Natural and synthetic colorants present in food can modulate hemostasis, which includes the coagulation process and blood platelet activation. Some colorants have cardioprotective activity as well. However, the effect of genipin (a natural blue colorant) and synthetic blue colorants (including patent blue V and brilliant blue FCF) on hemostasis is not clear. In this study, we aimed to investigate the effects of three blue colorants-genipin, patent blue V, and brilliant blue FCF-on selected parameters of hemostasis in vitro. The anti- or pro-coagulant potential was assessed in human plasma by measuring the following coagulation times: thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT). Moreover, we used the Total Thrombus formation Analysis System (T-TAS, PL-chip) to evaluate the anti-platelet potential of the colorants in whole blood. We also measured their effect on the adhesion of washed blood platelets to fibrinogen and collagen. Lastly, the cytotoxicity of the colorants against blood platelets was assessed based on the activity of extracellular lactate dehydrogenase (LDH). We observed that genipin (at all concentrations (1-200 µM)) did not have a significant effect on the coagulation times (PT, APTT, and TT). However, genipin at the highest concentration (200 µM) and patent blue V at the concentrations of 1 and 10 µM significantly prolonged the time of occlusion measured using the T-TAS, which demonstrated their anti-platelet activity. We also observed that genipin decreased the adhesion of platelets to fibrinogen and collagen. Only patent blue V and brilliant blue FCF significantly shortened the APTT (at the concentration of 10 µM) and TT (at concentrations of 1 and 10 µM), demonstrating pro-coagulant activity. These synthetic blue colorants also modulated the process of human blood platelet adhesion, stimulating the adhesion to fibrinogen and inhibiting the adhesion to collagen. The results demonstrate that genipin is not toxic. In addition, because of its ability to reduce blood platelet activation, genipin holds promise as a novel and valuable agent that improves the health of the cardiovascular system and reduces the risk of cardiovascular diseases. However, the mechanism of its anti-platelet activity remains unclear and requires further studies. Its in vivo activity and interaction with various anti-coagulant and anti-thrombotic drugs, including aspirin and its derivatives, should be examined as well.

BACKGROUND: Endometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV.
METHODS: This retrospective case-control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann-Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve.
RESULTS: The time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717-0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578-0.697), 0.71 (95% confidence interval: 0.656-0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862-0.927) with sensitivity of 88.9% and specificity of 77.7%.
CONCLUSIONS: In the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.

OBJECTIVE: To analyze the clinical phenotype and gene mutation of a genetic coagulation factor XII (FXII) deficiency pedigree and explore the molecular pathogenesis.
METHODS: The activated partial thromboplastin time (APTT) and FXII activity (FXII:C) were detected by clotting method. The FXII antigen (FXII:Ag) was tested with ELISA. All exons and flanks of F12 gene were determined by Sanger sequencing. ClustalX-2.1-win, PROVEAN and Swiss-Pdb Viewer software were used to analyze the conservatism of amino acids at the mutant site, forecast whether the mutant amino acids were harmful and confirm the influence of the mutation on protein structure.
RESULTS: The APTT of the proband prolonged to 71.3 s. The FXII:C and FXII:Ag were decreased to 5% and 6%, respectively. There were two heterozygous missense mutations c.580G>T and c.1681G>A detected in exon 7 and exon 14 of F12 gene, resulting in p.Gly175Cys and p.Gly542Ser, severally. Proband\'s father carried the p.Gly175Cys heterozygous mutation, while mother, brother and daughter had the p.Gly542Ser heterozygous mutation. Software analysis showed that both Gly175 and Gly542 were conserved, the two mutations were harmful and when mutations had occurred, the corresponding sites affected the protein local structure.
CONCLUSIONS: The p.Gly175Cys and p.Gly542Ser compound heterozygous mutations are the molecular pathogenesis of the hereditary coagulation FXII deficiency pedigree. The p.Gly175Cys mutation has been detected for the first time in the world.
UNASSIGNED: F12基因p.Gly175Cys和p.Gly542Ser复合杂合突变导致的遗传性凝血因子Ⅻ缺陷症的家系分析.
UNASSIGNED: 分析1例遗传性凝血因子Ⅻ（FⅫ）缺陷症家系的临床表型和基因突变情况，并探讨其分子致病机制。.
UNASSIGNED: 凝固法检测活化部分凝血活酶时间和FⅫ活性 ；ELISA方法检测FⅫ抗原；Sanger测序法测定F12基因所有外显子及侧翼序列；ClustalX-2.1-win、PROVEAN及Swiss-Pdb Viewer软件分析突变位点氨基酸的保守性、突变氨基酸是否为有害突变及该位点发生突变后对蛋白质结构的影响。.
UNASSIGNED: 先证者活化部分凝血活酶时间延长为71.3 s，FⅫ活性和FⅫ抗原分别降低为5%和6%；其F12基因第7和14外显子分别存在c.580G>T和c.1681G>A杂合错义突变，导致p.Gly175Cys和p.Gly542Ser；先证者父亲携带p.Gly175Cys杂合错义突变；先证者母亲、弟弟和女儿携带p.Gly542Ser杂合错义突变。软件分析结果表明Gly175和Gly542均保守，p.Gly175Cys和p.Gly542Ser为有害突变，突变发生后相应位点会对蛋白质局部结构产生影响。.
UNASSIGNED: p.Gly175Cys和p.Gly542Ser复合杂合突变是先证者家系遗传性FⅫ缺陷症的分子发病机制，其中p.Gly175Cys为国际上首次发现的新突变。.

