Fibrinolytic Parameters Research Articles

Hypofibrinogenemia Caused by Hemocoagulase Injection: A Retrospective Study on Clinical Laboratory Findings

ObjectiveHemocoagulase injection based on the venom of Agkistrodon halys Pallas is widely used in the treatment of hemorrhagic disorders. This study aimed to characterize the clinical laboratory findings of hemocoagulase-induced hypofibrinogenemia as the associated adverse reaction of hemocoagulase injection. MethodsWe retrospectively enrolled 27 in-patients who were treated with hemocoagulase injection for hemoptysis and developed hypofibrinogenemia during the period of January 1, 2015 to March 31, 2018. Clinical data were collected and investigated, including clinical manifestations, hemostatic and fibrinolytic parameters, dosage of hemocoagulase, the medication time, and the cryoprecipitate blood product infusion. Differences in fibrinogen, D-dimer, and fibrin/fibrinogen degradation products (FDP) before, during, and after the application of hemocoagulase injection were analyzed statistically. ResultsPlasma fibrinogen level during medication of hemocoagulase injection decreased significantly compared to that before the treatment (F= 1.80, P < 0.001), with the average decrease of 2.28 g/L (0.63-3.9 g/L). After withdrawal, fibrinogen level increased significantly compared to that during the medication (F = –1.20, P< 0.001), but was still lower than that before the medication (F = 0.59, P = 0.03). The D-dimer level and the FDP level after withdrawal decreased significantly compared to the levels during the medication (F = 0.83, P = 0.002; Wilcoxon-test, Z = –4.54, P<0.001). Spearman’s correlation analyses did not find either fibrinogen change during-before the administration or FDP change after-during the administration was associated with the dosage of hemocoagulase (r = –0.17, P=0.40; r = –0.28, P = 0.15; respectively) and the time of recovery from hypofibrinogenemia (r = –0.45, P = 0.05; r = 0.13, P = 0.61; respectively). ConclusionMonitoring both clotting and fibrinolysis parameters is essential in the management of hemoptysis patients treated with hemocoagulase injection. Clinicians should be aware of hypofibrinogenemia and consider discontinuation of the administration of hemocoagulase whenever necessary.

Trehalose decreases blood clotting in the cerebral space after experimental subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) frequently results in several serious complications, such as cerebral vasospasm. We previously reported the effect of trehalose on vasospasm, inflammatory responses, and lipid peroxidation induced by blood exposure. Herein, to further elucidate the mechanism of action of trehalose, we investigated whether or not post-administration of trehalose can directly influence blood clotting in the cistern. As a result of trehalose injection after the onset of experimental SAH, blood clotting around the basilar artery was clearly inhibited. We also found that trehalose positively impacted coagulation and fibrinolysis parameters in rat, rabbit and human plasma in vitro. These findings suggest that trehalose has suppressive effects on blood clotting in addition to vasospasm, inflammatory responses, and lipid peroxidation after SAH.

Evaluation of the prognostic value of fibrinolytic elements in invasive breast carcinoma patients.

Breast cancer (BrC) is one of the most serious oncological problems in the world. The aim of the study was to evaluate concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) and their ratios: t-PA/PAI-1 and PAI-1/t-PA in breast cancer patients and in healthy individuals and to estimate the ability of fibrinolytic parameters in predicting neoplasm disease and disease relapse. One hundred and five women were enrolled in the study, including 60 cases with primary BrC, (M0) and 45 healthy females. Follow-up was completed in all BrC patients with a 16.7% recurrence rate. An immunoassay of t-PA, PAI-1 in all cases was made as well as the immunohistochemistry of estrogen and progesterone receptors, human epidermal growth factor receptor 2, E-cadherin, and Ki-67 was performed in BrC subjects. A significantly higher PAI-1 concentration in breast cancer patients below the age of 55 than in controls was obtained. According to the ROC curve analysis, the PAI-1 concentration demonstrates the most accurate prognostic value with the cut-off point at 33.91 ng/ml, with 90% sensitivity and 36% specificity, which discriminates between controls and cancer patients. However, t-PA presents the highest area under the receiver-operating characteristic curves (AUCROC)=0.634 in predicting disease relapse with the cut-off value of 5.3 ng/ml. According to the Kaplan-Meier curves, a high concentration of t-PA (>5 ng/ml) and a lower PAI-1/t-PA ratio (<7.5) are associated with shorter survival. Evaluation of plasma t-PA and PAI-1 concentrations may deliver relevant prognostic information for breast cancer patients.

Relationship Between Severity of Fibrinolysis Based on Rotational Thromboelastometry and Conventional Fibrinolysis Markers.

