrophil elastase (NE). There were no differences in the pre-CPB values or duration of CPB between the two groups. There were no differences in the post-CPB values for platelet count, platelet aggregation, beta-TG, sPS, TAT, PTF1+2, C5b-9, NE, or IL-6. The additional use of aprotinin resulted in a significant decrease of PAP, D-dimers, and 12 h postoperative blood loss, whereas generation of the contact factor XIIa was increased. The administration of aprotinin significantly reduced postoperative blood loss after cardiac surgery and CPB. This most likely has to be attributed to the antifibrinolytic effects of aprotinin. No effects on thrombin generation, platelet activation, inflammatory response, or clinical outcome were noted. IMPLICATIONS: The use of half-dose aprotinin and heparin-level-based anticoagulation management during cardiopulmonary bypass leads to a significant reduction of postoperative blood loss after cardiac surgery. This effect can most likely be attributed to the antifibrinolytic effects of aprotinin, as we did not observe effects on other variables of activation of the hemostatic/inflammatory system.

Adult↗
PubMed2005

A triple-blinded randomized trial comparing the hemostatic effects of large-dose 10% hydroxyethyl starch 264/0.45 versus 5% albumin during major reconstructive surgery.

In Canada, hydroxyethyl starch 264/0.45 (HES 264/0.45; molar weight 264 kDa, molar substitution 0.45) has largely replaced albumin as the colloidal fluid of choice for perioperative intravascular volume expansion. The maximum recommended dose of HES 264/0.45 is 28 mL/kg; however, there are no clinical data supporting this limit. In this study we compared the hemostatic effects of HES 264/0.45 versus 5% albumin in doses up to 45 mL/kg over 24 h during major reconstructive head and neck surgery. Fifty patients were randomized to receive HES 264/0.45 or 5% human albumin from the induction of anesthesia until 24 h thereafter. Both albumin and HES 264/0.45 effectively maintained physiologic variables in the perioperative and postoperative periods. The partial thromboplastin time and international normalized ratio were significantly increased in the HES 264/0.45 group compared with the albumin group after infusion of 30 mL/kg and 45 mL/kg (P < 0.05). Factor VIII activity and von Willebrand factor level were significantly reduced in the HES 264/0.45 group compared with the albumin group after infusion of 15 mL/kg, 30 mL/kg, and 45 mL/kg (P < 0.05). Significantly more subjects in the HES 264/0.45 group received allogeneic red blood cell transfusions (P < 0.02). We conclude that HES 264/0.45 infusions >30 mL/kg over 24 h impair coagulation to a greater extent than albumin, possibly leading to more allogeneic transfusions.

Anesthesia↗
PubMed1989

Studies on the antihemostatic substances in herbs classified as hemostatics in traditional Chinese medicine. I. On the antihemostatic principles in Sophora japonica L.

By following the antihemostatic activity of the material according to Tajima's method, the antihemostatic principle was isolated from dried buds of Sophora japonica L., and identified as isorhamnetin [2-(3-methoxy-4-hydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one]. The antihemostatic specificity of isorhamnetin toward antihemorrhagic compounds isolated previously from hemostatic herbs used in traditional Chinese medicine was examined.

Animals↗
PubMed2005

Bronchoscopy-guided topical hemostatic tamponade therapy for the management of life-threatening hemoptysis.

STUDY OBJECTIVES: Massive hemoptysis is a life-threatening condition. Therapeutic strategies such as interventional angiography, surgery, and/or bronchoscopy have been applied in the clinical setting with variable results. We investigated the efficacy of bronchoscopy-guided topical hemostatic tamponade therapy (THT) using oxidized regenerated cellulose (ORC) mesh in the management of life-threatening hemoptysis. DESIGN: Seventy-six consecutive patients underwent emergency bronchoscopy for massive hemoptysis. Fifty-seven patients (75%) had persistent endobronchial bleeding despite bronchoscopic wedging technique, cold saline solution lavage, and instillation of regional vasoconstrictors. These patients subsequently underwent THT according to the same procedure. SETTING: Teaching hospital, bronchoscopy unit of a 300-bed tertiary pulmonary referral center. RESULTS: THT with ORC was successfully performed on 56 of 57 patients (98%) with an immediate arrest of hemoptysis. All patients successfully treated with THT remained free of hemoptysis for the first 48 h. None required intensive care support or immediate surgery. Mean procedure time (+/- SD) of THT was 11.5 +/- 4.2 min. Recurrence of hemoptysis that was characterized as being mild (< 30 mL) to moderate (30 to 100 mL) developed in six patients (10.5%) 3 to 6 days after THT. Post-obstructive pneumonia developed in five subjects (9%) after endoscopic THT. A subgroup of patients (n = 14) underwent bronchoscopic follow-up 4 weeks after discharge. The ORC mesh was absorbed in all of these patients without signs of foreign body reaction. CONCLUSIONS: Endobronchial THT using ORC is a safe and practicable technique in the management of life-threatening hemoptysis with a high success and a relatively low complication rate.

Adult↗
PubMed2003

Histologic study of use of microfibrillar collagen hemostat in rat dental sockets.

The aim of this paper was to evaluate if the placement of microfibrillar collagen hemostat (MCH) into a dental socket interfered with healing. General anesthesia was administered to 30 adult male Albinus Wistar rats and the maxillary right central incisor was extracted. In the control group after each tooth was extracted, the socket was sutured. In the MCH group after each tooth was extracted, MCH was placed into the socket before suturing. Postoperatively, 5 animals were sacrificed from each group at 7, 21 and 28 days. The right maxilla was removed from each animal and histologic slides were stained with Masson's trichromic and hematoxylin and eosin. Quantitative and qualitative analyses were done. The percentage of bone area in the dental socket was quantified using the Image Lab 98 image analysis system. The bone area formation for the control and MCH groups was: 8.1% and 3.3% at 7 days, 34.4% and 33% at 21 days and 41% and 41.3% at 28 days, respectively. We concluded that MCH interferes with the beginning of dental socket healing but does not interfere with the final healing of the dental socket.

Alveolar Process↗
PubMed1985

Collagen sponge as a topical hemostatic agent in mucogingival surgery.

Hemorrhage from palatal donor sites during periodontal mucogingival surgery was controlled by application of Collastat absorbable hemostatic sponges. The use of collagen sponges was evaluated in 20 free-graft cases. In contrast to microfibrillar collagen, which is normally delivered as clumps of material, a Collastat sponge was applied as a single piece that maintained structural integrity even when wet and was easy to maneuver into place. The highly porous sponges conformed to the wound, absorbed fluid and produced consistently reliable hemostasis with no secondary bleeding. By stemming the seepage of blood into the throat, patient safety and comfort were improved. The sponges were left on the wounds and removed at the 1-week postoperative visit, revealing well-formed granulation tissue. Healing proceeded normally with no evidence of infection, tissue reaction, or other adverse effects.

Collagen↗