Blood Coagulation & Fibrinolysis最新文献

Interpretation of coagulation mixing studies is complicated by interference arising from direct oral anticoagulants (DOACs), which are increasingly prescribed. In this retrospective study, we reviewed 1035 consecutive coagulation mixing studies performed from 2017 to 2021. Three hundred and ninety-nine cases with normal prothrombin time (PT) and activated partial thromboplastin time (aPTT) were excluded. aPTT mixing studies were performed at time 0 and after 60 min of incubation. We confirmed the presence of interfering factors with additional laboratory testing, medication records, and medical history. Mixing corrected most prolonged PT samples (93%), but 32 cases showed incomplete correction. Of these 32 cases, 18 were confounded by DOAC use, and 3 by factor V (FV) inhibitor. We observed an unusual pattern of prolongation of aPTT after incubation, which was previously considered a characteristic of specific factor inhibitors, most commonly FVIII inhibitor. However, we found that lupus anticoagulant (28%) and DOAC (25%) contributed to this pattern similarly as specific factor inhibitors (28%). Coagulation laboratories should be aware of interference arising from DOACs and other factors in PT/aPTT mixing studies, especially in some unusual correction patterns.

The aim of this study was to evaluate the activated partial thromboplastin time (APTT) and prothrombin time (PT)-based clot waveform analysis (CWA) in patients diagnosed with acute promyelocytic leukemia (APL). APTT-based and PT-based CWA parameters of patients diagnosed with APL were analyzed and compared with healthy volunteers. Four APTT-CWA parameters were noted, maximum velocity corresponding to the first peak of the first derivative (max1), maximum acceleration corresponding to the first peak of the second derivative (max2) and the corresponding peak times of max1 and max2 (Tmax1, Tmax2). For the PT-CWA, two PT-CWA parameters were noted, maximum velocity (max1') and the corresponding timing (Tmax1'). The results were expressed in medians. Mann-Whitney U test was used to compare the CWA parameters. Correlations were examined using the Spearman correlation test. Tmax1 and Tmax2 were significantly prolonged in patients with APL in comparison with healthy volunteers. Although max1 and max2 were lower in APL patients compared with healthy volunteers, no significant difference was noted. There was a strong and significant correlation between the DIC score and the parameters max1, max2 and max1' and a very strong and significant correlation between fibrinogen levels and max1, max2 and max1'. When comparing DIC patients with hypofibrinogenemia and DIC without hypofibrinogenemia, a significant difference was noted in max1, max2, Tmax1 and Tmax2. The APTT and PT-based CWA analysis is a good tool to evaluate the bleeding tendency in APL, as it offers a novel approach for evaluating global hemostasis, predicting the bleeding risk and delivering improvements to APL patients management.

The ISTH-BAT is a structured bleeding assessment tool to record and help diagnose patients with possible bleeding disorders. However, a few studies evaluated the utility of ISTH-BAT in diagnosing patients with platelet function defects (PFDs). In this study, we evaluated the diagnostic utility of ISTH-BAT in predicting PFDs among patients suspected of PFDs. Forty patients suspected of PFDs and 21 normal healthy controls were evaluated by the ISTH-BAT scoring system, light transmission aggregometry (LTA), ATP-releasing assays (lumi-aggregometry), and expression of CD62P for diagnosis of PFDs. Among 40 patients suspected of PFDs, 10 were diagnosed as PFDs using lumiaggregometry and CD62P. The ISTH-BAT score in patients suspected of PFDs [(6, interquartile range (IQR) 1-8] and patients with PFDs was significantly higher than the control group (0; IQR 0-0) ( P  < 0.001). Receiver operating characteristic curves indicate that ISTH-BAT is not able to discriminate patients with PFDs from those without PFDs (areas under the curve of 0.620 (95% confidence interval 0.415-0.825). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the ISTH-BAT in predicting the presence of PFDs, respectively, were 40, 73.3, 33.3, and 78.6% in the cut-off ISTH-BAT at least 4 in adult men, at least 6 in adult women, and at least 3 in children (age < 18). The ISTH-BAT scoring system has good discriminatory power in diagnosing patients with PFDs from healthy controls but is ineffective in differentiating them from those without PFDs.

