Coagulation Function Research Articles

A retrospective cohort study of coagulation function in patients with liver cirrhosis receiving cefoperazone/sulbactam with and without vitamin K1 supplementation.

Cefoperazone/sulbactam is commonly prescribed for the treatment of infected patients with cirrhosis. To investigate the effect of cefoperazone/sulbactam on coagulation in cirrhotic patients and assess the effectiveness of vitamin K1 supplementation in preventing cefoperazone/sulbactam-induced coagulation disorders. This retrospective cohort study compared coagulation function in 217 cirrhotic patients who received cefoperazone/sulbactam with and without vitamin K1 supplementation (vitamin K1 group, n = 108; non-vitamin K1 group, n = 109). Propensity score matching (PSM) was used to to reduce confounders' influence, the SHapley additive exPlanations (SHAP) model to explore the importance of each variable in coagulation disorders. In the non-vitamin K1 group, the post-treatment prothrombin time (PT) was 16.5 ± 6.5s and the activated partial thromboplastin time (aPTT) was 34.8 ± 9.4s. These were significantly higher than pre-treatment values (PT: 14.6 ± 2.4s, p = 0.005; aPTT: 30.4 ± 5.9s, p < 0.001). In the vitamin K1 group, no differences were observed in PT, thrombin time, or platelet count, except for a slightly elevated post-treatment aPTT (37.0 ± 10.4s) compared to that of pre-treatment (34.4 ± 7.2s, p = 0.033). The vitamin K1 group exhibited a lower risk of PT prolongation (OR: 0.211, 95% CI: 0.047-0.678) and coagulation disorders (OR: 0.257, 95% CI: 0.126-0.499) compared to that of the non-vitamin K1 group. Propensity score matching analysis confirmed a reduced risk in the vitamin K1 group for prolonged PT (OR: 0.128, 95% CI: 0.007-0.754) and coagulation disorders (OR: 0.222, 95% CI: 0.076-0.575). Additionally, the vitamin K1 group exhibited lower incidences of PT prolongation, aPTT prolongation, bleeding, and coagulation dysfunction compared to the non-vitamin K1 group. Cefoperazone/sulbactam use may be linked to a higher risk of PT prolongation and coagulation disorders in cirrhotic patients. Prophylactic use of vitamin K1 can effectively reduce the risk.

Bromadiolone may cause severe acute kidney injury through severe disorder of coagulation: a case report

BackgroundBromadiolone is a wide-use long-acting anticoagulant rodenticide known to cause severe coagulation dysfunction. At present, there have been no detailed reports of acute kidney injury (AKI) resulting from bromadiolone poisoning.Case presentationA 27-year-old woman was admitted to the hospital due to severe coagulopathy and severe AKI. Coagulation test revealed a prothrombin time exceeding 120 s and an international normalized ratio (INR) greater than 10. Further examination for coagulation factors showed significantly reduced level of factors II, VII, IX and X, indicating a vitamin K deficiency. The AKI was non-oliguric and characterized by gross dysmorphic hematuria. Following the onset of the disease, the patient’s serum creatinine rose from 0.86 to 6.96 mg/dL. Suspecting anticoagulant rodenticide poisoning, plasma bromadiolone was identified at a concentration of 117 ng/mL via gas chromatography/mass spectrometry. All other potential causes of AKI were excluded, except for the presence of a horseshoe kidney. The patient’s kidney function fully recovered after the coagulopathy was corrected with high doses of vitamin K and plasma transfusion. At a follow-up 160 days post-discharge, the coagulation function had normalized, and the serum creatinine had returned to 0.51 mg/dL.ConclusionBromadiolone can induce AKI through a severe and prolonged coagulation disorder. Kidney function can be restored within days following treatment with high-dose vitamin K1.

