Point-of-care blood coagulation assay enabled by printed circuit board-based digital microfluidics

The monitoring of coagulation function has great implications in many clinical settings. However, existing coagulation assays are simplex, sample-consuming, and slow in turnaround, making them less suitable for point-of-care testing....

Clinical Efficacy of Conventional Heparin Anticoagulation Combined with Apixaban in the Treatment of Patients with Cerebral Venous Thrombosis and Its Effect on Serum D-Dimer and FIB Expression

Objective. The aim of this study was to explore the clinical efficacy of conventional heparin anticoagulation in combination with apixaban in the treatment of patients with cerebral venous thrombosis (CVT) and its influence on serum D-dimer (D-D) and fibrinogen (FIB). Methods. One hundred and fifty-seven consecutive CVT patients admitted to our hospital from January 1, 2006, to December 31, 2013, were allocated into two groups according to the different treatment methods, of which 95 cases received standard anticoagulation therapy (standard group (SG)) and the remaining 62 cases were given apixaban therapy (research group (RG)). The curative effects and the changes of coagulation function during the treatment, as well as the incidence of adverse reactions, were analyzed in the two groups. The changes of D-D and FIB levels before treatment and at days 1, 4, and 7 posttreatment were detected. Results. In treatment efficacy, RG was superior to SG. No evident difference was observed in the incidence of adverse events or coagulation function between the two groups. At day 1 posttreatment, D-D level was increased largely in both SG and RG, but the increase was much more significant in RG. However, D-D level was decreased gradually with time in both groups, and the reduction was more notable in RG. The FIB level in SG declined gradually with time after treatment and was higher than that in RG at the same time point. In RG, FIB was decreased gradually at day 1 and day 4 posttreatment, and its level at day 7 posttreatment showed no difference compared with that at day 4 posttreatment. Spearman’s analysis identified that the higher the D-D level or the lower the FIB level at day 1 posttreatment was, the better the treatment efficacy was. After seven-day treatment, the lower the level of D-D and FIB was, the better the therapeutic effect was. Logistic analysis indicated that age, time of diagnosis, deep vein thrombosis (DVT), Glasgow Coma Scale (GCS) score, infection, Apixaban, D-D, and FIB all independently affect the treatment effect of patients. Conclusions. The combined use of Apixaban with heparin is high-performing and safe in the treatment of CVT. The changes of D-D and FIB levels during the treatment are strongly linked to the therapeutic effect, which can be used as plausible evaluation indexes for the efficacy of CVT.

Effect of Massive Transfusion Protocol on Coagulation Function in Elderly Patients with Multiple Injuries

Objective. To evaluate the effect of massive transfusion protocol on coagulation function in elderly patients with multiple injuries. Methods. In this retrospective cohort study, clinical data were collected from a total of 94 elderly patients with multiple injuries, including 44 cases who received routine transfusion protocol (control group) and 50 cases who concurrently received massive transfusion protocol in our hospital (research group). The changes in platelet parameters, coagulation function, and organ dysfunction scores at admission and 24 h after transfusion were compared between the two groups. The 24-hour plasma and red blood cell transfusion volume, length of stay, complications, and mortality of the two groups were analyzed statistically. Results. Twenty-four hours after blood transfusion, the hematocrit, platelets, and hemoglobin in the research group were higher than those in the control group, while the activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen, and scores of Marshall scoring system and Sequential Organ Failure Assessment were lower than those in the control group ( P < 0.01 ). The 24-hour plasma transfusion volume was higher, and the length of intensive care unit (ICU) stay and total length of stay were lower in the research group compared with the control group ( P < 0.01 ). No significant difference was found in the mortality rate between the research group and the control group (10.00% vs. 13.64%, P > 0.05 ). The incidence of complications in the research group was lower than that in the control group (12.00% vs. 31.82%, P < 0.05 ). Conclusion. Massive transfusion protocol for elderly patients with multiple injuries can improve their coagulation function and platelet parameters, alleviate organ dysfunction, shorten length of ICU stay, and decrease the incidence of complications, which is conducive to improving the prognosis of patients.

