Fibrinolytic Parameters Research Articles

Changes in the coagulation parameters in dogs with protein-losing enteropathy between before and after treatment.

Protein-losing enteropathy (PLE) is known to induce hypercoagulability and resultant thromboembolism in dogs. We hypothesized that hypercoagulability would improve if remission was obtained in dogs with PLE after treatment. This study aimed to evaluate the changes in the coagulation parameters after treatment in dogs diagnosed with PLE. As coagulation parameters, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, thrombin-antithrombin complex (TAT), D-dimer, and antithrombin (AT) were measured. In addition to these parameters, rotational thromboelastometry (ROTEM), which evaluates the comprehensive coagulation and fibrinolysis reactions of whole blood, was conducted and the data of clotting time (CT), clot formation time (CFT), α angle (α), maximum clot firmness (MCF) and lysis index at 60 min (LI60) were obtained. Eleven of the 14 dogs diagnosed with PLE were classified as responders to the treatment based on the changes in their plasma albumin (ALB) concentration after treatment. Significant increase in CFT and decrease of α and MCF indicating the resolution of hypercoagulability were found after treatment in responder dogs; however, there was no significant change in the coagulation and fibrinolysis parameters other than those measured by ROTEM. This study demonstrated that the hypercoagulability detected by ROTEM was significantly improved after treatment in dogs with PLE.

Comparison of Intravenous and Topical Dexamethasone for Total Knee Arthroplasty: A Randomized Double-Blinded Controlled Study of Effects on Dexamethasone Administration Route and Enhanced Recovery

BackgroundThe optimal route for dexamethasone (DEX) administration regimen for patients undergoing primary TKA has not been investigated. This study aims to determine whether intravenous and topical DEX provide different clinical effects in patients with TKA. MethodsIn this double-blinded, placebo-controlled trial, 90 patients undergoing primary TKA were randomized to intravenous DEX group (n = 45) or topical DEX group (n = 45, DEX applied in anesthetic cocktail for periarticular injection). The primary outcome was postoperative VAS pain score and morphine consumption. Secondary outcomes were included knee swelling, knee flexion, and extension angle, Knee Society Score (KSS), and postoperative hospital stays. Tertiary outcomes assessed the blood-related metrics, including inflammatory biomarkers and fibrinolysis parameters. Finally, nausea and vomiting and other adverse events were compared. ResultsThe topical administration of DEX provide lower pain score at 2h, 8h, 12h at rest (P < .05) and 12h, 24h with activity (P < .05), and less knee swelling in the first postoperative day (P < .05), while intravenous DEX was more effective in decreasing blood inflammatory biomarkers, including C-reactive protein (CRP) at postoperative 24h (P < .05) and interleukin-6 (IL-6) at postoperative 24h, 48h (P < .05), and reducing postoperative nausea (P < .05) for patients receiving TKA. However, there was no significant difference in knee flexion and extension angle, KSS, postoperative hospital stays, and complications occurrence (P > .05) between intravenous and topical DEX after TKA. ConclusionTopical administration of DEX provided better clinical outcomes on postoperative pain management and knee swelling early after TKA, while intravenous DEX was more effective in decreasing blood inflammatory biomarkers and preventing postoperative nausea.

Long-term differences in clot formation and endothelial function between STEMI patients with occlusion of infarct-related artery and those with spontaneous reperfusion