The association between severity of fibrinolysis, ascertained by rotational thromboelastometry to diagnose hyperfibrinolysis in patients with out-of-hospital cardiac arrest (OHCA), and conventional fibrinolysis markers (ie, tissue-plasminogen activator [t-PA], plasminogen, α2-plasmin inhibitor [α2-PI], and plasminogen activator inhibitor [PAI]) with key roles in the fibrinolytic system was investigated. This prospective observational study included 5 healthy volunteers and 35 patients with OHCA from the Hokkaido University Hospital. Blood samples were drawn immediately upon admission to the emergency department. Assessments of the extrinsic pathway using tissue factor activation (EXTEM) and of fibrinolysis by comparison with EXTEM after aprotinin addition (APTEM) were undertaken. Conventional coagulation and fibrinolysis markers were measured in the stored plasma samples. Significant hyperfibrinolysis observed in EXTEM disappeared in APTEM. Patients exhibited significantly higher levels of fibrinogen/fibrin degradation products, plasmin–α2-PI complex, and t-PA but lower levels of fibrinogen, plasminogen, and α2-PI than healthy controls. The PAI level was unchanged. Fibrinolytic parameters of EXTEM correlated with levels of lactate and conventional fibrinolysis markers, especially t-PA. Increased t-PA activity and decreased plasminogen and α2-PI significantly correlated with increased severity of fibrinolysis (hyperfibrinolysis).

The antifibrinolytic and anti-inflammatory effects of a high initial-dose tranexamic acid in total knee arthroplasty: a randomized controlled trial.

The aim of this study was to evaluate the effects of a high initial-dose (60mg/kg) intravenous tranexamic acid (IV-TXA) on fibrinolysis and inflammation after total knee arthroplasty (TKA). A total of 132 patients were categorized into two groups based on different TXA regimens: 20mg/kg before incision (A) or 60mg/kg before incision (B). All patients received five doses of 1g TXA at three, six, 12, 18, and 24 hours after the first dose. The primary outcomes were peri-operative blood loss and transfusion rate. Other outcome measurements such as, haemoglobin level, fibrinolysis parameters [fibrin(-ogen) degradation products (FDP), D-dimer], inflammatory factors [C-reactive protein (CRP), interleukin-6 (IL-6)], visual analog scale (VAS) score, consumption of analgesic rescue, coagulation parameters [activated partial thromboplastin time (APTT), prothrombin time (PT), platelet count, thrombelastography (TEG), and anti-factor Xa activity (AFXa)] and complications, were also compared. There was a favourable effect in reducing peri-operative blood loss and transfusion rate for patients in Group B, compared with patients in Group A. In addition, the levels of FDP, D-dimer, CRP, IL-6, and dynamic pain in Group B were significantly lower than those in Group A on post-operative days one, two and three. There were no statistically significant differences in postoperative coagulation parameters and complications between the two groups. A high initial-dose (60mg/kg) IV-TXA before surgery followed by five doses can further reduce blood loss, provide additional fibrinolysis and inflammation control, and ameliorate post-operative pain following TKA, without increasing the risk of treatment-related complications.

Pharmacology complex compound of pro-gly-pro-leu with heparin: hypoglycemic, fibrinolitic and anticoagulant effects in rats with hyperglycemia

Previously it was shown that the use of regulatory peptides of the glyprolin family helps to normalize the hemostasis system and blood glucose levels in experimental resistant hyperglycemia in rats, similar to type 2 diabetes mellitus in humans. It is also known that the anticoagulant heparin inhibits blood coagulation and exhibits a hypoglycemic effect in the body. The aim of the study is to obtain a complex of the Pro-Gly-Pro-Leu (PGPL) peptide and the unfractionated heparin, to study its effect on glucose and anticoagulant fibrinolytic properties and show its ability to restore the impaired functions of the insular and coagulating blood systems in experimental hyperglycemia in rats. Materials and Methods . Laboratory Wistar male rats, intact and with experimentally induced hyperglycemia, were used in the experiment. A complex compound of PGPL and heparin was created with a component ratio of 1:1 (mol/mol), which was administered intranasally to hyperglycemic rats once a day for 5 days at the dose of 1 mg/kg. Similarly, the constituent parts of the complex were administrated in equivalent amounts. The anticoagulant activity was determined by the test of activated partial thromboplastin time, fibrinolysis parameters - by tests of total, enzymatic and non-enzymatic fibrinolytic activities, as well as the activity of a tissue plasminogen activator. In addition, blood glucose was measured using special test strips. Results. The use of the PGPL-heparin complex in the animals with hyperglycemia led to normalization of blood glucose levels, an increase in the anticoagulant and fibrinolytic background of blood plasma. These effects persisted for 6 days after the cancellation of the peptide-heparin complex administration to rat. Conclusion . In the development of experimental hyperglycemia, the PGPL complex with heparin exhibits a combined hypo-glycemic, anticoagulant and fibrinolytic enzymatic and non-enzymatic nature of the effect. In the future, the studied peptide-heparin complex can be used for the prevention and treatment of type 2 diabetes mellitus, complicated by increased blood coagulation.

