Prothrombin Time Values Research Articles

Effects of sulfotanshinone sodium injection on the pharmacokinetics and pharmacodynamics of warfarin in rats in vivo

This study was to explore the effects of sulfotanshinone sodium injection (SSI) on the pharmacokinetics and pharmacodynamics of warfarin in rats.The studies of single dose and multiple dose of warfarin were designed to assess the interaction between warfarin and SSI. Rats were divided into different groups randomly and administered with warfarin in the absence or presence of SSI. Prothrombin time (PT) and activated partial thromboplastin time (APTT) values were detected by blood coagulation analyzer, and international normalized ratio (INR) values were calculated. Plasma concentrations of warfarin enantiomers were determined by UPLC–MS/MS method, pharmacokinetic parameters were calculated.The single-dose study demonstrated that the repeated doses of SSI alone had no effect on PT, APTT and INR values, but had a significant effect on PT and INR values produced by a single dose of warfarin, APTT values were unaffected. The Cmax, AUC of R-warfarin and S-warfarin were reduced, t1/2 were shortened. The multiple-dose study showed that PT, APTT, INR values, and the Cmax and AUC of R-warfarin and S-warfarin decreased significantly after administration of SSI.The finding implied that SSI could accelerate warfarin metabolism and weaken its anticoagulation. However, human SSI–warfarin interaction studies need to be conducted to confirm this finding.

Clinical Pharmacometrics for Rational Drug Treatment

Pharmacometrics is the mathematical study of pharmacokinetics, disease progression, and clinical outcomes. One objective of pharmacometrics is to facilitate rational drug treatment in patients, also termed clinical pharmacometrics. In this review, our clinical pharmacometric studies conducted over the last 10 years are discussed. Population pharmacokinetic analysis using therapeutic monitoring data for levetiracetam revealed that oral clearance allometrically scaled to both body weight and estimated glomerular filtration rate can accurately predict clinical data from patients of various ages (pediatric to elderly) with varying renal function. Dosage adjustments based on renal function in the package information are effective in controlling the trough and peak concentrations in similar ranges. In addition, a retrospective pharmacokinetic and pharmacodynamic study revealed that the efficacy of low-dose clobazam therapy was significantly influenced by CYP2C19 polymorphisms. Pharmacokinetic and pharmacodynamic models were successfully built using electronic medical information to explain retrospective international normalized ratio values of prothrombin time before and after catheter ablation in warfarin-treated patients. Simulation studies suggest that more than 20 mg of vitamin K2 is unnecessary in the preoperative period of catheter ablation. A physiologically based pharmacokinetic model adapted to tacrolimus pharmacokinetic data in patients who underwent living-donor liver transplantation was constructed, and clarified that oral clearance of this drug was affected by CYP3A5 genotypes in both the liver and intestine to the same extent. In conclusion, pharmacometrics is a useful methodology for individualized and optimized drug therapy.

Evaluation of albendazole treatment on coagulation profile in sheep naturally infected with Dicrocoelium dentriticum

The aim of the present study was to evaluate the selected coagulation profile parameters in sheep naturally infected with Dicrocoeliumdentriticum and effects of albendazole treatment. For this reason, 34 merino sheep, aged between 1 and 3 years, naturally infected with Dicrocoeliumdentriticumwere enrolled in the present study. Plasma and stool samples were withdrawn from each animal before and 10 days after treatment and egg per gram feces were evaluated with Mc Master technique. Prothrombin time activated partial thromboplastin time and fibrinogen levels were determined by semiautomated coagulometer by using commercial test kits before and 10 days after treatment.Noticeable clinical recovery was detected in all animals after albendazole treatment. There were significant differences on Prothrombin time and fibrinogen levels a p value of (p<0.001) between treatment intervals. In conclusion, this is the first study for selected coagulation parameters before and after albendazole treatment for ovine patients naturally infected with Dicrocoeliumdentriticum. It should be mentioned that the treatment resulted in lower prothrombin time and fibrinogen values, suggesting that dicrocoeliasis might alter coagulation profile and possibly induce an acute phase response. Furthermore, the clinical relevance in ovine medicine and related results possibly interacting to human medicine has to be determined by future studies.