Abstract Introduction Enhanced activation of endogenous fibrinolysis in ST-elevation myocardial infarction (STEMI) patients is the main cause of spontaneous reperfusion of the infarct-related artery (IRA) in the acute period. Whether this enhanced activation remains in the deferred period of myocardial infarction remains unclear. Purpose The main purpose of our work was to analyze the process of clot formation and endogenous fibrinolysis in patients with a history of myocardial infarction. Methods We included 51 patients with a history of myocardial infarction (median, 35 months). Of these patients, 19 had a spontaneous reperfusion of the IRA (SR group) during the index event, and 32 had a total occlusion of the IRA (occlusion group). We assessed parameters of clot formation and endogenous fibrinolysis using thromboelastometry and a thrombodynamics assay. We analyzed endothelial function using the flow-mediated dilation test (FMD). Results The process of clot formation was more active in the occlusion group than in the SR group. Thus, the initial, mean, and total clot velocity times were significantly higher in the occlusion group than in the SR group: 57.2 mcm/min vs. 60.25 mcm/min; 28,1 mcm/min vs. 31.9 mcm/min; and 28.7 mcm/min vs. 31.9 mcm/min, respectively; p&amp;lt;0.01. The clot size was much bigger in the occlusion group than in the SR group (1,190.5 mcm vs. 1,315 mcm; p&amp;lt;0.01). No differences in endogenous fibrinolysis parameters were observed between the two groups. Endothelium function was better in the SR-group than in the occlusion group (FMD 17.4% vs 11.3%, p&amp;lt;0.01). Conclusion STEMI patients with occlusion of the IRA and those with spontaneous reperfusion remain different in clot formation and endothelial function even after many years. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was supported by the Russian Science Foundation grant

Consumptive Coagulopathy Involving Amniotic Fluid Embolism: The Importance of Earlier Assessments for Interventions in Critical Care

Amniotic fluid embolism is a rare disease that induces fatal coagulopathy; however, due to its rarity, it has not yet been examined in detail. The strict diagnostic criteria by Clark for amniotic fluid embolism include severe coagulopathy complicated by cardiopulmonary insufficiency, whereas the Japanese criteria also include postpartum hemorrhage or Disseminated Intravascular Coagulation in clinical practice. Amniotic fluid embolism cases with preceding consumptive coagulopathy may exist and are potential clinical targets for earlier assessments and interventions among amniotic fluid embolism cases fulfilling the Japanese, but not Clark criteria. The present study was performed to compare coagulopathy in the earlier stage between the amniotic fluid embolism patients diagnosed by Clark criteria (Clark group, n = 6), those by the Japanese criteria (Non-Clark group, n = 10), and peripartum controls and identify optimal clinical markers for earlier assessments of amniotic fluid embolism-related consumptive coagulopathy. Retrospective case-control study. A single university-based center. Our amniotic fluid embolism registry program has accumulated clinical information and blood samples since 2003. Amniotic fluid embolism patients in the Clark and Non-Clark groups between 2009 and 2017 and peripartum controls. None. Clinical information was collected on hemoglobin levels, platelet counts, and coagulation- and fibrinolysis-related variables. Fibrinolytic parameters were also measured and compared among the three groups before blood transfusion. Fibrinogen levels in all patients in the Clark group and most in the Non-Clark group decreased earlier than hemoglobin levels, which was consistent with the high hemoglobin/fibrinogen ratio and, thus, is a promising clinical marker for the earlier assessment of amniotic fluid embolism-related consumptive coagulopathy. Earlier evaluations of consumptive coagulopathy and hyperfibrinolysis using the hemoglobin/fibrinogen ratio following preemptive treatment may reduce the occurrence or prevent the aggravation of severe coagulopathy in amniotic fluid embolism patients.

The effect of civil and military flights on coagulation, fibrinolysis and blood flow: insight from a rat model

BackgroundAir travel thrombosis continues to be a controversial topic. Exposure to hypoxia and hypobaric conditions during air travel is assumed a risk factor. The aim of this study is to explore changes in parameters of coagulation, fibrinolysis and blood flow in a rat model of exposure to hypobaric conditions that imitate commercial and combat flights.MethodsSixty Sprague-Dawley male rats, aged 10 weeks, were divided into 5 groups according to the type and duration of exposure to hypobaric conditions. The exposure conditions were 609 m and 7620 m for 2 and 12 h duration. Blood count, thrombin– antithrombin complex, D-dimer, interleukin-1 and interleukin-6 were analyzed. All rats went through flight angiography MRI at day 13-post exposure.ResultsNo effect of the various exposure conditions was observed on coagulation, fibrinolytic system, IL-1 or IL-6. MRI angiography showed blood flow reduction in lower limb to less than 30% in 50% of the rats. The reduction in blood flow was more pronounced in the left vessel than in the right vessel (p = 0.006, Wilcoxon signed rank test). The extent of occlusion differed across exposure groups in the right, but not the left vessel (p = 0.002, p = 0.150, respectively, Kruskal-Wallis test). However, these differences did not correlate with the exposure conditions.ConclusionIn the present rat model, no clear correlation between various hypobaric conditions and activation of coagulation was observed. The reduction in blood flow in the lower limb also occurred in the control group and was not related to the type of exposure.

