Fibrin Degradation Products Research Articles

Systematic Comprehensive Evaluation of the Mindray CX-9000 Coagulation Analyzer Performance.

The aim of the study was to conduct a comprehensive performance evaluation of the Mindray CX-9000 fully automated coagulation analyzer for the detection of the seven coagulation items. The performance of activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), thrombin time (TT), D-dimer (D-D), fibrinogen degradation product (FDP), and antithrombin Ⅲ (AT) was validated for precision, linear range, carryover contamination rate, reference interval validation, inter-method agreement, and anti-interference ability. The intra- and inter-precision (coefficient of variation, CV%) of all seven items was less than the target CV%; the carryover contamination rates for different concentrations and between items were < 10%. The slope of the linear regression equation for the theoretical and measured values of the linear range was within 1 ± 0.05 and R ≥ 0.975. The reference interval quoted from the manufacturer's reference interval passed ≥ 95%. The CX-9000 was compared with the results of the reference instrument STAGO R MAX (STA-R MAX) and the p-values for all items ranged from 0.822 to 0.987. Within the concentration range claimed by the manufacturer, the interference errors produced by all items met the manufacturer's claimed criteria, except for triglycerides which produced interference errors > 10% for the FIB, D-D, FDP, and bilirubin which produced interference errors for the FIB and D-D assays. The CX-9000 automatic coagulation analyzer has good stability and repeatability, a wide linear range of detection, low carryover contamination rate, and high resistance to interference, making it suitable for the testing of clinical specimens.

Beware of accidental ingestion of Colchicum autumnale mistaken for Allium victorialis.

Beware of accidental ingestion of Colchicum autumnale mistaken for Allium victorialis.

Diagnosis of Disseminated Intravascular Coagulation in Patients Suffering from Sepsis using the Modified International Society of Thrombosis and Haemostasis Criteria and Japanese Association of Acute Medicine Criteria

Introduction: The international task force defines sepsis as ‘life- threatening organ dysfunction caused by a dysregulated host response to infection’. Disseminated Intravascular Coagulation (DIC) is a coagulopathy syndrome that causes microvascular and macrovascular thrombosis and increases the risk of bleeding due to consumptive coagulopathy. Sepsis causes dysfunction in coagulation due to release of inflammatory markers which leads to inappropriate deposition of intravascular fibrin. In order to facilitate the diagnostic process for detecting DIC, the scoring system recommended by International Society of Thrombosis and Haemostasis (ISTH) and Japanese Association of Acute Medicine (JAAM) were used which are based on the global coagulation tests such as the platelet count, Prothrombin time, International Normalised Ratio (INR) and Fibrin Degradation Products (FDPs)/D-dimer. Aim: To determine the prevalence and outcome of DIC in patients suffering from sepsis using ISTH criteria and JAAM criteria. Materials and Methods: A prospective cohort was carried out from January 2021 to July 2022 in the haematology section of pathology department of Government Medical College and Hospital, Aurangabad, Maharashtra, India. Hundred patients suffering from clinically suspected sepsis were included in the study. Venous blood was collected from patients in Ethylene Diamine Tetra-acetic Acid (EDTA) and Citrate bulbs. The tests performed were Complete Blood Count (CBC), Prothrombin Time (PT), INR and D-Dimer. CBC was performed on Fully automated three part cell counter. PT, INR, D-Dimer testing was done on fully automated coagulometer. The above test results were used to diagnose DIC in patients suffering from sepsis using the modified ISTH and JAAM criterias. The results were analysed using Microsoft excel 2019 i.e., chi-square test was applied for p-value calculation. Results: Out of 100 patients with clinically suspected sepsis 35 patients (35%) suffered from Overt DIC using ISTH criteria and 58 patients (58%) suffered from DIC using JAAM criteria. The total mortality in patients with sepsis in the present study was 40%. The mortality in patients with DIC in sepsis using the ISTH criteria was 26 patients (74.28%) and 37 patients (63.79%) using the JAAM criteria. Conclusion: Coagulation abnormalities are widely prevalent in patients with sepsis and are likely to play a key role in multi- organ dysfunction. Both ISTH and JAAM criteria are good predictors of mortality.

Outcomes of Overt and Non-overt Disseminated Intravascular Coagulation Using the ISTH DIC Scoring System in Children: A Single-Center Study.