D-DIMER AS A POTENTIAL BIOMARKER OF COVID-19 DISEASE SEVERITY

Было продемонстрировано, что аномальная функция коагуляции участвует в прогрессировании COVID-19. Однако связь между уровнем D-димера и тяжестью COVID-19 не ясна. Исследование было направлено на изучение связи между уровнями D-димера и тяжестью COVID-19 на основе литературного обзора. Мы провели поиск в базах данных PubMed, Embase, Cochrane Library и Scopus до октября 2021 года. Изменения в уровнях D-димера и тенденции после антикоагуляции являются высокопрогнозирующими факторами внутрибольничной смертности и могут помочь в распределении ресурсов и будущих исследованиях новых методов лечения тяжелой формы COVID-19. It has been demonstrated that abnormal coagulation function is involved in the progression of COVID-19. However, the relationship between D-dimer levels and the severity of COVID-19 is not clear. The study aimed to investigate the relationship between D-dimer levels and the severity of COVID-19 based on a literature review. We searched PubMed, Embase, Cochrane Library and Scopus until October 2021. Changes in D-dimer levels and trends after anticoagulation are highly predictive factors for inhospital mortality and may aid resource allocation and future research into new treatments for severe COVID-19.

Clinical Manifestations and Maternal and Infant Outcomes of Pregnancy Complicated with Thrombocytopenia

Objective: To explore the clinical manifestations as well as maternal and infant outcomes of pregnancy complicated with thrombocytopenia. Methods: A total of 478 pregnant women with thrombocytopenia, treated in Shaanxi Provincial People’s Hospital from July 2019 to June 2021, were selected as the research group, while 200 normal pregnant women, treated during the same period, were selected as the control group to analyze gestational thrombocytopenia (GT), idiopathic thrombocytopenic purpura (ITP), pregnancy-induced hypertension (PIH), adverse maternal and infant outcomes, etc. Results: Among the 478 patients in the research group, the main causes of pregnancy complicated with thrombocytopenia were GT, ITP, and PIH, accounting for 75.51%, 6.49%, and 8.79%, respectively, while other causes accounted for 9.21%. There was no significant difference between the research group and the control group in the amount of intrapartum bleeding, premature delivery, stillbirth, thrombocytopenia, and neonatal asphyxia, but there was significant difference in the mode of delivery (P < 0.05). Conclusion: The traditional indexes of coagulation function are not abnormal with decreased platelets in pregnant women with thrombocytopenia, but the indexes of thromboelasticity are abnormal and can reflect the changes of coagulation function. The cesarean section rate of patients with thrombocytopenia in pregnancy increases with the decrease of platelet count, but the mode of delivery should be determined in consideration of specific conditions.

High Perceived Stress May Shorten Activated Partial Thromboplastin Time and Lead to Worse Clinical Outcomes in Patients With Coronary Heart Disease

Objective: To determine the association of perceived stress with coagulation function and their predictive values for clinical outcomes.Methods: This prospective cohort study derived from a cross-sectional study for investigating the psychological status of inpatients with suspicious coronary heart disease (CHD). In this study, the 10-item Perceived Stress Scale (PSS-10) as an optional questionnaire was used to assess the severity of perceived stress. Coagulation function tests, such as activated partial thromboplastin time (APTT), prothrombin time (PT), and fibrinogen were measured within 1 h after admission. Furthermore, 241 patients with CHD out of 705 consecutive inpatients were included in the analyses and followed with a median of 26 months for the clinical outcomes.Results: The patients in high perceived stress status (PSS-10 score &gt; 16) were with shorter APTT (36.71 vs. 38.45 s, p = 0.009). Shortened APTT ( ≤ 35.0 s) correlated with higher PSS-10 score (14.67 vs. 11.22, p = 0.003). The association of APTT with depression or anxiety was not found. Multiple linear models adjusting for PT estimated that every single point increase in PSS-10 was relevant to approximately 0.13 s decrease in APTT (p = 0.001) regardless of the type of CHD. APTT (every 5 s increase: hazard ratio (HR) 0.68 [0.47–0.99], p = 0.041) and perceived stress (every 5 points increase: HR 1.31 [1.09–1.58], p = 0.005) could predict the cardiovascular outcomes. However, both predictive values would decrease when they were simultaneously adjusted. After adjusting for the physical clinical features, the associated of perceived stress on cardiac (HR 1.25 [1.04–1.51], p = 0.020) and composite clinical outcomes (HR 1.24 [1.05–1.47], p = 0.011) persisted.Conclusions: For the patients with CHD, perceived stress strongly correlates with APTT. The activation of the intrinsic coagulation pathway is one of the mechanisms that high perceived stress causes cardiovascular events. This hints at an important role of the interaction of mental stress and coagulation function on cardiovascular prognosis. More attention needs to be paid to the patients with CHD with high perceived stress.

