Thrombosis Update最新文献

Thrombotic microangiopathies during pregnancy are rare but may be life-threatening diseases for both the mother and the fetus. Thrombotic thrombocytopenic purpura (TTP) patients present with hemolytic anemia and thrombocytopenia associated with low ADAMTS-13 activity, a cleaving von Willebrand factor protein. Pregnancy has been described not only as a trigger of TTP but also as a phenotype modifier. In addition, hormonal changes induced by assisted reproduction technology (ART) swift the thrombotic – thrombolytic state towards coagulation, while increasing the pregnancy complications’ rate. We present a case of a 34-year-old pregnant woman, who conceived via ART and diagnosed with TTP at 13 weeks of gestation. She was initially treated with corticosteroids and daily plasmapheresis. Due to gradual unresponsiveness to treatment, rituximab was also added. After 3 doses, she was diagnosed with mild ovarian hyperstimulation syndrome, which resolved spontaneously after several weeks. She delivered a healthy neonate at 39⁺¹ weeks via emergency cesarean section due to fetal distress, while the postpartum follow-up was uneventful. In conclusion, TTP should be suspected to a pregnant woman with raised hemorrhagic risk presenting with hematuria, anemia and thrombocytopenia.

Background

Type 2 diabetes mellitus (T2DM) and atrial fibrillation are risk factors for stroke. The potential preventive effects of cardiovascular and antidiabetic treatments on stroke risk in patients with these diseases remain insufficiently documented. Sulfonylureas have also been reported to be associated with stroke. This study aimed to assess the risk of stroke according to the use of drugs (anticoagulants, antiplatelet agents, and oral antidiabetic drugs [OADs]) in patients with T2DM and nonvalvular atrial fibrillation (NVAF).

Methods

Patients with a history of T2DM and NVAF were identified from two systematic registries: a registry of patients with stroke and a registry of patients with atrial fibrillation. Patients with stroke were randomly matched to patients without prior stroke events based on age, sex, body mass index, and index date. All treatments administered 12 months before the index date were documented. The associations between anticoagulants, antiplatelet agents, and OADs and stroke were assessed using multivariate conditional logistic models that yielded adjusted odds ratios (aORs) and 95 % confidence intervals, controlling for risk factors identified in the univariate comparison of cases and matched referents.

Results

Three-hundred and fifteen patients with stroke with both diabetes and NVAF were matched to 523 referents with both diabetes and NVAF but no history of stroke. The aORs for the use of drugs and stroke were 0.24 [0.15–0.40] for direct oral anticoagulants (DOACs), 0.42 [0.27–0.67] for vitamin K agonists (VKA), 0.80 [0.52–1.24] for antiplatelet agents, and 0.68 [0.45–1.02] for OADs. No significant associations were found between individual OAD use and stroke risk. Similar results were obtained for ischemic stroke. Only VKAs were significantly associated with hemorrhagic stroke (odds ratio = 4.25 [1.16–15.64]).

Conclusions

Anticoagulant use was associated with a protective effect against the risk of stroke in patients with diabetes and NVAF, with no increase in the risk of hemorrhagic stroke for DOAC. No increased risk of stroke was observed because of any OAD, including sulfonylureas.

Introduction

Oral anticoagulant therapy comes at the cost of a significant bleeding risk. However, it is hard to predict which patients are at risk of major bleeding. Previously we found associations of Calibrated Automated Thrombinography (CAT) parameters obtained in the presence of TIX-5 (an inhibitor of the FV activation by FXa), and plasma levels of TFPIα, γ’-fibrinogen and soluble thrombomodulin with major bleeding in the BLEEDS cohort, a cohort especially powered to find new biomarkers of major bleeding during VKA therapy.

Methods

To determine and compare the predictive capability for major bleeding in the BLEEDS cohort of the above biomarkers, also in a combined model with clinical risk factors, we performed Univariable Prentice-weighted Cox regression analyses and Bayesian variable selection.

