Thrombin Time Values Research Articles

Trends of Coagulation Parameters in Human Immunodeficiency Virus Patients.

Background and Objectives: HIV disease is recognized to cause inconsistencies in coagulation via various pathways during infection. Some studies have indicated that HIV-infected patients are prone to developing thrombocytopenia, thrombosis, or autoantibodies that may cause difficulties in diagnosis. This study is intended to measure the trend of coagulation parameters in Sudanese patients with HIV. Materials and Methods: A cross-sectional study was carried out in patients with HIV admitted to the Sudan National AIDS Program (SNAP) from January 2018 to December 2019. Prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), D-dimer (DD), hemoglobin (HB), total lymphocyte count (TLC), platelet count (PLT), and a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13), were evaluated among HIV Sudanese patients. Results: Out of the 44 HIV patients included, 6 (13.6%) were found to have thrombotic thrombocytopenic purpura-like events and 12 (27.2%) had antiphospholipid antibodies, of whom 8 (66.6%) showed anticardiolipin antibody (1gG (75%) and IgM (25%)) and 4 showed lupus anticoagulants. The HB, TLC, and PLT values were found to be significantly lower in HIV patients than in control (p = 0.000, 0.000, and 0.050, respectively). The PT and ADAMTS13 values showed no significant difference between HIV patients and control (p = 0.613 and 0.266, respectively). The PTT, TT, and DD values were found to be augmented in HIV patients versus the control (p = 0.000). Conclusions: Thrombotic thrombocytopenic purpura-like events among HIV Sudanese patients were explored. In addition, antiphospholipid antibodies were strikingly seen in these patients. Additional research is anticipated to confirm these diagnoses.

Investigation of the relationship between changes in maternal coagulation profile in the first trimester and the risk of developing preeclampsia

Normal pregnancy is a hypercoagulable state with an increase in coagulation factor levels and a decrease in natural anticoagulation. However, a higher hypercoagulable state with prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), increased D-dimer, and mean platelet volume is seen in women with preeclampsia at the time of onset. In addition, endothelial dysfunction occurs before the clinical symptoms of preeclampsia. Therefore, we undertook this study to investigate the coagulation profile in the first trimester in women who developed preeclampsia later. A total of 853 pregnant women with singleton births at the Obstetrics and Gynecology Hospital of Fudan University between January 2021 and December 2021 were included in this case-control study. In the comparison with the controls (n = 531), the mean value of D-dimer, APTT, thrombin time (TT), antithrombin (AT)), and fibrin degradation products (FDP) was significantly lower in preeclamptic women at the time of diagnosis (n = 322). The changes in the coagulation profile were not associated with the severity or the time of onset. The reduced values of D-dimer, AT, and FDP, and increased values of TT were also observed in the first trimester in women who developed preeclampsia later and were not associated with the severity, or the time of onset of preeclampsia. After adjusting for maternal age and BMI, the values of D-dimer and AT in the first trimester were correlated to the risk of developing preeclampsia. Our findings suggest that there is an abnormal maternal response to the hemostatic system in early gestational age in women who developed preeclampsia later and measuring the coagulation profile could be an additional predictive marker of preeclampsia.

Blood coagulation system state in breast cancer patients that recovered from coronaviral infection after undergoing antitumor medical treatment

Purpose of the study. An analysis of parameters of the blood coagulation system in breast cancer patients after coronavirus disease.Materials and methods. 50 breast cancer patients were divided into groups: the main group included 30 patients after coronavirus disease, the control group 1–20 patients without confirmed COVID‑19, and control group 2–20 non-cancer women after corona‑ virus disease. All cancer patients received appropriate chemotherapy. The following parameters were studied: activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), prothrombin index (PTI), fibrinogen, soluble fibrin monomer complexes (SFMCs), thrombin time (TT), antithrombin III, D-dimer and plasminogen, fibrin degradation products. Blood tests were performed 4–6 weeks after the infection and two negative PCR test results for COVID‑19.Results. Patients of the main group demonstrated differences in INR values after treatment in the subgroups with asymptomatic disease (Me = 1.24) and with mild symptoms (Me = 0.97) U = 10; Z = 2.766; р = 0.0057, in subgroups with asymptomatic disease (Me = 1.24) and with moderate to severe symptoms (Me = 0.98) U = 26.5; Z = 2.199; р = 0.027, and in TT values in subgroups with asymptomatic disease (Me = 14.5) and with moderate to severe symptoms (Me = 16.5) U = 18.5; Z = –2.725; р = 0.0064. The comparison of the parameters in patients after COVID‑19 before (Me = 0.83) and after treatment (Me = 0.4) showed differences in the D-dimer values in patients with moderate to severe disease U = 6.5; Z = –2.2861; р = 0.022 towards their decrease after the therapy. Differences were found in APTT values between the main group (Me = 30.65) and control group 1 (Me = 27.85) U = 119; Z = 3.574; р = 0.00035, in antithrombin values between the main group (Me = 94) and control group 1 (Me = 106) U = 112; Z = 3.713; р = 0.00021, and in SFMCs values between the main group (Me = 17) and control group 1 (Me = 8) U = 180.5; Z = 2.356; р = 0.018.Conclusions. Determination of plasminogen levels can become an independent factor in detecting thrombotic risk in cancer patients who recovered from COVID‑19. Previous infection with COVID‑19 should be considered an additional risk factor for venous thromboembolic complications for cancer patients.