Fibrinolytic parameters under ischemic stroke with diabetes mellitus combination

Abstract Background: Fibrinolysis and thrombosis alterations include important parts of stroke pathophysiology. At the same time fibrinolytic system disorders are a common feature of patients with metabolic syndrome and diabetes. So it may increase the possibility of developing atherosclerotic lesions and occlusive intravascular thrombi. The present study investigated the influence of type 2 diabetes mellitus presence on the indicators of fibrinolytic parameters (plasminogen activator inhibitor 1 (PAI-1), tissue-type plasminogen activator (tPA) content, streptokinase-activated plasminogen and α2-antiplasmin activities, euglobulin clot lysis time (ECLT) and Hageman-factor-dependent fibrinolysis time) under ischemic stroke (IS). Materials and methods: Participants were 87 subjects with IS, 22 of them had diabetes mellitus. Blood samples besides for aforementioned parameters were analyzed for glucose and glycosylated haemoglobin content. Results: The research established increase of plasma PAI-1 and tPA levels, ECLT, Hageman-factor-dependent fibrinolysis time in IS and IS with diabetes mellitus patient groups in comparison with the control. PAI-1 concentration in plasma was positively correlated with both lysis time tests but tPA content was negative correlated with glucose level and PAI-1 for only IS patients. But there was a high negative correlation between tPA and ECLT as well as Hageman-factor-dependent fibrinolysis time for both investigated IS forms. Conclusions: The results showed important differences in the characteristics of the fibrinolytic mechanism in IS patients compared with healthy population. The major differences were elevated PAI-1 and t-PA contents and prolonged ECLT in IS patients but no significant differences in these parameters were observed between the patients with IS and IS with diabetes.

Six-Dose Intravenous Tranexamic Acid Regimen Further Inhibits Postoperative Fibrinolysis and Reduces Hidden Blood Loss following Total Knee Arthroplasty.

There is no consensus regarding the ideal dosages and times of multiple-dose intravenous tranexamic acid (IV-TXA) administration in total knee arthroplasty (TKA). This study aimed to assess the effect of six-dose IV-TXA with the total dosage more than 6 g on postoperative fibrinolysis and hidden blood loss (HBL) after primary TKA. A total of 175 patients were randomized into three groups to receive placebo (group A), or a single preoperative dose of 20 mg/kg IV-TXA (group B), or six-dose IV-TXA from the beginning of the procedure to subsequent 24 hours with the total dosage more than 6 g (group C). The calculated HBL, maximum hemoglobin (Hb) drop, transfusion rate, and the incidence of thromboembolic events were compared among groups. The levels of fibrinolysis parameters in plasma including fibrin(-ogen) degradation products (FDP) and D-dimer were measured at six time points from preoperatively to 3-month postoperative period. The mean HBL and maximum Hb drop in group C (515.51 ± 245.79 mL, and 2.06 ± 0.73 g/dL, respectively) were significantly lower than those in groups B (756.06 ± 226.79 mL, p < 0.001; and 2.77 ± 0.78 g/dL, p < 0.001, respectively) and A (987.65 ± 275.38 mL, p < 0.001; and 3.49 ± 0.86 g/dL, p < 0.001, respectively). Such differences were also detected between groups A and B (p < 0.001 and p < 0.001, respectively). The levels of FDP and D-dimer in plasma were lower in group C than those in groups B and A on postoperative 24, 48, 72 hours (p < 0.001 for all). No episode of transfusion occurred, and the incidence of thromboembolic events were similar among groups (p > 0.05). The administration of six-dose IV-TXA during the first 24 hours resulted in reduced HBL following TKA without a measured increase in thromboembolic events.

Efficacy and safety of a loading high-dose tranexamic acid followed by postoperative five doses in total hip arthroplasty: A randomized controlled trial