Effects of thrombomodulin alfa on hemostatic parameters in disseminated intravascular coagulation: Post hoc analysis of a phase 3 randomized controlled trial

BackgroundThe efficacy and safety of thrombomodulin alfa (TM‐α), a cofactor protein promoting thrombin‐mediated protein C activation, have been examined in a phase 3 randomized, double‐blinded, parallel‐group trial in Japan. We have previously reported that TM‐α is noninferior to heparin for the resolution of disseminated intravascular coagulation (DIC). ObjectiveTo investigate the basis for the efficacy of TM‐α in the phase 3 clinical trial in Japan through post hoc analysis of coagulation and fibrinolysis parameters. Patients/MethodsThe 227 patients of the full analysis set population described in the original phase 3 trial in Japan were included in this analysis. Changes in parameters between before and after TM‐α or heparin administration in each of the two patient groups, with underlying diseases of either hematologic malignancy or infection, were studied separately and results were compared between TM‐α and heparin treatment groups in a post hoc manner. ResultsTM‐α administration did not prolong activated partial thromboplastin time but significantly decreased thrombin‐antithrombin complex levels compared with heparin treatment. TM‐α administration reduced consumption of endogenous anticoagulants such as antithrombin and protein C by DIC, compared with the heparin group. DIC scores were decreased in both TM‐α and heparin groups during the 6‐day treatment. ConclusionTM‐α can alleviate intravascular coagulation and consumption of anticoagulants without extending coagulation times. This may be associated with the relatively low risk of bleeding during TM‐α treatment.

Dynamic changes of coagulation and fibrinolytic biomarkers in peri operaive arthroplasty patients.

To evaluate coagulation and fibrinolytic parameters after total joint arthroplasty (TJA) and provide evidence for optimization of timing of perioperative anticoagulation medicine. The prospective study was conducted at the Jishuitan Hospital of Peking University from January to April in 2016, and comprised patients who were scheduled consecutively to undergo primary total knee arthroplasty (TKA) or total hip arthroplasty (THA). Blood samples were obtained at day 1 preoperatively and day1, day 3 postoperatively. Antigenic levels of protein C (PC), endothelial protein C receptor (EPCR), tissue factor pathway inhibitor (TFPI), antithrombin III (AT-III), plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (tPA) were measured with commercially available enzyme-linked immunosorbent assay kits. Postoperative levels of coagulation parameters TFPI and AT-III were increased compared to preoperative values (118.7±34.6 vs 70.0±20.5 μg/ml for AT-III, and 26.37±7.91vs 16.68±8.92 μg/l for TFPI), while postoperative levels of coagulation parameters PC and EPCR were decreased (0.88±0.30 vs 2.03±0.66 μg/ml for PC, and 100.8±31.0 vs 199.4±57.4 μg/ml for EPCR). Postoperative levels of fibrinolytic parameter tPA was increased compared to preoperative values (2.87±0.83 vs 2.03±1.03 μg/l), while its specific inhibitor PAI-1 was decreased (0.88±0.30 vs 2.03±0.66 μg/l). These results demonstrated the perturbation of the coagulation and fibrinolytic system of patients undergoing TJA. Hypercoagulation and hyperfibrinolysis were observed in postoperative patients, which suggested anticoagulant therapy is effective and necessary.

