BACKGROUND: There are significant differences in the activated partial thromboplastin time (APTT) critical values reported in different studies, most of which does not make recommendations for any specific clear detection systems. The International Council for Standardization in Hematology (ICSH) recommends that APTT critical values be established based on the reagent type, coagulation factor sensitivity and heparin response. The objective of this study was to establish APTT critical values by using different reagents and based on single coagulation factor deficiencies.
METHODS: The APTT values were determined in commercial endogenous coagulation factor-deficient plasma at concentrations of 1 IU/dL, 2 IU/dL, 5 IU/dL, 10 IU/dL, 20 IU/dL, and 30 IU/dL by using four assay systems. The retrospective collection of data from patients who lacked factor VIII (FVIII), FIX, or FXI alone was performed. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of APTT for identifying patients with an endogenous coagulation factor activity < 5 IU/dL.
RESULTS: The APTT values in the plasma samples with the same concentrations of endogenous coagulation factors were significantly different among the four assay systems (P < 0.001). The suggested critical values of APTT were 40.0 s for Sysmex CS5100 (Actin FSL), 58.0 s for Sysmex CS5100 (Actin), 51.8 s for STA-R Evolution (STA-PTTA), and 64.8 s for ACL TOP 700 (HemosIL SynthasIL). On the basis of the ROC curve, the optimal threshold values for APTT (STA-PTTA) were 55.8 s in patients with a simple deficiency of FVIII (sensitivity = 100%, specificity = 85.7%, area under the ROC curve (AUC) = 0.982), 54.3 s in patients with a simple deficiency of FIX (sensitivity = 100%, specificity = 92.9%, AUC = 0.986), and 71.7 s in patients with a simple deficiency of FXI (sensitivity = 100%, specificity = 94.1%, AUC = 0.992), which were closer (difference of 0.6-2.5 s) to the cutoff points for commercial plasma at equal factor levels.
CONCLUSIONS: APTT critical values need to be established for different reagents based on the presence of a single coagulation factor deficiency.

This study aimed to establish in vitro hemodilution and resupplementation assays for obstetric hemorrhage in pregnancy-induced hypertension (PIH) and to monitor the coagulation function dynamically using a coagulation and platelet function analyzer. Forty-seven singleton pregnant women were divided into normal (n = 24) and PIH (n = 23) groups. Peripheral blood samples were used to construct the assays, and the activated clotting time (ACT), clotting rate (CR), and platelet function index (PF) were measured. The results showed that the baseline ACT was higher in the PIH group (p < 0.01). Hemodilution assays showed decreased ACT and increased CR and PF, with ACT changes significantly lower in the PIH group (p < 0.05). CR changed most in both groups at lower dilution ratios (35% to 50%), while ACT changed most at a higher dilution ratio (75%). In the resupplementation assay, ACT exhibited the most significant response. The analyzer effectively detected differences between pregnant women with and without PIH. Thus, we need to pay more attention to the changes of ACT in the actual clinical application to assess the coagulation status of parturients.

To investigate the effect of reduced early-pregnancy activated partial thrombin time (APTT), prothrombin time (PT), and international standardized ratio (INR) on the risk of preeclampsia. A total of 8549 pregnant women with singleton births were included. Early pregnancy APTT, PT, and INR levels, with age, birth, prepregnancy body mass index, fibrinogen (FBG), thrombin time (TT), D-dimer (DD2), antithrombin III (ATIII), fibrin degradation products (FDP) as confounders, generalized linear model of APTT, the relative risk of PT and INR when INR reduction. After adequate adjustment for confounders, the relative risk of preeclampsia was 0.703 for every 1 s increase in plasma PT results in early pregnancy, and for every 0.1 increase in plasma INR results, the relative risk of preeclampsia was 0.767. With a PT less than the P25 quantile (<11 s), the relative risk of preeclampsia was 1.328. The relative risk of preeclampsia at an INR less than the P25 quantile (<0.92) was 1.24. There was no statistical association between APTT on the risk of preeclampsia. The relative risk of preeclampsia is strongly associated with a decrease in PT and INR in early pregnancy. PT and INR in early pregnancy were a potential marker in the risk stratification of preeclampsia. Focusing on reduced PT and INR levels in early pregnancy can help to identify early pregnancies at risk for preeclampsia.