Laboratory compliance implies to correlate instruments for coagulation parameter with a wide range of measure using patient samples or commercialized sets of frozen plasmas. The aim of this study was to evaluate the intra, inter-reproducibility and long-term stability of ExpertCor Routine (ECR) plasma sets (Stago) on different parameters. The study was realized in two laboratories on four different instruments. Inter-site and intra-site correlation of ECR sets for PT, aPTT, Fibrinogen, INR, factor V (FV) UFH and LMWH anti-Xa and intra-reproducibility of DDimer (DDI), factor VIII (FVIII:C) and antithrombin (AT) assays were tested. To evaluate ECR long-term stability, samples were tested until 180 after delivery in one laboratory. Intra-site evaluation correlation coefficients is around 1. All predefined criteria to fulfil good comparability between inter-site instruments are met with Passing slopes between 0.9 and 1.1 and intercepts ranging from -0.62 to 2.83%. Long-term stability evaluation does not show any deviation over 180 days for aPTT, fibrinogen, DDI, UFH, LMWH but a drift for FV with STA-NeoPTimal reagent. On contrary, AT and FVIII:C are not stable. PT in second has an excellent stability unlike PT in percentage. Our study validates the use of ECR sets for correlation between instruments and inter-sites agreement, as for parameters claimed on the products than for factor V and FVIII:C. The evaluation of stability confirming the possible extension of use for 180 days after delivery except for FVIII:C and AT. These plasmas sets are an excellent alternative to local plasma patient use to perform instrument comparison.

To examine real-life clinical data regarding hereditary factor XI (FXI) deficiency from a secondary care centre. Retrospective review of clinical records for every FXI:C 0.7 IU/ml or less reported from 2012 to 2020. Seventy-nine patients were included. Six (7.6%) had a severe deficiency (FXI:C <0.2 IU/ml). Only 55 (69.6%) patients were referred to the Haemostasis Centre. Among them, six (15%) were subsequently not identified at increased haemorrhagic risk before a surgical/obstetrical procedure. Thirty-three (41.8%) experienced at least one bleeding event, minor (25 patients) and/or major (16 patients). Minor bleedings were predominantly spontaneous and more frequent in women, major events were mainly provoked. No correlation was found between FXI:C and risk of bleeding ( P  = 0.9153). Lower FXI:C, but not a positive bleeding history, was related with higher likelihood of being referred to the Haemostasis Centre ( P  = 0.0333). Hereditary FXI deficiency prevalence is likely underestimated, real-life clinical practices outside reference centres could be suboptimal.

Preeclampsia is a worldwide contributor to maternal and fetal morbidity and mortality. Women with preeclampsia are in a hyper-coagulable state with increased risk of thromboembolic disease later in life compared with normal pregnant women. The contact system (CAS) in plasma can mediate thrombin generation and is an important contributor to thrombus growth, but the activation of CAS during pregnancy complicated by preeclampsia is not yet elucidated, and CAS may play a role in the pathophysiology of preeclampsia. Therefore, the aim of the study is to address thrombin generation, and in particular, the capacity of the CAS-mediated pathway in patients with preeclampsia compared with pregnant controls. One hundred and seventeen women with preeclampsia and matched controls were included. The project was registered at www.clinicaltrials.gov as NCT04825145. CAS and tissue factor induced thrombin generation, proteins C and S, antithrombin, and histidine-rich glycoprotein (HRG) were assessed. Women with preeclampsia had significantly increased CAS and tissue factor-induced endogenous thrombin potential (ETP), and HRG compared with controls, P  = 0.022, P  = 0.024, and P  = 0.02, respectively. The concentrations of protein C and antithrombin were significantly reduced in the preeclampsia group, P  = 0.024 and P  < 0.0001, respectively. No significant difference in the concentration of protein S was detected, P  = 0.06. This study demonstrates a significant increased CAS-induced ETP and an overall decrease of important regulators of coagulation in women with preeclampsia compared with controls. These aspects can contribute to the hyper-coagulable state characterizing preeclampsia.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a medical emergency requiring urgent plasma exchange and immunosuppressive agents. Recently, the therapeutic options have been expanded by the approval of a novel anti-von Willebrand factor (vWF) nanobody, caplacizumab, inhibiting vWF-platelet aggregation. Here, we present a rare case of a patient affected by immune-mediated TTP (iTTP) reporting ischemic stroke caused by a real iTTP exacerbation during caplacizumab administration and subsequent pancytopenia caused by cytomegalovirus (CMV) infection that mimicked another iTTP exacerbation. The case is a real-life example of a not-frequent iTTP exacerbation in the caplacizumab era and of the new management issues arising with the introduction of the new drugs in clinical practice, highlighting the need of new comprehensive response criteria and treatment guidelines.

