fibrin and Blood-Loss--Surgical

Liver resection is the optimal treatment for selected benign and malignant liver tumours, but it can be associated with significant blood loss. Numerous anaesthetic and surgical techniques have been developed to reduce blood loss and improve perioperative outcomes. One such technique is the application of topical fibrin-based haemostatic agents (FBHAs) to the resection surface. There is no standard practice for FBHA use, and a variety of commercial agents and devices are available, as well as non-FBHAs (e.g. collagen-based agents). The literature is inconclusive on the effectiveness of these methods and on the clinical benefits of their routine use.. To evaluate the benefits and harms of fibrin-based haemostatic agents in reducing intraoperative blood loss in adults undergoing liver resection.. We searched the Cochrane Hepato-Biliary Group (CHBG) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science up to 20 January 2023. We also searched online trial registries, checked the reference lists of all primary studies, and contacted the authors of included trials for additional published or unpublished trials.. We considered for inclusion all randomised clinical trials evaluating FBHAs versus no topical intervention or non-FBHAs, irrespective of publication type, publication status, language of publication, and outcomes reported. Eligible participants could have any liver pathology and be undergoing major or minor liver resections through open or laparoscopic surgery.. Two review authors independently screened the results of the literature search and used data extraction forms to collate the results. We expressed dichotomous outcome results as risk ratios (RRs) and continuous outcome results as mean differences (MDs), each with their corresponding 95% confidence interval (CI). We used a random-effects model for the main analyses. Our primary outcomes were perioperative mortality, serious adverse events, haemostatic efficacy, and health-related quality of life. Our secondary outcomes were efficacy as sealant, adverse events considered non-serious, operating time, and length of hospital stay. We assessed the certainty of the evidence with GRADE and presented results in two summary of findings tables.. We included 22 trials (2945 participants) evaluating FBHAs versus no intervention or non-FBHAs; 19 trials with 2642 participants provided data for the meta-analyses. Twelve trials reported commercial funding, one trial reported no financial support, and nine trials provided no information on funding. Below we present the most clinically relevant outcome results, also displayed in our summary of findings table. Fibrin-based haemostatic agents versus no intervention Six trials (1001 participants) compared FBHAs with no intervention. One trial was at low risk of bias in all five domains, and all other trials were at high or unclear risk of bias in at least one domain. Two trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with no intervention have an effect on perioperative mortality (RR 2.58, 95% CI 0.89 to 7.44; 4 trials, 782 participants), serious adverse events (RR 0.96, 95% CI 0.88 to 1.05; 4 trials, 782 participants), postoperative transfusion (RR 1.04, 95% CI 0.77 to 1.40; 5 trials, 864 participants), reoperation (RR 2.92, 95% CI 0.58 to 14.61; 2 trials, 612 participants), or postoperative bile leak (RR 1.00, 95% CI 0.67 to 1.48; 4 trials, 782 participants), as the certainty of evidence was very low for all these outcomes. Fibrin-based haemostatic agents versus non-fibrin-based haemostatic agents Sixteen trials (1944 participants) compared FBHAs with non-FBHAs. All trials had at least one domain at high or unclear risk of bias. Twelve trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with non-FBHAs have an effect on perioperative mortality (RR 1.03, 95% CI 0.62 to 1.72; 11 trials, 1436 participants), postoperative transfusion (RR 0.92, 95% CI 0.68 to 1.25; 7 trials, 599 participants), reoperation (RR 0.48, 95% CI 0.25 to 0.90; 3 trials, 358 participants), or postoperative bile leak (RR 1.15, 95% CI 0.60 to 2.21; 9 trials, 1115 participants), as the certainty of evidence was very low for all these outcomes. FBHAs compared with non-FBHAs may have little or no effect on the risk of serious adverse events (RR 0.99, 95% CI 0.95 to 1.03; 9 trials, 1176 participants; low-certainty evidence).. The evidence for the outcomes in both comparisons (FBHAs versus no intervention and FBHAs versus non-FBHAs) was of very low certainty (or low certainty in one instance) and cannot justify the routine use of FBHAs to reduce blood loss in adult liver resection. While the meta-analysis showed a reduced risk of reoperation with FBHAs compared with non-FBHAs, the analysis was confounded by the small number of trials reporting the event and the risk of bias in all these trials. Future trials should focus on the use of FBHAs in people undergoing liver resection who are at particularly high risk of bleeding. Investigators should evaluate clinically meaningful and patient-important outcomes and follow the SPIRIT and CONSORT statements.

Topics: Adult; Blood Loss, Surgical; Fibrin; Hemostatics; Humans; Liver; Quality of Life

Factor XIII (FXIII) is the final factor in the coagulation cascade. It converts soluble fibrin monomers into a stable fibrin clot, prevents premature degradation of fibrin, participates in wound healing, and helps prevent the loss of the endothelial barrier function. FXIII deficiency is believed to be rare, and this may explain why clinicians do not routinely take it into consideration. Congenital FXIII deficiency is a rare disease with a reported prevalence of 1 per million. However, the prevalence of acquired FXIII deficiency is much higher. Acquired forms have been described in patients with decreased hepatic or bone marrow synthesis, overconsumption and increased degradation by autoantibodies. This review offers guidance on how to suspect and diagnose FXIII deficiency in both the preoperative consultation and different surgical settings. We also analyze current scientific evidence in order to clarify when and why this clinical situation should be suspected, and how it may be treated.

Topics: Blood Coagulation; Blood Loss, Surgical; Factor XIII; Factor XIII Deficiency; Fibrin; Humans

Haemostasis is of fundamental significance in neurosurgery, and insufficient control of bleeding is associated with morbidity and mortality. Topical haemostatic agents play an important role, as the characteristics of neuronal tissue limit the use of classical surgical haemostasis techniques. Appropriate choice of agent depends on the location and type of bleeding, but also on knowledge of the products' mechanisms of action, indications, price and accessibility. Biological products are superior to the mechanical in efficacy but require more preparation and are significantly more cost-intensive.

Topics: Blood Loss, Surgical; Cellulose, Oxidized; Collagen; Fibrin; Hemostasis; Hemostatics; Humans; Hydrogen Peroxide; Neurosurgical Procedures; Palmitates; Sodium Chloride; Surgical Sponges; Thrombin; Waxes

Coagulation factor XIII (FXIII), a plasma transglutaminase, is best known as the final enzyme in the coagulation cascade, where it is responsible for cross-linking of fibrin. However, a growing body of evidence has demonstrated that FXIII targets a wide range of additional substrates that have important roles in health and disease. These include antifibrinolytic proteins, with cross-linking of α2-antiplasmin to fibrin, and potentially fibrinogen, being the principal mechanism(s) whereby plasmin-mediated clot degradation is minimised. FXIII also acts on endothelial cell VEGFR-2 and αvβ3 integrin, which ultimately leads to downregulation of the antiangiogenic protein thrombospondin-1, promoting angiogenesis and neovascularisation. Under infectious disease conditions, FXIII cross-links bacterial surface proteins to fibrinogen, resulting in immobilisation and killing, while during wound healing, FXIII induces cross-linking of the provisional matrix. The latter process has been shown to influence the interaction of leukocytes with the provisional extracellular matrix and promote wound healing. Through these actions, there are good rationales for evaluating the therapeutic potential of FXIII in diseases in which tissue repair is dysregulated or perturbed, including systemic sclerosis (scleroderma), invasive bacterial infections, and tissue repair, for instance healing of venous leg ulcers or myocardial injuries. Adequate levels of FXIII are also required in patients undergoing surgery to prevent or treat perioperative bleeding, and its augmentation in patients with/at risk for perioperative bleeding may also have potential clinical benefit. While there are preclinical and/or clinical data to support the use of FXIII in a range of settings, further clinical evaluation in these underexplored applications is warranted.