Hemostasis features in pregnant women with hypertensive disorders living in the highlands of Tadzhikistan Republic

Introduction.One of the actual problems of modern obstetrics is hypertensive disorders during pregnancy. Pregnant women living in highlands are exposed to adverse factors, the most important of which is decreased oxygen in the air. Hypertension of pregnant women in high altitude conditions is conjoin with exogenous hypobaric hypoxia, and as a total organ pathology leads to functional and morphological changes in all organs and systems.Aim:to study the features of hemostasis system in pregnant women with hypertensive disorders in highlands.Materials and Мethods.A prospective comparative study included 114 pregnant women with hypertensive disorders, which were divided into 2 groups: group 1 – 63 pregnant women living in highlands, and group 2 – 51 pregnant women living in lowlands. In group 1, 42 pregnant women (67 %) and in group 2, 24 (47 %) pregnant women were diagnosed with severe preeclampsia. Hemostasis parameters were studied: blood clotting time, prothrombin index, content of fibrinogen and soluble fibrin-monomer complexes (SFMC), international normalized ratio (INR), activated partial thromboplastin time (APTT) index, thrombin time, platelet count.Results.In pregnant mountaineers, compared with pregnant women in lowlands, a higher content of such hemostasis parameters as APTT index (1.654 ± 0.426 vs. 0.892 ± 0.1145; p < 0.001) and SFMC level (4.921 ± 0.753 mg% vs. 3.590 ± 0.5676 mg%; p < 0.001), thrombin time values (103.206 ± 3.734 seconds vs. 93.920 ± 7.8268 seconds; p < 0.001) were revealed, as well as lower fibrinogen concentration (3.762 ± 0.809 g/l vs. 4.160 ± 1,3015 g/l; p = 0.048).Conclusion.In pregnant women living in highlands compared with pregnant women in lowlands with the addition of severe forms of preeclampsia (67 % vs. 47 %) hypercoagulation characteristic of normal pregnancy disappears, but, on the contrary, iso- and hypocoagulation appears.

Managing argatroban in heparin-induced thrombocytopenia: Aretrospective analysis of 729 treatment days in 32 patients with confirmed heparin-induced thrombocytopenia.

Managing argatroban in heparin-induced thrombocytopenia: Aretrospective analysis of 729 treatment days in 32 patients with confirmed heparin-induced thrombocytopenia.

Synthesis and Hemostatic Activity of New Amide Derivatives.

Eight dipeptides containing antifibrinolytic agents (tranexamic acid, aminocaproic acid, 4-(aminomethyl)benzoic acid, and glycine—natural amino acids) were synthesized in a three-step process with good or very good yields. DMT/NMM/TsO− (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate) was used as a coupling reagent. Hemolysis tests were used to study the effects of the dipeptides on blood components. Blood plasma clotting tests were used to examine their effects on thrombin time (TT), prothrombin time (PT), and the activated partial thromboplastin time (aPTT). The level of hemolysis did not exceed 1%. In clotting tests, TT, PT, and aPTT did not differentiate any of the compounds. The prothrombin times for all amides 1–8 were similar. The obtained results in the presence of amides 1–4 and 8 were slightly lower than for the other compounds and the positive control, and they were similar to the results obtained for TA. In the case of amide 3, a significantly decreased aPTT was observed. The aPTTs observed for plasma treated with amide 3 and TA were comparable. In the case of amide 6 and 8, TT values significantly lower than for the other compounds were found. The clot formation and fibrinolysis (CFF) assay was used to assess the influence of the dipeptides on the blood plasma coagulation cascade and the fibrinolytic efficiency of the blood plasma. In the clot formation and fibrinolysis assay, amides 5 and 7 were among the most active compounds. The cytotoxicity and genotoxicity of the synthesized dipeptides were evaluated on the monocyte/macrophage peripheral blood cell line. The dipeptides did not cause hemolysis at any concentrations. They exhibited no significant cytotoxic effect on SC cells and did not induce significant DNA damage.