Results

The highest predictive value among the laboratory measures were found for thrombin generation lagtime in the presence of TIX-5 (TIX-5 lagtime per 25% increase, hazard ratio (HR) 1.11, 95%CI 1.04–1.18, p=0.001) and full-length tissue factor pathway inhibitor (TFPIα) (per 25% increase HR 1.12, 95%CI 1.03–1.21, p=0.008), which remained significant after correction for multiple testing, and independently associated with major bleeding after Bayesian variable selection. Only the addition of TIX-5 lagtime to the clinical risk factors improved prediction of major bleeding significantly (p<0.001).

Conclusion

We established predictive value of the lagtime of thrombin generation measured in the presence of TIX-5 for the risk of a major bleeding of patients on VKA therapy.

The incidence of venous thromboembolism (VTE) in cancer patients is 4–9 fold higher compared with the general population. The mortality rate of patients with cancer and VTE is more than 2-fold greater versus cancer patients without VTE. Given that the pathophysiology of thrombosis in cancer is multi-faceted, investigations of the mechanisms that regulate cancer-associated thrombosis (CAT) could improve the understanding and treatment of CAT. These mechanisms include activation of the coagulation and fibrinolytic systems. Tumor cells activate coagulation by expressing procoagulant molecules, releasing pro-inflammatory and pro-angiogenic cytokines, and adhering to vascular and blood cells. Tumor-secreted and tissue factor-positive extracellular vesicles are another major driver of CAT, while emerging studies have discovered a role for podoplanin (PDPN) in intratumoral thrombosis, hyper-coagulation, and enhanced VTE risk. In this article, we will review studies of PDPN in CAT, which together suggest that PDPN contributes not only to cancer progression and metastasis, but also to CAT. PDPN may therefore represent an attractive putative target for therapies that aim to simultaneously reduce cancer progression and associated VTE.

Background

For ambulatory cancer patients receiving systemic chemotherapy, adherence is low to recommended venous thromboembolism (VTE) prevention interventions. Previously, we identified implementation strategies to address barriers to adherence, including (1) conducting clinician education and training; (2) developing and distributing educational materials for clinicians; (3) adapting electronic health records to provide interactive assistance; and (4) developing and distributing educational materials for patients. The objective of this study was to develop these implementation strategies’ form (i.e., how and when) and content (i.e., information conveyed) as a critical step for implementation and dissemination.

Methods

To design and develop the form and content of the implementation strategies, we conducted multidisciplinary stakeholder panels with oncology clinicians, pharmacists, and hematologists. Over several panel discussions, we developed a low fidelity prototype. Participants performed preliminary usability testing, simulating patient care encounters. We also conducted interviews with three patients who provided additional feedback.

Results

The form and content for each strategy, respectively, included (1) concise training with a slide deck; (2) succinct summary of evidence for the interventions and support for anticoagulation management; (3) automated VTE risk-assessment and clinical decision support, including bleeding risk assessment and anticoagulation options; and (4) patient education resources. During development, audit and feedback was identified as an additional strategy, for which we created report cards to implement.

Conclusion

With stakeholder input, we successfully developed the form and content needed to put the implementation strategies into practice. The next step is to study the effect on the uptake of ambulatory VTE prevention recommendations in oncology clinics.

Anticoagulant therapy has always been tightly connected with bleeding risk, as two sides of the same coin. New insights in thrombosis and hemostasis prompted the development of intrinsic pathway inhibitors that promise to uncouple thrombosis and hemostasis. Treating and preventing thrombotic complications without the associated bleeding risk opens up many new possibilities for patients with an unmet need with the current anticoagulant drugs. Many candidate drugs are being investigated in phase I, II, and III clinical trials. In this review, we will introduce the new insights driving this evolution in drug development, whereafter the drugs under development and their clinical trials will be discussed.

