Thrombosis Update最新文献

Pulmonary embolism is a common disease associated with significant morbidity and mortality. Existing validated risk stratification tools have enabled the rapid identification of patients with low versus high-risk pulmonary embolism. Intermediate-high risk pulmonary embolism is defined as pulmonary embolism with haemodynamic stability, evidence of right ventricular dysfunction and elevated cardiac biomarkers. The therapeutic management of intermediate-high risk pulmonary embolism in the acute setting is challenging as these patients are often unwell, but do not fulfil criteria for high-risk pulmonary embolism. Although current guidelines recommend prompt first-line treatment with systemic anticoagulation and monitoring for deterioration, alternative strategies are being increasingly considered in this cohort. These include systemic or catheter-directed thrombolysis, surgical embolectomy, and mechanical circulatory support. In this case series, we discuss three cases of intermediate-high risk pulmonary embolism with a focus on multidisciplinary decision making in clinical management. Following on from this, we provide a brief narrative review of the current literature and guidelines surrounding this topic, considering the risks and benefits of alternative therapy options on patient outcomes.

Aims

The identification of venous thromboembolism (VTE) using administrative databases is frequently required for reporting and research. The accuracy of International Classification of Diseases 10th revision (ICD-10) codes for VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), remains unclear. We examined the accuracy of ICD-10 codes for identifying VTE in adult and pediatric inpatients and outpatients.

Methods

For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Web of Science, CENTRAL, Epistemonikos and McMaster Superfilters from inception to July 25, 2023 for studies evaluating the sensitivity, specificity, positive predictive value (PPV), and/or negative predictive value (NPV) of ICD-10 codes for VTE in any anatomical location. We assessed risk of bias using QUADAS and certainty of evidence using GRADE. We calculated pooled sensitivity and specificity with 95% confidence intervals (CI) using a random-effects model.

Results

We included 24 studies in the qualitative synthesis and 7 in the meta-analysis. Pooled sensitivity for any VTE based on ICD-10 codes was 72% (95% CI 60–85%, low certainty); pooled specificity was 82% (95% CI 76–88%, low certainty). The PPV for ICD-10 VTE codes ranged from 0% to 100% (median: 80%) while the NPV ranged from 95.4% to 100% (median: 100%). ICD-10 codes for PE had a higher pooled sensitivity (91%) than for DVT (58%).

Conclusion

ICD-10 codes have moderate-to-high sensitivity and specificity for the identification of VTE in electronic databases. The certainty of evidence is low due to inconsistency and risk of bias. Further robust studies validating ICD-10 VTE codes are needed to improve reporting and better understand coding limitations.

Background

Venous thromboembolism (VTE) remains one of the leading causes of morbidity and mortality during pregnancy and the postpartum period. Despite that, the prevention and management of VTEs in pregnant patients is an area of great debate.

Objectives

The aim of this systematic review was to evaluate the risk of VTE recurrence during pregnancy for pregnant patients with prior personal history of VTE and the effect of LMWH on such risk.

Methods

MEDLINE and EMBASE were searched between January 2000 to December 2022. We included studies that evaluated pregnant patients with previous personal history of VTE and assessed VTE recurrence with or without thromboprophylaxis. A meta-analysis of proportions was done through a Freeman–Tukey transformation using random effect models.

Results

30 studies were included in this systematic review. The studies included 5075 pregnant patients with a previous history of DVT or PE. We found a wide variability in thromboprophylaxis strategies. The estimated pooled proportions of VTE recurrence were 2.5% (95% CI 1.8–3.3) in patients who were consistently on anticoagulation during pregnancy (pre- and post-partum), 4.7% (95% CI 1.8–8.8) in patients who received anticoagulation in the postpartum period only, and 13.6% (95% CI 6.5 to 22.8) in patients who were not on anticoagulation.

Conclusions

In patients with a previous VTE history receiving prophylactic anticoagulation (either both pre- and post-partum or post-partum only), the estimates of VTE recurrence were lower than for patients who did not receive prophylaxis, however, a direct comparison was not possible. The optimal thromboprophylaxis strategy remains unknown.

Thrombosis is a common and serious event in cancer patients. While risk factors are well established in solid tumors and have lead to guidance regarding prophylaxis, similar data and recommendations are lacking for patients with hematologic malignancies. Likewise treatment for established venous thrombosis in cancer patients has shifted from low molecular weight heparin to direct oral anticoagulants (DOACs) based on favorable outcomes with the latter drugs in most tumor types while hematologic malignancies remain understudied and the appropriateness of DOAC use in these patients is less certain. Reasons for the knowledge gaps that have developed regarding management of thrombosis in hematologic malignancies include their relative rarity compared to solid organ cancer making large scale trials difficult to complete, and the particular nature of blood cancers and their treatment giving rise frequently to severe thrombocytopenia which is typically regarded as an exclusion from clinical trials.