USP Standardized Mixtures of Bovine, Ovine and Porcine Heparin Exhibit Comparable Biologic Effects to Referenced Single Sourced Heparins and May be Interchangeable,

Introduction: Unfractionated heparin (UFH) is the first line anticoagulant for the management of medical indications. UFH complexes with antithrombin to produce strong inhibition of thrombin and factor Xa. The UFHs are standardized using USP compliant amidolytic anti-Xa and IIa methods in defined conditions. Clinically used UFH is solely sourced from porcine mucosal tissue. Because of the shortage of porcine tissue and the African Swine Fever, the supply chain of this anticoagulant is compromised. Thus, there is a need for resourcing of this anticoagulant. Bovine and ovine mucosal sources represent alternate material for production of UFH. Previous studies have shown that bovine and ovine UFH exhibit anticoagulant effects which can be standardized by using the USP method. Additionally, the standardized heparins from various sources can be blended and their potency can be adjusted to exhibit comparable effects as the single sourced UFH. The purpose of this study is to evaluate the pharmacologic profile of the blended heparin and compare these activities to that of the single sourced porcine, ovine and bovine heparins.Methods: Two groups of heparins were evaluated in this study, porcine, ovine, bovine, and the blended heparin in gravimetric measurements (ug/ml) and these same four in potency adjusted measurements (U/ml). The pharmacologic profiles of the heparins in this study were investigated via global anticoagulant assays and anti-protease assays performed in plasma. Clot based assays such as the activated partial thromboplastin time (aPTT) and thrombin time (TT) were used to study the anticoagulant effects of the single source and blended heparins. The amidolytic anti-Xa and IIa assays were used to assess the inhibitory effects of these heparins on these proteases. USP compliant anti-Xa and IIa assays were used to determine potencies of the various heparins. Protamine sulfate (PS) neutralization studies were performed to evaluate the reversal of anticoagulant effects in each of the heparins.Results: The aPTT assay showed that at final concentrations of 5 ug/ml and 2.5 ug/ml porcine heparin significantly (p < .01) prolonged the aPTT compared to ovine, bovine, and blended heparins. When studied with potency adjusted heparins, all heparins demonstrated comparable aPTT values at all concentrations (U/ml). The TT assay showed that porcine and ovine heparins prolonged the TT at 1.25 ug/ml compared to bovine and blended heparins. When studied with potency adjusted heparins, all heparins demonstrated comparable TT values at all concentrations (U/ml). The anti-Xa assay showed that at all final concentrations between 10 ug/ml and 0.625 ug/ml porcine, ovine, and blended heparins produced significantly (p <.001) stronger Xa inhibition than bovine heparin. When studied with potency adjusted heparins, all heparins demonstrated comparable anti-Xa inhibition at all concentrations (U/ml). The anti-IIa assay showed that at final concentrations 2.5 ug/ml, 1.25 ug/ml, and 0.625 ug/ml porcine and ovine heparins produced significantly (p < .05) stronger IIa inhibition than bovine heparin. When studied with potency adjusted heparins, all heparins demonstrated comparable anti-IIa inhibition at all concentrations (U/ml). The USP compliant anti-Xa assay with gravimetric heparins showed potencies of 201, 201, 150, and 184 U for porcine, ovine, bovine, and blended heparins respectively. The USP compliant anti-Xa assay with potency adjusted heparins showed comparable potencies for all four heparins. The USP compliant anti-IIa assay with gravimetric heparins showed potencies of 204, 196, 127, and 167 U for porcine, ovine, bovine, and blended heparins respectively. The USP compliant anti-IIa assay with potency adjusted heparins showed comparable potencies for all four heparins. The protamine sulfate neutralization studies demonstrated complete neutralization at all concentrations for all of the potency adjusted heparins in the aPTT, TT, anti-Xa, and anti-IIa assays.Conclusion: These studies support the hypothesis that a blended heparin product from bovine, ovine, and porcine tissue, when standardized in USP unit-equivalent proportions, exhibits a comparable anticoagulant profile to the single species heparins. These findings suggest that there is a potential for development of blended heparin to stabilize supply chain of this important anticoagulant and warrant clinical validation. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Indicators of Hypoxia Tolerance as Determined by Cellular Elements of Rat Blood.