To evaluate the efficacy and safety of a loading high-dose tranexamic acid (TXA) followed by postoperative 5 doses in total hip arthroplasty (THA) by a randomized controlled trial. Seventy-two patients who underwent primary unilateral THA between December 2017 and March 2018 were randomly divided into two groups (36 patients in each group). A single dose of 20 mg/kg TXA was administered intravenously before 5-10 minutes of operation in group A; and a single dose of 40 mg/kg TXA was administered intravenously in group B at the same time point. All patients received 5 doses of 1 g TXA at 3, 6, 12, 18, and 24 hours after the first dose. There was no significant difference in gender, age, weight, height, body mass index, disease type, and combined medical diseases between the two groups ( P>0.05). Total blood loss (TBL), lowest postoperative hemoglobin (Hb) level, fibrinolysis parameters [fibrin (ogen) degradation products (FDP), D-dimer], inflammatory factors [C-reaction protein (CRP), interleukin-6 (IL-6)], adverse events (thrombosis, pulmonary embolism) were recorded and compared between groups. The TBL was significantly lower in group B than in group A ( P<0.05). Furthermore, the lowest postoperative Hb level was significantly higher in group B than in group A ( P<0.05). There was no significant difference in FDP and D-dimer before operation between the two groups ( P>0.05). The levels of FDP and D-dimer were significantly lower in group B than in group A at 12 and 36 hours postoperatively ( P<0.05). There was no significant difference in CRP and IL-6 before operation between the two groups ( P>0.05). The levels of CRP and IL-6 were significant lower in group B than in group A at 12, 24, and 36 hours postoperatively ( P<0.05). There was no significant difference at 14 days ( P>0.05). There were 2 patients with intramuscular venous thrombosis in group A and 1 in group B after operation, and there was no significant difference in the incidence of embolic events ( P>0.05). No deep venous thrombosis or pulmonary embolism occurred in all groups. A loading high-dose TXA followed by postoperative 5 doses can further reduce the blood loss, provide additional fibrinolysis and inflammation control in THA, without increasing the risk of embolic events.

Alterations in fibrin formation and fibrinolysis in early onset-preeclampsia: Association with disease severity

Objective; Early-onset preeclampsia is a rare pregnancy-specific disorder associated with significantly increased maternal and fetal morbidity and mortality. Whilst it is known that even normotensive pregnancies are associated with changes in clot formation and dissolution, the nature of how these changes differ in those with early onset preeclampsia has not been well established.We sought to evaluate parameters of fibrin formation and fibrinolysis in individuals with early onset preeclampsia in comparison to both pregnant and non-pregnant controls. Furthermore, such parameters were correlated with markers of disease severity in this patient cohort, including the presence of multiorgan involvement, the rate of disease progression and the extent of the anti-angiogenic state in this condition. Study design; Patients with early onset preeclampsia (N = 20) and both pregnant (N = 16) and non -pregnant (N = 16) controls were recruited from the cohort at a large urban maternity hospital which saw over 15,000 deliveries during the study period. Platelet poor plasma was prepared from collected whole blood and analysed for parameters of fibrin formation and fibrinolysis (lagtime to and rate of fibrin formation; PAI-1; PAI-2; D-dimer; plasmin-antiplasmin; tPA) in addition to markers of angiogenesis (sFLT-1; Endoglin) using commercially available specific immunoassays. Results; The maximum rate of fibrin formation as well as PAI-1, PAI-2 and D-dimer levels were all significantly increased in those with early onset preeclampsia and pregnant controls when compared to non-pregnant controls without significant differences between the 2 former groups. Plasmin-antiplasmin levels were significantly reduced in a similar manner. tPA levels were significantly elevated in EOP compared to both pregnant and non-pregnant controls. EOP was associated with significantly increased anti-angiogenic factors (sFLT-1; Endoglin) when compared to both pregnant and non-pregnant controls. Conclusion; Markers of fibrin formation and fibrinolysis are significantly alerted in early onset preeclampsia; furthermore, certain markers correlate with disease severity in this patient cohort.

Type 2 Diabetes and Cardiovascular Factors Contrasted with Fibrinolysis Disorders in the Blood of Patients with Peripheral Arterial Disease

Background and objectives: Both in the pathogenesis of type 2 diabetes (DM 2) and Peripheral Arterial Disease (PAD), a vital role is played by endothelial dysfunction. Metabolic disorders found in DM 2 (hyperglycemia, insulin resistance), endothelial dysfunction, and increased inflammation lead to intensified atherothrombosis. The fibrinolysis system comprises a natural compensatory mechanism in case of hypercoagulability. The aim of this study was to assess concentrations of selected fibrinolysis parameters in the blood of patients with symptomatic PAD, including in particular concurrent DM 2 and other cardiovascular factors. Materials and Methods: In the group of 80 patients with PAD (27 F/53 M) and 30 healthy volunteers (10 F/20 M), the following parameters were measured: Concentrations of fibrinogen, tissue-Plasminogen Activator (t-PA Ag), Plasminogen Activator Inhibitor-1 (PAI-1 Ag), D-dimer, and platelet (PLT) count. Results: In the blood of patients with PAD and concomitant DM 2 significantly higher concentrations of fibrinogen were found in comparison with patients with PAD and without diabetes (p = 0.044). No significant impact was observed in individuals with atherosclerotic complications (manifested by coronary artery disease, atherosclerosis of cerebral arteries) and selected cardiovascular risk factors (smoking, LDL and triglyceride concentrations, BP values) on the levels of t-PA, PAI-1, D-dimer, and PLT count. It was found that t-PA Ag and PAI-1 Ag values tended to rise along with a BMI increase in the subgroups of subjects (with normal body mass, overweight, and obesity), but no statistically significant differences were observed. However, two significant positive correlations were reported between t-PA Ag and BMI, as well as between PAI-1 Ag and BMI. Conclusions: Type 2 diabetes in peripheral arterial disease affects the concentration of fibrinogen causing its increase, which is connected with the inflammation and prothrombotic process in the course of both conditions. The concurrence of atherosclerosis of coronary or cerebral arteries, smoking, LDL and TG concentrations, and BP value do not have a significant impact on the levels of analyzed fibrinolysis parameters. A positive correlation between BMI and t-PA Ag and PAI-1 Ag concentrations needs to be supported in further studies on a larger number of overweight and obese patients.