PB1768 PREDICTIVE FACTORS OF SEVERE BLEEDING IN ACUTE PROMYELOCYTIC LEUKEMIA

Background:Acute promyelocytic leukemia (APL) is identified by the predomination of abnormal promyelocytes in the bone marrow (BM) and a specific chromosomal translocation – t(15;17) – resulting in a fusion transcript between the promyelocytic (PML) gene on chromosome 15 and the retinoic acid receptor alpha (RARα) gene on chromosome 17; this transcript is known as PML–RARα. The t(15;17) chromosomal translocation can cause hyperexpression of tissue factor (TF) in cells of patients with APL and render the patient hypercoagulable.Aims:The objective of the current study was to assure more appropriate therapeutic strategies for reducing severe hemorrhaging by assessing the recovery of abnormal coagulation indexes in patients with acute promyelocytic leukemia (APL) during induction therapy.Methods:Retrospective analyses of newly diagnosed with APL were performed during initial treatment. A total of 23 patients newly diagnosed with APL were treated at the Hematology department of Emergency Hospital (Semey, Kazakhstan), between April 2008 and January 2019. This cohort included 9 males and 14 females with a median age of 41 years (range: 12–75). The APL diagnostic criteria were based on the World Health Organization Classification of Tumors–Pathology and Genetics of Tumors of Hematopoietic and Lymphoid Tissues (2008) and French–American–British classification systems (1976) criteria. A molecular diagnosis was confirmed by identification of t(15;17) in a cytogenetic analysis and/or positive detection of PML–RARα using either fluorescence in situ hybridization or reverse transcription‐polymerase chain reaction. The immune phenotype diagnosis of APL was established by positivity for CD33, CD9, CD13, and CD117, and low expression of HLA‐DR and CD34. Early death (ED) was defined as death due to any cause within 30 days of diagnosiResults:Hemorrhage was the principal cause of death during the induction period. The values of white blood cell count, lactate dehydrogenase, prothrombin time (PT), fibrinogen (Fbg), hemoglobin, and bone marrow leukemic promyelocytes were significantly different in the high‐risk group compared to the low/intermediate‐risk groups. There were significant differences in the white blood cell count, bone marrow leukemic promyelocytes, platelet (PLT) count, and the levels of lactate dehydrogenase, d‐dimer, PT, and Fbg, as well as in FLT3‐ITD mutations between patients with major bleeding and those with minor bleeding. Hemostatic variables significantly improved over time during induction therapy. The recovery times of the PLT, PT, and Fbg values were significantly slower in patients with major bleeding than in those with minor bleeding. Particularly, the PLT level in patients with major bleeding was not similar to that in the minor bleeding group until after 4 weeks of treatment. Hemorrhages were the most common cause of induction death in this study. High‐risk patients were more prone to serious clinical bleeding symptoms. Patients with major bleeding had more rapid proliferation characteristics and an increased incidence of FLT3‐ITD mutations compared to patients with minor bleeding. Hemostatic variables recovered significantly more slowly in patients with major bleeding than in those with minor bleeding. Active induction therapy and blood product infusion are efficient in preventing severe bleedingSummary/Conclusion:Our results suggested that low PLT count might be the leading cause of fatal bleeding in patients newly diagnosed with APL.

Multicenter investigation of hemostatic dysfunction in 15 dogs with acute pancreatitis.

To characterize hemostatic profiles in dogs with acute pancreatitis. Prospective and observational study. Tertiary referral centers. Fifteen client-owned dogs with acute pancreatitis enrolled between December 1, 2011 and June 1, 2012. Blood samples were collected on admission for measurement of platelet count, PCV, thromboelastography (TEG), antithrombin, prothrombin time, activated partial thromboplastin time, D-dimer, von Willebrand factor, and fibrinogen values, which were compared to reference intervals derived from healthy dogs. The Wilcoxon rank-sum test was used to test for differences in continuous variables between study subjects and reference intervals. Dogs with acute pancreatitis were globally hypercoagulable using TEG when compared with reference intervals. Dogs with acute pancreatitis had significantly higher D-dimers (1,144μg/L vs 251μg/L [6264.5vs 1374.5nmol/L]; P=0.001), fibrinogen (837vs 232mg/dL [8.37vs 2.32g/L]; P<0.001), and von Willebrand factor (92.9%vs 65.1%; P=0.02) as well as significantly lower antithrombin (85.7% vs 120%; P<0.001) and prothrombin time values (3.8 vs 7.6 sec; P<0.001) than reference intervals. Laboratory evidence of hypercoagulability was present in dogs with acute pancreatitis. TEG may be useful in dogs with acute pancreatitis for monitoring response to therapy and guiding therapeutic interventions.