In this review we discuss landmark studies and other available literature regarding management of thromboembolism in hematologic malignancies and highlight unique features of these diseases and their treatment in this context.

Hospitalisation with an acute medical illness represents a significant risk factor for venous thromboembolism. Identification of patients at high risk of VTE at hospital admission and provision of appropriate thromboprophylaxis is a key intervention to improve patient safety during hospitalisation. The successful implementation of a systematic approach to VTE prevention in England highlights the effectiveness of this approach. However, the optimal strategy for identification of at-risk patients enabling targeted thromboprophylaxis provisions remains uncertain and many VTE events occur despite provision of appropriate thromboprophylaxis. In this narrative review, we discuss the pros and cons of commonly utilised VTE risk assessment tools for acutely ill medical patients, the current controversies in optimal dosing and duration of thromboprophylaxis and highlight special patient populations where further research is required.

Seronegative antiphospholipid syndrome has been suggested for patients with clinical manifestations highly suggestive of APS but persistently negative criteria-aPLs. Evidence gathered over the last years of research in thrombosis reported the pathogenic significance of non-criteria aPLs, among them IgA isotype. However, their role in the occurrence of neurological thrombosis, has not yet been studied. In this article, we aim to: (1) determine the prevalence of aβ2GP1 IgA in cerebral thrombosis, (2) study the association and (3) assess the diagnostic value of aβ2GP1. This study enrolled 70 patients with cerebral thrombosis without underlying autoimmune disease referred for thrombophilia assessment and 165 healthy controls. In addition to a coagulation screen and inherited thrombophilia testing, patients and controls were tested for criteria (LA; aβ2GP1; aCL IgM/IgG) and non-criteria aPLs (aβ2GP1 IgA; aCL IgA; aPS-PT; IgM/IgG). The overall aβ2GP1 IgA prevalence in patients was 61.4 % (43/70) mostly isolated in 50 % (35/70) while 50 % were positive for criteria-aPLs. aβ2GP1 IgA were the most prevalent aPLs in cerebral venous thrombosis compared with stroke (92.3 % vs 54.4 %). A significative relationship between aβ2GP1 IgA and the occurrence of CVT and stroke has been established (x² = 6.9, p = 0.008; x² = 4.03, p = 0.045). There was a high specificity of aβ2GP1 IgA testing for stroke (79 %) and CVT (100 %) despite a lower sensitivity (73 %; 52 %, respectively). The aβ2GP1 IgA testing improved considerably (50 %) the diagnosis of patients with cerebral thrombosis and negative criteria-aPLs, who may benefit from an adapted therapeutic care. Laboratory consensus criteria might consider aβ2GP1 IgA and set up a sequential approach improving APS diagnosis.

Introduction

Little is known about the clinical characteristics of women at increased risk for abnormal uterine bleeding (UB) during anticoagulation for venous thromboembolism (VTE).

Methods

We used the RIETE registry to identify the baseline characteristics of women developing abnormal UB during anticoagulation. We used logistic regression analysis to identify independent predictors for abnormal UB. Then, we built a prognostic score to identify at-risk women.

Results

From March 2001 through October 2022, there were 54,372 women with VTE. During anticoagulation (median, 181 days), 318 (0.6%) developed abnormal UB (major bleeding = 88, clinically relevant non-major (CRNM) = 230). On multivariable analysis, women aged <50 years, weighing >70 kg, with uterine cancer, recent UB, anemia, estrogen-related VTE, or receiving rivaroxaban or apixaban were at increased risk for abnormal UB. Using the prognostic score, 42,273 women (78%) were at low-risk, 8,828 (16%) intermediate-, and 3,271 (6.1%) at high-risk for abnormal UB. Their rates of abnormal UB were: 0.28 (95%CI: 0.23–0.35), 1.32 (95%CI: 1.07–1.61) and 7.12 (95%CI: 5.98–8.41) bleeds per 100 patient-years, respectively. The c-statistic was 0.80 (95%CI: 0.77–0.83). The rates of major UB were: 0.06 (95%CI: 0.04–0.09), 0.43 (95%CI: 0.30–0.60) and 1.85 (95%CI: 1.31–2.53) per 100 patient-years, respectively (c-statistic: 0.84; 95%CI: 0.80–0.89). The rates of CRNM uterine bleeding were: 0.21 (95%CI: 0.17–0.26), 0.85 (95%CI: 0.65–1.08), and 5.02 (95%CI: 4.09–6.10) bleeds per 100 patient-years, respectively (c-statistic: 0.78; 95%CI: 0.75–0.82).