OBJECTIVE: To evaluate the clinical and prognostic value of prothrombin time (PT) and activated partial thromboplastin time (APTT) in newly diagnosed patients with multiple myeloma (MM).
METHODS: The clinical data of 116 newly diagnosed MM patients in the Second Hospital and Third Hospital of Shanxi Medical University from October 2014 to March 2022 were analyzed retrospectively, and the patients were divided into two groups: normal PT and APTT group and prolonged PT or APTT group. The differences in sex, age, classification, staging, bleeding events, laboratory indicators [including hemoglobin (Hb), platelet count (PLT), serum calcium, serum albumin (ALB), lactate dehydrogenase (LDH), serum creatinine and β2-microglobulin], and cytogenetic characteristics between the two groups of patients were compared. The effect of prolonged PT or APTT on survival of patients with MM was analyzed.
RESULTS: Compared with patients in normal PT and APTT group, patients in prolonged PT or APTT group were more likely to experience bleeding events (χ2=5.087, P =0.024), with lower ALB levels (χ2=4.962, P =0.026) and PLT levels (χ2=4.309, P =0.038), and higher serum calcium levels (χ2=5.056, P =0.025). The positive rates of del17p, del13q and 1q21+ in prolonged PT or APTT group were higher than those in normal PT and APTT group, but the difference was not statistically significant (P >0.05). K-M survival analysis showed that the prolonged PT or APTT group had a shorter median progression-free survival (PFS) (P =0.032) and overall survival (OS) (P =0.032). Multivariate Cox analysis showed that prolonged PT or APTT (HR=2.116, 95%CI :1.025-4.372, P =0.043) and age ≥65 years (HR=2.403, 95%CI : 1.195-4.836, P =0.014) were independent risk factor for OS in newly diagnosed MM patients. However, prolonged PT or APTT had no significant effect on PFS of newly diagnosed MM patients (HR=1.162, 95%CI : 0.666-2.026, P =0.597).
CONCLUSIONS: Newly diagnosed MM patients with prolonged PT or APTT have worse clinical indicators, shorter PFS and OS. Prolonged PT or APTT is an independent risk factor for OS in MM patients.
UNASSIGNED: 凝血酶原时间和活化部分凝血活酶时间在初诊多发性骨髓瘤患者中的预后价值.
UNASSIGNED: 评估凝血酶原时间（PT）和活化部分凝血活酶时间（APTT）在初诊多发性骨髓瘤（MM）患者中的临床及预后价值。.
UNASSIGNED: 回顾性分析2014年10月至2022年3月在山西医科大学第二医院和第三医院血液科就诊的116例初诊MM患者的临床资料，并将患者分为PT和APTT正常组及PT或APTT延长组。比较两组患者在性别、年龄、分型、分期、出血事件、实验室指标[血红蛋白（Hb）、血小板计数（PLT）、血钙、血清白蛋白（ALB）、乳酸脱氢酶（LDH）、β2-微球蛋白、肌酐）]、细胞遗传学特征等方面的差异，分析PT或APTT延长对MM患者生存的影响。.
UNASSIGNED: 与PT和APTT正常组相比，PT或APTT延长组更容易发生出血事件（χ2=5.087，P =0.024）、具有更低的ALB水平（χ2=4.962，P =0.026）和PLT水平（χ2=4.309，P =0.038），以及更高的血钙水平（χ2=5.056，P =0.025）。PT或APTT延长组del13q、1q21扩增、del17p阳性率高于PT和APTT正常组，但差异无统计学意义（P >0.05）。K-M生存分析显示，PT或APTT延长组具有更短的中位无进展生存期（PFS）（P =0.032）和总生存期（OS）（P =0.032）；多因素Cox分析结果显示，PT或APTT延长（HR=2.116，95%CI : 1.025-4.372，P =0.043）、年龄≥65岁（HR=2.403，95%CI : 1.195-4.836，P =0.014）是影响初诊MM患者OS的独立危险因素；但PT或APTT延长对初诊MM患者的PFS没有明显影 响（HR=1.162，95%CI : 0.666-2.026，P =0.597）。.
UNASSIGNED: PT或APTT延长的初诊MM患者具有更恶化的临床指标、更短的PFS和OS；PT或APTT延长是影响MM患者OS的独立危险因素。.