Several disseminated intravascular coagulation (DIC) scoring systems are used for prognosticating the clinical outcomes of patients with DIC. However, research on children is scarce. Therefore, this study compared the clinical outcomes of overt and non-overt DIC using the International Society on Thrombosis and Hemostasis (ISTH) DIC scoring system. This retrospective study reviewed data on children aged one month to 15 years diagnosed with DIC between 2003 and 2014. Of 244 patients, 179 (73.4%) had overt DIC, and 65 (26.6%) had non-overt DIC. The most common causes were infection (84.8%), tissue injury (7%), and malignancies (2.9%). The 28-day case fatality rate was significantly higher for overt than non-overt DIC (76% vs. 15.6%; P < 0.001). DIC scores were significantly associated with mortality (R2 = 0.89). Each clinical parameter (platelet count, prothrombin time, and fibrin degradation products) was associated with mortality (P = 0.01). On multivariable analysis, the factors associated with death were platelet counts ≤ 50 000 cells/mm3 (OR, 2.42; 95% CI, 1.08-5.42; P = 0.031); overt DIC score (OR, 7.62; 95% CI, 2.94-19.75; P < 0.001); renal dysfunction (OR, 2.92; 95% CI, 1.34-6.37; P = 0.007); shock (OR, 39.62; 95% CI, 4.99-314.84; P = 0.001); and acute respiratory distress syndrome (OR, 25.90; 95% CI, 3.12-214.80; P = 0.003). The 28-day case-fatality rate was significantly higher for patients with overt than non-overt DIC and concordant with ISTH scores. ISTH DIC scores can be used as a clinical predictor for DIC in children.

Гормональная контрацепция в аспекте влияния на систему гемостаза

Aim: to study the hemostasis indicators in female patients with hyperandrogenism (HA) and menstrual disorders (MDs) during combined oral contraceptive (COC) intake, depending on the presence of undifferentiated connective tissue displasia (UCTD). Patients and Methods: the study results of 28 female patients with HA and MDs were divided into 2 groups: group 1 — 22 patients (mean age 22.1±3.2 years) with UCTD, group 2 — 6 patients (mean age 20.5±1.8 years) without UCTD. The content of hormones in the blood (on the 2nd–3rd day of the menstrual period), the parameters of hemostasis before and after 1 month of COCs intake, and the level of homocysteine were determined in all patients. Results: the analysis revealed an increase in the levels of platelet activation markers, coagulation link and fibrinolysis. During COCs intake, an increase in the fibrinogen content was noted in patients of both groups, which, however, did not exceed the reference values. During the correlation analysis, it was found that in groups 1 and 2, the parameters of the fibrinogen baseline, D-dimer and the corresponding indicators after 1 month of COCs intake had a strong correlation with each other (r=0.845, r=0.864). However, group 1 had higher levels of fibrinogen and fibrin degradation products (D-dimer) (p&lt;0.0001) versus those in group 2. The study on the trend of prothrombin time (PTT) and activated partial thromboplastin time (APTT) during COCs intake in female patients with HA and UCTD revealed an acceleration of indicators (p&lt;0.01) versus those before COCs intake. At the same time, the change in blood clotting markers was not realized by episodes of thrombosis in any of the patients. Conclusion: patients with UCTD had changes that characterized the activation of thrombogenesis. When planning hormonal contraception, it is necessary to single out a group of female patients with HA and signs of UCTD as the most vulnerable in relation to an increased risk of thrombogenic events. KEYWORDS: hyperandrogenism, combined oral contraceptive, thrombosis, connective tissue dysplasia, hyperhomocysteinemia. FOR CITATION: Kudinova E.G. Hormonal contraception in terms of effect on the hemostasis system. Russian Journal of Woman and Child Health. 2023;6(2):130–137 (in Russ.). DOI: 10.32364/2618-8430-2023-6-2-130-137.

Effects of Hemolysis on Routine Coagulation Tests when Tested on an Optical Coagulation Analyzer.

The Clinical and Laboratory Standards Institute recommends rejecting hemolyzed samples for coagulation tests. Sysmex CS5100 analyzer using an optical method is commonly used in laboratories. The influence of hemolysis on coagulation test has rarely been studied when tested on Sysmex CS5100. Determining this influence is necessary. Freshly collected samples were artificially hemolyzed to simulate the hemolysis processes. Coagulation tests were conducted on a Sysmex CS5100 coagulation analyzer. Detection values before and after hemolysis were compared. The results showed that after hemolysis detection, the prothrombin time (PT) statistically decreased, while the partial thromboplastin time (APTT) statistically increased. There were no significant differences in fibrinogen (Fg), thrombin time (TT), D-dimer (DD) or fibrinogen degradation products (FDPs). Antithrombin activity was elevated in hemolyzed samples. Although differences in PT and APTT were statistically significant, there was no need for rejection of hemolyzed samples due to insufficient clinical effects when tested on Sysmex CS5100 analyzer. Falsely elevated AT result may lead to misdiagnosis in patients with severe diseases, which should be carefully considered.