Although hypoxia tolerance is mainly determined genetically, it is important to study individual variability of animal organisms in order to identify the factors that underlie their tolerance to hypoxic exposure. We investigated blood cell counts and coagulograms in Wistar rats as predictors allowing the animal population to be split into hypoxia-tolerant and hypoxia-intolerant individuals. The validity of the specific predictors’ choice was proved by a coincidence between the population split in accordance with the detected individual parameters and the results of testing animals in a decompression chamber at a rarefaction corresponding to the “rise to an altitude” of 11500 m above sea level. Circulating blood cells were quantitatively assessed by eighteen indicators before and after hypoxic exposure. The differences between animals low-tolerant (LT), high-tolerant (HT), and medium-tolerant (MT) to hypoxia were determined by five indicators: white blood cell count (WBC), granulocyte count (Gran#), red blood cell count (RBC), reticulocyte count/percent (RTC), and mean corpuscular hemoglobin (MCH). The RBC, RTC, and MCH values in HT rats were significantly higher than in LT animals (by 1.4, 1.9, and 1.1 times, respectively). The WBC and Gran# values in HT rats were lower than in LT individuals. The hypoxia tolerance indices (HTI) were calculated using the original formula. It was established that in LT rats, the HTI ≤ 0.203, in HT rats ≥ 0.335, and in MT rats < 0.335 but > 0.203. After testing in a decompression chamber, the activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) decreased, but the fibrinogen level increased. LT rats were characterized by the lowest APTT, TT, and PT values and the highest values of the fibrinogen level. Our results indicate that one of the most important mechanisms underlying a high hypoxia tolerance in rats consists in sustaining reciprocal relationships between the complex of RBC indicators, which tend to increase under hypoxia, and Gran# indicators, which tend to decrease after hypoxic exposure.

Dynamic Metabolic Response, Clotting Times and Peripheral Indices of Central Fatigue in Horse Competing in a 44 Km Endurance Race

A deep knowledge on metabolic response of athlete horse to exercise is of paramount importance for the development of optimal training programs to attain equilibrium between good performance and animal welfare. This study investigated the dynamic change of metabolic, clotting times and peripheral indices of central fatigue in horses competing in an official 44 km endurance race. From 6 horses blood samples were collected at rest (TPRE), within 5 minutes from the end of race (TPE5), after 30, 60 minutes after the end of race (TPE30 and TPE60) to investigate the values of blood lactate, glucose, platelets (PLTs), serum leucine, isoleucine, valine, tryptophan, the ratio between tryptophan and branched-chain amino acids (BCAAs) levels (Try/BCAAs), total proteins, non-esterified fatty acids, plasma thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time and fibrinogen (Fb). Lactate, PLTs, non-esterified fatty acids, BCAAs and Try/BCAAs showed higher values at TPE5, TPE30and TPE60than TPRE(P < .0001); glucose showed lower values at TPE5, TPE30and TPE60than TPRE(P < .0001). Higher TT values were found at TPE5, TPE30and TPE60than TPRE, and at TPE5than TPE30 and TPE60(P < .0001); Fb was higher at TPE5than TPRE, T PE30and TPE60(P < .0001). This survey confirms that horses performing prolonged physical exercise experienced glycolysis, lipid mobilization and amino acid metabolism to provide substrates as fuel for muscle contraction.

Influence of means of prevention of adverse effects of space flight on the plasma component of the system of regulation of the aggregate state of human blood

Introduction. It is known that the factors of space flight shift the coagulation balance of blood in the direction of procoagulant. The effect of space flight factors on the hemostatic potential of human blood with the simultaneous effect of preventive measures and compensation for their adverse effects has not been practically studied. The aim of study was to study the effect of physical exertion, electromyostimulation, mechanical stimulation of the foot, and blood-substituting solutions on the main indicators of the human hemostasis system in experiments with 21-hour antiorthostatic hypokinesia, 7-day "dry" water immersion, and 120-day isolation in a hermetic volume. Materials and methods. Concentrations of fibrinogen, plasminogen, soluble fibrin-monomer complexes, D-dimer, antithrombin III, protein C, and α2-antiplasmin were determined in citrate plasma; values of thrombin time, activated partial thromboplastin time, and prothrombin time. Results. It was found that the infusion of blood-substituting colloidal solution "venofundin" prevents the tendency to increase the level of soluble fibrin-monomer complexes observed during 21-hour antiorthostatic hypokinesia. Electromyostimulation leads to increased levels of fibrinogen and D-dimer during 7-day immersion. The complex of physical activities used in the experiment with 120-day isolation helps to reduce the level of D-dimer. Conclusions. The results indicate that when modeling the impact of space flight factors, a favorable hypocoagulation effect is provided by an infusion of venofundin, as well as a complex of balanced physical activities.

Establishing reference intervals of coagulation indices based on the ACL Top 700 system for children in Southwestern Fujian, China

BackgroundTill date, China has not issued industry standards for reference intervals (RIs) of pediatric blood coagulation indices. Here, we evaluated changes in the coagulation indices in the venous blood of healthy children aged 29 days to 12 years derived using the ACL Top 700 system and established appropriate RIs. MethodsWe analyzed venous blood from 1770 healthy children for five coagulation indices. RIs were established according to the Clinical and Laboratory Standards Institute C28-A3c guideline. ResultsThe coagulation indices were grouped by age. For prothrombin time (PT) and international normalization ratio (INR), the RIs of infants and toddlers were identical; preschool children had the same RI as school-age children. Pediatric RIs for PT and INR were slightly lower than those for adults. The RIs of activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) in childhood were divided into two groups by age (1 month to 1 year and 1–12 years). The RI of APTT in infants was the widest; the overall level of FIB in infants was the lowest; children's APTT and FIB RIs were lower than those of adults. The pattern of TT values and RI trends in childhood were similar to those of APTT. ConclusionsThere were minor changes in the RIs of coagulation indices for children. The RIs of PT, INR, APTT, TT, and FIB must be grouped by age. The RIs of coagulation indices for children were different from those for adults; therefore, establishing separate RIs for children is necessary.