Effect of Low-Frequency Electric Pulse Technique Combined with Carboprost Methylate Suppositories on Recovery of Gastrointestinal Function and Postoperative Complications of Patients with Scarred Uterus Undergoing Secondary Cesarean Section

The study aims to explore the effect of low-frequency electric pulse technique combined with carboprost methylate suppositories on recovery of gastrointestinal function and postoperative complications of patients with scarred uterus undergoing secondary cesarean section (C-section). The clinical data of 120 patients with scarred uterus undergoing secondary C-section treated in our hospital from February 2019 to February 2020 were retrospectively analyzed, and the patients were equally divided into experimental and control groups according to their admission order, where each group included 60 patients. After the operation, patients in the control group received routine nursing and conducted breastfeeding, and carboprost methylate suppositories were used for postoperative hemostasis. Those in the experimental group received low-frequency electric pulse technique for comprehensive treatment to compare their coagulation function indicators, recovery of gastrointestinal function, incidence rates of postoperative complications, and involution of uterus. No significant between-group differences in patients’ general information such as gestational weeks, gravidity, and number of times receiving C-section were observed ( P > 0.05 ). Compared with the control group after the operation, patients in the experimental group obtained significantly better coagulation function indicators ( P < 0.001 ) and presented better gastrointestinal function recovery ( P < 0.001 ), significantly lower incidence rates of postpartum hemorrhage, retention of urine, deep venous thrombosis of lower limb, rupture of uterus, and endometrial cavity fluid ( P < 0.05 ), and significantly better involution of uterus ( P < 0.001 ). In conclusion, combining low-frequency electric pulse technique with carboprost methylate suppositories can lower the incidence rates of postoperative complications for patients with scarred uterus undergoing secondary C-section, improve their coagulation function, promote the recovery of gastrointestinal function, and present the desirable involution of uterus, which should be promoted in practice.

Global Coagulation Potentials and Breakthrough Bleeds in Emicizumab-Treated Hemophilia a Patients Were Similar to Mild Hemophilia a Patients