暂无摘要。

BACKGROUND: Hantaan virus (HTNV), Seoul virus (SEOV) and Puumala virus (PUUV) are major serotypes of the Hantavirus, which can cause hemorrhagic fever with renal syndrome (HFRS). The pathophysiology of HFRS in humans is complex and the determinants associated with mortality, especially the coagulation and fibrinolysis disorders, are still not been fully elucidated. Severe patients usually manifest multiple complications except for acute kidney injury (AKI). The aim of this study was to observe the levels of peripheral blood routine, biochemical and coagulation parameters during the early stage, so as to find independent risk factors closely related to the prognosis, which may provide theoretical basis for targeted treatment and evaluation.
METHODS: A total of 395 HFRS patients from December 2015 to December 2018 were retrospectively enrolled. According to prognosis, they were divided into a survival group (n = 368) and a death group (n = 27). The peripheral blood routine, biochemical and coagulation parameters were compared between the two groups on admission. The relationship between the parameters mentioned above and prognosis was analyzed, and the dynamic changes of the coagulation and fibrinolysis parameters during the first week after admission were further observed.
RESULTS: In addition to AKI, liver injury was also common among the enrolled patients. Patients in the death group manifested higher levels of white blood cell counts (WBC) on admission. 27.30% (107/392) of the patients enrolled presented with disseminated intravascular coagulation (DIC) on admission and DIC is more common in the death group; The death patients manifested longer prothrombin time (PT) and activated partial thromboplastin time (APTT), higher D-dimer and fibrinogen degradation product (FDP), and lower levels of platelets (PLT) and fibrinogen (Fib) compared with those of the survival patients. The proportion of D-dimer and FDP abnormalities are higher than PT, APTT and Fib. Prolonged PT, low level of Fib and elevated total bilirubin (TBIL) on admission were considered as independent risk factors for prognosis (death).
CONCLUSIONS: Detection of PT, Fib and TBIL on admission is necessary, which might be benefit to early predicting prognosis. It is also important to pay attention to the dynamic coagulation disorders and hyperfibrinolysis during the early stage in the severe HFRS patients.

Only limited information is available about the connection between massive blood transfusion and postoperative survival rates in pediatric liver transplantation. The aim of Gordon\'s study was to examine the potential impact of perioperative transfusion on postoperative complications and death in young children receiving pediatric living-donor liver transplantation (PLDLT). The authors concluded that transfusion of a red blood cell volume higher than 27.5 mL/kg during the perioperative period is associated with a significant increase in short- and long-term postoperative morbidity and mortality after PLDLT. However, viscoelastic coagulation monitoring was not utilized in the study; instead, only conventional coagulation monitoring was conducted. Overall, the choice of blood coagulation monitoring method during blood transfusion can have a significant impact on patient prognosis. Several studies have shown that the viscoelastic coagulation testing such as thrombelastography (TEG) is highly sensitive and accurate for diagnosing coagulation dysfunction. Indeed, a TEG-guided blood transfusion strategy can improve prognosis. Moreover, postreperfusion syndrome is one of the most common complications of liver transplantation and an important factor affecting the prognosis of patients and should also be included in regression analysis.