Changes in blood coagulation in middle-aged and elderly patients with fresh vertebral compression fractures

Objective To explore the short-term effects of fresh vertebral compression fracture on blood coagulation in middle-aged and elderly osteoporotic patients. Methods A retrospective analysis was conducted of the 140 middle-aged and elderly patients (70 ones with fresh vertebral compression fracture and 70 ones with degenerative spinal disease) who had been treated at Department of Orthopaedics, The First Affiliated Hospital to Peking University between January 2016 and December 2018. Collected were their baseline parameters including age, gender and American Society of Anesthesiologists (ASA) scores, preoperative blood parameters including coagulation indicators [D-Dimer, fibrinogen degradation product (FDP), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), international normalized ratio (INR) and thrombin time (TT)] and platelets indicators, and fracture parameters including number of fractured vertebrae and duration of fracture. The 2 patients groups were divided into 5 age groups: 4 age groups for each 10 between 50 and 90 years and one age group for >90 years. The values of D-Dimer and FDP were compared between the 2 patient groups in each corresponding age group. The proportions of patients with D-Dimer negative and correlations between coagulation parameters and platelets before and after age adjustment were statistically analyzed. Results There were no statistically significant differences in the baseline parameters between the 2 patient groups(P>0.05). The mean onset time for the fracture group was 6.7 days. The values of D-Dimer, FDP, PT, INR, TT and FIB in the fracture group were significantly higher than those in the degenerative disease group(P<0.001). After the D-Dimer threshold adjusted by age, 75.71%(53/70) of the patients in the fracture group were negative while 98.57%(69/70) of those in the degenerative disease group were negative. Meanwhile, the values of D-Dimer and FDP showed a significant correlation (P<0.001) with a Pearson correlation coefficient of 0.932. Compared with the degenerative disease group, the values of D-Dimer and FDP in the fracture group increased significantly in the age groups from 61 to 90 years(P< 0.001). Conclusions Fresh vertebral compression fractures may have a significant effect on the blood coagulation in osteoporotic patients. It is therefore presumed that the middle-aged and elderly patients with fresh vertebral compression fracture may face a higher risk of deep vein thrombosis than those with degenerative spinal disease. Key words: Osteoporosis; Aged; Spinal fractures; Blood coagulation; Deep vein thrombosis; D-Dimer

Age-Associated Changes of Coagulation Test and Coagulation Factor Activities in Healthy Chinese Children

Background: The concept of developmental hemostasis has been universally accepted. Plasma concentrations of many coagulation factors in childhood are significantly different from adults for both mean values and ranges of normal. Thus, an understanding of developmental hemostasis and the development of appropriate age-dependent reference ranges are pivotal for prevention, diagnosis, and treatment of hemostatic problems during childhood. However, no data of developmental hemostasis are available in healthy Chinese children. Methods: Coagulation data from children aged 0-18 years old receiving minor elective surgery in Chengdu Women and Children's Central Hospital, from Sep. 2017 to Feb. 2019 was collected, and patient medical records were reviewed. Ethical approval was obtained from the parents of all children and the study was approved by the Ethics Review Committee at Chengdu Women and Children's Central Hospital. To qualify for the study, enrolled subjects had to meet the following criteria: (1) Children aged 0-18 years receiving minor elective surgery.(2) No history of bleeding problems.(3)No family history of bleeding nor thrombosis .(4) No history of heart, lung, liver or kidney diseases, normal physical examination. (5) Normal blood routine test. Normal liver function and kidney function, (6)No history of medication use for at least two weeks prior to specimen collection.(7) The operation gone successfully, and postoperative recovery was well. Blood samples (3 mL) were obtained by venipuncture into plastic tube containing 3.2% (109 mmol/L) buffered sodium citrate (1 part citrate:9 parts blood). The specimens were centrifuged immediately at 2500 g for 15 min at room temperature to prepare platelet-poor plasma (PPP) for the preoperative coagulation screening tests, consisting of activated partial thromboplastin time (APTT), prothrombin time (PT)), international normalized ratio (INR), thrombin time (TT) and fibrinogen. Activity of coagulation factors VIII, IX, XI, XII,Ⅱ,Ⅴ,Ⅶ,Ⅹ were determined using one-stage clotting methods with respective factor-deficient plasma. Results: A total of 82 samples were collected, while only 67 met the enrollment criteria. Specimens with inappropriate ratio of blood to anticoagulant, hemolysis or abnormal values of coagulation tests (APTT, PT, TT, fibrinogen) were excluded from analysis. The total of 67 children (40 Male 27 female), with a median age of 2.0 years (range: 1month -14 years) were divided into three groups according to the age: &lt;1y group 15 cases, 1-5y group 45 cases, and &gt;6y group 7cases. (1) The values of APTT, PT, TT, and fibrinogen were (36.1±5.2) seconds, (11.1±0.85) seconds, (20.3±1.6) seconds, (2.4±0.89) g/L respectively. No significant differences were found between groups. (2) In all children ,the activities of factor VIII、IX、XI、XII、vWF、II、V、VII、X were(123.6±48.3)%、(75.9±16.9)%、(95.9±24.3)%、(43.7±16.3)%、(111.3±50.4)%、(90.2±14.0)%、(104.7±21.1)%、(81.6±19.1)%、(93.0±21.8)% respectively. Factor VIII and vWF activities were significantly higher than other factors, while factor XII activities were significantly lower than others. (3)Mean values of FII:C, FVIII:C, FIX:C, FXI:C were significantly lower in children below &lt;1year old group than those in 1-5y group. No significant difference were seen in FVII:C, FV:C, FX:C, FXII:C, vWF:C among three groups. Conclusions: Coagulation test is just a simple and easy screening test. Coagulation factor activities changed dynamically with age during childhood, especially the FII:C, FVIII:C, FIX:C and FXI:C. Physiological reference ranges for coagulation factor activities in Chinese children of different ages should be established in order to evaluate the children with congenital or acquired bleeding diseases correctively. Table Disclosures No relevant conflicts of interest to declare.