Topics: Angiogenesis Inducing Agents; Animals; Bacterial Infections; Blood Coagulation; Blood Loss, Surgical; Coagulants; Factor XIII; Factor XIII Deficiency; Factor XIIIa; Fibrin; Humans; Neovascularization, Physiologic; Postoperative Hemorrhage; Scleroderma, Systemic; Signal Transduction; Substrate Specificity; Thrombospondin 1; Wound Healing

Patient blood management strategies for total hip and knee arthroplasty are controversial. They range from pre-operative haemoglobin optimisation to intra- and post-operative interventions. The aim of this study was to assess the various treatment modalities with respect to blood loss, haemoglobin levels and blood transfusions.. The analysis was based on the principles of a systematic review. The literature was searched in PubMed for the period from 2004 to November 2014. The articles were reviewed with respect to blood loss, post-operative haemoglobin drop, blood transfusions and length of hospital stay. The papers were evidence-graded. Non-randomised clinical studies and papers not concerning total hip or knee arthroplasty were excluded as were studies lacking a control group. Subanalyses were performed for tranexamic acid, tourniquet and fibrin use.. A total of 49 studies were found eligible which is equivalent to a total of 4,752 patients. Tranexamic acid administered either orally, topically, intravenously or in combination decreased blood loss, increased the post-operative haemoglobin level, decreased the number of patients receiving blood transfusions and minimised the length of stay. A similar result was found for fibrin spray in total hip arthroplasty. However, for total knee arthroplasty, the outcome was blurred. Tourniquet use was uniformly not significant in the measured parameters.. Tranexamic acid is useful in managing anaemia and blood loss. Fibrin sealant also has this potential, but is not more potent than tranexamic acid. Tourniquet use is not advantageous.

Topics: Adult; Anemia; Antifibrinolytic Agents; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Blood Transfusion; Female; Fibrin; Hemoglobins; Humans; Length of Stay; Male; Postoperative Period; Tourniquets; Tranexamic Acid

Within Canada, 2.6 million in-hospital surgical procedures are completed annually. Significant bleeding following is the most common surgical complication, occurring in up to 25% of all surgeries. Bleeding causes increased mortality and morbidity, by increasing the number of transfusions required, secondary to increased cumulative blood loss, and by causing hemodynamic instability. A solution to this issue encountered during surgery is the use of hemostatic products. The objectives of this manuscript are (1) to review the spectrum of hemostatic products available in cardiovascular surgery and (2) to provide an update on new topical products soon available, or in development, for optimizing hemostasis during surgical procedures.

Topics: Blood Loss, Surgical; Blood Transfusion; Canada; Cardiac Surgical Procedures; Chitin; Chitosan; Collagen; Cyanoacrylates; Fibrin; Hemodynamics; Hemorrhage; Hemostasis; Hemostatics; Humans; Polysaccharides; Thrombin

Achieving surgical hemostasis plays a major role in the operating room. Occasionally, classical surgical techniques are ill suited or fail to achieve the desired control at the site of bleeding. Topical hemostasis may be seen as a useful addition to assist the surgeon in controlling surgical bleeding.. To provide a brief overview of available topical hemostatic agents with a focus on the different formulations of thrombin.. The scope of the review was limited to a keyword search on PubMed and Ovid (surgical hemostasis, thrombin, tissue adhesives).. Proven as adjuncts to surgical hemostasis, topical hemostatic agents have become quite valuable to bridge or to achieve permanent hemostasis.

Topics: Blood Loss, Surgical; Fibrin; Hemostasis; Humans; Thrombin

This study investigated whether a tailored approach to heparin and protamine management improved thromboelastometric parameters after cardiopulmonary bypass and reduced postoperative blood loss compared with activated coagulation time (ACT)-based fixed target heparin and protamine management.. Randomized controlled study.. Tertiary university hospital.. Patients undergoing elective valve surgery (n = 38).. Heparin and protamine management were based either on the ACT (n = 19) or hemostasis management system (HMS) measurements (n = 19; HMS Plus; Medtronic, Minneapolis, MN).. The target ACT for initiation of cardiopulmonary bypass was 480 seconds. Study variables included rotational thromboelastometry EXTEM (extrinsic coagulation), HEPTEM (intrinsic coagulation with heparinase), and FIBTEM (fibrin part of clot formation) tests and 24-hour blood loss. The use of HMS reduced the median protamine-to-heparin ratio from 1.00 (1.00-1.00) to 0.62 (0.56-0.66; p<0.001). The ACT group showed a prolonged postbypass clotting time for both EXTEM (86 ± 13 seconds v 78 ± 10 seconds; p = 0.05) and HEPTEM (217 ± 58 seconds v 183 ± 24 seconds; p = 0.03) tests. There was a moderate correlation between protamine dosing with the EXTEM and HEPTEM clotting time (r = 0.42; p = 0.009 and r = 0.38; p = 0.02, respectively). The number of patients with more than 450 mL/24 hours was higher in the ACT than in the HMS group (42% v 12%; p = 0.04).. Individualized heparin and protamine management decreased the protamine-to-heparin ratio, improved postbypass thromboelastometric hemostatic parameters, and reduced the incidence of severe blood loss compared with an ACT-based strategy, supporting the added value of this approach for hemostatic optimization during cardiac surgery.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Loss, Surgical; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Female; Fibrin; Heart Valve Prosthesis Implantation; Heart Valves; Hemostasis; Heparin; Heparin Antagonists; Heparin Lyase; Humans; Male; Middle Aged; Partial Thromboplastin Time; Precision Medicine; Protamines; Thrombelastography; Whole Blood Coagulation Time; Young Adult

This study evaluated the hemostatic effectiveness and safety of Fibrin Pad (Omrix Biopharmaceuticals Ltd.) vs absorbable hemostat in patients undergoing nonemergent surgery. Fibrin Pad is a topical absorbable hemostat designed to be effective in a variety of soft tissues and across multiple bleeding intensities.. Patients 18 years and older, requiring abdominal, retroperitoneal, pelvic, or thoracic (noncardiac) surgery and with an appropriate soft-tissue target bleeding site (TBS), were randomized to receive Fibrin Pad or absorbable hemostat (NCT00658723). Patients were stratified by bleeding severity at the TBS. Assessments included percentage of patients achieving hemostasis at 4 minutes after randomization with no rebleeding requiring treatment during the subsequent 6 minutes (primary endpoint), proportion of patients achieving hemostasis at 10 minutes, and incidence of treatment failure.. On the primary endpoint, 98.3% of patients with Fibrin Pad and 53.3% with absorbable hemostat achieved hemostasis at 4 minutes (p < 0.0001). The treatment differential was magnified (efficacy was maintained with Fibrin Pad but decreased with absorbable hemostat) with increasing bleeding intensity: in patients with mild bleeding, 100.0% vs 80.0% achieved hemostasis with Fibrin Pad and absorbable hemostat (p = 0.03), respectively; rates were 96.6% vs 26.7%, respectively (p < 0.0001) with moderate bleeding. Percentages of patients who achieved hemostasis at 10 minutes were: Fibrin Pad, 98.3% and absorbable hemostat, 73.3% (p < 0.0001). Incidences of adverse events were comparable between groups.. Fibrin Pad is superior to absorbable hemostat (SURGICEL Original Absorbable Hemostat [Ethicon]) in soft-tissue bleeding control and is safe and effective as an adjunct for rapidly and reliably achieving hemostasis for soft-tissue bleeding during surgery.