Objective: To evaluate the clinical application performance of a domestic D-dimer assay reagent (ADX D-dimer). Methods: A total of 546 residual sodium citrate anticoagulated plasma samples (530 of which were used for comparability validation and 16 for sample preparation of other validation components) were selected after the completion of clinical testing at Peking Union Medical College Hospital from Jun 2022 to May 2023. According to the American Clinical Laboratory Standards Institute (CLSI) guidelines, national health industry standards and relevant references, the performance of ADX D-dimer used in Sysmex CS 5100 fully automated coagulation analyzer which included accuracy, precision, linear range, carryover rate, interference resistance capability and reference interval were validated and the agreement compared with two mainstream imported detection reagents (reagent A: Vidas D-dimer reagent; reagent B: Innovance D-dimer detection reagent) was evaluated. The clinical diagnostic efficacy of the ADX D-dimer was evaluated using the ELISA D-dimer (reagent A) test results as criteria. Results: The linear correlation coefficient of the 6-point calibrated absorbance and target value was 0.998, the bias of accuracy met the requirements (-2.8%-8.4%), and the coefficient of variation (CV) of within-run and between-day precision of the two levels were 1.0%-2.7% and 2.7%-4.1%, respectively, which were less than the requirements of the manufacturer\'s statement and the national health industry standard. The linear range within 0.33-9.69 mg/L FEU was verified and the carryover rate was 0. There was no significant interference with the assay results at bilirubin F≤0.22 g/L, bilirubin C≤0.22 g/L, hemoglobin≤5.5 g/L and celiac≤2 800 FTU. The manufacturer\'s reference interval≤0.5 mg/L FEU was verified suitable for this laboratory. For 358 samples without suspicious heterophilic antibody whose D-dimer levels range from 0.06 to143.63 mg/L FEU, the correlation between ADX D-dimer and another two assay was good, with r values being 0.968 and 0.975, respectively, the percentage of deviation and relative deviation beyond the 95% confidence interval was 3.4%-4.5% and 5.3%-7.0%. The correlation between ADX D-dimer and ELISA D-dimer was better than that of reagent B in the concentration range of 0.06-1.00 mg/L FEU (r=0.858, 0.134). For 172 samples with heterophilic antibody, the correlation between ADX D-dimer and ELISA D-dimer was still good(r=0.827), with the percentage of deviation and relative deviation being 6.4% (11/172). The diagnostic efficacy was evaluated using 530 samples, and the sensitivity, specificity, positive predictive value, negative predictive value of ADX D-dimer was 97.4%, 77.6%, 91.9%, 91.9%. The area under the curve was 0.976 (95%CI: 0.964-0.987, P<0.001). Conclusion: The ADX D-dimer reagent has superior assay and diagnostic performance, and can meet the needs of clinical laboratories.
目的： 对一种国产D-二聚体检测试剂（ADX D-二聚体）的临床应用性能进行评价。 方法： 选取2022年6月至2023年5月北京协和医院就诊完成临床检测后的柠檬酸钠抗凝血浆标本546份（其中530份用于可比性验证，16份用于其他验证），根据美国临床和实验室标准协会（CLSI）指南、国家卫生行业标准和相关参考文献，分别对其在Sysmex CS 5100全自动凝血分析仪上的准确度、精密度、线性范围、携带污染率、抗干扰能力和参考区间进行验证，并与两种进口检测试剂（试剂A：Vidas D-dimer试剂；试剂B：Innovance D-二聚体检测试剂）的配套检测系统进行结果比对。以ELISA（试剂A）D-二聚体检测结果为金标准，对ADX D-二聚体检测试剂的临床诊断效能进行评估。 结果： 6点定标吸光度与靶值的线性相关系数为0.998，准确度偏倚为-2.8%~8.4%，满足≤10%的要求。两水平批内精密度和日间精密度变异系数（CV）分别为1.0%~2.7%和2.7%~4.1%，均小于厂家声明和国家卫生行业标准的要求。在0.33~9.69 mg/L［纤维蛋白原等量单位（FEU）］内线性范围验证通过；携带污染率为0；胆红素F≤0.22 g/L、胆红素C≤0.22 g/L、血红蛋白≤5.5 g/L和乳糜≤2 800 FTU时对检测结果无明显干扰。厂家声明的参考区间≤0.5 mg/L FEU验证通过，适用于本实验室。358份不含异嗜性抗体的样本，D-二聚体水平在0.06~143.63 mg/L FEU浓度范围，ADX D-二聚体检测试剂与试剂A和试剂B间检测结果的相关性好，r值分别为0.968、0.975，可比性偏差和百分偏差超出95%CI的结果比例分别为3.4%~4.5%和5.3%~7.0%。其中132份样本的D-二聚体水平在0.06~1.00 mg/L FEU浓度范围，ADX D-二聚体试剂与ELISA 法（试剂A）检测结果的相关性优于与试剂B检测结果的相关性（r=0.858、0.134）。172份疑似存在抗体干扰的样本，ADX D-二聚体试剂与ELISA 法（试剂A）检测结果的相关性仍较好（r=0.827），可比性偏差和百分偏差超出95%CI的结果比例为6.4%（11/172）。以530份样本的检测结果进行临床诊断效能评价，cut-off值为0.5 mg/L FEU时，ADX D-二聚体试剂的诊断灵敏度为97.4%，特异度为77.6%，阳性预测值为91.9%，阴性预测值为91.9%，曲线下面积为0.976（95%CI：0.964~0.987，P<0.001）。 结论： ADX D-二聚体试剂具有良好的检测性能，能够满足临床实验室的使用需求。.

