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Effectiveness and safety of manual hemostasis facilitated by the SyvekPatch with one hour of bedrest after coronary angiography using six-French catheters.

Manual hemostasis facilitated by a SyvekPatch with 1 hour of bedrest after coronary angiography using 6Fr catheters was evaluated in a study of 200 patients. There were no major adverse events and 2% minor adverse events, all of which were managed successfully with additional bedrest of 1 to 2 hours. The findings suggest that the 1-hour bedrest protocol using the SyvekPatch is safe and effective in low-risk patients.

Acetylglucosamine↗

Changes in hemostasis during pediatric heart surgery: impact of a biocompatible heparin-coated perfusion system.

BACKGROUND: This study describes the response in hemostasis during open-heart surgery with cardiopulmonary bypass (CPB) in children (<== 10 kg) and tests the hypothesis that the use of a biocompatible perfusion system, in comparison with a conventional system, causes less hemostatic activation. METHODS: Prospective, randomized, controlled clinical study. Forty consecutive children <== 10 kg were included and divided into two groups: group bioc. (n = 19) treated with a fully heparin-coated system, centrifugal pump, and a closed circuit, and group conv. (n = 21) treated with an uncoated system, roller pump, and a hard shell venous reservoir. Concentrations of plasma thrombin-antithrombin (TAT), D-dimer, tissue plasminogen activator antigen (t-PA ag), and the complex consisting of tissue plasminogen activator and its inhibitor plasminogen activator inhibitor-1 (t-PA-PAI-1) were measured. RESULTS: The biochemical variables measured increased significantly in both groups during the study period. There was less activation of fibrinolysis during cardiopulmonary bypass (t-PA ag: p = 0.009) in patients treated with the biocompatible perfusion system than in patients treated with the conventional system. A trend in favor of the biocompatible system based on the D-dimer and TAT data (p = 0.07 for both measurements) was observed but no significant intergroup differences regarding these variables or t-PA-PAI-1 were found. CONCLUSIONS: Open-heart surgery with cardiopulmonary bypass in children (<== 10 kg) causes transient activation of the coagulation and fibrinolytic systems. This study demonstrates that the use of a biocompatible perfusion system results in a lower extent of activation of fibrinolysis during CPB than the use of a conventional system.

Anticoagulants↗

Platelet-neutrophil-interactions: linking hemostasis and inflammation.

Platelets are essential for primary hemostasis, but they also play an important pro-inflammatory role. Platelets normally circulate in a quiescent state. Upon activation, platelets can secrete and present various molecules, change their shape as well as the expression pattern of adhesion molecules. These changes are associated with the adhesion of platelets to leukocytes and the vessel wall. The interaction of platelets with neutrophils promotes the recruitment of neutrophils into inflammatory tissue and thus participates in host defense. This interaction of neutrophils with platelets is mainly mediated through P-selectin and beta(2) and beta(3) integrins (CD11b/CD18, CD41/CD61). Platelets can also interact with endothelial cells and monocytes. Adherent platelets promote the 'secondary capture' of neutrophils and other leukocytes. In addition, platelets secrete neutrophil and endothelial activators inducing production of inflammatory cytokines. Thus, platelets are important amplifiers of acute inflammation.

Blood Platelets↗

Hemostasis by means of a cautery knife equipped with an air spray for burns over a large area.

In operations in which debridement is performed over a large area (e.g., surgery for whole-body burns), it is necessary to keep the length of the operation short and the amount of blood loss as small as possible to minimize stress to the patient's body. In this study, we developed a cautery knife to which an air spray is attached for surgical procedures in which debridement is performed as treatment for burns over a large area. We have demonstrated herein that this device is very effective for reducing both blood loss and the duration of surgery as well as for simplifying the achievement of hemostasis.

Air↗

Controversies regarding hormone therapy: Insights from inflammation and hemostasis.

Many observational studies and experimental and animal studies have demonstrated that estrogen therapy (ET) or hormone therapy (HT) significantly reduces the risk of coronary heart disease. Nonetheless, recent randomized controlled trials and the Nurses' Health Study in secondary prevention demonstrate trends toward an increased risk of cardiovascular events rather than a reduction of risk from HT. HT has both anti-inflammatory and pro-inflammatory effects, and it activates coagulation and improves fibrinolysis. These effects depend on the route of administration, doses of estrogen, age of women, and the presence of coronary artery disease or the coexistence of other risk factors for hypercoagulability. In this review, we discuss effects of HT on markers of inflammation, hemostasis, and fibrinolysis that may link endothelial dysfunction in cardiovascular diseases. We also briefly discuss effects of lower doses of HT and tibolone in postmenopausal women.