Coagulation and Circulating Heparin Profile in Patients with End‐Stage Renal Disease Undergoing Maintenance Hemodialysis

IntroductionUnfractionated heparin is widely used as an anticoagulant for maintenance hemodialysis in end‐stage renal disease (ESRD) patients. Since these patients are administered with heparin repeatedly throughout treatment, it is hypothesized that detectable circulating levels of heparin may be present in their blood 48 hours post‐dialysis session. Changes in the profile of coagulation factors for the intrinsic and extrinsic pathway may also be associated with repeated heparization and can be measured using global clotting assays. The profiling of these parameters may provide the hemostatic status of patients in reference to circulating residual heparin in the pre‐dialysis blood samples.Materials/ MethodsThis study included 95 patients with ESRD undergoing maintenance hemodialysis, which was administered 3 times per week in 48‐hour intervals. Citrated blood samples were collected, centrifuged, and platelet‐poor plasma was retrieved. Plasma samples were analyzed utilizing clot‐based methods including activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT). Employing a chromogenic assay, the circulating levels of heparin in each patient were measured. All of these samples were also analyzed for thrombin generation capacity using calibrated automated thrombogram (CAT, Diagnostica Stago. Paris, France).ResultsIn the clotting assays, prothrombin time was elevated (16.4 ± 20.3 sec.) in comparison to the normal control (11.1 ± 2.1 sec.). Activated partial thromboplastin time was also prolonged (43.09 ± 43.1 sec.) when compared to normal human plasma (32.3 ± 4.2 sec.). The thrombin time values were also higher (44.6 ± 83.1 sec.) in comparison to normal (11.2 ± 2 sec.). Circulating heparin levels, measured by anti‐Xa methods, were found to be 0.11 ± 0.21 U/ml and anti‐IIa levels being 0.25 ± 0.27 U/ml. The anti‐Xa/anti‐IIa ratio were determined to be 0.43. In the thrombin generation assay, the ESRD samples showed wide variation and a lowered thrombin generation value (107 ± 55.2 nM) in comparison to normal control (185 ± 16.5 nM).DiscussionThese results suggest patients undergoing maintenance hemodialysis exhibit a mild hypocoagulable state as determined by PT and aPTT methods. Although both methods demonstrated wide variation, this prolongation indicated defective intrinsic and extrinsic pathways. Moreover, the thrombin time elevation is suggestive of defective common pathway and the presence of circulating heparin. The circulating levels of heparin were lower in anti‐Xa compared to anti‐IIa, suggesting the presence of higher molecular weight components of heparin. This is likely due to impaired clearance of higher molecular weight heparin components caused by maintenance hemodialysis. The decreased thrombin generation observed in these patients may be partly due to the defects in the coagulation process and presence of heparin in the ESRD patients.Support or Funding InformationNAThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

An In Vitro Study to Evaluate and Compare the Hemocompatibility of Titanium and Zirconia Implant Materials after Sandblasted and Acid Etched Surface Treatment