Evaluation of the effect of a new oral contraceptive containing estetrol and drospirenone on hemostasis parameters

ObjectiveTo assess the effect on hemostasis parameters of a new combined oral contraceptive (COC). Study designIn this randomized, single centre, open-label, exploratory study, healthy women received either 15 mg estetrol/3 mg drospirenone (E4/DRSP) (n = 39), 30 mcg ethinylestradiol/150 mcg levonorgestrel (EE/LNG) (n = 30), or 20 mcg ethinylestradiol/3 mg drospirenone (EE/DRSP) (n = 32) for six 28-day cycles. Blood was collected at baseline, cycle 3, and cycle 6. Median change from baseline was evaluated for procoagulant, anticoagulant, and fibrinolytic parameters, and for sex hormone-binding globulin (SHBG). ResultsMedian change of endogenous thrombin potential (ETP) based activated protein C sensitivity resistance (APCr) at cycle 6 was +30% for E4/DRSP, +165% for EE/LNG (p-value <0.05 vs E4/DRSP), and +219% for EE/DRSP (p-value <0.05 vs E4/DRSP). Changes to prothrombin fragment 1 + 2 and SHBG for E4/DRSP, EE/LNG, and EE/DRSP were +23%, +71%, and +64% (p-value <0.05 vs E4/DRSP); and +55%, +74% and +251% (p-value <0.05 vs E4/DRSP), respectively. At cycle 6, changes to other hemostasis parameters for E4/DRSP were similar or smaller than for EE/LNG or EE/DRSP. ConclusionsIn this study, changes in hemostasis parameters after treatment with 6 cycles of E4/DRSP were smaller or similar to those observed for EE/LNG. Similar, but more pronounced changes were also observed versus EE/DRSP, which supports the hypothesis that the effect of COCs on hemostasis parameters is mainly mediated by the estrogenic component. Further studies are needed to provide more insight into the venous thromboembolic risk of E4/DRSP. Implications statementThis study reports that the effects on hemostasis parameters of a COC containing 15 mg E4/3 mg DRSP are less or similar to those for EE/LNG or EE/DRSP. It also demonstrates that the choice of estrogen modulates the effects of COCs on hemostasis parameters.

Hypofibrinolytic state and high thrombin generation may play a major role in SARS‐COV2 associated thrombosis

BackgroundThirty percent of Covid‐19 patients admitted to intensive care units present with thrombotic complications despite thromboprophylaxis. Bed rest, obesity, hypoxia, coagulopathy, and acute excessive inflammation are potential mechanisms reported by previous studies. Better understanding of the underlying mechanisms leading to thrombosis is crucial for developing more appropriate prophylaxis and treatment strategies. ObjectiveWe aimed to assess fibrinolytic activity and thrombin generation in 78 Covid‐19 patients. Patients and MethodsForty‐eight patients admitted to the intensive care unit and 30 patients admitted to the internal medicine department were included in the study. All patients received thromboprophylaxis. We measured fibrinolytic parameters (tissue plasminogen activator, PAI‐1, thrombin activatable fibrinolysis inhibitor, alpha2 anti‐plasmin, and tissue plasminogen activator‐modified ROTEM device), thrombin generation, and other coagulation tests (D‐dimer, fibrinogen, factor VIII, antithrombin). Results and ConclusionsWe observed two key findings: a high thrombin generation capacity that remained within normal values despite heparin therapy and a hypofibrinolysis mainly associated with increased PAI‐1 levels. A modified ROTEM is able to detect both hypercoagulability and hypofibrinolysis simultaneously in Covid‐19 patients with thrombosis.

Age-Related Differences in the Time Course of Coagulation and Fibrinolytic Parameters in Patients with Traumatic Brain Injury.

Coagulopathy and older age are common and well-recognized risk factors for poorer outcomes in traumatic brain injury (TBI) patients; however, the relationships between coagulopathy and age remain unclear. We hypothesized that coagulation/fibrinolytic abnormalities are more pronounced in older patients and may be a factor in poorer outcomes. We retrospectively evaluated severe TBI cases in which fibrinogen and D-dimer were measured on arrival and 3–6 h after injury. Propensity score-matched analyses were performed to adjust baseline characteristics between older patients (the “elderly group,” aged ≥75 y) and younger patients (the “non-elderly group,” aged 16–74 y). A total of 1294 cases (elderly group: 395, non-elderly group: 899) were assessed, and propensity score matching created a matched cohort of 324 pairs. Fibrinogen on admission, the degree of reduction in fibrinogen between admission and 3–6 h post-injury, and D-dimer levels between admission and 3–6 h post-injury were significantly more abnormal in the elderly group than in the non-elderly group. On multivariate logistic regression analysis, independent risk factors for poor prognosis included low fibrinogen and high D-dimer levels on admission. Posttraumatic coagulation and fibrinolytic abnormalities are more severe in older patients, and fibrinogen and D-dimer abnormalities are negative predictive factors.