Adult↗

Effects of particulate air pollution on hemostasis.

Exposure to particulate air pollution is associated with acute and chronic cardiovascular morbidity and mortality. The mechanisms involved in these effects are not fully elucidated. Research has proved that fine particles, principally the ultrafine fraction, which are predominantly derived from combustion of fossil fuel, are the most toxic. Recent clinical and experimental studies have reported mechanistic observations linking fine and ultrafine particles to the coagulation cascade, platelet function, and subsequent development of atherosclerosis and thrombosis. These effects have been explained either by release of soluble mediators by the lungs, which affect blood coagulation parameters, or by the direct translocation of ultrafine particles into the systemic circulation or the alteration of autonomic cardiac control. Despite recent advances, additional studies are needed to investigate the pathophysiologic mechanisms linking particulate air pollution and hemostasis.

Air Pollutants↗

High-density lipoprotein particles may regulate hemostasis in human pregnancy.

We explored the association of apolipoprotein A-I (the major protein constituent of high-density lipoprotein (HDL)) and fibrin fragment D-dimer (a marker of cross-linked fibrin turnover) in pregnant women. A significant inverse correlation between the levels of apolipoprotein A-I and fibrin fragment D-dimer was observed in both pre-eclamptic and normal pregnant women (rs = -0.459, n = 37 and rs = -0.290, n = 55, respectively), suggesting a major regulating role of HDL in hemostasis during pregnancy.

Female↗

Simulator training in endoscopic hemostasis.

Simulation of upper gastrointestinal (GI) hemorrhage provides the opportunity to practice endoscopic hemostasis without the risk of patient harm and time limitations. Various models have been developed to simulate an acute bleeding source in the upper GI tract to evaluate the feasibility of new endoscopic devices or to practice interventional techniques in a calm and controlled environment. Increasingly available ex vivo models provide this opportunity without the ethical concerns involved with live-animal courses. Validation studies have proven acceptance of ex vivo models and improved clinical performance by repetitive training using these models.

Animals↗

Hemodilution and surgical hemostasis contribute significantly to transfusion requirements in patients undergoing coronary artery bypass.

OBJECTIVE: We sought to determine the incidence of and risk factors for the development of low intraoperative hematocrit levels and of excessive postoperative bleeding in patients undergoing coronary artery bypass grafting, whether the risk factors are the same, and their effect on blood product transfusions. METHODS: We performed a prospective cohort study of 613 adult patients who underwent coronary artery bypass grafting in 3 tertiary, university-affiliated hospitals during the period from October 1, 2000, to March 31, 2001. RESULTS: Low intraoperative hematocrit levels (<19%) were found in 131 (24%) patients who had operations performed with extracorporeal circulation compared with in 3 (4%) patients with operations performed off pump. In multivariate analysis this was associated with older age, female sex, lower preoperative hemoglobin levels, lower body surface area, longer duration on bypass, and use of higher total volumes with more hydroxyethyl starch in the circuit. Low intraoperative hematocrit levels did not predict excessive postoperative hemorrhage (>1 L of mediastinal drainage in the first 12 hours). This occurred in 26% (n = 140) of patients undergoing on-pump operations and in 25% of patients undergoing off-pump operations and in multivariate analysis was associated with male sex, longer pump times, not receiving aprotinin, and operations performed by certain surgeons but not with total circuit or hydroxyethyl starch volume. CONCLUSIONS: We observed that the risk factors for the development of a low intraoperative hematocrit level and excessive postoperative bleeding differed. Our results suggest that decreasing these outcomes in patients undergoing cardiac surgery requires a comprehensive approach, including limiting hemodilution, particularly in female subjects with lower preoperative hemoglobin levels, and careful attention to surgical hemostasis.

Aged↗

Alternatively spliced tissue factor: a previously unknown piece in the puzzle of hemostasis.

Alternatively spliced tissue factor (asTF) has recently been discovered as a soluble form of tissue factor (TF), which circulates in blood and exhibits procoagulant activity. This soluble TF variant expanded the concept of circulating TF by a further element. Up to 30% of the TF antigen found in circulating blood was proposed to be derived from alternative splicing. We showed that cytokines induced the expression of asTF and the release from endothelial cells. The use of plasma asTF as a clinical marker for an inflammation-associated dysregulated hemostasis may therefore be a novel approach in predicting the patients' prognosis. This review covers the latest findings in the field of soluble TF focusing on asTF and its potential role besides the one in coagulation.

Alternative Splicing↗

Disturbances of anticoagulation and fibrinolytic systems in monoclonal gammopathies-another mechanism of M-protein interference with hemostasis.