UNASSIGNED: Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. In this study, analyses of activated partial thromboplastin time in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identifying synergistic anticoagulation effects. Both an FeCl 3 -induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.

Coagulopathy development in traumatic brain injury (TBI) is among the significant complications that can negatively affect the clinical course and outcome of TBI patients. Timely identification of this complication is of utmost importance in the acute clinical setting. We reviewed TBI patients admitted to our trauma center from 2015 to 2021. Demographic data, mechanism of injury, findings on admission, imaging studies, procedures during hospitalization, and functional outcomes were gathered. INR with a cutoff of 1.3, platelet count less than 100 × 10⁹/L, or partial thromboplastin time greater than 40s were utilized as the markers of coagulopathy. A total of 4002 patients were included. Coagulopathy occurred in 38.1% of the patients. Age of the patients (Odds Ratio (OR) = 0.993, 95% Confidence Interval (CI) = 0.986-0.999, p = 0.028), systolic blood pressure (OR = 0.993, 95% CI = 0.989-0.998, p = 0.005), fibrinogen level (OR = 0.998, 95% CI = 0.996-0.999, p < 0.001), and hemoglobin level (OR = 0.886, 95% CI = 0.839-0.936, p < 0.001) were independently associated with coagulopathy. Furthermore, coagulopathy was independently associated with higher mortality rates and longer ICU stays. Coagulopathy had the most substantial effect on mortality of TBI patients (OR = 2.6, 95% CI = 2.1-3.3, p < 0.001), compared to other admission clinical characteristics independently associated with mortality such as fixed pupillary light reflex (OR = 1.8, 95% CI = 1.5-2.4, p < 0.001), GCS (OR = 0.91, 95% CI = 0.88-0.94, p < 0.001), and hemoglobin level (OR = 0.93, 95% CI = 0.88-0.98, p = 0.004). Early coagulopathy in TBI patients can lead to higher mortality rates. Future studies are needed to prove that early detection and correction of coagulopathy and modifiable risk factors may help improve outcomes of TBI patients.

We studied the effectiveness of Xe/O2 mixture inhalation (30% Xe and 70% O2, 20 min for 5 days) in a model of experimental thromboplastin pneumonitis. Inhalation of the studied mixture decreased the intensity of the inflammatory process in the lung tissue assessed by the temperature response of animals, changed lung weight and lung weight coefficient. At acute stage of pneumonitis, an increase in xenon consumption was recorded due to its retention in the gas exchange zone and a natural decrease in oxygen consumption due to partial alveolar/capillary block. The formation of pneumonitis was accompanied by a pronounced procoagulant shift in the regulation system of the aggregate state of blood. The Xe/O2 inhalations ensured physiologically optimal levels of prothrombin and activated partial thromboplastin time against the background of a moderate decrease in fibrinogen level throughout the experiment. At the same time, the activity of the natural anticoagulant antithrombin III increased from day 5 to day 14.