Effectiveness of preemptive antifibrinolysis with tranexamic acid in rheumatoid arthritis patients undergoing total knee arthroplasty: a study protocol for a randomized controlled trial

BackgroundPatients with rheumatoid arthritis (RA) who have undergone total knee arthroplasty are at increased risk of requiring a blood transfusion. This study is designed to compare the effects of preemptive antifibrinolysis of single-dose and repeat-dose tranexamic acid (TXA) in in RA patients undergoing total knee arthroplasty (TKA).Methods/designThe study will be a double-blind randomized controlled trial with two parallel groups of RA patients. Group A will be given 100 ml normal saline twice daily starting from 3 days before the operation, Group B will be given TXA 1.5 g twice daily starting from 3 days before the operation. All patients will be given TXA 1.5 g 30 min before the operation. The primary outcomes will be evaluated with total blood loss and hidden blood loss. Other outcome measurements such as, fibrinolysis parameters, inflammatory factors, visual analogue scale for post-operative pain, analgesia usage, coagulation parameters, transfusion, the length of stay (LOS), total hospitalization costs, the incidence of thromboembolic events and other complications will be recorded and compared. Recruitment is scheduled to begin on 1 August 2020, and the study will continue until 31 May 2021.DiscussionIn current literature there is a lack of evidence with regard to the efficacy of TXA in RA patients. The findings of this study, whether positive or negative, will contribute to the formulation of further recommendations on the use of TXA in RA patients undergoing TKA.Trial registrationChinese Clinical Trial Registry, ChiCTR2000029720. Registered 14 February 2020.

Investigate of Haemostatic and Fibrinolytic System Parameters among Sickle Cell Anaemia Patients in the Khartoum State

Introduction: A sickle cell anaemia one of a haemoglobinopathy, which constituted as a model for genetically inherited disorders, the course of the disease involves may crises, the investigation of hemostatic components as fibrinogen and fibrinolysis as D-dimer, reflect the overall hemostatic status in the sickle cell anaemia patients. Aim: To investigates hemostatic and fibrinolytic system parameters among sickle cell anaemia patients in the Khartoum state. Methods: The study was conducted in Khartoum state, in JafarIbn Auf Reference Hospital for children as descriptive case-control, a laboratory-based study from 2017-18, specimens were collected randomly of the study population with irrespective to age and gender, blood draw in tri-sodium citrate container, the ethical and consent were obtained. The fibrinogen level was estimated by CA51 semi-automated coagulation analyzer optically based, and the D-dimer were assayed by MISPA-i2, a nephelometric based, the results for each parameter were recorded and using statistical package for the social sciences (SPSS) software for analysis by independent T-test and the statistical significance &gt; 0.05. Results: A hundred participants fifty as study group (HbSS) sickle cell anemic Sudanese child clinically and laboratory-confirmed and fifty healthy as the control group, in comparing a mean of fibrinogen show statistically insignificant (P value 0.645) study group 291.1 ± 107.8 mg/dL and control group 283.4 ± 49.1 mg/dL, but there was a significant difference in comparing a mean of D-dimer in study group 0.56 ± 0.33 μg/mL and control group 0.33 ± 0.14 the P. value 0.00015. Conclusion: The level of D-dimer may be used as a hypercoagulability biomarker in comparison to the level of fibrinogen level for sickle cell anaemia Sudanese child.