OBJECTIVE: To explore the predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome.
METHODS: A total of 121 antiphospholipid syndrome (APS) patients who hospitalized at Peking University People\'s Hospital from March 2022 to January 2023 were selected and divided into thrombus group (50 cases) and nonthrombus group (71 cases) according to whether thrombosis occurred. The differences of laboratory characteristics including antiphospholipid antibodies were compared between the thrombotic and non-thrombotic groups. Chemiluminescent immunoassay was used to detect thrombomodulin (TM), thrombin-antithrombin complex (TAT), Plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator inhibitor complex (t-PAIC) in plasma from venous. The independent risk factors of thrombosis in patients with APS were determined using binary Logistic regression. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the efficacy of each index on the prediction of thrombosis.
RESULTS: Compared with the patients without thrombosis, the patients with thrombosis were older [49 (32, 64) years vs. 36 (32, 39) years, P < 0.05]. The percentages of male, smoking, hypertension, and global antiphospholipid syndrome score (GAPSS)≥10 in the patients with thrombosis were significantly higher than those in the patients without thrombosis (P < 0.05). The positive rates of anticardiolipin antibody (aCL) and lupus anticoagulant (LA) in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05), and the levels of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation product in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05).Among the thrombosis group, venous thrombosis accounted for 19 (38.00%), including deep vein thrombosis (16, 84.21%) and pulmonary embolism accounted (5, 26.32%); Arterial thrombosis accounted for 35 (70.00%), including myocardial infarction (6, 17.14%) cerebral infarction (30, 85.71%). The patients in the thrombotic group had significantly greater TM levels than those in the non-thrombotic group (P < 0.05).There were no significant dif-ferences between the two groups in TAT (Z=-1.420, P=0.156), PIC (Z=-0.064, P=0.949), and t-PAIC (Z=-1.487, P=0.137). Univariate and binary Logistic regression analysis of relevant variables showed that advanced age [OR=1.126, P=0.002], elevated TM [OR=1.325, P=0.048], prolonged prothrombin time (PT) [OR=4.127, P=0.008] were independent risk factors for thrombosis in the patients with APS. ROC curve analysis of the above three independent risk factors showed that the combined detection of age, PT and TM had the highest Yoden index (0.727) and sensitivity (83.0%), with a specificity of 89.7%.
CONCLUSIONS: TAT, PIC, TM, and t-PAIC may reflect thrombus formation from the coagulation system, fibrinolysis system, and endothelial system. The combined of age TM and PT is superior to the application of a single marker, which has diagnostic value for the early identification of APS thrombosis.