Impact of low volume citrate tubes on results of first-line hemostasis testing.

Pediatric tubes are increasingly used for drawing blood for hemostasis testing. This study has investigated the potential impact of low volume citrate tubes on results of first-line hemostasis testing. The study population comprised 34 patients on warfarin therapy and 17 ostensibly healthy volunteers. Blood was collected into five different evacuated blood tubes from each subject. On right arm, blood was drawn directly into two standard evacuated blood tubes (3-mL Vacuette and 2-mL Vacutest) and one evacuated low volume blood tube (1-mL Vacuette) by straight needle venipuncture. On left arm, blood was drawn using a 5-mL syringe and then transferred within two nonevacuated microtubes (0.5mL MiniCollect and 0.5mL Micro Test). Prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen were assayed on ACL TOP 700. Spearman's correlation of PT, APTT, and fibrinogen values obtained using different tubes was always satisfactory (ie, ≥0.93).A statistically significant bias was frequently found by comparing values obtained in different tubes. Nevertheless, the minimum quality specifications for bias were exceeded only by comparing data of Vacuette 1mL with those of all other blood tubes for PT, by comparing data of Micro Test 0.5mL with those of all other blood tubes for APTT, and by comparing data of Micro Test 0.5-mL blood tubes with those of Vacuette 3mL and Vacuette 1. First-line hemostasis testing using low volume citrate tubes may display differences sometimes exceeding the minimum quality specifications.

Modified Glasgow Coma Scale Using Serum Factors as a Prognostic Model in Traumatic Brain Injury

Traumatic brain injury (TBI) is a major cause of death and disability. This study evaluated a possible relationship between serum factors at admission and the outcome of TBI. We propose a statistically validated scale for patients with TBI that combines serum factors and the Glasgow Coma Scale (GCS). Between May 2011 and July 2016, 219 patients underwent decompressive craniectomy for TBI. We assessed laboratory data on admission, and correlations with GSC and Glasgow Outcome Scale were investigated. The modified GCS was developed from a multivariable logistic regression model, which was validated with the backward stepwise method. Of 219 patients with TBI enrolled in our study, 175 were men (79.9%) and 44 were women (20.1%) with a mean age of 49.1 ± 11.5 years. Initial serum values of hemoglobin, platelets, prothrombin time, and lactate dehydrogenase were associated with in-hospital mortality. The factor score was derived by adding the following points: hemoglobin (≥13.0 g/dL= 0, <13.0 g/dL= 1), platelets (≥150× 103/mm3= 0, <150× 103/mm3= 1), prothrombin time (<13.2 seconds= 0, ≥13.2 seconds= 1), and lactate dehydrogenase (<271 U/L= 0, ≥271 U/L= 1). The modified GCS score (GCS score [range, 6-15]- FS [range, 0-4]) was calculated. The modified GCS score using serum factors extended the information provided about patient outcomes to be comparable to more complex methods. The modified GCS score may be useful to predict in-hospital mortality in patients with TBI.

A Retrospective Analysis of the Effect of Tigecycline on Coagulation Function.

A number of clinical trials demonstrated that tigecycline was effective and well tolerated in the treatment of patients with various bacterial infections, but few literatures had shown the coagulopathy induced by tigecycline. To address this concern, we performed a retrospective analysis to assess the impact of tigecycline treatment on coagulation parameters in 50 patients with bacterial infections in our hospital (Shandong Provincial Hospital, China). These patients were treated with tigecycline at Shandong Provincial Hospital in 2015-2016 at either a recommended (50 mg q12h) or a higher dose (100 mg q12h). Coagulation parameters, including Fibrinogen (FIB) levels, prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet count (PLT) and D-dimer, were evaluated in order to assess the impact of tigecycline treatment in these severely infected patients. What we found was that the plasma fibrinogen (FIB) level was 4.63 ± 1.56 g/L before tigecycline treatment, and decreased to 2.92 ± 1.23 g/L during treatment, which was statistically significant (p < 0.001). The mean values of aPTT and PT were significantly increased from 39.58 ± 8.72 to 44.05 ± 10.45 s (p = 0.002), and from 15.37 ± 1.53 to 16.37 ± 2.64 s (p = 0.004), respectively. This study demonstrates that treatment of tigecycline could reduce FIB, prolong aPTT and PT. In conclusion, we advise that it is necessary for practitioners routinely monitor coagulation level in at-rick patient populations treated with tigecycline.