A retrospective study on safety and efficacy of recombinant human soluble thrombomodulin to acute aortic dissection with disseminated intravascular coagulation

ObjectivesRecombinant human soluble thrombomodulin (rTM) has recently been used as a promising therapeutic natural anti-coagulant drug for disseminated intravascular coagulation (DIC). Here we investigated the safety and efficacy of rTM after aortic surgery in patients with acute aortic dissection (AAD).MethodsA total of 316 patients diagnosed with AAD underwent emergent ascending aortic replacement or total arch replacement between 2010 and 2019. We retrospectively analyzed the clinical information of 62 patients with the Japanese Association for Acute Medicine’s acute-stage DIC diagnostic criteria (JAAM criteria) with a score of ≥ 4. We assigned 62 patients to two groups, either non-rTM group (n = 29) or rTM group (n = 33). Patient characteristics, surgical procedures, and postoperative outcome data including coagulation function and the JAAM DIC score in both groups were collected.ResultsThe decrease in the number of platelets was clearly suppressed on days 1–3 in the rTM group. On days 1–4, fibrin degradation product levels were upregulated in the non-rTM group but significantly downregulated in the rTM group. Five operative deaths occurred within 30 days postoperative (two [6.9%] in the non-rTM group vs. three [9.1%] in the rTM group). The JAAM DIC score showed a gradually improving trend from postoperative day 1 in the rTM group.ConclusionsPostoperative rTM administration for AAD may be a safe and promising novel treatment strategy for improving the JAAM DIC score.

Effects of Indobufen Combined with Clopidogrel on Left Ventricular Function and Inflammatory Factors in Patients after PCI

Background: Percutaneous intracoronary intervention (PCI) is the preferred method for treating coronary heart disease. However, the insufficient coagulation function after the procedure may lead to poor vascular reperfusion, thereby affecting cardiac function. Indobufen and clopidogrel have antiplatelet and anti-inflammatory effects, but the impact of their combined use on left ventricular function and inflammatory factors in patients after PCI remains unclear. This study aimed to explore the influence of indobufen combined with clopidogrel on left ventricular function and inflammatory factors in patients after PCI. Methods: Medical records of 100 patients who underwent PCI surgery were selected for retrospective analysis. Their admission time ranged from January 2022 to June 2023. All research subjects who met the inclusion criteria were assigned to two groups according to different treatment methods with 57 cases in the control and 43 cases in the observation. The left ventricular function, inflammatory factors, coagulation function levels, and occurrence of complications were compared between the two groups. Results: After going through treatment, the levels of left ventricular end-diastolic volume, left ventricular end-systolic diameter, and left ventricular end-diastolic diameter of the observation group were significantly lower than those of the control. The ejection fraction significantly increased in the observation group, and the difference between two groups was significant (p &lt; 0.05). Furthermore, the level of high-sensitivity C-reactive protein in the observation was significantly lower than that of the control benefiting from treatment with a significant difference (p &lt; 0.05). The activated partial thromboplastin time, prothrombin time, and thrombin time levels of all patients significantly increased (p &lt; 0.05) with no difference between the two groups (p &gt; 0.05). The complication rate in the control patients was 17.54% (10/57), and that in the observation patients was 9.30% (4/43). No significant difference existed between the two groups (p &gt; 0.05). Conclusions: Indobufen combined with clopidogrel treatment for patients after PCI significantly improved left ventricular function, inhibited inflammatory response, enhanced coagulation function, and had high safety. These results can provide some basis for the treatment of patients after clinical PCI.

Incidence, characteristics, and risk factors of hypofibrinogenemia induced by generic tigecycline: a retrospective study.