Altered clot formation and lysis are associated with increased fibrinolytic activity in ascites in patients with advanced cirrhosis

Analysis of coagulation disorders and assessment of rebalanced hemostasis with the use of traditional coagulation assays is challenging in cirrhotic patients. Therefore, alternative tests are under investigation for the evaluation of coagulopathy in this specific setting. Aim of this study was to analyze the modifications of clot structure and function in cirrhotic patients with different degrees of severity. Cirrhotic patients referred to our Unit were consecutively enrolled. Global test measurements, including clot and lysis assays, clot lysis time, and determination of other fibrinolytic parameters, were performed. Analyses of clot formation, morphology, and lysis were performed with a turbidimetric clotting and lysis assay (EuroCLOT). Lysis of a tissue factor-induced clot by exogenous tissue plasminogen activator was analyzed by studying the modifications of turbidity during clot formation and the following lysis. We evaluated coagulative and fibrinolytic parameters in both plasma and ascites. Urokinase plasminogen activator (uPA) and gelatinase activity in ascites were also measured. We analyzed data from 33 cirrhotic patients (11 in Child-Pugh class A; 22 in class B or C and with ascites) and 21 healthy subjects (HS). In class B/C patients prolonged latency time, a decline in clotting absorbance, and decreased fibrin formation were observed in comparison with class A and HS. Generated curves and Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) progressively declined from HS to class C patients, whereas levels of plasminogen activator inhibitor-1 and tissue plasminogen activator increased. D-dimer levels were markedly increased in ascites, together with significantly smaller levels of TAFI, αlfa2-antiplasmin, and plasminogen. Caseinolytic activity was also present. Class C patients showed smaller amount of uPA and significantly lower levels of matrix metallopeptidases (MMP)2 in ascites in comparison with Class B subjects. Clot formation and lysis are altered in cirrhosis and fibrinolysis is activated in ascites. Ascitic levels of uPA and MMP2 are reduced and inversely related to the severity of liver disease.

ROTEM diagnostic capacity for measuring fibrinolysis in neonatal sepsis

BackgroundHypofibrinolysis has been demonstrated in several studies in adult sepsis. Although fibrinolysis is an important and integral part of the hemostatic system, few data are available regarding its role in neonatal sepsis. Our purpose was to define fibrinolytic profiles across neonatal sepsis spectrum using rotational thromboelastometry (ROTEM). Material and methodsThis study was performed in a Greek tertiary General Hospital during an 18 month-period and included 44 neonates with confirmed sepsis and 22 with suspected sepsis; 110 healthy neonates served as controls. Whenever sepsis was suspected, EXTEM and APTEM assays were performed, clinical findings and laboratory data were recorded. ResultsAlthough most EXTEM parameters were significantly different among the 3 groups, Maximal Lysis (ML) and Lysis Index at 60 min (LI60) levels were similar (p = 0.11 and p = 0.20, respectively). Hyperfibrinolysis, as defined by ROTEM parameters, did not significantly differ among the study populations (p = 0.41). On the contrary, fibrinolysis shutdown, defined as an EXTEM LI60 ≥98%, was more common in septic neonates than in healthy (p < 0.001) and neonates with suspected sepsis (p = 0.042). A weak to moderate correlation of LI60 and ML with mortality (Spearman rho = 0.43 and − 0.40, p = 0.005 and 0.007, respectively) and SNAPE score (Spearman rho = 0.35 and − 0.33, p = 0.02 and 0.03, respectively) was noticed in sepsis group. ConclusionsROTEM, based on fibrinolytic parameters, showed a more frequent fibrinolysis shutdown in neonatal sepsis, but it could neither effectively discriminate septic neonates, nor predict their clinical outcome. The considerable overlap among numerical ROTEM values probably compromises their diagnostic clinical utility in neonatal sepsis.

Haematological Effects of Intermittent Pneumatic Compression for Deep Vein Thrombosis Prophylaxis.

Intermittent pneumatic compression (IPC) is a widely used and recommended method to prevent deep vein thrombosis. While the haemodynamic effects of IPC are well understood, the objective of this systematic review was to analyse the evidence for additional haematological changes. Forty-eight studies were identified where the haematological effects of IPC were measured. The many differences between the studies prevented meta-analysis, but there was a significant amount of evidence that global fibrinolytic activity was increased by IPC, and that levels of D-dimer and tissue factor pathway inhibitor in the blood also increased. There was less consistent evidence for changes in tissue plasminogen activator, plasminogen activator inhibitor and other fibrinolytic parameters. The evidence for changes in pro-coagulant factors and many measures of platelet activation was weak, but there was evidence for increases in prostacyclin. There is sufficient evidence to conclude that IPC does produce haematological changes, but not enough data to clarify the detail of those changes or to determine if it is mediated more by direct compression of the blood vessels, or by the flow changes.