OBJECTIVE: To analyze the results of activated partial thromboplastin time (APTT) mixing test in coagulation factor Ⅷ inhibitor-positive hemophilia patients, so as to increase the value of APTT mixing test in the screen of factor Ⅷ inhibitor.
METHODS: Eighty plasmas samples with different titers of coagulation factor Ⅷ inhibitors had been collected and diluted for routine immediate APTT mixing test and at 37 ℃ 2 hours incubation APTT mixing test. Fifteen samples were selected for immediate and normal temperature incubation for 15 min, 30min, 1 hour, 2 hours and 37 ℃ for 30 min, 1 hour, 2 hours APTT mixing test.
RESULTS: The results of APTT mixing test were significantly correlated with the titers of coagulation factor Ⅷ inhibitors. The ROC curve result showed that the best diagnostic cut-off value for 2 hours incubation APTT mixing test at 37 ℃ to determine the presence or absence of coagulation factor Ⅷ inhibitors was 43.8 s (sensitivity and specificity was 85.90% and 100%, respectively), while the best diagnostic cut-off value for distinguishing high-titer and low-titer Ⅷ inhibitors was 52.4 s (sensitivity and specificity was 98.18% and 95.65%, respectively). The critical coagulation factor Ⅷ inhibitor titer that could not be corrected by immediate APTT was 5.14 BU/ml, while that could not be corrected by 37 ℃ 2 hours incubation APTT was 1.31 BU/ml. Paired samples t -test was performed on the APTT mixing test results at different times and temperatures, and the differences were statistically significant (P < 0.05).
CONCLUSIONS: The APTT mixing test can be used as a screening index for coagulation factor Ⅷ inhibitors. APTT mixing test result shows a significant time-temperature dependence with lower titers of coagulation factor Ⅷ inhibitor. Patients with hemophilia who cannot be corrected by immediate APTT mixing test should be alert to the possibility of high titer of coagulation factor Ⅷ.
UNASSIGNED: 凝血因子Ⅷ抑制物阳性血友病患者APTT纠正试验结果分析.
UNASSIGNED: 分析凝血因子Ⅷ抑制物阳性血友病患者APTT纠正试验结果，提高APTT纠正试验在凝血因子Ⅷ抑制物筛查中的价值。.
UNASSIGNED: 收集并稀释制备不同滴度凝血因子Ⅷ抑制物血浆80份进行常规的即刻及37 ℃孵育2 h APTT纠正试验，选取15份样本进行即刻和常温孵育15 min、30 min、1和2 h及37 ℃孵育30 min、1和2 h APTT纠正试验。.
UNASSIGNED: APTT纠正试验结果与凝血因子Ⅷ抑制物滴度呈明显的相关性，ROC曲线下37 ℃孵育2 h APTT纠正试验判断有无凝血因子Ⅷ抑制物最佳诊断界点是43.8 s（敏感度85.90%，特异度100%），区分高滴度与低滴度Ⅷ抑制物的最佳诊断界点为52.4 s（敏感度98.18%，特异度95.65%）。即刻APTT无法纠正的临界凝血因子Ⅷ抑制物滴度为5.14 BU/ml，37 ℃孵育2 h APTT不能纠正对应的凝血因子Ⅷ抑制物的滴度为1.31 BU/ml。对不同时间和温度下APTT纠正试验结果进行配对t 检验，差异有统计学意义（P <0.05）。.
UNASSIGNED: APTT纠正试验结果可作为凝血因子Ⅷ抑制物的筛查指标，较低Ⅷ抑制物滴度时呈明显的对温度-时间的依赖性，血友病患者即刻APTT无法纠正则应警惕较高滴度凝血因子Ⅷ抑制物存在的可能。.

In recent years, exciting developments in disease modifying treatments for Alzheimer\'s disease (AD) have made accurate and timely diagnosis of this disease a priority. Blood biomarkers (BBMs) for amyloid pathology using improved immunoassay and mass spectrometry techniques have been an area of intense research for the last 10 years and are coming to the fore, as a real prospect to be used in the clinical diagnostics of the disease.
The following review will update and discuss blood biomarkers that will be most useful in diagnosing AD and the context necessary for their implementation.
It is clear we now have BBMs, and technology to measure them, that are capable of detecting amyloid pathology in AD. The challenge is to validate them across platforms and populations to incorporate them into clinical practice. It is important that implementation comes with education, we need to give clinicians the tools for appropriate use and interpretation. It is feasible that BBMs will be used to screen populations, initially for clinical trial entry but also therapeutic intervention in the foreseeable future. We now need to focus BBM research on other pathologies to ensure we accelerate the development of therapeutics for all neurodegenerative diseases.