The objective of this study was to evaluate the incidence, clinical features, and risk factors of generic tigecycline-associated hypofibrinogenemia. A single-center retrospective study was conducted in adult patients treated with generic tigecycline. Clinical data were extracted from the electronic medical records. The endpoint was tigecycline-related hypofibrinogenemia, defined as a condition with no abnormality in fibrinogen before tigecycline application, but developing hypofibrinogenemia upon prescription. The risk factors were determined by logistic regression analysis, and the ROC curve was subsequently established. A total of 240 adults prescribed generic tigecycline from May 1st to November 30th 2023 were included. It was shown that hypofibrinogenemia is a frequent side effect of generic tigecycline, with an adverse reaction rate of 42.9% (103/240). However, the incidence of adverse reactions to generic drugs was lower than in previous studies. The cumulative dose of tigecycline (OR:1.002, 95%CI 1.001-1.002, P < 0.001), baseline FIB (OR:0.995, 95%CI 0.992-0.997, P < 0.001), baseline PT (OR:1.247, 95%CI 1.071-1.452, P = 0.004) and baseline ALB (OR:0.931, 95%CI 0.879-0.986, P = 0.025) were identified as independent prognostic factors of tigecycline-related hypofibrinogenemia. We recommend intensive monitoring of coagulation function in patients exhibiting the aforementioned risk factors for generic tigecycline-associated hypofibrinogenemia to ensure patients safety.

Plasmin generation analysis in patients with bleeding disorder of unknown cause

AbstractBleeding disorder of unknown cause (BDUC) is a diagnosis of exclusion after evaluation of plasma coagulation and platelet function. Patients with BDUC (n = 375) recorded in the Vienna Bleeding Biobank were analyzed in comparison with healthy controls (HCs; n = 100) in this case-control study. Plasmin generation (PG) parameters were analyzed using calibrated fluorescence detection in citrated plasma. Turbidimetric plasma clot formation/lysis of 293 (78%) BDUC patients and confocal microscopy of clots from representative BDUC patients (n = 6) and HCs (n = 9) were assessed. In the PG analysis, BDUC patients exhibited lower velocity and peak plasmin levels but a higher endogenous plasmin potential than HCs. Peak plasmin levels correlated with maximum clot absorbance but not with clot lysis time. Clot absorbance is an indicator of clot fiber density. Confocal microscopy analysis revealed a tendency towards thicker fibers in clots of BDUC patients, which negatively correlated with peak plasmin (r = −0.561; P = .030). Peak plasmin correlated weakly with factor XIII, but not with other fibrinolytic factors (alpha2-antiplasmin, thrombin activatable fibrinolysis inhibitor, or plasminogen activator inhibitor 1) or bleeding severity. A model comprising fibrinogen and parameters of PG yielded high predictive power in discriminating between patients with BDUC and HCs across a fivefold stratified cross validation (80% of data; mean area under the curve [AUC], 0.847). The model generalized well to unseen data (20% of data; AUC, 0.856). Overall, patients with BDUC counterintuitively exhibited reduced peak plasmin levels, potentially related to altered clot structure.

Component Blood Transfusion with Restrictive Fluid Resuscitation in Ectopic Pregnancy Hemorrhage with Hemorrhagic Shock

Objective: To study the effect of using component blood transfusion with restrictive fluid resuscitation in ectopic pregnancy hemorrhage complicating hemorrhagic shock. Methods: 50 cases of ectopic pregnancy hemorrhage complicating hemorrhagic shock were selected for data study, and after grouping, 25 cases in each group were grouped, and the use of component blood transfusion with restrictive fluid resuscitation was used in the study group and restrictive fluid resuscitation was used in the control group, and the differences in the data were compared. Results: Compared with the control group, the study group had a significantly higher resuscitation success rate, significantly fewer complications, significantly higher hemodynamic indexes 2 h after treatment, significantly better coagulation function indexes, and significantly fewer various quantities in the therapeutic situation, P &lt; 0.05. Conclusion: The use of component blood transfusion with restrictive fluid resuscitation in ectopic pregnancy hemorrhage-complicating hemorrhagic shock has an ideal effect.