Impact of lipoprotein apheresis on thrombotic parameters in patients with refractory angina and raised lipoprotein(a): Findings from a randomized controlled cross-over trial

Raised lipoprotein(a) [Lp(a)] is a cardiovascular risk factor common in patients with refractory angina. The apolipoprotein(a) component of Lp(a) exhibits structural homology with plasminogen and can enhance thrombosis and impair fibrinolysis. The objective of the study was to assess the effect of lipoprotein apheresis on markers of thrombosis and fibrinolysis in patients with high Lp(a). In a prospective, single-blind, crossover trial, 20 patients with refractory angina and raised Lp(a)>50mg/dL were randomized to three months of weekly lipoprotein apheresis or sham. Blood taken before and after apheresis/sham was assessed using the Global Thrombosis Test, to assess time taken for invitro thrombus formation (occlusion time) and endogenous fibrinolysis (lysis time), as well as von Willebrand Factor, fibrinogen, D-dimer, thrombin/anti-thrombin III complex, prothrombin fragments 1+2, and thrombin generation assays. Lp(a) was significantly reduced by apheresis (100.2 [interquartile range {IQR}, 69.6143.0] vs 24.8 [17.2,34.0] mg/dL, P=.0001) but not by sham (P=.0001 between treatment arms). Apheresis prolonged occlusion time (576±116 s vs 723±142 s, P<.0001) reflecting reduced platelet reactivity and reduced lysis time (1340 [1128, 1682] s vs 847 [685,1302] s, P=.0006) reflecting enhanced fibrinolysis, without corresponding changes with sham. Apheresis, but not sham, reduced von Willebrand Factor (149 [89.0, 164] vs 64.2 [48.5, 89.8] IU/dL, P=.0001), and fibrinogen (3.12±0.68 vs 2.20±0.53g/L, P<.0001), and increased prothrombin fragments 1+2 (158.16 [128.77, 232.09] vs 795.12 [272.55, 1201.00] pmol/L, P=.0006). There was no change in D-dimer, thrombin/anti-thrombin III complex, or thrombin generation assay with apheresis or sham. Lipoprotein apheresis reduces Lp(a) and improves some thrombotic and fibrinolytic parameters in patients with refractory angina.

Bothrops snakebites in the Amazon: recovery from hemostatic disorders after Brazilian antivenom therapy

Introduction: Bothrops atrox snakebites are a major public health problem in the Amazon region and also cause hemostatic disorders. In this study, we assessed the recovery from hemostatic disorders in Bothrops snakebite patients after being given antivenom therapy.Methods: This is a prospective study of Bothrops snakebite patients (n = 100) treated at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazilian Amazon, between January 2016 and December 2017. Blood samples were taken for the measurement of venom concentrations, platelets, clotting time and factors of patients on admission, 12, 24 and 48 h after antivenom therapy, and taken again on discharge. The presence of systemic bleeding was recorded during the follow-up.Results: On admission, systemic bleeding was observed in 14% of the patients. Thrombocytopenia was noted in 10% of the patients. A total of 54% of the patients presented unclottable blood with low levels of fibrinogen and alpha 2-antiplasmin, and high levels of fibrin/fibrinogen degradation product (FDP) and D-dimers. Unclottable blood and systemic bleeding were overcome in most patients 12 h after the antivenom therapy. Three patients developed systemic bleeding 48 h after antivenom therapy. Levels of fibrinogen and alpha 2-antiplasmin, FDP and D-dimer returned to normal around 48 h after the treatment or on discharge. The frequency of thrombocytopenia with high mean platelet volume increased in the first 24 h after antivenom therapy, and decreased on discharge. Bothrops venom levels in patients decreased 12 h after antivenom therapy and were not correlated with coagulation and fibrinolytic parameters. There were no deaths.Conclusion: Laboratorial parameters of coagulopathy returned to normal values within 48 h after the antivenom therapy until discharge. A few patients still presented bleeding signs within 48 h after beginning antivenom therapy. However, the Brazilian antivenom was able to overcome the hemostatic disorders in these cases of envenomation.

