scholarly journals Comparative study of the effect of tranexamic acid and exogenous fibrin monomer on fibrin formation in the injury area during stimulation of fibrinolysis by streptokinase

2021 ◽  
Vol 66 (4) ◽  
pp. 556-566
Author(s):  
A. P. Momot ◽  
V. M. Vdovin ◽  
D. A. Orekhov ◽  
I. P. Bobrov ◽  
I. I. Shakhmatov ◽  
...  
Keyword(s):  
Liver Injury ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Blood Cells ◽  
Low Dose ◽  
Venous Blood ◽  
Fibrinogen Concentration ◽  
Morphological Pattern ◽  
Injury Area ◽  
Stimulation Of

Introduction. Earlier studies of low-dose fibrin monomer (FM) demonstrated that low-dose FM has unique hemostatic properties in vivo.Aim — to compare the morphological consequences of intravenous administration of tranexamic acid (TXA) and FM with the hemostatic and hemostasiological effects in hypofibrinogenemia caused by the use of streptokinase after controlled liver injury.Materials and methods. The morphological pattern of fibrin formation in the liver injury area after spontaneous arrest of bleeding in the animals treated with streptokinase or placebo was studied in 73 male rabbits of the Chinchilla breed, split into four groups. In three groups, the study was performed under the conditions of intravenous administration of placebo, TXA, or FM against the background of fibrinolysis activation by streptokinase. Platelet count in the blood, the concentration of fibrinogen, as well as the results of calibrated thrombography, were taken into account.Results. Sequential administration of streptokinase and TXA was accompanied by decreased fibrinogen concentration (by 29.6 %) and, at the same time, a reduction in blood loss (by 15.4 times) in comparison with animals where placebo was used instead of TXA. A decrease in blood loss was associated with increased thickness of thrombotic deposits at the edge of the wound, mainly consisting of red blood cells. These observations were combined with data on the acceleration of thrombin formation in venous blood plasma in a calibrated thrombography test (Peak thrombin 65.4 nmol/L to 109.6 nmol/L in the placebo group). Compared to the observations where placebo was administered instead of FM, however, the sequential use of streptokinase and FM also led to a decrease in blood loss (by 11.0 times) despite decreased fibrinogen concentration (by 23.3 %). A decrease in blood loss was also associated with platelet consumption in venous blood and with increased thickness of thrombotic deposits on the injury surface, where, in addition to red blood cells, the accumulation of fibrin masses was determined by the morphological pattern.Conclusion. The mechanisms of the systemic hemostatic effect of TXA and FM are different, despite the similarity of the achieved hemostatic effects in the conditions of stimulation of blood fibrinolytic activity. These findings expand the understanding of new therapeutic possibilities for reducing post-traumatic blood loss.

scholarly journals Effects of tranexamic acid and exogenous fibrin monomer on the liver injury area and systemic circulation in pharmacological suppression of platelet function in an experiment

2021 ◽  
Vol 102 (5) ◽  
pp. 642-653
Author(s):  
V M Vdovin ◽  
A P Momot ◽  
I I Shakhmatov ◽  
I P Bobrov ◽  
D A Orekhov ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Liver Injury ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Morphological Features ◽  
Fibrinogen Concentration ◽  
Fibrin Monomer ◽  
Significant Difference ◽  
Induced Aggregation ◽  
Injury Area

Aim. To identify and compare the morphological, hemostatic and hemostasiological consequences of intravenous administration of tranexamic acid and fibrin monomer in controlled liver injury against drug-induced thrombocytopathy. Methods. The morphological features of fibrin formation in the area of liver injury after spontaneous bleeding arrest combined with the indicators of blood loss in the animals treated with intravenous placebo, tranexamic acid or fibrin monomer was studied in 69 male rabbits. The effects of these drugs were assessed against thrombocytopathy associated with the combined use of acetylsalicylic acid and clopidogrel. Platelet number and function (adnosine diphosphate-induced aggregation), the data of thromboelastometry and calibrated automated thrombogram, fibrinogen concentration and D-dimer level were considered in the blood test. The feature distribution in the samples was assessed using the ShapiroWilk test. Depending on the distribution, Student's t-test, MannWhitney U test or Wilcoxon signed-rank test were used to test for a significant difference between the features. Differences in mortality rate were established by using Fisher's exact test. The differences were considered statistically significant at p 0.05. Results. A model of thrombocytopathy which showed decreased platelet aggregation function (by 4.5 times), increased blood loss (by 40%), and high mortality (53.9%) was reproduced. Only a small accumulation of thrombotic material was noted on the injured surface of such animals. The use of tranexamic acid led to decreased post-traumatic bleeding (2.5 times) and animal mortality (20%). The latter was provided on the wound surface by increasing the thickness of both thrombotic deposits and fibrin strands. When fibrin monomer was used, the phenomenon of an overcompensated decrease in blood loss (by 6.7 times) accompanied by zero mortality was noted despite a pronounced decrease in platelet aggregation. The maximum increase in the thickness of thrombotic material and fibrin strands was morphologically determined in the injury area compared with other animal groups. Conclusion. Morphological features of traumatic hemostatic effect at the injured area when using tranexamic acid and fibrin monomer have a number of differences despite the similarity of the achieved results in minimizing blood loss.