The Use of Machine Learning Techniques to Predict Deep Vein Thrombosis in Rehabilitation Inpatients.

Rehabilitation is crucial to recovering patients' dysfunction, improving their life quality, and promoting an early return to their family and society. In China, most patients in rehabilitation units are patients transferred from neurology, neurosurgery, and orthopedics, and most of these patients face problems such as continuously bedridden or varying degrees of limb dysfunction, all of which are risk factors for deep venous thrombosis. The formation of deep venous thrombosis can delay the recovery process and result in significant morbidity, mortality, and higher healthcare costs, so early detection and individualized treatment are needed. Machine learning algorithms can help develop more precise prognostic models, which can be of great significance in the development of rehabilitation training programs. In this study, we aimed to develop a model of deep venous thrombosis for inpatients in the Department of Rehabilitation Medicine at the Affiliated Hospital of Nantong University using machine learning methods. We analyzed and compared 801 patients in the Department of Rehabilitation Medicine using machine learning. Support vector machine, logistic regression, decision tree, random forest classifier, and artificial neural network were used to build models. Artificial neural network was the better predictor than other traditional machine learnings. D-dimer levels, bedridden time, Barthel Index, and fibrinogen degradation products were common predictors of adverse outcomes in these models. Risk stratification can help healthcare practitioners to achieve improvements in clinical efficiency and specify appropriate rehabilitation training programs.

Performance evaluation of the Sysmex CN-6000-automated coagulation analyzers for routine coagulation tests.

The Sysmex CN-6000 is a novel automated multiparameter coagulometer that performs clotting, chromogenic and immunological assays, and platelet aggregation tests in a single system. Here we evaluated its performance of routine coagulation assays. The precision, linearity, carryover and establishment of reference ranges of the CN-6000, as well as correlations between it and the currently used Diagnostica Stago STA-R Max were determined according to Clinical and Laboratory Standards Institute guidelines. The evaluated parameters included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FBG), antithrombin (AT), d-dimers (DDi), and fibrin and FBG degradation products (FDP). The intra-run and inter-run precisions of the six tests were determined using normal and pathological control materials; all coefficients of variation were acceptable and within the allowable ranges. The CN-6000 showed excellent linearity for FBG, AT, DDi, and FDP (R = 0.999-1.00). Passing-Bablok regression (R2 > 0.95) demonstrated good agreement between the analyzers. In the carryover study, APTT, PT, FBG, AT, DDi, and FDP values were all acceptable. The establishing reference intervals revealed that each manufacturer's range was acceptable. Significant differences were observed in the APTT reference range because of using different detection systems and reagents. The CN-6000 analyzer showed reliable performance and good correlation with the currently used STA-R Max automated hemostatic analyzer. As CN-6000 uses an optical clot-detection method, its reference ranges for PT and APTT are lower than those of the STA-R Max; thus, the difference should be considered before its use.

Immunohistochemical analysis of the distribution of RANKL: a case of disseminated carcinomatosis of bone marrow as the first presentation of relapse in curatively resected colorectal cancer.

Poorly differentiated adenocarcinoma of colorectal carcinoma (CRC) is a rare condition with poor prognosis. In this report, we describe a case of a 69-year-old man who underwent laparoscopic low anterior resection after being diagnosed with stage IIIB CRC. At 10months post-operation, he developed fever and loss of appetite. Laboratory examination revealed > 120.0μg/dL fibrin degradation products and > 60.0μg/dL D-dimer. Bone marrow (BM) examination showed malignant epithelioid infiltrate with CK20 and CDX2 expression, leading to diagnosis of disseminated carcinomatosis of BM, which is rare in CRC and indicative of widespread disease throughout the body. Furthermore, immunohistochemistry revealed high expression of receptor activator of nuclear factor κB ligand (RANKL) in tumor cells, including budding cells of CRC and BM tissues. Thus, RANKL expression, which is known to indicate metastatic behavior of cancer cells, may play a critical role in promoting osteoclast formation, which has been associated with the pathogenesis of BM lesions.