Topics: Abdomen; Blood Loss, Surgical; Cellulose, Oxidized; Female; Fibrin; Hemostasis, Surgical; Hemostatics; Humans; Male; Middle Aged; Pelvis; Prospective Studies; Retroperitoneal Space; Thoracic Surgery; Treatment Outcome; United States

Haemostasis after liver resection may be difficult to achieve as a result of the presence of challenging bleeding, the anatomic landscape of the liver and the quality of tissue making up the hepatic parenchyma. The fibrin pad (FP) is a topical absorbable haemostat designed to be effective in a variety of tissues and across multiple bleeding intensities. This is the first clinical trial to evaluate the hemostat's safety and effectiveness in controlling bleeding during elective hepatic resection.. This prospective, randomized, controlled superiority trial enrolled 104 subjects undergoing elective hepatectomy in 5 countries. After parenchymal transection, subjects with an appropriately defined target bleeding site (TBS) were stratified according to the type of hepatic parenchyma and immediately randomized 1:1: FP versus Standard of Care (SoC). SoC comprised manual compression with the use of an approved topical absorbable haemostat. The primary endpoint was haemostasis at 4 min from identification of the TBS, with no re-bleeding requiring re-treatment prior to abdominal closure. Results were stratified for both normal and abnormal (steatosis or cirrhosis) hepatic parenchyma. All subjects were followed for 60 days post-operatively.. The intent-to-treat (ITT) analysis showed an overall treatment difference of 53.0% (P < 0.001), 82.5% (33/40 FP) versus 29.5% (13/44 SoC) in achieving haemostasis at 4 min with no re-bleeding requiring treatment up to wound closure. The per protocol analysis showed an overall treatment difference of 65.7% (P < 0.001), with 33/35 successes (94.3%) in the FP group and 12/42 in the SoC group (28.6%). The stratification results showed treatment differences between the normal parenchyma group, 63.6% (95.8% FP versus 32.3% SoC P < 0.001) and a larger difference of 72.7% in the abnormal parenchyma group (90.9% FP versus 18.2% SoC P = 0.0003). Post-operative intra-abdominal fluid collections were less frequent in the FP group (3.4% FP versus 13.3% SoC P = 0.059). There was no difference in the safety profile between the FP or SoC groups.. The FP is safe and effective when used as an adjunct to achieve haemostasis during hepatic surgery. The success rate of achieving haemostasis with a FP remained high compared with the SOC group, especially in steatotic or cirrhotic liver tissue where the control success rates diminish. In addition, FP treatment of hepatic parenchymal surfaces may reduce the risk of post-operative biliary and fluid collections.

Topics: Adolescent; Adult; Aged; Australia; Blood Loss, Surgical; Blood Transfusion; Elective Surgical Procedures; Europe; Female; Fibrin; Hemostatic Techniques; Hemostatics; Hepatectomy; Humans; Male; Middle Aged; New Zealand; Postoperative Complications; Pressure; Prospective Studies; Time Factors; Treatment Outcome; Young Adult

A prospective, randomised controlled trial compared the effects of two medications intended to reduce blood loss from total knee arthroplasty. Patients were randomised to one of the following three treatment groups: 10mg/kg tranexamic acid at given at induction of anaesthesia, 10 ml of fibrin spray administered topically during surgery, or to a control group receiving neither treatment. Sixty six patients underwent elective cemented total knee arthroplasty; computer navigation was used in all cases. There was no significant difference in blood loss between the tranexamic acid and fibrin spray groups (p=0.181). There was no significant difference in blood loss between the tranexamic acid and fibrin spray groups(p=0.181). The fibrin spray led to a significant reduction in blood loss compared to control (p=0.007). The effect of tranexamic acid did not reach significance (p=0.173). We conclude that fibrin spray was effective in reducing blood loss but that with a study of this power, we were unable to detect an effect of tranexamic acid in cemented navigated total knee replacement at the dose used.

Topics: Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Fibrin; Fibrinogen; Fibronectins; Humans; Prospective Studies; Thrombin; Tranexamic Acid

  Treatment of dilutional coagulopathy by transfusing fresh frozen plasma (FFP) remains sub-optimal. We hypothesized that partial replacement of transfused FFP by fibrinogen concentrate results in improved coagulant activity and haemostasis. This was tested in a controlled clinical intervention trial with patients experiencing massive bleeding during major surgery..   Patients undergoing major elective surgery were treated according to current protocols. When transfusion with FFP was required, patients were randomized as follows: group A received 4 units FFP and group B received 2 units FFP plus 2 g fibrinogen concentrate. Blood samples were taken before and after the intervention. Analysts were blinded to the treatment type..   Group A (B) consisted of 21 (22) patients, in 16 (17) of whom bleeding stopped after intervention. Plasma fibrinogen increased significantly more in group B (0·57 g/l) than in group A (0·05 g/l). However, levels of prothrombin and factors VIII, IX and X increased more in group A than in group B. Rotational thromboelastometry (ROTEM) of whole blood and plasma revealed improved fibrin clot formation in group B but not in group A. Thrombin generation [calibrated automated thrombogram (CAT)] in plasma increased more in group A. Principal parameters determining whole-blood thromboelastometry were the fibrinogen level and platelet count. In vitro addition of fibrinogen and prothrombin complex concentrate to pre-intervention samples restored both ROTEM and CAT parameters..   Partial replacement of transfused FFP by fibrinogen increases fibrin clot formation at the expense of less improved thrombin generation. Coagulation factors other than fibrinogen alone are required for full restoration of haemostasis.

Topics: Aged; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Blood Loss, Surgical; Female; Fibrin; Fibrinogen; Hemostasis; Humans; Male; Middle Aged; Plasma; Platelet Count; Postoperative Hemorrhage; Prospective Studies; Surgical Procedures, Operative; Thrombelastography

The purpose of this study was to investigate the effects of acute hypervolemic fluid infusion (AHFI) of 6% hydroxyethyl starch (HES) 130/0.4 or 4% succinylated gelatin (GEL) on hemostasis and the possible mechanisms.. Thirty-six gastric cancer patients were randomized to receive AHFI of either HES, GEL or lactated Ringer's (RL) solution at the rate of 30 mL x kg(-1) x h( -1) from 20 minutes before to 40 minutes after induction of general anesthesia.. Group HES and GEL had significantly prolonged PT and aPTT, decreased VIII:C and vWF immediately after AHFI. Statistically prolonged reaction time and coagulation time, and decreased growth angle were seen immediately after HES infusion. Maximum amplitude decreased significantly in group HES and GEL immediately after and 4 hours after AHFI.. Gelatin reduced clot quality associated with derangements of fibrin polymerization and HES 130/0.4 delayed initiation of sufficient thrombin generation to convert fibrinogen to fibrin and impaired platelet function.