Patients with Waldenström macroglobulinemia have impaired platelet and coagulation function

AbstractClinical features in patients with the B-cell lymphoma, Waldenström macroglobulinemia (WM), include cytopenias, immunoglobulin M (IgM)–mediated hyperviscosity, fatigue, bleeding, and bruising. Therapeutics such as Bruton's tyrosine kinase inhibitors (BTKis) exacerbate bleeding risk. Abnormal hemostasis arising from platelet dysfunction, altered coagulation or vascular impairment have not yet been investigated in patients with WM. Therefore, this study aimed to evaluate hemostatic dysfunction in samples from these patients. Whole blood (WB) samples were collected from 14 patients with WM not receiving therapy, 5 patients receiving BTKis and 15 healthy donors (HDs). Platelet receptor levels and reticulation were measured by flow cytometry, plasma thrombin generation with or without platelets by fluorescence resonance energy transfer assay, WB clotting potential by rotational thromboelastometry, and plasma soluble glycoprotein VI (sGPVI) and serum thrombopoietin (TPO) by enzyme-linked immunosorbent assay. Donor platelet spreading, aggregation, and ability to accelerate thrombin generation in the presence of WM-derived IgM were assessed. WM platelet receptor levels, responses to physiological agonists, and plasma sGPVI were within normal ranges. WM platelets had reduced reticulation (P = .0012) whereas serum TPO levels were increased (P = .0040). WM plasma displayed slower thrombin generation (P = .0080) and WM platelets contributed less to endogenous thrombin potential (ETP; P = .0312). HD plasma or platelets incubated with IgM (50-60 mg/mL) displayed reduced spreading (P = .0002), aggregation (P < .0001), and ETP (P = .0081). Thus, alterations to thrombin potential and WB coagulation were detected in WM samples. WM IgM significantly impaired hemostasis in vitro. Platelet and coagulation properties are disturbed in patients with well-managed WM.

RNAi targeting LMAN1-MCFD2 complex promotes anticoagulation in mice.

Combined deficiency of coagulation factor V (FV) and factor VIII (FVIII) is a rare bleeding disease caused by variants in either lectin mannose binding 1 (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) gene. Reducing the level of FVIII by inhibiting the LMAN1-MCFD2 complex may become a new anticoagulant approach. We aimed to find a new therapeutic option for anticoagulation by RNA interference (RNAi) targeting LMAN1 and MCFD2. siRNA sequences with cross-homology between mice and humans were designed based on LMAN1 or MCFD2 transcripts in NCBI and were screened with the Dual-Luciferase reporter assay. The optimal siRNAs were chemically modified and conjugated with three N-acetylgalactosamine molecules (GalNAc-siRNA), promoting their targeted delivery to the liver. The expression of LMAN1 and MCFD2 in cell lines or mice was examined by RT-qPCR and western blotting. For the mice administered with siRNA, we assessed their coagulation function by measuring APTT and the activity of FVIII factor. After administration, siRNAs GalNAc-LMAN1 and GalNAc-MCFD2 demonstrated effective and persistent LMAN1 and MCFD2 inhibition. 7 days after injection of 3mg/kg GalNAc-LMAN1, the LMAN1 mRNA levels reduced to 19.97% ± 3.78%. MCFD2 mRNA levels reduced to 32.22% ± 13.14% with injection of 3mg/kg GalNAc-MCFD2. After repeated administration, APTT was prolonged and the FVIII activity was remarkably decreased. The tail bleeding test of mice showed that the amount of bleeding in the treated group did not significantly increase compared with the control group. Our study confirms that therapy with RNAi targeting LMAN1-MCFD2 complex is effective and can be considered a viable option for anticoagulation drugs. However, the benefits and potential risk of bleeding in thrombophilic mice model needs to be evaluated.

Application Value and Safety Analysis of Warfarin, Rivaroxaban, and Dabigatran Ester in Elderly Patients With Atrial Fibrillation.