Predictive value of serum chlorine and interleukin-6 combined with coagulation indexes on severity of severe acute pancreatitis

To explore the predictive value of combined detection of serum interleukin-6 (IL-6), chloride (Cl-), D-dimer and fibrin degradation products (FDP) for severity of acute pancreatitis (AP). From December 2020 to March 2022, 132 AP patients who met the criteria for inclusion were screened for retrospective analysis from 292 AP patients admitted in emergency surgery at the First Affiliated Hospital of Zhengzhou University and they were divided into severe acute pancreatitis (SAP) group and non-SAP group, with 63 in SAP group and 69 in non-SAP group, according to classification criteria. The data including lab results, abdominal doppler ultrasound and chest and abdominal CT, etc. The bedside index for severity in acute pancreatitis (BISAP) score was calculated. Multivariate Logistic regression analysis was carried out to find the risk factors for the severity of AP patients. The receiver operator characteristic curve (ROC) was drawn to judge the clinical predictive value of each factor. A total of 132 AP patients were enrolled. The serum IL-6, D-dimer, FDP levels and the BISAP score in SAP group were significantly higher than those in non-SAP group [serum IL-6 (ng/L): 62.73 (21.54, 187.47) vs. 8.22 (4.13, 14.70), D-dimer (mg/L): 5.36 (2.94, 8.25) vs. 0.94 (0.42, 2.21), FDP (mg/L): 13.54 (6.76, 22.45) vs. 3.20 (2.50, 6.10), BISAP score: 2.00 (1.00, 3.00) vs. 1.00 (0, 2.00), all P < 0.05], while the serum Cl- level was significantly lower than that of non-SAP group (mmol/L: 97.90±4.86 vs. 101.73±4.32, P < 0.05). Multivariate Logistic regression analysis showed that increased levels of IL-6 [odds ratio (OR) = 1.02, 95% confidence interval (95%CI) was 1.01-1.04], D-dimer (OR = 1.21, 95%CI was 1.05-1.40) and decreased Cl- level (OR = 0.88, 95%CI was 0.79-0.98) were risk factors for SAP (all P < 0.05). The ROC curve analysis showed that the area under the ROC curve (AUC) of IL-6, Cl-, D-dimer and FDP combined to predict the severity of AP patients was larger (0.89), and the sensitivity (82.50%) and specificity (85.50%) were higher. Compared with single index, the combined detection of serum IL-6, Cl-, D-dimer and FDP is more precise in determining the condition of AP.

Utility and safety of nafamostat mesilate for anticoagulation in dogs.

Surgical interventions are recommended for cases of advanced mitral regurgitation, however, limited facilities are available. The most prominent complication in such procedures is heparin-derived bleeding. An alternative anticoagulant to heparin, nafamostat mesilate (NM), can reduce the occurrence of complications associated with heparin such as bleeding or shock. This study aimed to evaluate the utility and safety of using NM during anaesthesia in canines. Six healthy adult Beagle dogs were anaesthetised, and NM was administered intravenously as a 10mg/kg bolus dose over 5min, followed by a continuous infusion of 10mg/kg/h over 20min. Blood tests and blood pressure measurements were performed at 0, 5, 25 and 55min after NM administration. Activated thromboplastin times at 0, 25 and 55min were 13.0 ± 0.7 s, 106.7 ± 13.3 s and 28.2 ± 2.9 s, respectively, with a significant difference between 0 and 25min (p < 0.01) only. No significant differences were observed in prothrombin time, antithrombin, fibrinogen and fibrin degradation product concentrations between timepoints. Activated clotting times (ACTs) at 0, 5, 25 and 55min were 119.5 ± 9.6 s, 826.7 ± 78.6 s, 924.8 ± 42.4 s and 165.2 ± 13.5 s, respectively. Significant differences were observed between 0 and 5min (p < 0.05) and between 0 and 25min (p < 0.05). Blood pressure changes occurred in four dogs (66.7%). No other serious adverse effects were observed. ACT results indicated that NM use in anaesthetised healthy dogs was sufficient to obtain procedural anticoagulation with minimal adverse effects. However, these preliminary data require validation in further studies on cardiopulmonary bypass surgery.

The indicators for early blood transfusion in patients with placental abruption with intrauterine fetal death: a retrospective review

BackgroundPlacental abruption (PA) with intrauterine fetal death (IUFD) is associated with a high risk of postpartum hemorrhage (PPH) resulting from severe disseminated intravascular coagulation (DIC). Therefore, blood products that are sufficient for coagulation factor replacement must be prepared, and delivery should occur at referral medical institutions that are equipped with sufficient blood products and emergency transfusion protocols. We retrospectively reviewed the records of patients with PA and IUFD (PA-IUFD) to identify possible factors that may indicate the need for early blood transfusion and investigated whether the Japanese scoring system for PPH can be applied in such cases.MethodsWe used a database of 16,058 pregnant patients who delivered at Yokohama City University Medical Center between January 2000 and February 2016. Thirty-three patients were diagnosed with PA-IUFD before delivery and categorized into two groups–blood transfusion and non-transfusion–to compare the maternal characteristics and pregnancy outcomes.ResultsIn patients with PA-IUFD, the transfusion group exhibited significantly more blood loss; lower fibrinogen levels and platelet counts; higher levels of fibrin degradation products (FDP), D-dimer, and prothrombin time; and a tendency for tachycardia on admission, compared to the non-transfusion group. Many patients in the transfusion group had normal fibrinogen levels on admission but later displayed markedly decreased fibrinogen levels. The Japan Society of Obstetrics and Gynecology (JSOG) DIC score was significantly higher in the transfusion than in the non-transfusion group.ConclusionsIn PA-IUFD, the fibrinogen level, platelet count, D-dimer, FDP, heart rate, and JSOG DIC score on admission may indicate the need for blood transfusion. However, even with normal fibrinogen levels on admission, continuous monitoring is indispensable for identifying progressive fibrinogen reductions in patients with PA-IUFD.