Data on the pathophysiological mechanisms of hemostatic alterations in the thrombotic events that occur during Ramadan intermittent fasting (RIF), particularly in the natural coagulation inhibitors, are very limited. Thus, our objective was to evaluate the effect of RIF on the natural anticoagulants level, antithrombin, protein C, and total and free protein S (PS) in healthy participants. Participants were divided into two groups. Group I consisted of 29 healthy fasting participants whose blood samples were taken after 20 days of fasting. Group II included 40 healthy non-fasting participants whose blood samples were taken 2-4 weeks before the month of Ramadan. Coagulation screening tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and plasma fibrinogen level, natural anticoagulants; antithrombin, protein C, free and total PS and C4 binding protein (C4BP) levels were evaluated in the two groups. High levels of total and free PS without change in antithrombin, protein C, and C4BP levels were noted in the fasting group as compared with non-fasting ones (p < 0.05). PT and APTT showed no difference between the two groups. However, the fibrinogen level was higher in the fasting group. In conclusion, RIF was found to be associated with improved anticoagulant activity in healthy participants, which may provide temporal physiological protection against the development of thrombosis in healthy fasting people.

BACKGROUND: Coronavirus 2019 symptoms include coagulopathy and thromboembolic risk. Using one parameter to diagnose coagulopathy has little predictive value.
OBJECTIVE: This study will examine if D-dimer and APTT testing can predict COVID-19 severity and aid triage and manage patients.
METHODS: 214 COVID-19 patients were enrolled and classified into two categories based on their respiratory manifestations; mild (126 cases) and severe (88 cases). Patient data regarding age, gender, D-Dimer level, and APTT level were collected. When both D-Dimer and APTT levels were abnormal, in this study, the patient was considered to have a coagulation disorder. Indicators of coagulation in the COVID-19 patients were collected and compared between the two groups. Chi-square (χ2) tests were used to determine the significant differences between coagulation disorders in the two groups.
RESULTS: Our findings showed that patients with coagulopathies were more likely to belong to the severe group. Within the two groups of patients, the rate of coagulation disorders was as follows: mild = 8.8 % within coagulation disorders, 4.8% within the two Groups; severe = 91.2 % within coagulation disorders, 77.8 % within the two Groups. There was a statistically significant relationship between coagulation disorder and severe COVID-19 patients compared to mild patients (p < 0.05).
CONCLUSIONS: Coagulation disorders are more likely to occur in severe COVID-19 patients. D-Dimer and APTT tests are significant indicators for predicting COVID-19 severity. Our research found an abnormal pattern of coagulation disorders and COVID-19 severity that should be considered in the COVID-19 treatment protocol.

OBJECTIVE: Preeclampsia, a pregnancy complication associated with significant maternal and perinatal mortality and morbidity, has been found to be closely linked to dysfunction in the blood coagulation-fibrinolysis system. However, the relationship between hematologic data and severity and onset time of preeclampsia remains unclear. This study aimed to identify specific hematologic parameters in both preeclamptic and normotensive pregnant women and determine their potential significance in the pathogenesis of preeclampsia.
METHODS: A total of 112 patients with gestational hypertension disease were divided into two groups: early-onset preeclampsia (32 cases) and late-onset preeclampsia (80 cases). A control group of 82 normotensive pregnant women matched for age and parity was also selected. Blood samples were collected from all participants to test for specific hematologic parameters.
RESULTS: Mild and severe preeclampsia were associated with lower hemoglobin level (P = 0.01 and P = 0.03, respectively), higher mean platelet volume (P = 0.01 and P = 0.01, respectively) and fibrinogen (P = 0.01 and P = 0.01, respectively), and shorter prothrombin time (P = 0.02 and P = 0.01, respectively) and activated partial thromboplastin time (P = 0.01 and P = 0.02, respectively).
CONCLUSIONS: These findings have provided evidence on the hematologic coagulative actors in the pathogenesis and severity of preeclampsia.