Evaluation of Coagulation Parameters in Dogs with Overweight or Obesity

Background: Hemostatic alterations have already been well characterized in humans with body fat excess, being included in the list of obesity related comorbidities. Overweight and obesity are common in dogs; however, there is little information about the blood coagulation parameters in dogs with these conditions. The aim of this study was to compare hematological and coagulation parameters between lean dogs and overweight or obese dogs, including platelets count; prothrombin time (PT); activated partial thromboplastin time (aPTT), coagulation time (CT) and plasma fibrinogen concentration.Materials, Methods &amp; Results: A total of 22 dogs (aged 1 to 10 years, neutered) were evaluated, 10 of them presented ideal body condition score (BCS 4-5) and formed the group 1 (control) and 12 were overweight or obese (BCS 7-9) and formed the group 2. The dogs were submitted to clinical evaluation and then to blood collection for the following laboratory tests: blood count (performed on automatic analyzer), quantification of plasma proteins by refractometry, determination PT, aPTT and plasma fibrinogen concentration using specific commercial kits, and CT by Lee-White method. Compared to group 1, group 2 presented a lower leukocytes and lymphocytes counts (P &lt; 0.05) and a higher concentration of plasma fibrinogen (P = 0,026), but compatible with reference values. No difference was observed in the erythrogram, platelets count, total plasma protein concentration, PT, aPTT and CT between the groups. BCS was negatively correlated with leukocytes (r = -0.45) and lymphocytes (r = -0.60) counts and positively with plasma fibrinogen concentration (r = +0.56).Discussion: The reduction in lymphocytes led to a lower leukocytes count in the dogs of group 2. The migration of peripheral blood lymphocytes to adipose tissue has been reported in the early phase of the inflammatory process induced by obesity and could justify the reduction of circulating lymphocytes in overweight or obese dogs evaluated in this study; however, cytopathological assessment of adipose tissue was not performed. Fibrinogen has to be converted to fibrin for clot formation, so the concentration of this plasma protein is an important parameter for the evaluation of hemostasis. However, there are reports of increase in plasma fibrinogen as a result of infammatory processes. In group 2, formed by dogs with overweight or obese, the higher value of plasm fibrinogen concentration, associated with lower lymphocyte count, may suggest an early-stage inflammatory process. Similar results were described in obese humans, but also evidenced in obese dogs. Supporting this suggestion, the correlation analysis indicates that the higher the body fat excess (estimated by the BCS), the higher the fibrinogen concentration and the lower the lymphocyte count in evaluated dogs. Despite the higher concentration of plasma fibrinogen in group 2, no change was observed in the hemostasis of overweight or obese dogs, due to the normal values for platelets count, PT, aPTT and CT, excluding a hypercoagulability condition as already hypothesized by other authors for dogs and obese humans. The difference between our findings and the literature may be in the time of evolution of the disease, since we evaluated younger dogs. In conclusion, the body fat excess did not alter the erythrogram and the activity of the clotting factors, estimated by PT, aPTT and CT, but it interfered in the leukogram and increased the plasma concentration of fibrinogen in the evaluated dogs.

Analytical Assessment of the New Roche Cobas t 711 Fully Automated Coagulation Analyzer.