What's New in Adult Reconstructive Knee Surgery.

What's New in Adult Reconstructive Knee Surgery.

Low molecular weight heparin combined with aspirin to prevent perioperative venous thromboembolism in patients with splenic rupture and lower extremity fracture

To investigate the effectiveness and safety of low molecular weight heparin combined with aspirin for perioperative prophylactic anticoagulation in patients with lower extremity fracture after splenectomy. The clinical data of 50 patients with splenic rupture combined with lower extremity fracture between January 2009 and June 2022 were retrospectively analyzed. All patients were given enoxaparin sodium at 48 hours after splenectomy, and stopped at 24 hours before fracture surgery. After fracture surgery, the patients were divided into aspirin group (group A, 15 cases), low molecular weight heparin group (group B, 16 cases), and low molecular weight heparin combined with aspirin group (group C, 19 cases) according to different anticoagulation regimens. The treatment course was 28 days. There was no significant difference in gender, age, body mass index, cause of injury, fracture site, time from injury to operation, complications, and other general data between groups ( P>0.05). The occurrence of venous thromboembolism (VTE) was observed; hemoglobin (Hb), platelet (PLT), D-D dimer, and fibrinogen degradation product (FDP) were recorded before operation and at 1, 3, and 7 days after operation, and the effect of anticoagulation regimen on coagulation function was observed. The incidences of wound complications and bleeding related complications were recorded, and the total perioperative blood loss, hidden blood loss, and overt blood loss were calculated. The incidences of VTE in groups A, B, and C were 13.33% (2/15), 12.50% (2/16), and 5.26% (1/19), respectively, and there was no significant difference between groups ( χ 2=0.770, P=0.680). There was no portal vein thrombosis and no VTE-related death in the 3 groups. There was no significant difference in the levels of Hb, PLT, D-D dimer, and FDP between groups before and after operation ( P>0.05); and there was no significant difference in total perioperative blood loss, hidden blood loss, and overt blood loss between groups ( P>0.05). No local skin necrosis was found in all patients. In group A, 1 case occurred redness and swelling of incision; in group B, 1 case had incision discharge, redness, and swelling, and 1 case had fat liquefaction; in group C, 1 case had repeated incision exudation accompanied by local tissue redness and swelling, and 1 case had local hematoma. The incidences of adverse incision in groups A, B, and C were 6.66% (1/15), 12.50% (2/16), and 11.76% (2/19), respectively, with no significant difference ( χ 2=0.302, P=0.860). There were 4 cases of bleeding related complications, including 1 case of incision ecchymosis in groups A and B respectively, with the incidence of 6.66% and 6.25%, respectively; there was 1 case of incision hematoma and 1 case of bleeding in group C, with the incidence of 11.76%; showing no significant difference in the incidence of bleeding related complications between groups ( χ 2=0.268, P=0.875). Perioperative combined use of low molecular weight heparin and aspirin for prevention of anticoagulation in patients with splenic rupture and lower extremity fracture can effectively prevent the occurrence of VTE without increasing the incidence of complications, which is an effective and safe treatment method. However, whether the incidence of VTE can be reduced needs to be further studied by expanding the sample size.

Measurement of Plasma Fibrinogen and D-dimer Levels in Sudanese Hypertensive Patients at Khartoum state