Monoclonal gammopathies (MG) may be associated with unique monoclonal immunoglobulin (MIg)-induced disturbances of either primary hemostasis or plasma coagulation. We have investigated the possible interference of MIg with antithrombotic systems in 49 patients with MG. Although an increase of tissue-type plasminogen activator (t-PA) activity was the most frequent abnormality in our group, defect of anticoagulation factors was found in 26.5% of patients. The relationship between MIg type and concentration and frequency of antithrombotic factor abnormalities was not found. The risk of venous thrombosis was higher in patients with the defect in comparison with the unaffected group (46% vs. 22%), but the difference was not statistically significant. Bleeding complications were markedly less frequent in the group of patients with defect of anticoagulation mechanisms (0% vs. 17%). In conclusion, we have found abnormalities in anticoagulation and/or fibrinolytic system, analogous to well-known disturbances of hemostatic mechanisms, in more than a quarter of patients with MG. The interference of M-protein with antithrombotic pathways is supposed to be another mechanism of secondary deficiencies of antithrombin III (AT III), protein C (PC), protein S (PS), plasminogen and APC resistance. Together with other factors, it could contribute to higher risk of thromboembolism in myeloma patients.

Adult↗

Effects of cardiac surgery on hemostasis.

Cardiac surgery affects both coagulation and platelet function. Revision of surgery due to bleeding has to be performed in 2% to 6% of patients undergoing cardiac surgery and is generally associated with a marked deterioration in prognosis. Factors contributing to acquired hemostatic abnormalities in cardiac surgery include the use of anticoagulants as well as the activation and consumption of coagulation factors and platelets induced by the extracorporeal circulation. Prophylactic use of antifibrinolytic agents such as aprotinin and tranexamic acid has been demonstrated to reduce the blood loss by half. Adequacy of heparin-induced anticoagulation in the perioperative setting is commonly controlled by the activated clotting time. This method also indicates the correct reversal of the heparin effect by protamine. In recent years, thrombelastography has proved to be valuable for diagnosis of coagulopathy associated with cardiac surgery. In addition, the use of thrombelastography-based algorithms has been shown to reduce transfusion requirements. In contrast to point of care methods, laboratory assessment of hemostasis is more time-consuming and, thus, often not as rapidly available as required. At this time, the therapy for perioperative hemostatic abnormalities is based mainly on the administration of blood components (fresh frozen plasma and platelet concentrates). In the future, recombinant activated factor VIIa might prove to be a therapeutic option in patients with otherwise untractable bleeding, but the efficacy of recombinant activated factor VIIa has yet to be defined for this indication.

Blood Coagulation Disorders↗

Jararhagin and its multiple effects on hemostasis.

Jararhagin is a 52 kDa hemorrhagic P-III metalloproteinase isolated from the venom of the medically important Brazilian pit-viper Bothrops jararaca. It is a member of the reprolysin family of zinc metalloproteinases containing a catalytic metalloproteinase domain followed by a disintegrin-like and a cysteine-rich domain. The impact of jararhagin on hemostasis has been extensively studied using in vitro and in vivo model systems as well as in clinical studies. Jararhagin-induced hemorrhage is the result of the degradation of sub-endothelial matrix proteins leading to the disruption of the blood vessel endothelium, with accompanying disturbances in platelet function. The versatility of jararhagin is further demonstrated by its direct action on von Willebrand factor, the degradation of fibrinogen, by its inhibition of platelet adhesion to collagen and by its inability to be affected by the plasma inhibitor alpha(2)-macroglobulin. Collagen-induced platelet aggregation is inhibited by jararhagin though the binding of the molecule to the alpha(2) subunit I domain of the platelet surface alpha(2)beta(1) integrin (collagen receptor). Jararhagin also cleaves the beta(1) subunit of the same integrin, inhibiting platelet interaction and ultimately causing impairment of signal transduction. The effect of jararhagin on cell systems other than platelets is evaluated; in fibroblasts, jararhagin functions as a collagen-mimetic substrate and, in endothelial cells, it causes apoptosis and indirectly inhibits cell proliferation by release of angiostatin-like compounds. Jararhagin induces a strong pro-inflammatory response characterized by intense leukocyte accumulation at the site of the injection. Although hemorrhage and edema are a response to the direct effect of jararhagin, jararhagin-induced inflammation and necrosis are dependent on macrophages and key pro-inflammatory cytokines or their receptors. Some data also indicate that the toxin possesses anti-tumorgenic properties. Methods for inhibiting jararhagin are reviewed; this encompasses the use of synthetic peptides to the isolation of naturally occurring mammalian peptides and the development of toxin-specific antibodies through DNA immunisation and monoclonal antibody technologies. The availability of jararhagin makes it an important tool for research into the mechanisms of action of similar toxins, for insights into cellular interactions and for clinical investigations into the treatment of envenomings from B. jararaca.