This study aimed to evaluate the application value and safety of Warfarin, Rivaroxaban, and Dabigatran in elderly patients with atrial fibrillation. A total of 180 elderly patients with atrial fibrillation admitted to our hospital were retrospectively analyzed. According to their anticoagulant treatment regimen, patients were divided into three groups: Warfarin (57 cases), Rivaroxaban (61 cases), and Dabigatran (62 cases). General demographic information was collected, and coagulation function indicators-including fibrinogen (FIB), thrombin time (PT), activated partial thrombin time (APTT), and D-dimer (D-D)-as well as liver function indexes-including total bilirubin (TbiL), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine transferase (ALT)-were compared before and after 4 weeks of treatment. There were no significant differences in demographic characteristics such as gender, age, body mass index, or disease course among the three groups. The total effective rate in the Warfarin group (84.21%) was significantly lower than in the Rivaroxaban (98.36%) and Dabigatran (96.77%) groups (p < 0.05). However, there was no significant difference in the total effective rate between the Rivaroxaban and Dabigatran groups (p > 0.05). Additionally, no significant differences were found in the effects of the three drugs on coagulation function, liver function, or the incidence of bleeding (p = 0.052). Warfarin, Rivaroxaban, and Dabigatran can effectively prevent thrombosis in elderly patients with atrial fibrillation, with Rivaroxaban and Dabigatran showing superior effectiveness. All three drugs demonstrated similar low rates of bleeding events and had no significant impact on coagulation and liver function.

Whether coagulation dysfunction influences the onset and progression of diabetic peripheral neuropathy: A multicenter study in middle-aged and aged patients with type 2 diabetes.

Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN. Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves. Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (β 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated. Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice.

Efficacy and safety of tranexamic acid use in elderly patients undergoing anterior cervical discectomy and fusion: a retrospective study.

To evaluate the safety and efficacy of intravenous tranexamic acid (TXA) administration in anterior cervical discectomy fusion (ACDF) for the treatment of cervical spondylosis in the elderly. Data from elderly patients who underwent ACDF between January 2020 and January 2023 were retrospectively reviewed. Patients who received 1 g intravenous TXA administration before skin incision (TXA group) were compared with patients who did not receive TXA (controls). Total and hidden blood loss were calculated, and the following outcomes were recorded: haemoglobin and haematocrit drop, operation time, drainage duration, drain volume, length of hospitalization, coagulation changes, and incidence of complications. A total of 114 patients were included (TXA group, n = 53 and controls, n = 61). Total blood loss, hidden blood loss, and postoperative drainage volume, haemoglobin and haematocrit drop were significantly lower in the TXA group than the control group. There were no significant differences in operation time, intraoperative blood loss, drainage duration, length of hospitalization, or coagulation function between the two groups. The incidence of complications did not differ significantly between the two groups during 3 months of follow-up. Intravenous TXA is effective in reducing perioperative blood loss in elderly patients undergoing ACDF without changing the coagulation function or increasing the risk of complications.

Diagnostic Value of Serum Amylase and Coagulation Function Indices in Distinguishing Acute Pancreatitis from Aortic Dissection.

Due to similar symptoms of abdominal pain, acute pancreatitis (AP) is often difficult to differentiate from acute aortic dissection (AAD) in clinical practice. It is unknown whether serum amylase and coagulation function indices can be used to distinguish AP from AAD. In this retrospective study, 114 AP patients (AP group) and 48 cases with AAD (AAD group) admitted for acute abdominal pain were enrolled for a final analysis. The levels of serum amylase and coagulation function indices, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), and D-dimer (DD), were tested before or on admission and compared between the two groups. Student's t-test was adopted for comparing the mean. Model discrimination was evaluated by using the area under the receiver operating characteristic curve (AUC). Comparison of AUC was performed by using the Z-test. Compared with the AAD group, amylase and FIB were both significantly increased, while DD was significantly lower in the AP group (all p < 0.01). There were no statistically significant differences of PT, INR, and APTT between AP and AAD (all p > 0.05). The AUCs in distinguishing AP from AAD were 0.913, 0.854, and 0.837 for amylase, FIB, and DD, respectively, but there were no significant differences observed among amylase, FIB, and DD (all p > 0.05). Finally, the cutoff values (specificity, sensitivity, and Youden index) in distinguishing between AP and AAD were 114 µ/L (80.70%, 95.83%, 0.765) for amylase, 2.62 g/L (76.32%, 85.42%, 0.617) for FIB, and 2.74 mg/L (95.61%, 62.50%, 0.581) for DD, respectively. Amylase, FIB, and DD can demonstrate accurate and reliable diagnostic values, suggesting that they are useful and potential biomarkers in distinguishing AP from AAD.