Background: Hypertension is a chronic elevation of blood pressure that, in the long-term, causes end organ damage and results in increased morbidity and mortality. Thrombosis often appears to complicate the course of patients with hypertension; thrombosis in some patients with hypertension could be developed to organ damage. The aim of this study was to measure fibrinogen and D-dimer level among sudanese patients with hypertension.&#x0D; Materials and method: This was a case control study conducted at Khartoum state, Sudan during the period from May 2022 to August 2022 to measure fibrinogen and D-dimer levels in sudanese patients with hypertension. Blood samples were collected, 50 from the patients as case group, and 50 from normal healthy subjects as control group. A total of three ml of whole blood were collected from each participant in sodium citrated tube. The fibrinogen and D-dimer level measurement was done by using coagulometer (M1 coatron) and ichroma II device respectively.&#x0D; Results: The results of this study revealed that when compared Fibrinogen level and D-dimer between cases and control group; the results revealed that fibrinogen level was significant increase in hypertensive patients with P-value of 0.000. Also, D-dimer was significant increase in hypertensive patients when compared with the results of control group, and showed significant association with P-value of 0.000. There was a negative correlation between hypertension and the gender, but the age showed positive correlation with hypertension and with D-dimer, where both fibrinogen and D-dimer showed positive correlation with the duration of hypertension.&#x0D; Conclusion: This study concluded; when compared the fibrinogen level and D- dimer between cases and control group, there was significant increase in fibrinogen and D- dimer.&#x0D; Keywords: Hypertension, fibrinogen level, D-dimer, coronary artery disease, ischemic heart disease, Cardiovascular disease, DIC, fibrin degradation products

New CMC Algorithm for Evaluation of Lupus Anticoagulant

Introduction: Lupus Anticoagulant (LA) is an autoantibody that in vitro inhibit phospholipid-dependent coagulation reactions in the absence of specific coagulation factor inhibition Primary laboratory criteria for LA detection include prolonged clotting time of a phospholipid dependent test, failure of correction on mixing study, shortening of the clotting time in the presence of high phospholipid concentrations & absence of other inhibitors. (1) According to guidelines,for diagnosing LA two tests based on different principles should be used- dRVVT(Dilute Russel's Viper Venom Time) should be the first test considered. Second test should be a sensitive aPTT (Activate Partial Thromboplastin Time).LA is a multistep procedure with screening, mixing and confirmation tests. Devreese et al recently concluded that integration of screening and confirmation in a single procedure and skipping the mixing tests result in a poor diagnostic efficacy for LA (2).LA is an in-vitro inhibitor and elevated Screening test without mixing studies does not prove inhibitor effect & it wastes time & resources to perform confirmatory tests skipping the mixing. Hence, we devised a new algorithm- Christian Medical College (CMC) Algorithm as shown in figure-1 which starts with DRVVT Screen Mix. To identify interferences due to anticoagulants like heparin and fibrin degradation products (FDP) thrombin time (TT) was also included. If Screen Mix is normal APTT Screen Mix was performed. Aim of our new algorithm was to reduce false positives and avoid interferences in LA Materials and methods: Four hundred and ninety-one (491) samples were analysed retrospectively for a period of 5 months from January 2022 to May 2022. The new algorithm was incorporated into STA R Max2 (Diagnostica Stago) analyser and automatic calculation of ratios and interpretation of results were done based on flow charts. LA testing was performed using DRVVT screen and confirm reagents (STA-Staclot DRVV Screen and STA-Staclot DRVV Confirm) and/or APTT reagent (STA-PTT Synthasil). LA test was considered positive when Screen/ Confirm(S/C) ratio was >1.2. We compared this result to the three hundred forty seven(347) samples, over a period of 4 months(September 2021 - December 2021) analyzed in old algorithm where DRVVT screen & APTT were done as the initial steps instead of DRVVT mixing studies as the 1st step. Results: In the new algorithm result were classified into 7 categories. Category 1 had normal DRVVT screen Mix and normal APTT; these represent true negative cases comprising 68.8 % of the cases. Category 2 had normal DRVVT screen Mix, prolonged APTT Screen Mix with normal TT. 1 case in this category had other Antiphosholipid Antibody (APLA) negative & repeat testing for LA was advised. Category 3 had normal DRVVT Screen mix, prolonged APTT Screen Mix with prolonged TT. There was 1 case in this category, who was on heparin, APLA antibody was negative. Repeat testing was advised at a later date. Category 4 had prolonged DRVVT Screen Mix, normal S/C ratio , with normal TT. There were 61 cases (12%) in this category among which 5 cases had normal DRVVT Screen with prolonged Mix Category 5 had Prolonged DRVVT Screen Mix, with normal S/C Ratio, prolonged TT and this category had 13 (2 %) cases. On further evaluation they were found to be on anticoagulants. Category 6 had prolonged S/C Ratio with normal TT, which are the true positive cases, n=67 (13.6%). There were 4 cases where Screen mix was more prolonged than Screen, and Screen fell below the cut off & could have been missed if mixing step was not done Category 7 had prolonged S/C ratio with prolonged TT. There were 10 cases (2%) in this category. On further evaluation 6 patients had history of anticoagulants and 2 had features of DIC. These 8 patients could represent false positive LA and would have been misclassified if TT was not done. Old algorithm had 20 % positive cases & 80 % negative cases. Since the algorithm were incorporated into STA R Max2 hands on time decreased from 240 minutes to 80 minutes. Cost of the reagents were similar by 2 algorithms. Conclusion: The new algorithm gives better clarity in classification of patients into true positive and true negative & detection of interference due to heparin as thrombin time is also done in parallel. Possible false positive cases could be identified at the onset even before repeat confirmatory lupus testing. This study concludes the importance of mixing studies in avoiding false negatives. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Early myocardial injury and coagulation activation in thoracoscopic left atrial appendage clipping.