Topics: Adult; Anesthesia, General; Blood Coagulation Tests; Blood Loss, Surgical; Blood Platelets; Blood Volume; Female; Fibrin; Fluid Therapy; Gastrectomy; Gelatin; Hemostasis; Humans; Hydroxyethyl Starch Derivatives; Isotonic Solutions; Male; Middle Aged; Plasma Substitutes; Ringer's Lactate; Stomach Neoplasms; Succinates; Thrombelastography; Thrombin

Heparinization requires monitoring, but optimal methods for measuring the anticoagulant effects of heparin remain to be determined. We compared prothrombinase-induced clotting time (PiCT) and two chromogenic anti-factor Xa activity (anti-Xa) assays in monitoring high-dose heparinization during cardiopulmonary by-pass (CPB). Heparin effects were serially measured with PiCT and two anti-Xa assays in 100 patients. Antithrombin and protein C activities were measured preoperatively, and antithrombin activity was measured during CPB. Activation of coagulation was assessed with measurements of prothrombin fragment F1+2, soluble fibrin complexes, and D-dimer before, during, and after CPB. During CPB mean ranges of PiCT and of anti-Xa heparin levels measured with (anti-Xa A) and without (anti-Xa B) dextran sulfate and antithrombin supplementation were 5.0-5.2, 4.7-5.0, and 4.5-4.9 IU/ml, respectively. There was poor agreement between PiCT and anti-Xa and between the two anti-Xa assays (r = 0.32-0.65 and broad limits of agreement). Patients with low preoperative antithrombin or protein C levels had lower PiCT (p = 0.028 and p = 0.01) and anti-Xa A (both p<0.001) levels during CPB than others. Patients with the lowest heparin activities during CPB (lowest deciles of PiCT and anti-Xa A) had higher subsequent F1+2 after CPB (p = 0.002 and p = 0.02), and patients with high heparin levels required fewer transfusions of packed red blood cells than others. In conclusion, in the challenging setting of CPB there is poor agreement between anti-Xa assays and PiCT. However, coagulation-based PiCT could provide an alternative to the chromogenic anti-Xa assays. Higher heparin levels during CPB were confirmed to associate with reduced transfusion requirements.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Blood Coagulation; Blood Coagulation Tests; Blood Loss, Surgical; Cardiopulmonary Bypass; Chromogenic Compounds; Coronary Artery Bypass; Coronary Artery Disease; Drug Monitoring; Erythrocyte Transfusion; Factor Xa; Factor Xa Inhibitors; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Male; Middle Aged; Monitoring, Intraoperative; Peptide Fragments; Prospective Studies; Protein C; Prothrombin; Thromboplastin

We performed a randomised, controlled trial involving 150 patients with a pre-operative level of haemoglobin of 13.0 g/dl or less, to compare the effect of either topical fibrin spray or intravenous tranexamic acid on blood loss after total knee replacement. A total of 50 patients in the topical fibrin spray group had 10 ml of the reconstituted product applied intra-operatively to the operation site. The 50 patients in the tranexamic acid group received 500 mg of tranexamic acid intravenously five minutes before deflation of the tourniquet and a repeat dose three hours later, and a control group of 50 patients received no pharmacological intervention. There was a significant reduction in the total calculated blood loss for those in the topical fibrin spray group (p = 0.016) and tranexamic acid group (p = 0.041) compared with the control group, with mean losses of 1190 ml (708 to 2067), 1225 ml (580 to 2027), and 1415 ml (801 to 2319), respectively. The reduction in blood loss in the topical fibrin spray group was not significantly different from that achieved in the tranexamic acid group (p = 0.72).

Topics: Administration, Topical; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; C-Reactive Protein; Fibrin; Hemostasis, Surgical; Humans; Prospective Studies; Tranexamic Acid; Treatment Outcome

Total knee arthroplasty (TKA) is often associated with a considerable amount of post-operative blood loss, necessitating the transfusion of allogeneic blood, which can add to the complications. Optimization of strategies to reduce the need for blood transfusion is desired. This study was designed to evaluate the efficacy of autologous platelet gel and fibrin sealant in unilateral TKA.. Consecutive patients were operated on and assigned to the study and control groups. Study group patients (n = 85) were operated on according to our standard TKA protocol, with the application of autologous platelet gel and fibrin sealant on the wound tissues at the end of surgery. Eighty patients were operated on according to the same protocol, but without the use of platelet gel and fibrin sealant, and served as the control group. All blood transfusions, occurrence of wound leakage, wound healing disturbances and incidences of post-operative infections were recorded.. Patients in the treatment group had a significantly higher post-operative haemoglobin level (11.3 vs. 8.9 g/dl, respectively) and a decreased need for allogeneic blood products (0.17 vs. 0.52 units, respectively) than those in the control group (P < 0.001). The incidences of wound leakage and wound healing disturbance were significantly less (P < 0.001) in patients managed with platelet gel and fibrin sealant. Four patients in the control group, who received blood products, developed wound infection. The hospital stay was decreased by 1.4 +/- 1.5 days for patients in the treatment group (P < 0.001).. Peri-operatively applied platelet gel and fibrin sealant may reduce the incidence of allogeneic blood transfusions and complications associated with TKA.

Topics: Aged; Algorithms; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Blood Platelets; Blood Transfusion; Female; Fibrin; Gels; Hemoglobins; Hemostatics; Humans; Male; Postoperative Period; Prospective Studies; Surgical Wound Infection; Thrombin; Wound Healing

An estimation of influence of different doses of aprotynin on bleeding, coagulation parameters and safety of its use after coronary artery bypass grafting (CABG) in pts without coagulation disorders.. 91 patients underwent CABG, 73 men, 18 women in age 37 to 76 +/- 56.5 years. Patients were randomly assigned to 3 groups; Group I; 38 pts. 6.5 mln KIU aprotynin. Group II; placebo--30 pts. Group III; 23 pts. 2 mln. KIU. There were 4 measurements 1.--before operation, 2. after discontinuing CPB, 3.--6 h after operation, 4.--24 h after operation. We measured Hb, Ht, PLT Glucose, D-dimers, APTT, TT Fibrynogen, INR, AT3, Ca2+, factor V, VIII, GOT GPT CK, CK-MB, CRP, ACT concentration of Hb in drainage 6 h after operation. There were estimated: renal function profile, drainage loss, perioperative MI, mortality, reoperation rate due to bleeding.. The level of blood count and coagulation parameters did not differ between the groups in any test periods. D-dimer levels were significantly higher in the placebo group than in group I and III. The decrease of fibrin degradation was not related to the dose of aprotynin. Drainage was insignificantly higher in placebo group. Renal function was impaired in neither group. Reoperation rate perioperative infarction and mortality did not differ between the groups, however was highest in group I.. Aprotynin reduces blood loss after operation in CPB and decrease fibrin degradation independently to the dose of the drug. The high-dose of aprotynin may increase the risk of early graft occlusion in patients without coagulation disorders.

Topics: Adult; Aged; Aprotinin; Blood Coagulation; Blood Loss, Surgical; Cardiovascular Surgical Procedures; Dose-Response Relationship, Drug; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Hemostatics; Humans; Male; Middle Aged; Reoperation

The purpose of this study was to estimate the in vivo rates of plasmin and D-dimer generation for comparison with the rate of fibrin formation during cardiopulmonary bypass (CPB), a procedure known to induce a hyperfibrinolytic state. Plasmin and D-dimer generation rates were based on measured levels of antiplasmin, plasmin-antiplasmin complex and D-dimer obtained before, during and after CPB from nine males, combined with a computer model of each patient's vascular system that continuously accounted for secretion, clearance, hemodilution, blood loss and transfusion. At baseline the average plasmin and D-dimer generation rates were 0.27 +/- 0.07 and 0.18 +/- 0.07 pmol/s, respectively. Within 5 min of CPB initiation, plasmin generation increased over 100-fold to 36 +/- 40 pmol/s while D-dimer generation increased 200-fold to 37 +/- 39 pmol/s. For the remainder of the CPB, average plasmin and D-dimer generation remained 20-fold to 30-fold above baseline levels. During CPB, the rate of D-dimer generation was similar to the rate of total fibrin formation, indicating that, in the absence of fibrinolytic inhibitors, CPB induces plasmin-mediated removal of fibrin from the vascular system at a rate similar to the rate of fibrin formation.