This study aimed to provide a preliminary evaluation of the analytical performance of the new Roche COBAS T 711: fully automated coagulation analyzer, which uses both liquid and lyophilized reagent cassettes. The analytical assessment included analysis of imprecision and linearity of prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen on COBAS T 711: analyzer. Test results of 120 routine plasma samples were also compared with those obtained using two other coagulation analyzers (Instrumentation Laboratory ACL TOP 700 and Stago STA-R MAX). The accuracy, imprecision, and comparability of manual and automatic lyophilized material resuspension were also evaluated using 200 routine plasma samples. Overall, automatic resuspension was found to be more precise than, and equally accurate as, manual reconstitution, with coefficient of variations (CV%) three- to sixfold lower compared with manual reconstitution. The analytical imprecision was found to be excellent, as attested by total CV% of 0.7% for PT, 1.7 to 1.8% for APTT, and 1.9 to 3.2% for fibrinogen. Linearity was excellent over a clinically significant range of PT, APTT, and fibrinogen values, displaying correlation coefficients comprised between 0.994 and 0.999. Methods comparison studies revealed that results of PT, APTT, and fibrinogen on COBAS T 711: are globally aligned with those obtained using identical plasma samples on IL ACL TOP 700 and Stago STA-R MAX, displaying correlation coefficients of 0.97 for PT, 0.81 and 0.88 for APTT, 0.90 and 0.94 for fibrinogen, respectively. In conclusion, the results of this preliminary evaluation demonstrate that PT, APTT, and fibrinogen on COBAS T 711: coagulation analyzer displays excellent performance for routine use in clinical laboratories.

Clinical Importance of Drug-Drug Interaction Between Warfarin and Prednisolone and Its Potential Mechanism in Relation to the Niemann-Pick C1-Like 1-Mediated Pathway.

Warfarin is an anticoagulant drug used to prevent thromboembolic disorders, but its pharmacological effect is affected by co-administered drugs. Therefore, careful management of warfarin-related drug-drug interactions (DDIs) is necessary for its safety and effectiveness. Recently, intestinal vitamin K1absorption through the Niemann-Pick C1-like 1 (NPC1L1)-mediated pathway was found to affect the pharmacological effect of warfarin. This study aimed to identify high-frequency warfarin-related DDIs in a clinical setting and elucidate their mechanism(s) in terms of changes in NPC1L1 expression and/or activity. Methods and Results: Prednisolone was the most frequently suspected drug in retrospective surveys of medical records of patients who experienced warfarin-related DDIs. Prednisolone significantly increased the international normalized ratio of prothrombin time (PT-INR) values in warfarin-treated patients. To demonstrate the involvement of NPC1L1 in warfarin-prednisolone DDI, we conducted an in vitro vitamin K1uptake assay using NPC1L1-overexpressing cells and found that prednisolone inhibited NPC1L1-mediated vitamin K1uptake. Additionally, we found that prednisolone downregulates NPC1L1 in a glucocorticoid receptor α-dependent manner. Co-administration of warfarin and prednisolone frequently enhanced the anticoagulant effect of warfarin in a clinical setting. Prednisolone-mediated suppression of NPC1L1 expression and activity could be the mechanism of DDI between warfarin and prednisolone. To manage warfarin therapy, the potential of concomitant drugs to change its anticoagulant effect through NPC1L1-related mechanisms merits consideration.

Critical pharmacokinetic and pharmacodynamic drug-herb interactions in rats between warfarin and pomegranate peel or guava leaves extracts

BackgroundIn-depth information of potential drug-herb interactions between warfarin and herbal compounds with suspected anticoagulant blood thinning effects is needed to raise caution of concomitant administration. The current study aimed to investigate the impact of co-administration of pomegranate peel and guava leaves extracts, including their quality markers namely; ellagic acid and quercetin, respectively, on warfarin’s in vivo dynamic activity and pharmacokinetic actions, in addition to potential in vitro cytochrome P450 enzymes (CYP) inhibition.MethodsInfluence of mentioned extracts and their key constituents on warfarin pharmacodynamic and kinetic actions and CYP activity were evaluated. The pharmacodynamic interactions were studied in Sprague Dawley rats through prothrombin time (PT) and International Normalized Ratio (INR) measurements, while pharmacokinetic interactions were detected in vivo using a validated HPLC method. Furthermore, potential involvement in CYP inhibition was also investigated in vitro on isolated primary rat hepatocytes.ResultsPreparations of pomegranate peel guava leaf extract, ellagic acid and quercetin in combination with warfarin were found to exert further significant increase on PT and INR values (p < 0.01) than when used alone (p < 0.05). Pomegranate peel extract showed insignificant effects on warfarin pharmacokinetics (p > 0.05), however, its constituent, namely, ellagic acid significantly increased warfarin Cmax (p < 0.05). Guava leaves extract and quercetin resulted in significant increase in warfarin Cmax when compared to control (p < 0.01). Furthermore, guava leaves extract showed a significant effect on changing the AUC, CL and Vz. Significant reduction in CYP2C8, 2C9, and 3A4 was seen upon concomitant use of warfarin with ellagic acid, guava leaves and quercetin, unlike pomegranate that insignificantly affected CYP activities.ConclusionAll combinations enhanced the anticoagulant activity of warfarin as the results of in vivo and in vitro studies were consistent. The current investigation confirmed serious drug herb interactions between warfarin and pomegranate peel or guava leaf extracts. Such results might conclude a high risk of bleeding from the co-administration of the investigated herbal drugs with warfarin therapy. In addition, the results raise attention to the blood-thinning effects of pomegranate peel and guava leaves when used alone.