This study was aimed to investigate the hemocompatibility of zirconia and titanium implant materials after surface treatment with sandblasting and acid etching (SLA). Sixty specimens were procured from manufacturers of dimension 10mm × 3mm, thirty of each were prefabricated medical grade titanium (Ti-6Al-4V) and thirty of sintered zirconia. Silicon carbide grit papers of 240 to 1200pm, was used to polish the specimen surface. The surfaces were rinsed with water to remove any remnant particles after polishing. Later ultrasonic cleaning was done for 5 minutes using distilled water. The control specimens included 15 specimens each from titanium (groups A1) and zirconia (groups B1). The remaining 15 specimens (groups A2 and B2) were sandblasted using alumina particles of 150 microns particle size and using 20% hydrochloric acid, acid etching was done for 30 seconds. The specimens were scanned under electron microscope after surface treatment for analysis purpose and evaluated for surface characteristics. Before the exposure of specimens to blood, percentage hemolysis, prothrombin, platelet aggregation and activation, and thrombin time values were calculated. one mL of blood was added to each specimen for testing. The values before and after the exposure of specimens to blood were noted. Using a t-test, the values noted were statistically Results: A1 (polished titanium) showed highest mean values after exposure, in platelet count (184.67 ± 1.29), leucocyte count (7.27 ± 0.08), and thrombin time (10.15 ± 0.34) while prothrombin time's highest mean value after exposure were showed by A2 (SLA treated titanium) with a mean value of 10.04 ± 0.24. Surface treatment with sandblasting and acid etching (SLA) using 150 microns alumina particles and 20% hydrochloric acid increased the surface roughness of the titanium and zirconia implant materials and polished titanium showed maximum hemocompatibility. The implant's success depends on its biocompatibility and its property of osseointegration. The adverse interaction between blood and the artificial surface is detected by the hemocompatibility test for medical materials, to know if the surface can activate or destruct the blood components. The success of implant placement also depends on the interaction between the blood and the specimen.

Preparation, characterization and in vitro anticoagulant activity of corn stover xylan sulfates

A new anticoagulant agent was prepared by introducing sulfate groups into corn stover xylan through homogeneous reactions. Three organic solvents, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and formamide (FA), were adopted as reaction media, with the assistance of LiCl. Structural characterization by FT-IR and 13CNMR showed that xylan sulfate (XS) could be successfully synthesized with SO3∙Pyridine (SO3∙Py) complexes sulfation reagent in the three media. The effect of sulfation temperature, sulfation time, media type and molar ratio of −SO3/−OH on the degree of substitution (DS) and degree of the polymerization (DP) were studied. DMF/LiCl were more effective than DMSO/LiCl and FA/LiCl in preparation of xylan sulfate with high DS. The optimal conditions for sulfation were obtained when SO3∙Py complex was added to DMF/LiCl with −SO3/−OH ratio of 1.5:1 and maintained at 50 °C for 3 h. Degree of polymerization of xylan was decreased during the sulfation process and DMF/LiCl offered the least xylan degradation as compared with DMSO/LiCl or FA/LiCl. Anticoagulant activities of the resultant xylan sulfates with different DS were evaluated by using activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). Results indicated that the introducing of sulfate groups into xylan did endow the polysaccharides with anticoagulant activity. The APTT and TT of XS with DS of 1.20 reached 141 and 45.3 s at a dosage of 20 μg/mL, while the APTT and TT values for the blank sample were only 35.5 and 15.6 s. Furthermore, coagulation time was prolonged with the increase of DS and the concentration of XS. Our findings provide new insights into the value-added utilization of agricultural biomass.

Super-Anticoagulant Heparin-Mimicking Hydrogel Thin Film Attached Substrate Surfaces to Improve Hemocompatibility.

In this study, heparin-mimicking hydrogel thin films are covalently attached onto poly(ether sulfone) membrane surfaces to improve anticoagulant property. The hydrogel films display honeycomb-like porous structure with well controlled thickness and show long-term stability. After immobilizing the hydrogel films, the membranes show excellent anticoagulant property confirmed by the activated partial thromboplastin time values exceeding 600 s. Meanwhile, the thrombin time values increase from 20 to 61 s as the sodium allysulfonate proportions increase from 0 to 80 mol%. In vitro investigations of protein adsorption and blood-related complement activation also confirm that the membranes exhibit super-anticoagulant property. Furthermore, gentamycin sulfate is loaded into the hydrogel films, and the released drug shows significant inhibition toward E. coli bacteria. It is believed that the surface attached heparin-mimicking hydrogel thin films may show high potential for the applications in various biological fields, such as blood contacting materials and drug loading materials.

Impacts of laparoscopic hysterectomy on functions of coagulation and fibrinolysis system.