Influence of alcohol consumption on blood coagulation in rotational thromboelastometry (ROTEM): an in-vivo study.

BackgroundTwenty-five to 85% of trauma patients are under the influence of alcohol in addition to experiencing injury-related coagulation impairment. Viscoelastic point-of-care tests (thrombelastography [TEG], rotational thromboelastometry [ROTEM]) are popular tools for rapid hemostasis assessment and therapeutic decision-making in this and other settings. While alcohol affects these tests in-vitro, their specific effects in-vivo are unclear. Therefore, we evaluated the effects of alcohol ingestion on ROTEM parameters.MethodsTwenty volunteers provided informed consent to drinking red wine, whisk(e)y, or vodka to a target blood alcohol concentration of 1‰ within one hour, calculated with the Widmark formula. Blood samples were collected before drinking, at a breath alcohol concentration of 0.5‰, and at 1.0‰, but no later than one hour. After each blood collection, ExTEM and FibTEM tests were performed directly "at the bedside."ResultsAll participants had a blood alcohol concentration (BAC) of 0.00‰ at the beginning. The mean BACs at the second and third collection were 0.48 and 0.76‰, respectively. There were no significant differences in the ExTEM parameters. FibTEM measurements showed a significant difference at the A10 value (13.0 vs. 14.0 mm, P = 0.014) and a trend at the maximum amplitude (maximum clot firmness 13.7 vs. 16.2 mm, P = 0.075). We saw no significant differences in fibrinolysis parameters and no hyperfibrinolysis in our ROTEM measurements.ConclusionsEthanol ingestion can impair early fibrin polymerization. These results might be of special relevance in trauma and support routine application of ROTEM/TEG in such cases.

Rosuvastatin use increases plasma fibrinolytic potential: a randomised clinical trial.

We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor‐1 (PAI‐1) and thrombin‐activatable fibrinolysis inhibitor (TAFI) were measured before and after four weeks of rosuvastatin or no treatment in participants with prior confirmed VTE, after ending anticoagulant therapy. In the non‐rosuvastatin group (n = 121), plasma fibrinolytic potential and individual fibrinolysis parameters did not change at the end of the study versus the baseline, whereas in the rosuvastatin group (n = 126), plasma fibrinolytic potential increased: the mean clot lysis time decreased by 8·75 min (95% CI −13·8 to −3·72), and plasmin inhibitor levels and TAFI activity were lower at the end of the study (−0·05 U/ml; 95% CI −0·07 to −0·02 and −4·77%; 95% CI −6·81 to −2·73, respectively). PAI‐1 levels did not change and fibrinogen levels were 0·17 g/l (95% CI 0·04–0·29) higher. In participants with prior VTE, rosuvastatin use led to an increased fibrinolytic potential compared with non‐statin use. Our findings support the need for further studies on the possible role for statins in the secondary prevention of VTE.

Additional benefits of multiple-dose tranexamic acid to anti-fibrinolysis and anti-inflammation in total knee arthroplasty: a randomized controlled trial.