Animals↗

Releasing or expression modulating mediator involved in hemostasis by Berythractivase and Jararhagin (SVMPs).

PIII snake venom metalloproteases (SVMPs) are structurally related to ADAMs (a disintegrin and metalloprotease human family of proteins). Berythractivase and Jararhagin are PIII SVMPs with 69% homology with different hemostatic properties. In order to clarify these differences and further characterize the biological effects of these proteins, we compared the effect of both proteases on human umbilical vein endothelial cell (HUVEC) for evaluating the release and modulation of coagulation and fibrinolysis mechanisms as well as the expression of their correlated genes. We found that both proteins increase the von Willebrand factor liberation, but did not modulate gene expression. Berythractivase, differently from Jararhagin increased the expression of tissue factor. Our results showed that both SVMPs (Berythractivase and Jararhagin) activate HUVEC releasing or modulating mediators involved in hemostasis. Meanwhile, we can suggest through the up-regulation of TF gene that the studied SVMP acts in a specific manner, suggesting that Jararhagin has preferentially a local action, while Berythractivase can be assumed as a systemic pro-coagulant protein with activity on the surface of HUVECs.

Cell Line↗

Platelet-Independent defect in hemostasis associated with sirolimus use.

Sirolimus is currently used to prevent rejection of solid organ transplant, and sirolimus-eluting stents have shown promise for the prevention of coronary artery restenosis. Thrombocytopenia is a well-known adverse effect of sirolimus limiting its use. Herein we report on a patient in whom sirolimus caused a platelet-independent hemostasis defect. The patient was a 52-year-old woman who underwent renal transplant with consequent normal kidney function. The immunosuppressive regimen included basiliximab, steroids, and cyclosporine induction later shifted to sirolimus and mycophenolate due to biopsy findings of tubular necrosis on day 6 posttransplantation. At discharge the serum creatinine was 0.7 mg/dL. Four months after transplantation the patient was admitted to our hospital because of fever (37.5 degrees C to 38 degrees C), anorexia, and asthenia. Blood analysis showed: creatinine 1.7 mg/dL, Hb 9.6 g/dL, WBC 6 x 10(3)/microL, PLT 123 x 10(3)/microL, liver function tests normal, LDH 720 mU/mL, fibrinogen 628 mg/dL, d-dimer 0.42 ng/mL, FDP > 40 ng/mL, INR 1.10, PT 87%, aPTT 40 seconds. Cultures and tests for infection were negative. Serum sirolimus level was 25.9 ng/mL. The following day the serum creatinine rose to 2.3 mg/dL and diuresis fell to 20 mL/h. Multiple bleeding times (Ivy test) performed before the renal biopsy were repeatedly over 30 minutes (normal 3 to 5 minutes), despite normal platelet count and platelet function studies. There was no spontaneous aggregation and in vitro aggregation was normal (collagen, ADP, adrenalin, and ristocetin induced). Coagulation studies showed a defect in fibrin formation and a reduction of fibrinolysis. Suspension of sirolimus treatment was followed by remission of fever, improvement of renal function (serum creatinine 1.2 mg/dL), and normalization of bleeding time.

Blood Platelets↗

A feasibility study of high intensity focused ultrasound for liver biopsy hemostasis.

This study was conducted to demonstrate the feasibility of high intensity focused ultrasound (HIFU) application to control post-liver-biopsy hemorrhage. Anesthetized Yorkshire pigs (n = 3; mean weight = 23.0 kg) were used and the liver organ was exposed surgically by an open laparotomy. Core biopsies were performed on the hepatic parenchyma with 14-gauge (n = 41) and 18-gauge (n = 33) core biopsy needles. The focus of HIFU (4.23 MHz) field was applied for 15 to 45 s to the needle entry site in the liver immediately after needle retraction. Blood loss from a biopsy site was determined using surgical sponges as absorbent applied at the site. Mean blood loss for control sites was 6.16 g (14-gauge, n = 20) and 1.22 g (18-gauge, n = 10). Virtually no blood loss was measured for biopsies after HIFU application (n = 44) for using needles of both sizes. Our results indicate that intraoperative HIFU application could successfully induce hemostasis after liver biopsy in a porcine model.

Animals↗

Laparoscopic temporary packing for hemostasis.

Control of bleeding from the renal parenchyma remains one of the challenges of laparoscopic partial nephrectomy. If adjuvant measures fail, packing of the surgical bed may achieve hemostasis. We report a novel series of temporary laparoscopic packing of the surgical bed with minimally invasive kidney surgery. Technique and potential complications are also discussed.

Aged↗