The main objective of the study is to compare the impacts of laparoscopic hysterectomy and total abdominal hysterectomy on the functions of coagulation and fibrinolysis system. Seventy-five patients who had undergone hysterectomy were randomly divided into laparoscopic hysterectomy group (n = 38) and total abdominal hysterectomy group (n = 37). The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, D-dimer, von Willebrand factor, α-granule membrane protein-140, thrombin-activated fibrinolysis inhibitor (TAFI) and platelet count were detected at preoperative 24 h (N0), postoperative 24 h (N1) and postoperative 48 h (N2). Compared with N0, values of PT, APTT and TT were significantly decreased at N1 in both groups, whereas von Willebrand factor, platelet count and α-granule membrane protein-140 levels at N1 were significantly increased (P < 0.05). There was no significant difference between N0 and N2 (P > 0.05). Compared with N0, fibrinogen, D-dimer and TAFI levels in both groups were significantly higher at N1 (P < 0.05), and there was no significant difference between N0 and N2 (P > 0.05). The intergroup comparison showed no significant difference of above indexes between two groups (P > 0.05). The univariate analysis showed that TAFI was negatively correlated with TT (r = -0.365, P < 0.01), APTT (r = -0.183, P < 0.05) and PT (r = -0.121, P < 0.05), whereas not correlated with other indicators. Laparoscopic hysterectomy may increase the risk of postoperative venous thrombosis.

Comparison of postoperative hidden blood loss and deep venous thrombosis between dynamic hip screw, InterTan and proximal femoral nail antirotation-II in treatment of femoral intertrochanteric fracture

Objective To compare dynamic hip screw (DHS), InterTan and proximal femoral nail antirotation-Ⅱ (PFNA-Ⅱ) in the treatment of femoral intertrochanteric fracture in terms of their effects on postoperative hidden blood loss (HBL) and deep venous thrombosis (DVT). Methods We retrospectively analyzed the 133 patients with femoral intertrochanteric fracture who had been treated in our hospital from November 2011 to November 2015. Of them, 42 received DHS treatment, including 22 males and 20 females; 43 underwent InterTan fixation, including 21 males and 22 females; 48 had PFNA-Ⅱ treatment, including 25 males and 23 females. At preoperation, 1, 3 and 7 days postoperation, all of them had tests of hemoglobin (Hb), hematocrit value (Hct), blood platelet (PLT), thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT), human fibrinogen (FIB) and D-dimer. DVT was detected using color Doppler ultrasound at 7 days postoperation. Results At 1, 3 and 7 days postoperation, the DHS patients had the smallest values of Hb, Hct, TT, PT and APTT while the PFNA-Ⅱ patients the largest. The DHS patients had the largest values of intraoperative bleeding, PLT, FIB and D-dimer while the PFNA-Ⅱ patients the smallest. There were significant differences between the 3 groups in all the indexes (P 0.05). The incidence of DVT in the InterTan group (2.3%, 1/43) and in the PFNA-Ⅱ group (0) was significantly lower than in the DHS group (7.1%, 3/42) (P<0.05). Conclusion In the treatment of femoral intertrochanteric fracture, PFNA-Ⅱ may be superior to InterTan and DHS in reducing postoperative HBL and control of DVT. Key words: Hip fractures; Fracture fixation, internal; Bone nails; Postoperative hemorrhage; Embolism and thrombosis

Diluted thrombin time reliably measures low to intermediate plasma dabigatran concentrations.

Direct oral anticoagulant dabigatran was first introduced as a fixed-dose drug without routine coagulation monitoring, but current recommendations suggest that diluted thrombin time can be used to estimate plasma drug level. The aim of this study was to assess a diluted thrombin time assay based on the same thrombin reagent already used for traditional thrombin time measurements that reliably measure low to intermediate plasma dabigatran levels. We included 44 patients with atrial fibrillation who started treatment with dabigatran 150 mg (23 patients) or 110 mg (21 patients) twice a day. Blood samples were collected at baseline (no dabigatran) and 2-4 weeks after the beginning of dabigatran therapy at trough and at peak. Plasma dabigatran levels were measured with diluted thrombin time and compared to liquid chromatography with tandem mass spectrometry as the reference method. The performance of the diluted thrombin time was compared to Hemoclot® Thrombin Inhibitor and Ecarin Chromogenic Assay. In ex vivo plasma samples, diluted thrombin time highly correlated with the liquid chromatography with tandem mass spectrometry (Pearson's R = 0.9799). In the low to intermediate range (dabigatran concentration ≤ 100 µg/L) diluted thrombin time correlated significantly more closely to the liquid chromatography with tandem mass spectrometry (R = 0.964) than Hemoclot® Thrombin Inhibitor (R = 0.935, p = 0.05) or Ecarin Chromogenic Assay (R = 0.915, p < 0.01). It was also the only functional assay without any significant bias in the low to intermediate range. Both trough and peak diluted thrombin time values were similar to liquid chromatography with tandem mass spectrometry. We conclude that the diluted thrombin time assay presented in this study reliably detects dabigatran and that it is superior to the Hemoclot® Thrombin Inhibitor assay in the low to intermediate range.