The Changes in Coagulation Test Results in Subjects with Varying Levels of Thyroid Stimulating Hormone.

The aim is to investigate the changes in coagulation test results in subjects with varying serum levels of thyroid stimulating hormone. We performed a one-year retrospective analysis to retrieve combined results of activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (Fib), D-dimer, free thyroxine (fT4), tri-iodothyronine (fT3), and thyroid stimulating hormone (TSH) from inpatients who were referred by general practitioners for routine blood testing. Cumulative results were retrieved for 2,794 such inpatients. Patients with a TSH level < 0.34 µIU/mL had higher PT values (10.43 ± 1.02 vs. 10.27 ± 0.91) and Fib values (3.00 ± 0.92 vs. 2.7 ± 0.56) compared with patients with 0.34 µIU/mL < TSH < 5.6 µIU/mL. Conversely, the PT values (10.01 ± 0.95 vs. 10.27 ± 0.91) were lower and APTT (33.70 ± 4.17 vs. 32.56 ± 4.12) values higher in patients with TSH > 5.6 µIU/mL compared to patients with 0.34 µIU/mL < TSH < 5.6 µIU/mL. There are changes in coagulation test results in subjects with varying levels of thyroid stimulating hormone.

Effect of some preanalytical variables on some screening tests of coagulation: a single center experience

Background Preanalytical circumstances are significant in laboratory assessment. Prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (Fbg), measurements are basic coagulation tests used to evaluate variations of coagulation systems. Aim Investigate to what extent the storage temperature and time influence the results of routine coagulation tests (PT, APTT, and Fbg). It included a total of 120 participants were assayed for different storage temperatures. Patients and methods The platelet poor plasma was assayed for baseline values for PT, APTT, and Fbg on Sysmex 1500 apparatus, and then it was assayed for different storage temperature and time. Results The PT results showed no significant difference when compared with the baseline when samples were kept at 4°C for 12 h storage and at −20°C for 12 h. The APTT results showed significant difference when compared with the baseline at all temperatures. The Fbg results showed no significant difference when compared with the baseline when the sample were kept at 4 and −20°C for 24 h. Conclusion It is not recommended that the PT samples in normal persons be stored at room temperature but can be stored at 4 or −20°C for 12 h. APTT samples in normal persons cannot be stored up to 12 h at any temperature. Fbg samples in normal persons cannot be stored up to 24 h at any temperature. So estimation of APTT and Fbg must be done as early as possible.

Analysis of hemocoagulation tests for prediction of venom-induced consumption coagulopathy development after Viperidae bite.

Viperidae snakes are responsible for 95 % of the bites caused by exotic-bred snakes in our country. Their envenoming may be associated with a severe acute coagulation disorder - venom-induced consumption coagulopathy (VICC). Thus, its early prediction is vital for an adequate therapy including antivenom delivery. Laboratory coagulation tests of 14 patients suffering from VICC were processed and statistically analyzed to evaluate the importance of individual parameters in the time after the bite. The pathological values of D-dimer (D-dim) and fibrinogen (FBG) were found to be the first indicators of VICC development, with a median time of 4.55 hours since the bite, while median values for prothrombin time and international normalized ratio (PT/INR), activated partial thromboplastin time (APTT), and thrombin time (TT) were 5.9 h, 8.15 h, and 5.5 h, respectively. In the first samples, the values of D-dim were found to be pathologically increased in all 14 patients, while pathological levels of FBG were seen only in 11 cases. PT/INR and APTT were prolonged in 8 and 6 cases, respectively. An increase in D-dim values was found to be the first parameter signaling developing VICC in all analyzed cases (Tab. 2, Ref. 12).