Variations of plasma D-dimer level at various points of normal pregnancy and its trends in complicated pregnancies: A retrospective observational cohort study.

D-Dimer (DD) is the smallest fragment of plasmin-mediated cleavage of fibrin. There is a progressive increase in DD concentration with advancing gestation in normal pregnancies, making the upper limit of 0.5 μg/ml used in non-pregnant population an unfavorable marker during pregnancy. Coagulation and fibrinolysis parameters are also markedly disturbed in pregnancies complicated by various pathologies.We designed this retrospective observational cohort study to investigate the trimester specific reference range for DD throughout normal pregnancy, and to compare the distribution of DD in third trimester healthy pregnancies and those complicated by preeclampsia (PE), severe preeclampsia (SPE), gestational diabetes mellitus (GDM), premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM). In addition, we aimed to determine the diagnostic value of DD in PE and SPE.In this retrospective observational cohort study, 250 normal and 178 complicated pregnancies were included. Normal pregnancies included 88-first trimester, 101-second trimester and 61-third trimester pregnancies. Complicated pregnancy included 34 PE, 44 SPE, 32 GDM, 33 PROM, and 35 PPROM cases during the third trimester. Predefined exclusion criteria were used.The period of gestation (POG) accounted for 41.9% of the variance in DD, with strong correlation between the POG and DD. The trimester specific reference intervals were computed. The distribution for severe preeclampsia was statistically different compared to other categories in the third trimester. This exceptional distribution led to the generation of a receiver operating characteristic (ROC) curve with an area under curve of 0.828, attesting its possible role in predicting severe preeclampsia.We determined trimester specific reference intervals of DD. The role of DD has been explored, and it may be of diagnostic value in severe preeclampsia.

Hexachloronaphthalene as a hemostasis disturbing factor in female Wistar rats – A pilot study

Although Persistent Organic Pollutants (POPs) are some of the most dangerous environmental toxicants, data on their impact on hemostasis are virtually limited. 1,2,3,5,6,7-hexachloronaphthalene (PCN67) seems to be one of the most toxic congeners of polychlorinated naphthalenes (PCNs), which have recently been listed as POPs. The toxic effects of PCNs are similar to other chlorinated aromatics, e.g. polychlorinated dibenzo-p-dioxins (PCDDs), so an impact on hemostasis could not be excluded. Therefore, this study examines, for the first time, if short-term (two and four weeks) exposure of a mixture of hexachloronaphthalene congeners with a PCN67 as a predominant component to female Wistar rats may have an impact on selected hemostasis parameters, such as overall potential and kinetic parameters of clot formation and fibrinolysis; hematology and basic coagulology parameters. It also examines the influence of PCN67 on the stability of erythrocyte membranes. Obtained results indicate that PCN67 may be an important disturbing factor regarding both coagulation and fibrinolysis processes, as well as platelet count. Exposure to PCN67 significantly affected clot formation and lysis processes and diminished fibrinogen concentration after both administration periods. After two weeks of administration, an increased activated partial thromboplastin time (APTT) was noted; after four weeks - decreased platelet count with concomitant increased in mean platelet volume. Moreover, PCN67 may exert adverse effects on the red blood cells membrane stability, which were manifested by a statistically significant increase of red blood cells lysis.

The efficacy and safety of multiple doses of oral tranexamic acid on blood loss, inflammatory and fibrinolysis response following total knee arthroplasty: A randomized controlled trial