Consensus is lacking regarding the dose and timing of tranexamic acid (TXA). The aim of this study was to determine whether multiple-dose intravenous TXA further reduced blood loss and attenuated inflammation after total knee arthroplasty (TKA). We prospectively studied four regimens on TXA: no TXA (A), before incision, 3, 6, and 12h later (B), before incision, 3, 6, 12, and 18h later (C) and before incision, 3, 6, 12, 18, and 24h later (D). The primary outcome was hidden blood loss (HBL). Other outcome measurements such as total blood loss (TBL), intraoperative blood loss (IBL), fibrinolysis parameters [fibrin(-ogen) degradation products, D-dimer], inflammatory factors (C-reactive protein, interleukin-6), visual analog scale (VAS) score, transfusion rate, length of stay (LOS) and complications were also compared. The mean HBL and TBL were significantly lower in Group D than in Groups C, B and A. The level of inflammatory factors and fibrinolysis parameters were significantly lower in Group D than in Groups C, B and A at 24 and 72h postoperatively. The VAS score on postoperative days 1 and 3 (POD1 and POD3) was significantly lower in Group D than in Groups C, B and A. There was no significant difference in LOS among groups. No patient underwent blood transfusion. No episodes of deep venous thrombosis or pulmonary embolism occurred in all the groups. The repeated doses of TXA up to 24h can further diminish HBL, provide additional fibrinolysis and inflammation control and ameliorate postoperative pain following TKA. I.

Effect of crocin on antioxidant gene expression, fibrinolytic parameters, redox status and blood biochemistry in nicotinamide-streptozotocin-induced diabetic rats

BackgroundDiabetes is regarded as an epidemiological threat for the twenty-first century. Phytochemicals with known pharmaceutical properties have gained interest in the field of alleviating secondary complications of diseases. Such a substance is crocin, a basic constituent of saffron (Crocus sativus). The present study aimed at examining the beneficial effects of per os crocin administration on the antioxidant status, blood biochemical profile, hepatic gene expression and plasminogen activator inhibitor-1 activity (PAI-1) in the liver, kidney and plasma (an important marker of pre-diabetic status and major factor of thrombosis in diabetes) of healthy rats, as well as of rats with nicotinamide-streptozotocin-induced diabetes.ResultsDiabetes disrupted the oxidation-antioxidation balance, while crocin improved the antioxidant state in the liver by significantly affecting SOD1 gene expression and/or by restoring SOD and total antioxidant capacity (TAC) levels. In the kidney, crocin improved hydrogen peroxide decomposing activity and TAC. In blood, hepatic transaminases ALT and AST decreased significantly, while there was a trend of decrease regarding blood urea nitrogen (BUN) levels. The expression of PAI-1 gene was affected in the liver by the dose of 50 mg kg−1.ConclusionsCrocin treatment contributed in restoring some parameters after diabetes induction, primarily by affecting significantly hepatic transaminases ALT and AST, SOD1 and PAI-1 gene expression and nephric H2O2 decomposing activity. In conclusion, crocin did contribute to the alleviation of some complications of diabetes.

Characteristics Behaviors of Coagulation and Fibrinolysis Markers in Acquired Thrombotic Thrombocytopenic Purpura.

Patients with acquired thrombotic thrombocytopenic purpura (TTP) show no severe abnormalities in coagulation or fibrinolysis. However, the exact extent of the abnormalities is unclear. This study analyzed 138 patients with acquired TTP and 46 patients with septic disseminated intravascular coagulation (DIC) who were included in a Japanese registry. Complete blood cell counts and 8 coagulation or fibrinolysis parameters were compared between the 2 groups. Platelet counts in the acquired TTP group were significantly lower than those in the septic DIC group (P < .001). The international normalized ratio of prothrombin time and the activated partial thromboplastin time in the septic DIC group were significantly higher and longer, respectively, than those in the acquired TTP group (P < .01). The antithrombin (AT) values were significantly lower in the septic DIC group than in the acquired TTP group (P < .001), the latter of which were almost normal. Although both groups revealed elevations of fibrinogen degradation product (FDP) and D-dimer, these levels were significantly higher in the septic DIC group than in the acquired TTP group (P < .001). Of 138 patients with acquired TTP, 25 (18.1%) were diagnosed with septic DIC by the diagnostic criteria of the Japanese Ministry Health, Labour and Welfare, and 78 (56.5%) by those of the Japanese Association of Acute Medicine. Receiver operating characteristic curve analysis showed that acquired TTP could be diagnosed based on severe thrombocytopenia (<20 × 109/L), normal AT level (>87%), and mildly elevated FDP (<23 µg/mL). Our results indicate that 3 routine laboratory tests could differentiate between acquired TTP and septic DIC.