Real-Time Monitoring of Lower Limb Oxygen Saturation in Children with Indwelling Catheters Using Near-Infrared Spectroscopy to Assess the Risk of Deep Vein Thrombosis and Nursing Strategies

Objectives: To analyze the risk of deep vein thrombosis (DVT) in children with indwelling catheters through near-infrared spectroscopy (NIRS) detection of lower limb crSaO2, and to implement corresponding nursing countermeasures against the risk. Methods: Using a convenience sampling method, 80 children with indwelling catheters were selected from the first pediatric intensive care unit of our hospital between January 2022 and December 2022. They were divided into two groups: The DVT group (N = 20) and the non-DVT group (N = 60), based on whether DVT occurred within 3 days of catheterization. Single-factor and multivariate logistic regression analyses were conducted using SPSS 27.0 software. Non-DVT patients were randomly divided into a study group and a control group using a random number table method, with 30 cases in each group. The control group received routine nursing measures, while the study group received nursing measures based on NIRS for detecting DVT risk in lower limb crSaO2 in children with indwelling catheters. The blood coagulation indexes [thrombin time (TT); activated partial thromboplastin time (APTT); fibrinogen (FIB); D-dimer (D-D)] of the two groups were compared at 3 days (T0), 7 days (T1), and 14 days (T2) after catheterization. The symptoms related to lower limb DVT during the study period were also recorded. Results: Multivariate logistic analysis showed that the independent risk factors for DVT in critically ill children with deep vein catheterization were bed rest time ≥ 3 days (OR = 2.963, 95% CI = 1.282 - 6.852), limb immobilization (OR = 2.843, 95% CI = 1.209 - 6.685), FIB (OR=57.765, 95% CI = 11.308 - 295.094), and D-D (OR = 3.415, 95% CI = 1.396 - 8.359) (P &lt; 0.05). Overall, there were statistical differences in the TT, APTT, FIB, and D-D indicators, as well as time and interaction among the study group's children (P &lt; 0.05). Before catheterization, there was no statistically significant difference in TT, APTT, FIB, and D-D between the two groups of children (P &gt; 0.05). Compared between groups, the TT, APTT, FIB, and D-D at T1 and T2 in the study group were significantly lower than those in the control group, while lower limb crSaO2 was significantly higher than in the control group (P &lt; 0.05). Intra-group comparison showed statistically significant differences in TT, APTT, FIB, and D-D between the two groups of children (P &lt; 0.05). The incidence of DVT-related symptoms in the study group was significantly lower than in the control group (P &lt; 0.05). Conclusions: After deep vein catheterization, critically ill children are prone to be affected by extended bed rest and limb immobilization, resulting in the passive activation of the fibrinolytic system. Moreover, multidisciplinary team collaborative nursing measures based on NIRS technology can effectively improve coagulation function and lower limb oxygen saturation, thereby avoiding the occurrence of DVT-related symptoms.

Contemplating Screening for Protein S Deficiency: To Screen or Not?