BackgroundThe aim of the study was to identify the efficacy and safety of multiple doses of oral tranexamic acid (TXA) on reducing blood loss and minimizing the postoperative inflammatory and fibrinolytic responses following primary total knee arthroplasty (TKA). Materials and methodsIn this prospective, double-blinded, randomized trial, we randomly assigned a total of 151 patients into three groups to receive 2 g of oral TXA 2 h preoperatively (group A); an additional dose of 2 g of oral TXA 4 h postoperatively (group B); or additional doses of 2 g of oral TXA at 4, 10, and 16 h postoperatively (group C). The primary outcome was total blood loss (TBL). The secondary outcomes were maximum drop in hemoglobin (Hb) and hematocrit (Hct), level of inflammatory and fibrinolytic parameters, transfusion rate, and the incidence of complications. ResultsThe results were represented as mean ± standard deviation. The mean TBL was 607 ± 254 mL in group C, 743 ± 347 mL in group B (p = 0.027 vs group C), and 978 ± 335 mL in group A (p<0.001 vs group C). The maximum Hb and Hct drop was 18.3 ± 7.7 g/L and 0.051 ± 0.025 in group C, 22.3 ± 9.7 g/L and 0.070 ± 0.028 in group B (p = 0.022 and p = 0.001 vs group C), 29.6 ± 11.7 g/L and 0.090 ± 0.034 in group A (p<0.001 and p<0.001 vs group C). In addition, C-reactive protein and interleukin-6 in group C were lower than in group A (p<0.001 and p = 0.003) and in group B (p = 0.031 and p < 0.001) on postoperative day (POD) 3. Moreover, fibrin degradation products and D-dimer in group C were lower than in groups A and B on both POD 1 and POD 3. The incidence of complications did not differ significantly between the three groups (p > 0.05). ConclusionMultiple postoperative doses of oral TXA could further reduced blood loss and the drop in Hb and Hct, and diminished the postoperative inflammatory and fibrinolytic responses in primary TKA with no apparent increase in the incidence of complications. Level of evidenceLevel Ⅰ, therapeutic study.

Faster fibrin clot degradation characterizes patients with central pulmonary embolism at a low risk of recurrent peripheral embolism

It is unclear whether thrombus location in pulmonary arteries is associated with particular clot characteristics. We assessed 156 patients following either central or peripheral pulmonary embolism (PE). Plasma clot lysis time, the rate of D-dimer release from plasma clots (D-Drate) with the maximum D-dimer concentration achieved (D-Dmax), as well as fibrin formation on turbidimetry, plasma clot permeation, thrombin generation, and fibrinolytic parameters were measured 3–6 months after PE. Patients following central PE (n = 108, 69.3%) were more likely smokers (38.9% vs 18.8%; p = 0.01), less likely carriers of factor XIII Val34Leu allele (40.7% vs 62.5%, p = 0.01), exhibited 16.7% higher D-Drate and 12.7% higher tissue plasminogen activator antigen (tPA:Ag) compared with peripheral PE (p = 0.02 and p < 0.0001, respectively). Saddle PE patients (n = 31, 19.9%) had 11.1% higher D-Drate and 7.3% higher D-Dmax compared with central PE (both p < 0.05). Twenty-three recurrent PE episodes, including 15 central episodes, during a median follow-up of 52.5 months were recorded. Plasma D-dimer and tPA:Ag were independent predictors for central recurrent PE, whereas D-Drate and peak thrombin predicted peripheral recurrent PE. Plasma clots degradation is faster in patients following central PE compared with peripheral PE and fibrinolysis markers might help to predict a type of recurrent PE.

Разработка и апробация нового метода определения параметров гемостаза у больных с психической патологией

Introduction: hemostasis is one of the most important protective systems of the organism, and its deviations from the norm can lead to fatal results. Changes in hemostasis are observed in many diseases, including mental pathology. In addition, parameters of this system may also change during antipsychotic therapy. Objective: Development and testing of a new method and device for estimating plasma hemostasis parameters in patients with mental pathologies in order to optimize treatment and eliminate fatal outcomes. Materials and methods: in the study we used frozen (-80 °C) platelet-free blood plasma (PFP) samples from patients with schizophrenia (16 patients), taken at admission to the clinic FSBSI «Mental Health Research Centre». Plasma coagulation of patients and healthy donors was assessed with the device of our design. Hemostasis assessment is based on the determination of the clot size in proportion to the brightness of the image, which changes as a result of clot formation and lysis. Results: optimal concentrations of coagulation and fibrinolysis activators, as well as concentrations of calcium ions were determined during the first stage of testing the method and device. The median values of all parameters of coagulation and fibrinolysis except «time before the formation of a clot» in patients upon admission to the clinic were reduced relative with combined plasma donors. The rates of clot formation and lysis in patients are significantly reduced at discharge compared with these parameters at admission. Consequently, these parameters can serve as an estimate of the change in the state of the coagulation and fibrinolysis systems during treatment. Conclusion: during approbation of the device and method in the process of coagulation and fibrinolysis research in patients with schizophrenia, lower levels of parameters were detected compared to donors, and a decrease in the activity of plasma coagulation and fibrinolysis during treatment with antipsychotics was shown.

Correlation between coagulation and inflammation state in patients with diabetes mellitus type 2 in relation to gender differences: Is there any impact of eight-week exercise training?