Comparison of Two Doses of Tranexamic Acid in Adults Undergoing Cardiac Surgery with Cardiopulmonary Bypass

2014 ◽  
Vol 120 (3) ◽  
pp. 590-600 ◽  
Author(s):  
Stéphanie Sigaut ◽  
Benjamin Tremey ◽  
Alexandre Ouattara ◽  
Roland Couturier ◽  
Christian Taberlet ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Primary Endpoint ◽  
Low Dose ◽  
Blood Product ◽  
High Dose ◽  
Blood Product Transfusion ◽  
Repeat Surgery ◽  
Frozen Plasma

Abstract Background: The optimal dose of tranexamic acid (TA) is still an issue. The authors compared two doses of TA during cardiac surgery in a multicenter, double-blinded, randomized study. Methods: Patients were stratified according to transfusion risk, then randomized to two TA doses: 10 mg/kg bolus followed by 1 mg·kg−1·h−1 infusion (low dose) until the end of surgery or 30 mg/kg bolus followed by 16 mg·kg−1·h−1 infusion (high dose). The primary endpoint was the incidence of blood product transfusion up to day 7. Secondary ones were incidences of transfusion for each type of blood product and amounts transfused, blood loss, repeat surgery, TA-related adverse events, and mortality. Results: The low-dose group comprised 284 patients and the high-dose one 285. The primary endpoint was not significantly different between TA doses (63% for low dose vs. 60% for high dose; P = 0.3). With the high dose, a lower incidence of frozen plasma (18 vs. 26%; P = 0.03) and platelet concentrate (15 vs. 23%; P = 0.02) transfusions, lower amounts of blood products (2.5 ± 0.38 vs. 4.1 ± 0.39; P = 0.02), fresh frozen plasma (0.49 ± 0.14 vs.1.07 ± 0.14; P = 0.02), and platelet concentrates transfused (0.50 ± 0.15 vs. 1.13 ± 0.15; P = 0.02), lower blood loss (590 ± 50.4 vs. 820 ± 50.7; P = 0.01), and less repeat surgery (2.5 vs. 6%; P = 0.01) were observed. These results are more marked in patients with a high risk for transfusion. Conclusions: A high dose of TA does not reduce incidence of blood product transfusion up to day 7, but is more effective than a low dose to decrease transfusion needs, blood loss, and repeat surgery.

Prothrombin Complex Concentrate or Idarucizumab in a Multimodal Hemostatic Approach with Tranexamic Acid and Fibrinogen for the Acute Reversal of Dabigatran

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2275-2275
Author(s):  
Oliver Grottke ◽  
Markus Honickel ◽  
Rolf Rossaint ◽  
Till Braunschweig
Keyword(s):  
Liver Injury ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Research Funding ◽  
Prothrombin Complex Concentrate ◽  
Line Treatment ◽  
First Line ◽  
Coagulation Parameters ◽  
Hemostatic Therapy ◽  
First Line Treatment

