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British Medical Journal (Clinical... Nov 1981
Topics: Antifibrinolytic Agents; Cerebrovascular Circulation; Humans; Intracranial Aneurysm; Recurrence; Subarachnoid Hemorrhage
PubMed: 6797534
DOI: 10.1136/bmj.283.6303.1347 -
Blood Sep 2022
Topics: Antifibrinolytic Agents; Blood Platelets; Hematologic Neoplasms; Humans; Tranexamic Acid
PubMed: 36107459
DOI: 10.1182/blood.2022017207 -
Cell Chemical Biology Dec 2021Aberrant protein citrullination is associated with many pathologies; however, the specific effects of this modification remain unknown. We have previously demonstrated...
Aberrant protein citrullination is associated with many pathologies; however, the specific effects of this modification remain unknown. We have previously demonstrated that serine protease inhibitors (SERPINs) are highly citrullinated in rheumatoid arthritis (RA) patients. These citrullinated SERPINs include antithrombin, antiplasmin, and t-PAI, which regulate the coagulation and fibrinolysis cascades. Notably, citrullination eliminates their inhibitory activity. Here, we demonstrate that citrullination of antithrombin and t-PAI impairs their binding to their cognate proteases. By contrast, citrullination converts antiplasmin into a substrate. We recapitulate the effects of SERPIN citrullination using in vitro plasma clotting and fibrinolysis assays. Moreover, we show that citrullinated antithrombin and antiplasmin are increased and decreased in a deep vein thrombosis (DVT) model, accounting for how SERPIN citrullination shifts the equilibrium toward thrombus formation. These data provide a direct link between increased citrullination and the risk of thrombosis in autoimmunity and indicate that aberrant SERPIN citrullination promotes pathological thrombus formation.
Topics: Animals; Antifibrinolytic Agents; Antithrombins; Disease Models, Animal; Female; Male; Mice; Mice, Inbred C57BL; Peptide Hydrolases; Plasminogen Inactivators; Serine Proteinase Inhibitors; Venous Thrombosis
PubMed: 34352225
DOI: 10.1016/j.chembiol.2021.07.009 -
Interactive Cardiovascular and Thoracic... Dec 2013A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'Does tranexamic acid stop haemoptysis'? Altogether... (Review)
Review
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'Does tranexamic acid stop haemoptysis'? Altogether 49 papers were found using the reported search strategy, of which 13 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. This consisted of one systematic review including a meta-analysis of two double-blind randomized controlled trials (RCTs), the two RCTs, one cohort study, two case-series and seven case reports. Main outcomes included bleeding time, bleeding volume and occurrence of thromboembolic complications after start of treatment. Based on results from the meta-analysis, no difference in remission of bleeding within 1 week was found between tranexamic acid (TA) and placebo groups (odds ratio 1.56, 95% CI: 0.44-5.46). However, overall bleeding time was significantly shorter for the TA group (weighted mean difference -19.47, 95% CI: -26.90, -12.03 h). In one RCT, TA reduced both the duration and the volume of bleeding compared with patients receiving placebo (both P < 0.0005). However, the other RCT failed to find a difference in bleeding time (P = 0.2). In these studies, no patient suffered from thromboembolic complications. Two case reports, however, describe development of pulmonary embolism during TA treatment. Several case reports on the use of TA for treatment of haemoptysis secondary to cystic fibrosis were found. In general, they suggest that TA may be a useful and well-tolerated medication for the treatment of intractable haemoptysis in this patient group. We conclude that limited research on the use of TA for treatment of haemoptysis exists. As aetiology of haemoptysis as well as length of treatment, dosage and form of TA administration varied between the studies, strong recommendations are difficult to give. Current best evidence, however, indicates that TA may reduce both the duration and volume of bleeding, with low risk of short-term thromboembolic complications, in patients with haemoptysis.