Thoracoscopic left atrial appendage clipping as a new strategy for stroke prevention. This study was established to observe the changes in myocardial injury and coagulation during the perioperative to provide the basis for anticoagulation strategy. Fifty-two patients with nonvalvular atrial fibrillation who completed thoracoscopic left atrial appendage clipping alone and 52 matched controls with thoracoscopic lobectomy were included in the study. The changes in coagulation and myocardial enzyme during the perioperative period were compared by t-test or nonparametric test. Linear correlation analysis was performed on the trend changes of each indicator in the left atrial appendage clipping group. Compared with the control group, the postoperative cardiac troponin I level in the thoracoscopic left atrial appendage clip group was significantly higher than that before the operation; there was no significant difference in the increase of myoglobin between the two groups. In the coagulation function, there was no significant difference in the increase of fibrinogen between the two groups. Postoperative D-dimer and fibrin degradation products were significantly increased, especially the left atrial appendage clip group was significantly higher than the control group, and even showed a trend of secondary increase. Cardiac troponin I was positively correlated with C-reactive protein, fibrinogen and von Willebrand Factor activity, and the Spearman nonparametric correlation coefficients were 1, 0.829, and 0.829, respectively (all p < .05). Thoracoscopic left atrial appendage closure surgery presents early myocardial injury and activation of coagulation function. The secondary increase of coagulation index needs our attention.

Factor X Activator for Hemophilia Patients with Inhibitors: A Phase 1, First-in-Human, Multi-Center, and Open-Label Trial

Background Bleeding episodes of hemophilia A (HA) or B (HB) patients with inhibitor are difficult to control. Bypass treatment agents have been widely used as hemostatic treatment agents, which provide imperfect treatment for bleeding episodes. Non-factor replacement treatments with different mechanisms have also been explored. There are still some limitations whether in terms of complications or efficacy. Blood coagulation factor Xa (FXa) is straightforward and faster acting for boosting thrombin generation in hemophilia patients, then STSP-0601, a specific FX activator purified from the venom of Daboia Russellii siamensis was developed. Methods This is a phase I, first-in-human, multi-center, open-label, dose-escalation study to investigate the safety, immunogenicity, pharmacokinetics (PK) and pharmacodynamics (PD) of STSP-0601. This study was divided into two parts, the single-dose part (Part A) and the multiple-dose part (Part B). Both HA and HB patients with inhibitors were eligible for this study. Patients received a single intravenous injection of STSP-0601 (0.01 U/kg, 0.04 U/kg, 0.08 U/kg, 0.16 U/kg, 0.32 U/kg or 0.48 U/kg) in Part A or at a maximum six injections of STSP-0601(0.16U/kg) every four hours in Part B in non-bleeding state. This study was registered at www.clinicaltrials.gov with trial number as NCT-04747964 and NCT-05027230. Findings A total of 16 inhibitor patients were enrolled in Part A and 7 inhibitor patients enrolled in Part B. Eight (22.2%) adverse events (AE) in Part A and 18 (75%) AEs in Part B were reported to related to STSP-0601. The most common AEs were increased level of D-Dimer and fibrin and fibrinogen degradation products (FDP). All of these AEs (100%) in Part A and 94.4% (17/18) in Part B were grade 1. Neither serious adverse event (SAE) nor dose-limiting toxicity (DLT) events were reported in both Parts. The change of coagulation factor X compared with the baseline was still within 10% in single dose and 20% in multi-dose administrations. Anti-drug antibody of the administration of STSP-0601 was not detected. In Part A, STSP-0601 exhibited a linear PK profile. Maximum plasma concentration (Cmax) was 110.04±32.03 pg/mL at 0.16U/kg, 163.51±50.79 pg/mL at 0.32U/kg and 296.48±122.65 pg/mL at 0.48U/kg. The elimination half-life (t1/2) were 7.33±0.55h, 8.33±0.41h and 7.57±0.68h respectively. In Part B, the area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞) was 3342.02 h*pg/mL, and the t1/2 was 8.40 h. In Part A and B, both peak height and endogenous thrombin-generating potential (ETP) of thrombo-generation assay (TGA) increased in a dose-dependent manner and reached a maximum value 5-10min after STSP-0601 administration. After four doses of STSP-0601, the increase of TG peak height and the shortening of APTT reached the plateau stage. Compared to the baseline, the decreased value of APTT reached a maximum of 36.2% in 0.48U/kg dose cohort in Part A and 42.8% in Part B after 4 doses. Interpretation Both single and multiple injections of STSP-0601are safe and well tolerated. Starting from the single dose of 0.16 U/kg, STSP-0601 significantly improved the coagulation-related laboratory indicators. These results indicate that STSP-0601 has potential to be used as a hemostatic treatment for bleeding episodes in HA or HB patients with inhibitor.