Liver transplantation in patients with liver failure related to exertional heatstroke

Severe acute liver injury is a grave complication of exertional heatstroke. Liver transplantation (LT) may be a therapeutic option, but the criteria for LT and the optimal timing of LT have not been clearly established. The aim of this study was to define the profile of patients who require transplantation in this context. This was a multicentre, retrospective study of patients admitted with a diagnosis of exertional heatstroke-related severe acute liver injury with a prothrombin time (PT) of less than 50%. A total of 24 male patients were studied. Fifteen of the 24 patients (median nadir PT: 35% [29.5-40.5]) improved under medical therapy alone and survived. Nine of the 24 were listed for emergency LT. At the time of registration, the median PT was 10% (5-12) and all had numerous dysfunctional organs. Five patients (nadir PT: 12% [9-12]) were withdrawn from the list because of an elevation of PT values that mainly occurred between day 2 and day 3. Ultimately, 4 patients underwent transplantation as their PT persisted at <10%, 3 days (2.75-3.25) after the onset of exertional heatstroke, and they had more than 3 organ dysfunctions. Of these 4 patients, 3 were still alive 1 year later. Histological analysis of the 4 explanted livers demonstrated massive or sub-massive necrosis, and little potential for effective mitoses, characterised by a "mitonecrotic" appearance. The first-line treatment for exertional heatstroke-related severe acute liver injury is medical therapy. LT is only a rare alternative and such a decision should not be taken too hastily. A persistence of PT <10%, without any signs of elevation after a median period of 3 days following the onset of heatstroke, was the trigger that prompted LT, was the trigger adopted in order to decide upon LT. Acute liver injury due to heatstroke can progress to acute liver failure with organ dysfunction despite medical treatment; in such situations, liver transplantation (LT) may offer a therapeutic option. The classic criteria for LT appear to be poorly adapted to heatstroke-related acute liver failure. We confirmed thatmedication is the first-line therapy acute liver injury caused by heatstroke, with LT only rarely necessary. A decision to perform LT should not be made hastily. Fluctuations in prothrombin time and the patient's clinical status should be considered even in the event of severe liver failure.

Chitosan-graft-poly(N-hydroxy ethyl acrylamide) copolymers: Synthesis, characterization and preliminary blood compatibility in vitro

Poly(N-hydroxy ethyl acrylamide) was grafted onto chitosan in aqueous acidic medium using potassium per sulphate initiator to obtain polymer surfaces with blood compatibility for potential biomedical applications. Thermally cross-linked products were obtained upon drying at 60 °C overnight. Chemically cross-linked films were prepared using methylene bis acrylamide (MBA) cross-linker. The products were characterized by FTIR, XRD and SEM analyses. Protein adsorption onto the film surfaces gave, on the average, 30% bovine serum albumin (BSA) and 10% human serum albumin (HSA) removal from aqueous solution, in vitro. Blood compatibility was evaluated with respect to activated prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet adhesion. PT and APTT values remained within normal ranges after blood-polymer contact, with chitosan-graft-polyHEAA films, in vitro. Chitosan-graft-MBA or chitosan-graft-(polyHEAA;MBA), and blank chitosan films produced higher PT and APTT values under similar experimental conditions with chitosan-graft-polyHEAA films, exhibiting blood anticoagulant activity. SEM pictures taken before and after contact with blood sample did not reveal any significant blood component adhesion on the chitosan-graft-(polyHEAA;MBA) film surface contrary to the observation made on the blank chitosan film.