Protein S (PS) deficiency is a thrombophilia disorder due to the reduced activity of protein S which regulates coagulation function leading to venous thromboembolism (VTE) event. It is an autosomal dominant disorder whereby it can be heterozygous or homozygous. A positive family history of protein S deficiency is a significant risk factor for developing thromboembolism. We report a case of an infant born to a mother with suspected protein S deficiency. The dilemma is whether we should screen this infant for protein S deficiency. His baseline coagulation profile was normal according to age and had no thrombotic event throughout his neonatal period.

Changes of coagulation function and platelet parameters in preeclampsia and their correlation with pregnancy outcomes.

Preeclampsia (PE) is a severe pregnancy complication characterized by significant alterations in coagulation function. This study aims to analyze the correlation between coagulation function, platelet parameters, and pregnancy outcomes in PE patients. Clinical data, along with blood and urine samples, were collected from 168 PE patients and 128 healthy pregnant women. General demographic and laboratory testing data were recorded, and maternal and fetal outcomes were followed up. Data were analyzed using Kaplan-Meier and logistic regression analyses. In mild PE patients, thrombin time (p=.000), platelet distribution width (PDW) (p=.000), and clot formation time (p=.000) were increased, while prothrombin time (p=.000) and fibrinogen (p=.045) were reduced. With increasing PE severity, prothrombin time (p=.000), platelet count (PLT) (p=.000), mean platelet volume (MPV) (p=.000), plateletcrit (p=.000), maximum amplitude (MA) (p=.000), and coagulation index (p=.001) decreased, whereas activated partial thromboplastin time (APTT) (p=.000), thrombin time (p=.002), D-dimer (p=.026), and PDW (p=.000) increased. Lower prothrombin time (p=.048), PLT (p=.004), and coagulation index (p=.026) or higher APTT (p=.032), thrombin time (p=.044), D-dimer (p=.023), and PDW (p=.016) were associated with a higher risk of poor pregnancy outcomes. Thrombin time was identified as an independent risk factor (p=.025, OR=2.918, 95% CI: 1.145-7.436), whereas gestational age was an independent protective factor (p=.000, OR=0.244, 95% CI: 0.151-0.395). This study demonstrates that specific coagulation and platelet parameters are significantly associated with PE severity and adverse pregnancy outcomes. These findings highlight the importance of monitoring coagulation function in PE patients to improve clinical management and outcomes.

Using heart rate variability to evaluate the association between the autonomic nervous system and coagulation function in patients with endometrial cancer.

The incidence of endometrial cancer (EC) is increasing worldwide, but the specific mechanism of coagulation dysfunction in EC is not fully understood. The objective of the present study was to explore the relationship between autonomic nervous system function and coagulation function in patients with EC using heart rate variability (HRV) analysis. The study included 100 patients with EC who were treated at the Department of Gynecological Oncology of The First Affiliated Hospital of Bengbu Medical University (Bengbu, China) from December 2021 to March 2023. A 5-min resting electrocardiogram was collected from each patient to analyze HRV parameters, including the time domain parameters standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD), and the frequency domain parameters low-frequency power and high-frequency power (HF). Blood samples were submitted to biochemistry tests to measure coagulation markers, namely prothrombin time (PT), international normalized ratio of PT (PT-INR), prothrombin activity (PTA), activated partial thromboplastin time (APTT) and fibrinogen. Bivariate Spearman correlation analyses revealed that PT, PT-INR and APTT were significantly positively correlated with SDNN, RMSSD and HF, while PTA was significantly negatively correlated with RMSSD. Following adjustments for confounding factors, namely age, body mass index, menopause, ligation of the fallopian tubes, diabetes, hypertension, adjuvant chemotherapy and mean heart rate, linear regression analysis demonstrated that SDNN, RMSSD and HF were independent factors influencing PT and PT-INR in patients with EC. The findings of the present study indicate that certain HRV parameters correlate with coagulation markers in EC and provide new insight into the occurrence of cancer-associated coagulation dysfunction.