Abstract Background: Reversal of dabigatran anticoagulation in traumatized patients with massive bleeding using idarucizumab (IDA) or prothrombin complex concentrate (PCC) together with other resuscitation measures will be first line treatment. In cases of continuous bleeding and/or elevated dabigatran levels, further hemostatic therapy with coagulation factors (tranexamic acid: TX, fibrinogen concentrate: FGN) may be required. This study tested the safety and efficacy of IDA or PCC, given as first or second line therapy in a two hit polytrauma model under dabigatran anticoagulation. A multimodal approach using TX plus FGN was also tested. In addition to the primary endpoint, reduction in blood loss (BL), a panel of coagulation parameters and the safety of these hemostatic measurements was investigated. Methods: Dabigatran etexilate (30 mg/kg bid) was given to 28 male pigs for 3 days after ethical approval. On day 4, pigs were anesthetized and given a dabigatran infusion before blunt liver injury and bilateral femur fractures. Animals were randomized to receive either 60 mg/kg IDA or 50 U/kg PCC after the first injury. One hour later these animals received the opposite treatment post second liver injury. In a second step, TX (20 mg/kg) plus FGN (100 mg/kg) were added to hemostatic therapy (IDA or PCC) after the first injury, and received the opposite hemostatic therapy (IDA 60 mg/kg or PCC 50 U/kg) after the second liver injury. BL, hemodynamic and coagulation parameters were monitored over 5 h or until death. Results: IDA as first line treatment resulted in a significant reduction in BL (IDA: 1040±202 mL) as compared to PCC (1389 ±194 mL) 60 min post injury. Despite increasing blood loss following the second trauma, the difference between groups remained significant (IDA-PCC: 1556 ± 205 mL, PCC-IDA: 1981±361 mL, P<0.0001). Likewise, in the initial TX+FGN+PCC (1696 ± 186 mL) and TX+FGN+IDA group (1416 ± 139 mL) blood loss was significantly lower compared to PCC mono-therapy (P=0.023 and P<0.0001). However, no significant difference between IDA monotherapy or TX+FGN+IDA was observed. Survival in all groups was 100%. Animals that received first IDA showed a complete reversal of coagulation parameters (e.g. aPTT, PT, thromboelastometry variables); PCC showed an improvement of clot initiation (CT) and PT, but parameters were not normalized to baseline values. The addition of FGN increased plasma concentration of fibrinogen and improved clot strength. Pathological analyses and clinical parameters including pulmonary pressure exhibited no adverse events in any of the investigated groups. Conclusion: Under conditions of ongoing blood loss after polytrauma and dabigatran anticoagulation, both IDA and PCC prevented exsanguination, although therapy with IDA was more effective. This can be explained by differences in mechanisms, IDA binds dabigatran and inhibits its anticoagulant effect, whereas PCC has no impact on dabigatran anticoagulation but nonspecifically enhances thrombin generation. Their different effects on coagulation parameters also reflect this. Moreover our data imply that clinically used multimodal hemostatic therapy with TX plus FGN and PCC or IDA appears safe under these conditions. Disclosures Grottke: NovoNordisk: Research Funding; Portola Pharmaceuticals: Consultancy; CSL Behring: Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding; Biotest: Research Funding. Rossaint:CSL Behring: Research Funding; Bayer Healthcare: Honoraria; Boehringer Ingelheim: Honoraria, Research Funding.

Topical and low-dose intravenous tranexamic acid in cyanotic cardiac surgery

2017 ◽  
Vol 25 (2) ◽  
pp. 118-122 ◽  
Author(s):  
Jigar Patel ◽  
Mrugesh Prajapati ◽  
Hardik Patel ◽  
Hemang Gandhi ◽  
Shilpa Deodhar ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Cardiac Surgery ◽  
Intensive Care ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Low Dose ◽  
Blood Product ◽  
Sternal Closure ◽  
Topical Tranexamic Acid ◽  
Ventilator Time

Background Coagulopathy is a major problem in surgery for cyanotic congenital heart disease. Tranexamic acid has been used both topically and systemically and plays a vital role in pediatric cardiac surgery by reducing blood loss and blood product requirement. We aimed to determine the anti-fibrinolytic effectiveness of low-dose systemic or topical tranexamic acid or a combination of both. Methods Seventy-five patients were divided in 3 groups of 25. Group A patients were given tranexamic acid 20 mg kg−1 intravenously after sternotomy and 20 mg kg−1 after heparin reversal. Group B patients were given tranexamic acid 50 mg kg−1 in 20 mL of saline intrapericardially before sternal closure, with the drain clamped for 20 min. Group C patients were given tranexamic acid 20 mg kg−1 intravenously after sternotomy and 50 mg kg−1 intrapericardially before sternal closure. A number of clinical variables were recorded in the first 3 postoperative days. Ventilator time, intensive care unit stay, and outcome were also recorded. Results Chest tube drainage and blood product requirements were lowest in group C. Blood urea and serum creatinine levels were higher in groups A and C ( p < 0.05). Intensive care unit stay and ventilator time were similar in all 3 groups. No patient died and none had a seizure or other neurological event or thromboembolic complication postoperatively. Conclusion The combination of low-dose intravenous and topical tranexamic acid reduces postoperative blood loss and blood product requirement without incurring neurological, renal or thromboembolic complications. We recommend the routine use of topical and low-dose systemic tranexamic acid in cyanotic pediatric cardiac surgery.

scholarly journals Effect of low dose tranexamic acid on intra-operative blood loss in neurosurgical patients

2015 ◽  
Vol 9 (1) ◽  
pp. 42 ◽  
Author(s):  
BidkarPrasanna Udupi ◽  
MunaganuriVenkata Siva Satya Prakash ◽  
Sethuramachandran Adinarayanan ◽  
Sandeep Mishra ◽  
Lenin Babu ◽  
...  
Keyword(s):  
Blood Loss ◽  
Tranexamic Acid ◽  
Low Dose ◽  
Operative Blood Loss ◽  
Neurosurgical Patients
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