Topics: Aged; Blood Loss, Surgical; Blood Transfusion; Cardiopulmonary Bypass; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinolysis; Hemodilution; Humans; Male; Middle Aged

Of 35 acetylsalicylic acid (ASA)-treated patients undergoing coronary artery bypass surgery, 10 received a high dose of aprotinin (mean 5.2 x 10(6) KIU) during cardiopulmonary bypass (CPB); in 15 cases low-dose aprotinin (2 x 10(6) KIU) was added to the CPB priming solution, and 10 patients made up a control group without aprotinin. Median total blood loss was 52% less in aprotinin-treated patients, irrespective of dose, than in the controls. Fibrin-D dimer levels remained low in patients treated with high-dose aprotinin, but increased significantly in the control group. Platelet adhesion and platelet adenosine triphosphate secretion were reduced after CPB in all patients. Whole-blood aggregation after bypass was enhanced in aprotinin-treated patients. Aprotinin inhibited fibrinolysis and seemingly preserved platelet function despite ASA treatment. In view of the possible risks and relatively high cost of aprotinin, use of a high dose seems unnecessary, since a low dose was equally effective in reducing blood loss in ASA-treated patients.

Topics: Adenosine Triphosphate; Adult; Aged; Angina, Unstable; Aprotinin; Aspirin; Blood Loss, Surgical; Blood Transfusion; Cardiopulmonary Bypass; Confidence Intervals; Dose-Response Relationship, Drug; Female; Fibrin; Fibrinolytic Agents; Hemostatics; Humans; Injections, Intravenous; Male; Middle Aged; Platelet Adhesiveness; Platelet Count; Preoperative Care; Reference Values; Treatment Outcome

This study was performed to evaluate whether the combination of heparin-coated extracorporeal circuits (ECC) and aprotinin treatment reduce blood activation during coronary artery operations.. Sixty patients were prospectively divided into two groups (heparin-coated ECC and uncoated ECC groups), which were comparable in terms of age, sex, left ventricular function, preoperative aspirin use and consequent intraoperative aprotinin use, number of grafts, duration of aortic cross-clamping, and duration of cardiopulmonary bypass. Blood activation was assessed at different times during cardiopulmonary bypass by determination of complement activation (C3 and C4 activation products C3b/c and C4b/c and terminal complement complex), leukocyte activation (elastase), coagulation (scission peptide fibrinopeptide 1 + 2), and fibrinolysis (D-dimers).. Univariate analysis showed that heparin-coated ECC, under conditions of standard heparinization, did not reduce perioperative blood loss and need for transfusion. Heparin coating, however, reduced maximum values of C3b/c (446 +/- 212 nmol/L versus 632 +/- 264 nmol/L with uncoated ECC; p = 0.0037) and maximum C4b/c values (92 +/- 48 nmol/L versus 172 +/- 148 nmol/L with uncoated ECC; p = 0.0069). Levels of terminal complement complex, elastase, fibrinopeptide 1 + 2, and D-dimers were not significantly modified by the use of heparin-coated ECC. Multivariate analysis showed that the intergroup differences in maximum C3b/c and C4b/c values were more pronounced in women in part with high baseline values of C3b/c. We also found that aprotinin contributed to the reduction of maximum values of fibrinopeptide 1 + 2 and D-dimers, whereas heparin coating had no significant influence on these parameters.. We found no evidence of combined properties of heparin-coated ECC and aprotinin in reducing complement activation, coagulation, and fibrinolysis. We therefore recommend use of both together to achieve maximal reduction of blood activation during cardiopulmonary bypass for coronary artery operations.

Topics: Aprotinin; Blood Loss, Surgical; Complement Activation; Coronary Artery Bypass; Extracorporeal Circulation; Female; Fibrin; Fibrinolysis; Hemostatics; Heparin; Humans; Intraoperative Care; Leukocyte Elastase; Male; Middle Aged; Postoperative Care; Prospective Studies; Sex Factors

Aprotinin reduces blood loss in operations done with cardiopulmonary bypass, whereas the use of desmopressin remains controversial. We compared aprotinin, desmopressin, and placebo in a double-blind, randomized trial to evaluate bleeding and transfusion requirements.. One hundred forty-nine patients (48 received aprotinin, 50 desmopressin, 51 placebo) were included. Blood loss and transfusion requirements were recorded and levels of Factor VIII coagulant activity, von Willebrand's factor, thrombin-antithrombin complexes, and D-dimer were measured. Overall blood loss was 195 +/- 146 ml/m2 in the aprotinin group, 400 +/- 192 ml/m2 in the desmopressin group, and 489 +/- 361 ml/m2 in the placebo group (95% confidence intervals: difference between desmopressin and aprotinin 98 to 312 ml/m2, p < 0.001; difference between placebo and aprotinin 190 to 398 ml/m2, p < 0.001). Twenty-six percent of patients treated with aprotinin, 66% of those treated with desmopressin, and 56% of those treated with placebo were given transfusion (95% confidence intervals: difference between aprotinin versus placebo plus desmopressin 51% to 71%, p < 0.001). Fibrinolytic activation throughout cardiopulmonary bypass was markedly higher with placebo or desmopressin administration. D-dimer level correlated with overall blood loss in patients receiving desmopressin or placebo, but not in those receiving aprotinin.. Aprotinin administration reduces blood loss and transfusion requirements in cardiopulmonary bypass. This benefit may be explained by a lower activation of fibrinolysis.

Topics: Antithrombin III; Aprotinin; Blood Loss, Surgical; Cardiopulmonary Bypass; Cross-Linking Reagents; Deamino Arginine Vasopressin; Double-Blind Method; Erythrocyte Transfusion; Factor VIII; Female; Fibrin; Hemostatics; Humans; Male; Middle Aged; Peptide Hydrolases; von Willebrand Factor

Quantitative and qualitative differences in the hemostatic systems exist between neonates and adults, including the presence of "fetal" fibrinogen, a qualitatively dysfunctional form of fibrinogen that exists until 1 yr of age. The consequences of "fetal" fibrinogen on clot structure in neonates, particularly in the context of surgery-associated bleeding, have not been well characterized. Here, the authors examine the sequential changes in clotting components and resultant clot structure in a small sample of neonates undergoing cardiac surgery and cardiopulmonary bypass (CPB).. Blood samples were collected from neonates (n = 10) before surgery, immediately after CPB, and after the transfusion of cryoprecipitate (i.e., adult fibrinogen component). Clots were formed from patient samples or purified neonatal and adult fibrinogen. Clot structure was analyzed using confocal microscopy.. Clots formed from plasma obtained after CPB and after transfusion were more porous than baseline clots. Analysis of clots formed from purified neonatal and adult fibrinogen demonstrated that at equivalent fibrinogen concentrations, neonatal clots lack three-dimensional structure, whereas adult clots were denser with significant three-dimensional structure. Clots formed from a combination of purified neonatal and adult fibrinogen were less homogenous than those formed from either purified adult or neonatal fibrinogen.. The results of this study confirm that significant differences exist in clot structure between neonates and adults and that neonatal and adult fibrinogen may not integrate well. These findings suggest that differential treatment strategies for neonates should be pursued to reduce the demonstrated morbidity of blood product transfusion.

Topics: Adult; Blood Coagulation; Blood Loss, Surgical; Blood Transfusion; Cardiopulmonary Bypass; Factor XIII; Female; Fibrin; Fibrinogen; Humans; Infant; Infant, Newborn; Male; Microscopy, Confocal; Prothrombin

Assays based on the formation of thrombin and fibrin are frequently used, and results are considered exchangeable in research/clinical settings. However, thrombin generation and fibrin formation do not always go hand in hand and flow profoundly influences thrombus formation. We describe the technical/clinical evaluation of an assay to simultaneously measure thrombin generation and fibrin formation under conditions of flow. Introduction of a fluorometer into a 'cone and base principle'-based rheometer allowed the measurement of thrombin generation (using a thrombin-sensitive substrate) and fibrin formation (changes in viscosity), while applying a linear shear flow. Increasing shear rates inversely related with thrombin generation and fibrin formation. Increasing fibrinogen concentrations in defibrinated plasma resulted in increased thrombin generation and fibrin formation. In pre-operative samples of 70 patients undergoing cardiothoracic surgery, fibrin formation and thrombin generation parameters correlated with fibrinogen content, rotational thromboelastometry (ROTEM) and whole blood Calibrated Automated Thrombinography (CAT) parameters, respectively. Upon dividing patients into two groups based on the median clot strength, a significant difference in perioperative/total blood loss was established. In conclusion, we clinically evaluated a method capable of simultaneously measuring thrombin generation and fibrin formation in plasma/whole blood under continuous flow, rendering our method one step closer to physiology. Importantly, our test proved to be indicative for the amount of blood loss during/after cardiothoracic surgery.