Cardiovascular adverse events associated with PARP inhibitors for ovarian cancer: a real world study (RWS) with Bayesian disproportional analysis based on the FDA adverse event reporting system (FAERS)

ABSTRACT Background To investigate the pharmacovigilance (PV) and make pairwise comparisons on reporting proportion, seriousness, and severity of outcomes of major adverse cardiovascular events (MACE) among poly(ADP-ribose) polymerase-inhibitors (PARPis) in treating ovarian cancer, fallopian tube carcinoma, and primary peritoneal cancer (collectively named EOC) from the US Food and Drug Administration Adverse Event Reporting System (FAERS). Research design and methods Data on adverse cardiovascular events reports related to EOC treatment submitted to FAERS from the first quarter of 2015 to the second quarter of 2023 were harvested. Three PARPis were identified: olaparib, niraparib, and rucaparib. Results Eventually, a total of 258,596 eligible records were enrolled with 12,331 reports including 5,292 reports of MACE and 7,039 reports of other cardiovascular events. For the primary composite endpoint, a PV signal associated with MACE was detected in niraparib (ROR = 1.12; IC025 = 0.03), whereas it was not detected in olaparib and rucaparib; For the secondary endpoint, PV signals associated with other cardiovascular events were detected in niraparib (ROR = 1.17;IC025 = 0.04), but not in olaparib and rucaparib. Conclusions For EOC patients, close monitoring of blood pressure, heart rate, and coagulation function should be conducted when selecting niraparib for treatment.

Metabolic pathways altered by air pollutant exposure in association with coagulation function among the rural elderly

Air pollution exposure has been linked with coagulation function. However, evidence is limited for the relationships between air pollution, coagulation function and metabolomics in humans. We recruited a panel of 130 rural elderly from the Chayashan township in China, all of whom were free of pre-existing cardiovascular diseases and had provided residential address information. We conducted clinical examinations and collected blood samples from these rural elderly for the detection of coagulation biomarkers (e.g, activated partial thromboplastin time, fibrinogen, thrombin time, and prothrombin time) and untargeted metabolites in both December 2021 and August 2022. We used mini ambient air quality monitor to measure the mean levels of five air pollutants (e.g., PM2.5, SO2, NO2, CO and O3) during 1 to 2 weeks before blood sample collection. The Mummichog pathway analysis was used to identified potential metabolic features and pathways. In this study, we identified 5 pathways associated with both air pollution and coagulation function, and further pinpointed eight metabolic features within these pathways. The majority of these features were lipids, including arachidonic acid and linoleic acid. Overall, the findings of this study offer insights into potential mechanisms, particularly lipid metabolism, that may underlie the association between air pollution and coagulation function.

Changes in coagulation potential over time after administration of recombinant activated factor VII in an emicizumab-treated hemophilia A patient with inhibitors.

We describe a 67-year-old patient with hemophilia A and inhibitors (PwHA-I) receiving emicizumab prophylaxis who underwent surgical treatment for pseudoaneurysm. He was treated with a bolus infusion of recombinant factor VIIa (rFVIIa; 79μg/kg) immediately before surgery, and a second dose of rFVIIa after an initial treatment on day 1. A third rFVIIa bolus was infused 17h after the second dose on day 2, and the treatment was continued every 24h on day 3 and day 4. Treatment with rFVIIa was discontinued on day 4. No perioperative bleeding or thrombotic events were observed. Coagulation potentials at 8h after rFVIIa administration determined by clot waveform analysis (CWA) and thrombin generation assay (TGA) were within near-normal ranges, and results at 17h after rFVIIa administration showed coagulation function comparable to that in the patient without rFVIIa. Our experimental data suggest that the coagulation potential in FVIII-deficient plasma spiked with both 0.28µg/mL (11.2μg/kg) rFVIIa and emicizumab was equivalent to or greater than that spiked with 2.2µg/mL (90μg/kg) rFVIIa alone. Thus, administration of rFVIIa every 8h may be feasible for managing perioperative treatment in emicizumab-treated PwHA-I.