Background/Aim. The hypercoagulable state and inflammation state in diabetics has been widely studied by previous researchers, but there is a lack of research about a possible impact of exercise training on this relationship. The aim of this study was to assess and compare correlation between the coagulation and inflammation status in patients with type 2 diabetes mellitus taking into account the gender differences as well as an impact of the 8-week exercise training on the correlation coefficient and parameters of the inflammation and coagulation state. Methods. A total of 60 patients in stable clinical condition and well-regulated diabetic status passed through all phases of the study. The exercise training included the exercise program as interval training with estimated intensity uphill to 75% of a maximal heart rate in particular individual, 5 times a week for 8 weeks, and walking for 30 minutes with a speed of 5 km/h, 5 times a week for 8 weeks. Further fibrinolytic, coagulation and inflammatory parameters were analyzed before and after the study: D-dimer, von Willebrand factor (vWF), fibrinogen, high sensitivity CRP (hs-CRP), leukocytes, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and coagulation factors: FII, FV, FVII and FX. Results. Our research showed a statistically significant reduction in the mean vWF levels after intervention both at the males (p &lt; 0.001) and females (p &lt; 0.001). According to a correlation analysis between hs-CRP and fibrinogen, there was a positive correlation as baseline both at the males (p &lt; 0.05, r = 0.492) and females (p &lt; 0.01, r = 0.516) which became weaker in the males (p &lt; 0.01, r = 0.449) and disappeared in the females (p &lt; 0.05, r = 0.059) after intervention. The correlation which existed as baseline in the males between D-dimer and either hs-CRP (p &lt; 0.01, r = 0.633) or fibrinogen (p &lt; 0.01, r = 0.673) as well as the correlation between hs-CRP and FII (p &lt; 0.01, r = 0.728), FV (p &lt; 0.05, r = 0.366), FVII (p &lt; 0.05, r = 0.373) coagulation as well as between D-dimer and FII (p &lt; 0.01, r = 0.851), FVII (p &lt; 0.05, r = 0.367)was absent in the females. Our research demonstrated a weakening correlations in the males after intervention between D-dimer and hs-CRP (p &lt; 0.05, r = 0.378), between hs-CRP and FII (p &lt; 0.01, r = 0.501), FV (p &lt; 0.05, r = 0.298), FVII (p &lt; 0.05, r = 0.351) as well as between D-dimer and FII (p &lt; 0.01, r = 0.759), and FVII (p &lt; 0.05, r = 0.296). The increase of the FX values (p &lt; 0.05) in the females after intervention suggested the possible antiinflammatory effect of exercise training. Conclusion. According to previous research, the higher levels of vWF was associated with a risk of cardiovascular disease in people with type 2 diabetes mellitus and vWF may be a risk factor unique to these populations. We demonstrated that the 8-week exercise training can significantly reduce the value of vWF in the males and females, suggesting a potential beneficial effect on the endothelial function parameters. Our research demonstrated a stronger correlation between the coagulation and inflammation parameters as baseline in the males than in the females with type 2 diabetes mellitus. According to our results, the 8-week exercise training lead to a weakening of the strength of correlation between the coagulation and inflammation parameters in the males and complete disappearance of this correlation in the females, suggesting a unique effect of exercise training that should be explored in future research.

In patients with superficial vein thrombosis the inflammatory response is increased and related to the recanalization rate.

IntroductionLittle is known about pathogenetic mechanisms of superficial venous thrombosis (SVT). We aimed to investigate the systemic inflammatory response in the acute phase of SVT, the time course of inflammatory markers and involvement of inflammation in resolution of thrombus in SVT.Material and methodsThe circulatory inflammatory parameters high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), interleukins 6, 8 and 10 (IL-6, IL-8, IL-10), and markers of fibrinolytic activity tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and fibrinogen were determined in 68 patients with acute SVT of lower limbs, who were allocated to two groups, dalteparin 5000 IU once daily or 10 000 IU once daily. Recanalization of occluded veins was monitored by ultrasonography at regular intervals. Blood was drawn in the acute phase and after 12 weeks.ResultsIn the acute phase a majority of the measured inflammatory markers were increased, while after 12 weeks most of them significantly dropped: hsCRP: 13.6 ±11.9 vs. 7.4 ±4.4, p < 0.001; IL-6: 3.8 ±3.1 vs. 2.6 ±1.9, p = 0.007. Significant changes in endogenic fibrinolytic parameters were also observed: t-PA activity decreased (0.81 ±0.35 vs. 0.68 ±0.34, p = 0.003), while PAI-1 levels increased (5.6 ±5.1 vs. 8.8 ±8.5, p < 0.001). Levels of inflammatory markers at inclusion and after 12 weeks were related to less effective thrombus resolution: CRP: r = 0.386, p = 0.001; IL-6: r = 0.384; TNF-α: r = 0.255, p = 0.037.ConclusionsIn the acute phase of SVT, most of the circulating inflammatory markers were increased and most of their levels decreased after 12 weeks. Levels of inflammatory markers were negatively correlated with the recanalization rate.