Topics: Antifibrinolytic Agents; Benchmarking; Evidence-Based Medicine; Hemoptysis; Humans; Patient Selection; Risk Factors; Thromboembolism; Time Factors; Tranexamic Acid; Treatment Outcome
PubMed: 23966576
DOI: 10.1093/icvts/ivt383 -
Brazilian Journal of Anesthesiology... 2020
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Dose-Response Relationship, Drug; Humans; Tranexamic Acid
PubMed: 32773239
DOI: 10.1016/j.bjan.2020.07.001 -
Texas Heart Institute Journal 1995Bleeding remains an important complication after repeat and complicated cardiac surgery. Although aprotinin has recently been approved by the Food and Drug... (Review)
Review
Bleeding remains an important complication after repeat and complicated cardiac surgery. Although aprotinin has recently been approved by the Food and Drug Administration for use as an antifibrinolytic agent, many surgeons continue to have concerns about its added cost and potential side effects. We review here the current state of antifibrinolytic therapy for excessive bleeding in cardiothoracic surgery and suggest the use of a single intravenous dose of 10 g of epsilon-aminocaproic acid immediately before cardiopulmonary bypass as a safe, inexpensive, and effective alternative to aprotinin. Further clinical and laboratory studies are needed to confirm or modify this protocol.
Topics: Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Blood Coagulation Tests; Blood Loss, Surgical; Cardiopulmonary Bypass; Dose-Response Relationship, Drug; Heart Diseases; Humans; Postoperative Hemorrhage; Premedication
PubMed: 7580358
DOI: No ID Found -
Drugs Sep 2017Von Willebrand disease (VWD) is the most common inherited bleeding disorder with an estimated prevalence of ~1% and clinically relevant bleeding symptoms in... (Review)
Review
Von Willebrand disease (VWD) is the most common inherited bleeding disorder with an estimated prevalence of ~1% and clinically relevant bleeding symptoms in approximately 1:10,000 individuals. VWD is caused by a deficiency and/or defect of von Willebrand factor (VWF). The most common symptoms are mucocutaneous bleeding, hematomas, and bleeding after trauma or surgery. For decades, treatment to prevent or treat bleeding has consisted of desmopressin in milder cases and of replacement therapy with plasma-derived concentrates containing VWF and Factor VIII (FVIII) in more severe cases. Both are usually combined with supportive therapy, e.g. antifibrinolytic agents, and maximal hemostatic measures. Several developments such as the first recombinant VWF concentrate, which has been recently licensed for VWD, will make a more "personalized" approach to VWD management possible. As research on new treatment strategies for established therapies, such as population pharmacokinetic-guided dosing of clotting factor concentrates, and novel treatment modalities such as aptamers and gene therapy are ongoing, it is likely that the horizon to tailor therapy to the individual patients' needs will be extended, thus, further improving the already high standard of care in VWD in most high-resource countries.
Topics: Antifibrinolytic Agents; Aptamers, Nucleotide; Deamino Arginine Vasopressin; Factor VIII; Genetic Therapy; Hemorrhage; Hemostatic Techniques; Humans; Interleukin-11; von Willebrand Diseases; von Willebrand Factor
PubMed: 28791655
DOI: 10.1007/s40265-017-0793-2 -
PloS One 2015Routine use of antifibrinolytic agents in spine surgery is still an issue of debate. (Meta-Analysis)
Meta-Analysis Review
Efficacy and Safety of Antifibrinolytic Agents in Reducing Perioperative Blood Loss and Transfusion Requirements in Scoliosis Surgery: A Systematic Review and Meta-Analysis.
BACKGROUND
Routine use of antifibrinolytic agents in spine surgery is still an issue of debate.
OBJECTIVE
To gather scientific evidence for the efficacy and safety of antifibrinolytic agents including aprotinin, tranexamic acid (TXA) and epsilon aminocaproic acid (EACA, traditionally known as Amicar) in reducing perioperative blood loss and transfusion requirements in scoliosis surgery.
METHODS
We conducted a systematic review and meta-analysis for randomized controlled trials (RCTs), retrospective case-control studies, and retrospective cohort studies on the use of antifibrinolytic agents in scoliosis surgery by searching in the MEDLINE and EMBASE databases and the Cochrane Database of Systematic Reviews and Controlled Trials of papers published from January 1980 through July 2014. Safety of the antifibrinolytic agents was evaluated in all included studies, while efficacy was evaluated in RCTs.