Emicizumab prophylaxis dramatically reduces bleeding events in severe patients with hemophilia A (PwHA) with and without FVIII inhibitors. Recently, some real-world experiences on PwHA with emicizumab prophylaxis have been reported. The effectiveness of emicizumab could be attributed to an earlier report that the coagulant potential in emicizumab at clinical dosage appeared to correspond to 10-15 IU/dL of factor VIII activity (FVIII:C) (Muto, JTH 2014), indicating that emicizumab enables to transform severe PwHA to mild PwHA. However, the comparison of coagulation potential and bleeding characteristics in PwHA receiving emicizumab (Emi-PwHA) and mild PwHA (PwMHA) remains to be investigated. Here, we examined the clinical and laboratory characteristics in Emi-PwHA and PwMHA. Clinical data of bleeding episodes and coagulation potentials were collected from 64 Emi-PwHA and 15 PwMHA (median FVIII:C 13 IU/dL [IQR 8.5-17.0]). Comprehensive coagulation function was evaluated using Ca 2+-triggered rotational thromboelastometry (ROTEM) and/or ellagic acid/tissue factor-triggered clot waveform analysis (CWA). Furthermore, we compared the features of breakthrough bleeds in two groups. We first compared with the clinical characteristics and coagulation function between the Emi-PwHA with and without the experience of breakthrough bleeds. The age, treatment period, annual bleeding rates (ABR), the percentage of inhibitor-positive, and prophylaxis regimen were not significantly different between both groups. There was no significant difference in ROTEM and CWA-based coagulation potential between Emi-PwHA with and without breakthrough bleeds (median; CT+CFT 1,703s [IQR 1,547-1,849] and 1,837s [IQR 1,671-2,216], Ad|min1| 4.92 [IQR 4.63-5.27] and 4.78 [IQR 4.4-5.11], respectively). We examined clinical data and ROTEM-based coagulation function between the Emi-PwHA and PwMHA. The age in PwMHA (median 25 years [IQR 20-49]) was older than that in Emi-PwHA (median 13 years [IQR 6-25]; p=0.004). The ABR and coagulation function in Emi-PwHA (median; ABR 0 [IQR 0-0.4], CT+CFT 1,795s [IQR 1,659-2,135]) were not significantly different from that in PwMHA (median; ABR 0.3 [IQR 0-0.49], CT+CFT 2,077s [IQR 1,627-2,449]), suggesting that the global coagulation potential in Emi-PwHA was equivalent to that in PwMHA. We next investigated bleeding features in Emi-PwHA (19 cases) and PwMHA (12 cases). Bleeding patterns of them were similar and divided into 3 groups; spontaneous, early post-traumatic (bleeding associated with trauma within 1-2 days) and late post-traumatic (bleeding involved with trauma within 1-2 weeks). Emi-PwHA experienced spontaneous (5/19), early post-traumatic (14/19) and late post-traumatic (3/19) bleedings, and PwMHA experienced spontaneous (4/12), early post-traumatic (7/12) and late post-traumatic (5/12) bleedings. Some patients of them had both spontaneous and early post-traumatic bleeding or both early and late post-traumatic bleeding. The majority of their bleedings was trauma-induced. Severe bleeding symptoms such as muscle bleeds, hemarthrosis or fracture in Emi-PwHA were required FVIII (total 60-200 IU/kg) and hospitalization for 3-5 days. In contrast, those severe breakthrough bleedings in PwMHA were required higher doses of FVIII (total 140-705 IU/kg) and hospitalization for 1-2 weeks. Although the coagulation potential in Emi-PwHA was similar to that in PwMHA, the treatment period and hospitalization for breakthrough bleeds in PwMHA appeared to be longer than those in Emi-PwHA. We speculated that this discrepancy might be due to the difference of physical activities or preventive managements for bleeding because Emi-PwHA was originally severe PwHA. In conclusion, the coagulation potential and bleeding characteristics in Emi-PwHA appeared to be similar to PwMHA, suggesting that emicizumab-mediated coagulation potential reflected the mild type in clinical severity. Disclosures Nakajima: Chugai Pharmaceutical Co., Ltd.: Research Funding; Takeda Pharmaceutical company: Research Funding. Mizumachi: Chugai Pharmaceutical Co., Ltd.: Research Funding. Shimonishi: CSL Bering: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding. Furukawa: Chugai Pharmaceutical Co., Ltd.: Research Funding. Ogiwara: Chugai Pharmaceutical Co., Ltd.: Research Funding. Takeyama: Chugai Pharmaceutical Co., Ltd.: Research Funding. Shima: Fujimoto Seiyaku: Consultancy, Speakers Bureau; Sanofi S.A.: Speakers Bureau; BioMarin Pharmaceutical Inc.: Membership on an entity's Board of Directors or advisory committees; Bayer AG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novo Nordisk A/S: Honoraria, Speakers Bureau; Takeda: Research Funding; CSL Behring: Research Funding, Speakers Bureau; F. Hoffmann-La Roche Ltd.: Membership on an entity's Board of Directors or advisory committees; Chugai Pharmaceutical Co., Ltd.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Inventor of patents related to anti-FIXa/FX bispecific antibodies, Research Funding, Speakers Bureau. Nogami: Chugai Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda Pharmaceutical Co., Ltd.: Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding, Speakers Bureau; Novo Nordisk A/S: Honoraria, Research Funding, Speakers Bureau; Bayer AG: Honoraria, Research Funding, Speakers Bureau; Sanofi S.A.: Honoraria, Research Funding, Speakers Bureau; KM Biologics Co., Ltd.: Honoraria, Research Funding, Speakers Bureau.

Parameters in complete blood cell count and coagulation function test predict in pediatric critical illness：A retrospective study

Background. The complete blood cell count is associated with the prognosis of critically ill children. Pediatric critical illness score (PCIS) is often used to evaluate the criticality of pediatric critical illness. We aimed to determine most parameters in the complete blood cell count (CBC) and coagulation function test of patients who were admitted to PICU in our hospital and compare those parameters of critically ill and non-critically ill children grouped by PCIS and whether CBC can identify and assess the severity of illness in critically ill children. Methods. We performed a retrospective study of pediatric intensive care population who took both blood routine examination and coagulation function test within 24 hours of admission in PICU of The First Affiliated Hospital of Bengbu Medical College, from April 2015 to December 2019. Data collected include patient demographics and clinical data. Statistical analysis including Mann-Whitney U Test, binary logistic regression and so on. Results. The parameters in the complete blood cell count and coagulation function test showed a significant difference between critical illness and non-critical illness in this study. Multivariate logistic regression analysis showed that RDWSD and PT prolongation are associated with PCIs (p<0.001, p=0.006, respectively). We created a nomogram for pediatric critical illness by using these risk factors. The area under of ROC curve (AUC) of pediatric critical illness for the combination of RDWSD and PT prolongation was 0.664(95%confidence interval 0.609-0.720). The nomogram had a bootstrapped-concordance index of 0.58. Conclusion. RDWSD and PT prolongation are reliable indicators for predicting pediatric critical illness.