Disseminated intravascular coagulation (DIC) is a complex disorder characterized by widespread activation of blood clotting mechanisms throughout the body. Understanding the role of vascular endothelial glycocalyx in the pathogenesis and treatment of DIC is crucial for advancing our knowledge in this field. The vascular endothelial glycocalyx is a gel-like layer that coats the inner surface of blood vessels. It plays a significant role in maintaining vascular integrity, regulating fluid balance, and preventing excessive clotting. In the pathogenesis of DIC, the disruption of the vascular endothelial glycocalyx is a key factor. Pathological conditions trigger the activation of enzymes, including heparanase, hyaluronase, and matrix metalloproteinase. This activation leads to glycocalyx degradation, subsequently exposing endothelial cells to procoagulant stimuli. Additionally, the ANGPTs/Tie-2 signaling pathway plays a role in the imbalance between the synthesis and degradation of VEG, exacerbating endothelial dysfunction and DIC. Understanding the mechanisms behind glycocalyx degradation and its impact on DIC can provide valuable insights for the development of targeted therapies. Preservation of the glycocalyx integrity may help prevent the initiation and propagation of DIC. Strategies such as administration of exogenous glycocalyx components, anticoagulant agents, or Tie-2 antibody agents have shown promising results in experimental models. In conclusion, the vascular endothelial glycocalyx plays a crucial role in the pathogenesis and treatment of DIC. Further research in this field is warranted to unravel the complex interactions between the glycocalyx and DIC, ultimately leading to the development of novel therapies.

Introduction: Venous thromboembolism (VTE) remains a significant source of postinjury morbidity and mortality. Beta-hydroxy beta-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (rosuvastatin) significantly reduced pathologic clotting events in healthy populations in a prior trial. Furthermore, acetylsalicylic acid (ASA) has been shown to be noninferior to prophylactic heparinoids for VTE prevention following orthopedic surgery. We hypothesized that a combination of rosuvastatin/ASA, in addition to standard VTE chemoprophylaxis, would reduce VTE in critically ill trauma patients.

Methods: This was a double-blind, placebo-controlled, randomized trial, evaluating VTE rates in two groups: ASA + statin (Experimental) and identical placebos (Control). Injured adults, 18-65 years old, admitted to the surgical intensive care unit without contraindications for VTE prophylaxis were eligible. Upon initiation of routine VTE chemoprophylaxis (i.e. heparin/heparin-derivatives), they were randomized to the Experimental or Control group. VTE was the primary outcome.

Results: Of 112 potentially eligible patients, 33% (n = 37, median new injury severity scale = 27) were successfully randomized, of whom 11% had VTEs. The Experimental group had no VTEs, while the Control group had 6 VTEs (4 PEs and 2 DVTs) in 4 (22%) patients (P = 0.046). The Experimental treatment was not associated with any serious adverse events. Due to the COVID-19 pandemic, the study was interrupted at the second interim analysis at <10% of the planned enrollment, with significance declared at P < 0.012 at that stage.

Discussion: The combination of ASA and rosuvastatin with standard VTE prophylaxis showed a favorable trend toward reducing VTEs with no serious adverse events. An appropriately powered phase III multicenter trial is needed to further investigate this therapeutic approach.

Level of evidence: Level II, Therapeutic.

Determinants of thrombotic events remain uncertain in patients with atrial fibrillation treated with direct oral anticoagulants (DOACs). Our aim was to identify risk factors associated with thromboembolism in patients with at atrial fibrillation on DOACs and to construct and externally validate a predictive model that would provide a validated tool for clinical assessment of thromboembolism. In the development cohort, prediction model was built by logistic regression, the area under the curve (AUC), and Nomogram. External validation and calibration of the model using AUC and Hosmer-Lemeshow test. This national multicenter retrospective study included 3263 patients with atrial fibrillation treated with DOACs. The development cohort consisted of 2390 patients from three centers and the external validation cohort consisted of 873 patients from 13 centers. Multifactorial analysis showed that heavy drinking, hypertension, prior stroke/transient ischemic attack (TIA), cerebral infarction during hospitalization were independent risk factors for thromboembolism. The Alfalfa-TE risk score was constructed using these four factors (AUC = 0.84), and in the external validation cohort, the model showed good discriminatory power (AUC = 0.74) and good calibration (Hosmer-Lemeshow test P value of 0.649). Based on four factors, we derived and externally validated a predictive model for thromboembolism with DOACs in patients with atrial fibrillation (Alfalfa-TE risk score). The model has good predictive value and may be an effective tool to help reduce the occurrence of thromboembolism in patients with DOACs.