Topics: Adult; Aged; Blood Loss, Surgical; Blood Viscosity; Cardiac Surgical Procedures; Dose-Response Relationship, Drug; Equipment Design; Female; Fibrin; Healthy Volunteers; Hemorheology; Humans; In Vitro Techniques; Male; Middle Aged; Oligopeptides; Predictive Value of Tests; Protein Multimerization; Thoracic Surgical Procedures; Thrombelastography; Thrombin; Tissue Plasminogen Activator

Optimal hemostatic management during orthotopic liver transplantation (OLT) remains a challenge. The cause of bleeding during OLT is multifactorial, and may include hemostatic imbalance. Fibrinogen concentrates are increasingly being used to control perioperative bleeding during OLT. However, administration is based on arbitrary thresholds of fibrinogen levels. Importantly, studies on fibrin clot structure during OLT are lacking.. We determined the hemostatic efficacy of fibrinogen concentrate in correcting the fibrin structure.. Plasma samples taken at various times during OLT from 15 patients and 15 healthy controls were spiked with 1 g L(-1) fibrinogen concentrate or saline. Turbidity, fibrin fiber density and permeability of the fibrin clots were assessed.. Clotting rate and turbidity were significantly decreased at the start of surgery, and decreased even further during surgery. Addition of fibrinogen significantly increased the clotting rate and turbidity at all time points, but did not normalize it. Fibrin density was significantly reduced after reperfusion as compared with the density at the start of surgery and in healthy controls. Fibrin density improved significantly after addition of fibrinogen in samples taken at the start of surgery and after reperfusion. The severely impaired polymerization and decreased density after reperfusion were accompanied by significantly increased permeability of the clot as compared with the start of surgery and in controls, which was completely restored after addition of fibrinogen.. Ex vivo addition of fibrinogen concentrate during OLT substantially improves the structural properties of the fibrin clot, which, particularly after reperfusion, shows hypocoagulable features. These data support the use of fibrinogen concentrate to control bleeding complications during OLT.

Topics: Adult; Aged; Blood Coagulation; Blood Coagulation Tests; Blood Loss, Surgical; Case-Control Studies; Factor XIII; Female; Fibrin; Fibrinogen; Hemostatics; Humans; Liver Transplantation; Male; Middle Aged; Permeability; Polymerization; Porosity; Time Factors

Rotational thromboelastometry (ROTEM®)-based FIBTEM is used perioperatively to assess the extent of fibrin polymerization in whole blood. In FIBTEM, cytochalasin D eliminates the contribution of platelets to whole blood clotting, but changing levels in fibrin(ogen) and erythrocytes may differently affect clot formation. Because dynamic changes of hematocrit are not reflected in plasma fibrinogen measurements, we hypothesized that the lack of erythrocytes in isolated plasma measurements would affect the relationship between the Clauss method and whole blood-based FIBTEM during cardiac surgery. Therefore, in the current study we investigated the influence of perioperative hematocrit changes on FIBTEM and fibrinogen measurements.. Blood samples were collected from 6 consenting healthy volunteers. FIBTEM tests were run before and after serial in vitro dilutions of whole blood with saline or autologous plasma (5:1, 2:1, and 1:1 v/v). We then evaluated the relationship between FIBTEM-maximal clot firmness (MCF) and the Clauss fibrinogen method in relation to hematocrit values before and after cardiac surgery. Pearson correlation coefficients were determined between laboratory test results and ROTEM variables.. Upon in vitro hematocrit reduction, FIBTEM-MCF was progressively decreased depending on the extent of saline dilution, but it was increased by 31% after 1:1 volume replacement with autologous plasma (P < 0.05). In samples from cardiac patients (150 measurements in 50 patients), the overall correlation coefficient between FIBTEM-MCF and plasma fibrinogen was 0.80 (P < 0.001). In hemodiluted blood samples (during surgery or at intensive care unit), FIBTEM-MCF 10 mm corresponded to plasma fibrinogen levels of 200 mg/dL. In the subgroup analysis (n = 50 each), according to hematocrit levels (<25%, ≥25% to 30%, ≥30%), plasma fibrinogen levels of 200 mg/dL corresponded to 11 mm, 10 mm, and 8 mm of FIBTEM-MCF, respectively. The correlation between FIBTEM-MCF and plasma fibrinogen was higher at lower hematocrit (<25%) than at higher hematocrit (>30%) (r = 0.88 and 0.67, respectively).. Perioperative changes in hematocrit affect the correlation between plasma fibrinogen levels and FIBTEM-MCF values. The higher correlation between FIBTEM-MCF and plasma fibrinogen with lower hematocrit (<25%) indicates that FIBTEM is a practical method to determine the need for fibrinogen replacement in bleeding patients who typically develop perioperative anemia.

Topics: Adult; Blood Coagulation; Blood Loss, Surgical; Blood Transfusion; Cardiac Surgical Procedures; Erythrocytes; Female; Fibrin; Fibrinogen; Georgia; Hematocrit; Hemodilution; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Thrombelastography; Time Factors

Patients subjected to haemodilution during surgery are at increased risk of bleeding. We hypothesised that, in the acquired dilutional coagulopathy, insufficient haemostasis is due to either insufficient thrombin generation or insufficient fibrin clot formation. In tissue factor-activated plasmas from patients with coagulation deficiency, we measured time curves of thrombin generation and fibrin clot formation (thromboelastography). Investigated were in study A: 10 patients treated with vitamin K antagonist and five healthy subjects; in study B: 30 patients undergoing cardiopulmonary bypass (CPB) surgery and infused with on average 2,000 ml crystalloids and colloids (no major bleeding); in study C: 58 patients undergoing major general surgery, and transfused with >5,000 ml crystalloids, colloids and red cell concentrates, who experienced major bleeding and were post-transfused with fresh frozen plasma. The treatment with vitamin K antagonist led to a progressive reduction in thrombin generation but not fibrin clot formation. In CPB patients, plasma factor levels post-surgery were 53-60% of normal. This was accompanied by moderate reduction in both haemostatic processes. In plasmas from patients undergoing major surgery, factor levels were 38-41% of normal, and these levels increased after plasma transfusion. Taking preset thresholds for normal thrombin generation and fibrin clot formation, at least one of these processes was low in 88-93% of the patients with (persistent) bleeding, but only in 40-53% of the patients without bleeding. In conclusion, the ability of thrombin generation and fibrin clot formation is independently reduced in acquired dilutional coagulopathy, while minimal levels of both are required for adequate haemostasis.