A Retrospective Case-Control Study on the Diagnostic Values of Hemostatic Markers in Hypertensive Disorder of Pregnancy.

The purpose of this study was to evaluate the diagnostic performance of the following hemostatic markers in hypertensive disorder of pregnancy (HDP): tissue-type plasminogen activator and inhibitor-1 complex (tPAI-C), thrombomodulin, thrombin-antithrombin complex, plasmin inhibitor-plasmin complex, D-dimer, and fibrinogen degradation products. A total of 311 individuals diagnosed with HDP and 187 healthy controls (HC) of matched gestational age were admitted, including 175 subjects with gestational hypertension, 94 with mild preeclampsia, and 42 with severe preeclampsia. Compared with those of the HC group, the plasma concentrations of all the hemostatic markers continuously increased with the clinical severity of the hypertensive disorder, regardless of their statistical significance. In the receiver operating characteristic analysis, tPAI-C displayed the best discrimination performance. The tPAI-C level was consistently and significantly elevated across the different HDP groups when compared with the HC group, suggesting aggravated fibrinolysis disorder increasing with the severity of the HDP.

Correlation analysis of clinical indicators and liver failure-related prognostic score associated with prognosis in patients with amanita phalloides poisoning

To analyze and compare the clinical indicators and the liver failure-related prognostic score of patients with amanita phalloides poisoning with different prognoses, and to explore potential prognostic indicators. A retrospective case-control study was conducted. The clinical data of 52 patients with amanita phalloides poisoning admitted to the department of emergency of Xijing Hospital Affiliated to Air Force Medical University from September 2016 to September 2021 were collected, including general information (gender, age), clinical indicators at admission [mean arterial pressure (MAP), total bilirubin (TBil), aspartate transaminase (AST), alanine transaminase (ALT), albumin (ALB), serum creatinine (SCr), blood urea nitrogen (BUN), creatine kinase (CK), D-dimer, fibrinogen degradation product (FDP), prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PTA), international normalized ratio (INR), white blood cell count (WBC), platelet count (PLT)], liver failure-related prognostic score [sequential organ failure assessment (SOFA), chronic liver failure (CLIF)-SOFA score, European Foundation for the Study of Chronic Liver Failure-organ failure (CLIF-C OF)], and 28-day outcome. The clinical indicators and liver failure-related prognostic scores of the patients with different prognoses were compared. Receiver operator characteristic curve (ROC curve) was used to determine the prognostic value of statistically significant indicators between different prognosis of patients with amanita poisoning. A total of 45 patients were enrolled, of which 38 survived and 7 died within 28 days. The coagulation indicators including PT, APTT, INR, and liver failure-related prognostic scores including SOFA score, CLIF-SOFA score, and CLIF-C OF score in the patients of death group were significantly higher than those in the survival group [PT (s): 69.59±15.94 vs. 25.99±4.64, APTT (s): 83.44±17.82 vs. 42.64±3.79, INR: 6.13±1.47 vs. 2.07±0.33, SOFA score: 11.57±1.38 vs. 6.03±0.77, CLIF-SOFA score: 9.86±2.17 vs. 5.55±0.67, CLIF-C OF score: 11.71±0.97 vs. 8.37±0.35], and PLT was significantly lowered (×109/L: 80.57±29.65 vs. 169.60±11.80, all P < 0.05). ROC curves showed that coagulation indicators including PT, APTT, INR, PLT, and liver failure-related prognostic scores including SOFA score and CLIF-C OF score were associated with the prognosis of patients with amanita phalloides poisoning, with the area under the ROC curve (AUC) of > 0.75. The sensitivity of the clinical indicators was above 85%, and the AUC and specificity of INR were the highest, which were 0.88 [95% confidence interval (95%CI) was 0.74-1.00] and 83.0%, respectively; meanwhile, the sensitivity of the liver failure-related prognostic scores was 100%, and the AUC and specificity of the CLIF-C OF score were the highest, which were 0.86 (95%CI was 0.74-0.99) and 66.0%, respectively. INR and CLIF-C OF score can be used to evaluate the poor prognosis of patients with amanita phalloides poisoning.