Cancer associated thrombosis (CAT) is the second leading cause of death in oncologic patients and includes both venous thromboembolism (VTE) and arterial thrombotic events (ATE). In addition, cancer patients have an increased risk of developing atrial fibrillation (AF), which represents an additional risk factor for systemic thromboembolism in these patients. Both CAT and AF may be the first presentation of the oncologic disease or develop because of chemotherapy or radiotherapy. The management of the anticoagulation in cancer patients with CAT or AF is challenging, and data on these patients are lacking in specific settings/situations. Low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) represent the preferred treatment strategies in CAT, and DOACs in cancer patients with AF. However, the possible drug-drug interactions of DOACs and the bleeding risks in thrombocytopenic patients should be considered. The use of vitamin K antagonists (VKAs) in cancer patients with CAT or AF is challenging because of the unpredictable therapeutic response and high bleeding risk in patients with active disease who are undergoing chemotherapy and who may experience thrombocytopenia and/or changes in renal or hepatic function and, according to the recent guidelines, it is limited to specific situations (i.e. severe renal insufficiency, AF associated with prosthetic mechanical valves and severe mitral stenosis). A careful evaluation of the antithrombotic strategy with the best efficacy/safety ratio (in terms of doses or drugs) is always needed in cancer patients and anticoagulation for CAT and AF should be tailored individually. An ongoing consultation of oncologists/hematologists with cardiologists and coagulation experts in a multidisciplinary approach, with a periodic re-assessment of the benefit/risk ratio of anticoagulation with changes in cancer status/advancement and treatment plans is needed.

Background

Management with warfarin therapy becomes challenging globally due to the increased risk of adverse clinical outcomes from its use. In Africa, warfarin-related bleeding events and thromboembolic complications range from 0.006 % to 59 % and 1.6 %–7.5 %, respectively.

Objectives

This study aimed to determine adverse clinical outcomes of warfarin therapy and predictors among adult outpatients at Wallaga University Referral and Nekemte Comprehensive Specialized Hospitals from April 1, 2021 to March 31, 2023.

Methods

An institutional-based retrospective cross-sectional study was conducted from June 1 to July 31, 2023, by reviewing the patient's medical charts with warfarin indications. Descriptive statistics such as frequencies, percentages, means, and standard deviations were computed. Bivariable and multivariable logistic regression analyses were performed to check the association between dependent and independent variables. In multivariable logistic regression analysis, an adjusted odds ratio (AOR) with 95 % CI was determined and statistical significance was declared at a p-value <0.05.

Results

A total of 402 patients' medical charts with warfarin indications were reviewed. The mean age of the study participants was 38.9 ± 17.9 years and 271(67.4 %) were female patients. Bleeding events 19(4.7 %) and thromboembolic complications 32(8 %) were adverse clinical outcomes of warfarin therapy observed in this study. Warfarin therapy used for 4–6 months (AOR = 3.270; [CI: 1.043–10.252]; p-value = 0.042), hypertension comorbidity (AOR = 3.582; [CI: 1.015–12.642]; p-value = 0.047) and aspirin use (AOR = 5.043; [CI: 1.964–12.948]; p-value = 0.001) were the independent predictors of warfarin related bleeding events. Patients aged 41–64 years were 67.4 % less likely to develop warfarin-related thromboembolic complications than those patients aged 18–40 years (AOR = 0.326; [CI: 0.108–0.983]; p-value = 0.046).

Conclusions

Adverse clinical outcomes were found to be observed in less than one-fourth of the study participants in our study. Warfarin use for 4–6 months, hypertension comorbidity, and concomitant use of aspirin were identified as the independent predictors of warfarin-related bleeding events. The age range of 41–64 years was less likely predictive of warfarin-related thromboembolic complications. Institutional-based guidelines and clinical pharmacist involvement in anticoagulation management play a vital role in preventing adverse clinical outcomes.

Bleeding is the main complication of treatment with anticoagulants, the most common adverse drug event that leads to emergency department visits, hospital admission, and death. While direct oral anticoagulants (DOACs) reduce the risk of major, fatal and intracranial bleeding compared to vitamin K antagonists, DOAC-associated bleeding is associated with substantial short-term mortality rates. To optimize management and improve outcomes, a standardized approach to managing severe bleeding includes rapid recognition, provision of treatments to reverse anticoagulation or enhance hemostasis, resumption of anticoagulation safety after bleed cessation and attention to secondary prevention measures and long-term monitoring. This narrative review outlines a pragmatic multimodal framework for severe DOAC bleed management with case examples to illustrate key principles.