Topics: Aged; Blood Coagulation; Blood Coagulation Disorders; Blood Loss, Surgical; Blood Transfusion; Crystalloid Solutions; Female; Fibrin; Hemodilution; Hemorrhage; Hemostasis; Humans; Isotonic Solutions; Kinetics; Male; Middle Aged; Perioperative Care; Postoperative Hemorrhage; Thrombin; Vitamin K

To explore relevant changes in unexplained intraoperative bleeding, we evaluated elements of the final steps of the coagulation cascade in 226 consecutive patients undergoing elective surgery. Patients were stratified for the occurrence of unexplained intraoperative bleeding according to predefined criteria. Twenty patients (8.8%) developed unexplained bleeding. The median intraoperative blood loss was 1350 mL (bleeders) and 400 mL (nonbleeders) (P < 0.001). Fibrinogen and Factor XIII (F. XIII) were more rapidly consumed in bleeders (P < 0.001). Soluble fibrin formation (fibrin monomer) was increased in bleeders throughout surgery (P < or = 0.014). However, F. XIII availability per unit thrombin generated was significantly decreased in bleeders before, during, and after surgery (P < or = 0.051). Computerized thrombelastography showed a parallel, significant reduction in clot firmness. We suggest that mild preexisting coagulopathy is not rare in surgical patients and probably can result in clinically relevant intraoperative bleeding. This hemostatic disorder shows impaired clot firmness, probably secondary to decreased cross-linking (due to a loss of F. XIII, both in absolute measures and per unit thrombin generated). We suggest that the application of F. XIII might be worthwhile to test in a prospective clinical trial to increase clot firmness in patients at risk for this intraoperative coagulopathy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Coagulation; Blood Loss, Surgical; Body Mass Index; Data Interpretation, Statistical; Factor XIII; Female; Fibrin; Fibrinogen; Hematocrit; Humans; Male; Middle Aged; Plasma; Thrombelastography; Thrombin

High-intensity focused ultrasound (HIFU) has been shown to be effective in controlling hemorrhage from punctures in blood vessels. The objective of the current study was to investigate the capability of HIFU to stop bleeding after a more severe type of vascular injury, namely longitudinal incisions of arteries and veins.. The superficial femoral arteries, common femoral arteries, carotid arteries, and jugular veins of four anesthetized pigs were exposed surgically. A longitudinal incision, 2 to 8 mm in length, was produced in the vessel. HIFU treatment was applied within 5 seconds of the onset of the bleeding. The HIFU probe consisted of a high-power, 3.5-MHz, piezoelectric transducer with an ellipsoidal focal spot that was 1 mm in cross section and 9 mm in axial dimension. The entire incision area was scanned with the HIFU beam at a rate of 15 to 25 times/second and a linear displacement of 5 to 10 mm. A total of 76 incisions and HIFU treatments were performed.. Control of bleeding (major hemosatsis) was achieved in all 76 treatments, with complete hemostasis achieved in 69 treatments (91%). The average treatment times of major and complete hemostasis were 17 and 25 seconds, respectively. After the treatment, 74% of the vessels in which complete hemostasis was achieved were patent with distal blood flow and 26% were occluded. The HIFU-treated vessels showed a consistent coagulation of the adventitia surrounding the vessels, with a remarkably localized injury to the vessel wall. Extensive fibrin deposition at the treatment site was observed.. HIFU may provide a useful method of achieving hemostasis for arteries and veins in a variety of clinical applications.

Topics: Animals; Arterial Occlusive Diseases; Blood Loss, Surgical; Carotid Arteries; Elastic Tissue; Female; Femoral Artery; Fibrin; Hemostasis, Surgical; Jugular Veins; Male; Regional Blood Flow; Swine; Time Factors; Transducers; Ultrasonic Therapy; Vascular Patency

The quality of autologous fresh frozen plasma and autologous fibrin glue prepared in our hospital was evaluated. The Auto-FFP was separated from whole blood or collected using a cell separator and the Auto-FG was then prepared from the Auto-FFP. The Auto-FFP showed significantly higher levels of fibrinogen, Factor-V and Factor-VIII than commercially available FFP. The Auto-FG contained approximately 10 times the concentration of fibrinogen, Factor-VIII, Factor-XIII, von Willbrand factor and fibronectin and 1.5 times that of alpha 2-Plasminogen inhibitor compared to those of the Auto-FFP. When the Auto-FG was sprayed over diffusely bleeding sites from surgical wounds, hemostasis occurred within 5 s. These results suggest that Auto-FFP and Auto-FG may have sufficient utility and quality to reduce the use of allogeneic blood products.

Topics: Adult; Aged; Blood Coagulation Factors; Blood Loss, Surgical; Blood Proteins; Blood Transfusion, Autologous; Evaluation Studies as Topic; Female; Fibrin; Fibrinogen; Hemostasis, Surgical; Humans; Japan; Male; Middle Aged; Plasma; Retrospective Studies; Time Factors; Tissue Adhesives

Local and systemic immune and haemostatic responses were studied in 10 patients, aged 57-78 years, undergoing elective hip arthroplasty. Cytokines, soluble cytokine receptors, interleukin-1 receptor antagonist, soluble adhesion molecules, antithrombin, fibrin, soluble and fibrin D-dimer were analysed in wound drainage blood and in blood taken from the systemic circulation for up to 24 h post-operatively. Wound drainage blood concentrations of cytokines, interleukin-1 receptor antagonist and soluble cytokine receptors were increased compared with those in the systemic circulation except for the soluble interleukin-6 receptor. In wound drainage blood, soluble tumour necrosis factor receptors (P < 0.05), interleukin-1 receptor antagonist (P < 0.05) and interleukin-6 (P < 0.05-< 0.01) increased during the study period. In blood from the systemic circulation interleukin-6 increased (P < 0.05) while the soluble interleukin-6 receptor decreased (P < 0.05) compared with pre-operative values. Concentrations of soluble adhesion molecules did not change. Wound drainage blood showed marked hypercoagulation. After hip arthroplasty pro-inflammatory cytokines and their inhibitors were mainly confined to the local trauma site. A predominance for inhibitors was noted.

Topics: Aged; Antifibrinolytic Agents; Antithrombin III; Arthroplasty, Replacement, Hip; Blood Coagulation; Blood Loss, Surgical; Cell Adhesion Molecules; Cytokines; Elective Surgical Procedures; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Hemostasis; Humans; Inflammation Mediators; Interleukin-6; Lymphotoxin-alpha; Male; Middle Aged; Receptors, Cytokine; Receptors, Interleukin-1; Receptors, Interleukin-6; Receptors, Tumor Necrosis Factor; Serine Proteinase Inhibitors

Transinterstitial blood loss at implantation and the degree of graft incorporation and inner capsule thickening was compared in serial explants of albumin-coated Dacron versus blood preclotted Dacron grafts in the canine thoracoabdominal aortic position (8 mm internal diameter x 30 cm length). The coated grafts were Bard DeBakey Vasculour II knitted Dacron prostheses impregnated with carbodiimide-cross-linked human albumin. Control grafts were otherwise identical and preclotted with the recipients' whole blood before heparinization during surgery. Transinterstitial blood loss after establishing flow was measured by weighing sponges wrapped around the grafts. Albumin pretreatment resulted in significantly less median blood loss (5.1 g versus 11 g, P=0.04; Mann-Whitney rank sum test). Grafts were explanted at 1 week, 4 weeks, 10 weeks, and 20 weeks. Patency was 100% in both groups. Graft incorporation at explantation was graded by the surgeon as: 1 = none, 2 = minimal, 3 = moderate, or 4 = extensive. No significant differences were noted at any time period. Inner capsule thickness measurements were made every 2.5 mm along the length of all explants. Grafts explanted at 1 week displayed no inner capsules. By 20 weeks, median inner capsule thickness was significantly less in albumin-coated grafts (190 microm versus 235 microm; P<0.0001). These inner capsules in both groups formed as islands, containing abundant myofibroblasts and collagen, covered by endothelial cells and surrounded by residual fibrin coagula. In conclusion, albumin-coated knitted Dacron grafts displayed less transinterstitial blood loss at implantation, and qualitatively similar incorporation, but significantly thinner inner capsules at 20 weeks.