Conclusions

Using 7 variables easily available at admission, we built a prognostic score that reliably identified women with VTE at increased risk for abnormal UB during anticoagulation.

Introduction

D-dimer is a crucial test to exclude deep vein thrombosis (DVT). We aimed to evaluate the performance of three D-dimer assays: STA-Liatest D-Di Plus (Diagnostica Stago), Tina-quant D-Dimer Gen. 2 (Roche Diagnostics), and INNOVANCE D-Dimer (Siemens Healthineers Diagnostics) in the exclusion of DVT.

Methods

Samples (n = 1032) and clinical data were acquired from a prospective outcome study (Rivaroxaban for Scheduled Work-up of Deep Vein Thrombosis – the Ri-Schedule study), which included patients referred to the emergency department with suspected lower-limb DVT. D-dimer was determined with STA-Liatest, and only patients with positive D-dimer values (≥0.5 μg/mL) as stand-alone, were referred for compression ultrasonography to confirm or exclude DVT. Patients were followed up 90 days after inclusion. Samples were also analyzed with Tina-quant Gen. 2, and INNOVANCE assays. The diagnostic performances of the three assays were investigated.

Results

Positive D-dimer (≥0.5 μg/mL) was found in 733 patients (71%) with STA-Liatest, 691 patients (67%) with Tina-quant Gen. 2, and 766 (74%) with INNOVANCE. DVT was confirmed by compression ultrasonography in 196 patients (27%) with positive D-dimer with STA-Liatest. Of those, six (3%) had negative D-dimer (<0.5 μg/mL) with at least one of the three assays yielding a failure rate of 0.7% with STA-Liatest, 2% with Tina-quant Gen. 2, and 2% with INNOVANCE. The sensitivity and negative predictive value (NPV) for STA-Liatest were 99.0% (95% CI 96.4–99.9) and 99.3% (95% CI 97.4–99.8), for Tina-quant Gen. 2 97.5% (95% CI 94.1–99.2) and 98.5% (95% CI 96.6–99.4), and for INNOVANCE 98.0% (95% CI 94.9–99.0) and 98.5% (95% CI 96.1–99.4) respectively. The efficiency to exclude DVT based on D-dimer as a stand-alone test was 29% (95% CI 26–33) for STA-Liatest, 33% (95% CI 30–37) for Tina-quant Gen. 2, and 26% (95% CI 23–29) for INNOVANCE.

Conclusion

STA-Liatest, Tina-quant Gen. 2, and INNOVANCE showed good performances with sensitivity ≥97% and NPV ≥98%. The efficiency to exclude DVT varied and was highest for Tina-quant Gen. 2, whereas the failure rate was lowest for STA-Liatest.

Background

Atrial fibrillation (AF) is common among patients with cancer. Patients with cancer and AF require anticoagulant therapy [direct oral anticoagulants (DOAC) or vitamin K antagonist (VKA)] for stroke and systemic embolism (SE) prevention. We sought to assess the rates of stroke/SE and major bleeding in patients with cancer and AF on oral anticoagulant therapy (DOAC or VKA).

Methods

A systematic search of MEDLINE and EMBASE was conducted. The primary efficacy and safety outcome were stroke/SE and major bleeding (as per the International Society on Thrombosis and Haemostasis definition), respectively. Incidence rates (IR) were pooled using random effects model (event per 100 patient-years). Incidence rate ratios (IRR) were computed using a Poisson regression model with associated 95% confidence intervals (CI) using R software (version 4.0.3).

Results

Of the total 2,153 article records that were screened, 22 observational studies from 12 different countries were included in the meta-analysis (n = 94,980 patients). The IR of stroke/SE was 1.81 (95% CI: 0.89 to 3.68) and 3.41 (95% CI: 1.38 to 8.41) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.63 (95%CI: 0.47–0.84)). The IR of major bleeding was 2.59 (95%CI: 1.54 to 4.38) and 3.60 (95% CI: 1.68 to 7.71) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.76 (95% CI: 0.55 to 1.04)).

Conclusion

DOACs compared to VKA seem to provide a significant reduction in the risk of stroke/SE and a good risk-benefit ratio profile for safety outcomes in this patient population.