RESULTS
Eighteen papers with a total of 1,158 patients were eligible for inclusion in this study. Among them, 8 RCTs with 450 patients were included for evaluation of pharmacologic efficacy (1 RCT was excluded because of a lack of standard deviation data). Mean blood loss was reduced in patients with perioperative use of antifibrinolytic agents by 409.25 ml intraoperatively (95% confidence interval [CI], 196.57-621.94 ml), 250.30 ml postoperatively (95% CI, 35.31-465.30), and 601.40 ml overall (95% CI, 306.64-896.16 ml). The mean volume of blood transfusion was reduced by 474.98 ml (95% CI, 195.30-754.67 ml). The transfusion rate was 44.6% (108/242) in the patients with antifibrinolytic agents and 68.3% (142/208) in the patients with placebo. (OR 0.38; 95% CI; 0.25-0.58; P<0.00001, I2 = 9%). All studies were included for evaluation of safety, with a total of 8 adverse events reported overall (4 in the experimental group and 4 in the control group).
CONCLUSION
The systematic review and meta-analysis indicated that aprotinin, TXA, and EACA all significantly reduced perioperative blood loss and transfusion requirements in scoliosis surgery. There was no evidence that the use of antifibrinolytic agents was a risk factor for adverse events, especially thromboembolism, in scoliosis surgery.
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Blood Transfusion; Humans; Scoliosis; Spinal Fusion; Treatment Outcome
PubMed: 26382761
DOI: 10.1371/journal.pone.0137886 -
International Journal of Molecular... Jan 2022Aortic aneurysms are sometimes associated with enhanced-fibrinolytic-type disseminated intravascular coagulation (DIC). In enhanced-fibrinolytic-type DIC, both... (Review)
Review
Aortic aneurysms are sometimes associated with enhanced-fibrinolytic-type disseminated intravascular coagulation (DIC). In enhanced-fibrinolytic-type DIC, both coagulation and fibrinolysis are markedly activated. Typical cases show decreased platelet counts and fibrinogen levels, increased concentrations of fibrin/fibrinogen degradation products (FDP) and D-dimer, and increased FDP/D-dimer ratios. Thrombin-antithrombin complex or prothrombin fragment 1 + 2, as markers of coagulation activation, and plasmin-α plasmin inhibitor complex, a marker of fibrinolytic activation, are all markedly increased. Prolongation of prothrombin time (PT) is not so obvious, and the activated partial thromboplastin time (APTT) is rather shortened in some cases. As a result, DIC can be neither diagnosed nor excluded based on PT and APTT alone. Many of the factors involved in coagulation and fibrinolysis activation are serine proteases. Treatment of enhanced-fibrinolytic-type DIC requires consideration of how to control the function of these serine proteases. The cornerstone of DIC treatment is treatment of the underlying pathology. However, in some cases surgery is either not possible or exacerbates the DIC associated with aortic aneurysm. In such cases, pharmacotherapy becomes even more important. Unfractionated heparin, other heparins, synthetic protease inhibitors, recombinant thrombomodulin, and direct oral anticoagulants (DOACs) are agents that inhibit serine proteases, and all are effective against DIC. Inhibition of activated coagulation factors by anticoagulants is key to the treatment of DIC. Among them, DOACs can be taken orally and is useful for outpatient treatment. Combination therapy of heparin and nafamostat allows fine-adjustment of anticoagulant and antifibrinolytic effects. While warfarin is an anticoagulant, this agent is ineffective in the treatment of DIC because it inhibits the production of coagulation factors as substrates without inhibiting activated coagulation factors. In addition, monotherapy using tranexamic acid in cases of enhanced-fibrinolytic-type DIC may induce fatal thrombosis. If tranexamic acid is needed for DIC, combination with anticoagulant therapy is of critical importance.
Topics: Anticoagulants; Antifibrinolytic Agents; Aortic Aneurysm; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinolysis; Heparin; Humans; Partial Thromboplastin Time; Prothrombin Time; alpha-2-Antiplasmin
PubMed: 35163216
DOI: 10.3390/ijms23031296 -
Anesthesiology Oct 2014
Topics: Antifibrinolytic Agents; Blood Transfusion; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Female; Humans; Male; Tranexamic Acid
PubMed: 25247859
DOI: 10.1097/ALN.0000000000000379