Topics: Animals; Aorta; Blood Loss, Surgical; Blood Vessel Prosthesis; Dogs; Endothelium, Vascular; Fibrin; Humans; Polyethylene Terephthalates; Prosthesis Design; Serum Albumin; Surface Properties; Vascular Patency

22 patients undergoing elective hip arthroplasty were studied. In 12 patients, a closed-loop autotransfusion system, without anticoagulant, was used and 10 had an ordinary wound drainage allowing repeated blood sampling from the wound. Plasma concentrations of antithrombin (AT), fibrin, soluble (SF) and fibrin D-dimer were determined preoperatively, 3, 8, and 24 hours after starting surgery. Wound drainage blood had increased concentrations of SF and fibrin D-dimer and decreased concentrations of AT compared to reference values and systemic concentrations in patients. Plasma concentrations of SF, fibrin D-dimer and AT did not differ between patients receiving retrieved blood and those receiving stored red blood cell concentrates (RBCs). Patients receiving blood transfusions had lower AT concentrations at 8 hours after starting surgery than those not receiving such a transfusion.

Topics: Aged; Aged, 80 and over; Antithrombin III; Blood Coagulation; Blood Loss, Surgical; Blood Transfusion, Autologous; Blood Volume; Drainage; Erythrocyte Transfusion; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Follow-Up Studies; Hip Prosthesis; Humans; Male; Middle Aged; Wounds and Injuries

Twenty-one cardiothoracic surgical patients have been treated with fibrin as a topical hemostatic/sealing agent, prepared from bovine fibrinogen clotted with bovine thrombin. Serum samples have been collected before treatment with fibrin and postoperatively between 1 and 9 days, 3 and 12 weeks, and 6 and 8 months. The titers of anti-bovine fibrinogen antibodies, measured by ELISA specific for immunoglobulins IgG or IgM, increased to maximal values after about 8 or 6 weeks, respectively. After 8 months, IgG titers were on average 20-fold lower than the mean maximal value, while IgM titers returned to the normal range. IgG was the predominant anti-bovine fibrinogen immunoglobulin as documented by ELISA, affinity chromatography and electrophoresis. Anti-bovine fibrinogen antibodies present in patients reacted readily with bovine fibrinogen, but did not cross-react with human fibrinogen as measured by ELISA or by immunoelectrophoresis. A significant amount of antibodies against bovine thrombin and factor V has been found, many cross-reacting with the human counterparts. No hemorrhagic or thrombotic complications, or clinically significant allergic reactions, occurred in any patient, in spite of antibody presence against some bovine and human coagulation factors. The treatment of patients with bovine fibrin, without induction of immunologic response against human fibrinogen, appeared to be an effective topical hemostatic/sealing measure.

Topics: Animals; Blood Loss, Surgical; Cardiac Surgical Procedures; Cattle; Fibrin; Fibrinogen; Humans; Immunoglobulin G; Immunoglobulin M

Topics: Animals; Anticoagulants; Antithrombin III; Blood Loss, Surgical; Cardiopulmonary Bypass; Dermatan Sulfate; Fibrin; Heart Diseases; Heparin; Heparin Cofactor II; Intracranial Embolism and Thrombosis; Sternum; Surface Properties; Swine; Thoracotomy; Thrombin; Thrombosis; Whole Blood Coagulation Time

The effect of high-dose aprotinin treatment on hemostatic activation during cardiopulmonary bypass in pediatric patients having cardiac operations was investigated. Sixty patients weighing less than 10 kg undergoing cardiac operations for different types of congenital heart diseases were studied: 20 patients were treated with aprotinin 2 x 15,000 KIU/kg, 20 patients with 2 x 30,000 KIU/kg, and 20 patients without aprotinin treatment served as the control group. Different split products of fibrinogen and/or fibrin and the fibrinolytic activity on fibrin plates were measured to assess fibrinolytic activation. F1/F2 prothrombin fragments, thrombin-antithrombin III-complex, and fibrin monomers were measured to estimate thrombin activation. There was a significant dose-dependent reduction in fibrin-fibrinogen split product formation during cardiopulmonary bypass: In the high-dose aprotinin group the concentration of the split products at the end of bypass was 1.5 +/- 0.6 micrograms/ml, compared with 3.4 +/- 3.0 micrograms/ml in the low-dose aprotinin group and 6.7 +/- 3.5 micrograms/ml in the control group (p < 00.5). Fibrinolytic activation on fibrin plates was also significantly reduced by aprotinin. Fibrin monomer formation was significantly diminished at the end of cardiopulmonary bypass in the high-dose group: 9.2 +/- 5.2 micrograms/ml compared with 21.6 +/- 14 micrograms/ml in the control group (p < 00.5). Elastase in complex with alpha 1-protease inhibitor at the end of bypass was increased to the same amount in the three groups: 784 +/- 278 ng/mL (control group), 693 +/- 189 ng/ml (low-dose aprotinin), and 719 +/- 270 ng/mL (high dose aprotinin) (no significant difference). Blood loss 6 hours postoperatively was significantly (p < 00.5) less in the high-dose group (99 +/- 32 ml/m2) than in the control group (164 +/- 87 ml/m2; low-dose group: 160 +/- 106 ml/m2). These observations suggest an attenuation of hemostatic activation during cardiopulmonary bypass with less plasmin formation and, because of inhibition of contact activation, less thrombin generation with aprotinin treatment. Thus the thrombotic-thrombolytic equilibrium is kept more balanced after cardiopulmonary bypass. High-dose aprotinin treatment is recommended for pediatric patients undergoing cardiac operations.

Topics: Antithrombin III; Aprotinin; Blood Loss, Surgical; Cardiopulmonary Bypass; Dose-Response Relationship, Drug; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hemostasis, Surgical; Humans; Infant; Infant, Newborn; Peptide Hydrolases; Prothrombin; Time Factors

Recombinant (r) hirudin is a potent thrombin-specific inhibitor originally derived from the natural hirudin of the leech (Hirudo medicinalis). We have studied the efficacy of r-hirudin compared to heparin in a dog model of cardiopulmonary bypass (CPB) surgery. Two administration regimens were used for r-hirudin: Group I received 1.0 mg/kg intracardiac (i.c.) bolus then intravenous (i.v.) bolus at 30 min (n = 10); Group II received 1.0 mg/kg (i.c.) bolus with 1.25 +/- 0.04 mg/kg/h (i.v.) infusion (n = 8). Group III was given heparin 1.66 mg/kg (i.c.) bolus (n = 9). Aspiration of blood from the chest cavity revealed no significant difference between the three groups. Measurement of fibrin deposits in the pump line filter revealed higher amounts in the r-hirudin groups (P = 0.02). Decreases in platelets, fibrinogen and haematocrit due primarily to haemodilution were the same in each group. The bleeding time was less prolonged for r-hirudin than for heparin (p less than 0.001). No antagonist for r-hirudin was used; however, due to its short half-life, all coagulation parameters returned to baseline within 30 min after CPB. Since r-hirudin has no effect on platelets, is a poor immunogen, does not require a plasma cofactor, and may not require an antagonist, it may provide an alternative anticoagulant to heparin in CPB. Additional studies are, however, needed to optimize the dose and to evaluate other clinical aspects of r-hirudin.

Topics: Animals; Bleeding Time; Blood Loss, Surgical; Cardiopulmonary Bypass; Dogs; Extracorporeal Circulation; Fibrin; Hematocrit; Heparin; Hirudin Therapy; Hirudins; Infusions, Intravenous; Injections; Male; Recombinant Proteins; Thrombin Time; Thrombosis

Topics: Blood Loss, Surgical; Blood Transfusion; Blood Transfusion, Autologous; Coronary Artery Bypass; Fibrin; Hematocrit; Humans; Mediastinum; Oxygenators