Динаміка показників гепатодепресивного синдрому у хворих з механічною жовтяницею пухлинного ґенезу після ендоскопічної і лапароскопічної паліативної декомпресії загальної жовчної протоки

Мета роботи з’ясувати динаміку показників гепатодепресивного синдрому у хворих із механічною жовтяницею пухлинного генезу після ендоскопічної і лапароскопічної паліативної декомпресії загальної жовчної протоки.&#x0D; Матеріали і методи. Під спостереженням в період з 2011 до 2017 р. перебували 48 пацієнтів, в яких внаслідок комплексного обстеження виявили інкурабельні пухлини на тлі вираженої механічної жовтяниці. Усім хворим виконано паліативну декомпресію загальної жовчної протоки: 30 пацієнтів – із застосуванням ендоскопічних методів; 18 пацієнтів – із використанням лапароскопічної гепатикоєюностомії. Кожну підгрупу рандомізували за віком, статтю, тривалістю жовтяничного періоду та основними біохімічними показниками, визначеними до операції. Пацієнти перебували під спостереженням протягом 6 міс. після декомпресії. До операції, через 1, 7 і 14 діб, а також 3 і 6 міс. у пацієнтів визначали маркери гепатодепресивного синдрому: протромбіновий час, вміст загального білка й альбумінів у сироватці крові за загальновідомими методами.&#x0D; Результати досліджень та їх обговорення. Лапароскопічна декомпресія загальної жовчної протоки шляхом формування гепатикоєюноанастомозу порівняно з ендоскопічними методами супроводжується швидшим відновленням функціонального стану печінки, що проявляється сталим зниженням протромбінового часу індексу INR і збільшенням вмісту в сироватці крові загального білка та альбумінів через 3–6 міс. після декомпресії. На тлі ендоскопічної декомпресії в цей період протромбіновий час і індекс INR статистично вірогідно більші, вміст у сироватці крові загального білка і альбумінів – менший, порівняно з лапароскопічною декомпресією. Через 3-6 міс. після втручання за умов ендоскопічної декомпресії показники гепатодепресивного синдрому суттєво погіршуються, що пов’язано з розвитком у 30 % пацієнтів ускладнень.

Modification of chitosan grafted with collagen peptide by enzyme crosslinking

Free radicals are closely related to the occurrence and development of aging, cancer and inflammation. In this paper, the microbial transglutaminase (MTGase) was used as a catalyst to graft the collagen peptide (COP) molecules on the amino group of carboxymethyl chitosan sulfate (CMCS) to improve the antioxidant effects. FT-IR and NMR spectroscopy were used to confirm the successful grafting of COP to CMCS. Degree of substitution (DS) of CMCS-COP could be controlled by adjusting the reaction conditions. With the increase of concentration, the ability of each sample on scavenging capacity and reducibility tends to increase obviously. The results of anticoagulant experiments showed that the ability of CMCS and CMCS-COP with three different degrees of substitution on activated partial thrombin time (APTT) and prothrombin time (PT) values were all increased to compare with the control group. No relevant cytotoxicity against NIH-3T3 mouse fibroblasts was found for the copolymers. These results suggested that CMCS-COP would appear to be a promising candidate for wound dressing application.

Effects of cigarette smoking on coagulation screening tests and platelet counts in a Sudanese male adults population.

Objectives:To study the effects of heavy cigarette smoking on coagulation (CGG) screening tests and platelet counts (PLTs) in a Sudanese male adults population.Methods:A case control study was conducted at both Kosti and Gabalein towns, Sudan, during October 2016 to May 2017. A 100 adult cigarette smokers were selected and another 100 matched non-smokers were selected as healthy controls. Blood samples were collected in trisodium citrate anti-coagulant for prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR), analyzed using standard methods (co-agulometer machine) and Ethylenediaminetetraacetic acid for the platelet counts, using an automated haematology analyzer (Sysmex, Tokoyo, Japan).Results:The results showed that the mean platelet counts were significantly lower in the smokers (183x103/cmm±64x103/cmm) versus (244x103/cmm±38x103/cmm) in non-smokers, (p<0.000). Pearson correlation analysis suggested a weak negative correlation between platelet counts with the duration of smoking (r= -0.289, p<0.004) and the age of the smokers (r= -0.238, p<0.017). The mean PT and INR were also significantly lower in smokers (12.9±1.2 seconds) compared with the non-smokers (13.7±1.04 seconds, p<0.000), for PT and (0.95±0.09 versus 1.01±0.08, p<0.000) for INR. In contrast, PTT had no significant variation in smokers (30.5±3.8 seconds) and the non-smokers (37.9±4.6 seconds). A p-value>0.05 was considered significant.Conclusion:Cigarette smokers tend to have lower platelet counts, shorter PT, and INR values, compared to non-smokers. Therefore, smoking might be associated with bleeding disorders but further investigations are needed.