Thrombosis Update最新文献

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.

Introduction

Pulmonary embolism (PE) is a frequent complication in COVID-19. However, the influence of PE on the prognosis of COVID-19 remains unclear as previous studies were affected by misclassification bias. Therefore, we evaluated a cohort of COVID-19 patients whom all underwent systematic screening for PE (thereby avoiding misclassification) and compared clinical outcomes between patients with and without PE.

Materials and methods

We included all COVID-19 patients who were admitted through the ED between April 2020 and February 2021. All patients underwent systematic work-up for PE in the ED using the YEARS-algorithm. The primary outcome was a composite of in-hospital mortality and ICU admission. We also evaluated long-term outcomes including PE occurrence within 90 days after discharge and one-year all-cause mortality.

Results

637 ED patients were included in the analysis. PE was diagnosed in 46 of them (7.2%). The occurrence of the primary outcome did not differ between patients with PE and those without (28.3% vs. 26.9%, p = 0.68). The overall rate of PE diagnosed in-hospital (after an initial negative PE screening in the ED) and in the first 90 days after discharge was 3.9% and 1.2% respectively. One-year all-cause mortality was similar between patients with and without PE (26.1% vs. 24.4%, p = 0.83).

Conclusions

In a cohort of COVID-19 patients who underwent systematic PE screening in the ED, we found no differences in mortality rate and ICU admissions between patients with and without PE. This may indicate that proactive PE screening, and thus timely diagnosis and treatment of PE, may limit further clinical deterioration and associated mortality in COVID-19 patients.

Introduction

Intravenous drug use continues to pose a substantial burden worldwide and little is known about the risk of venous thromboembolism (VTE) and its sequelae in people who inject drugs (PWID).

Methods

A systematic literature search was conducted on the prevalence of VTE and chronic venous disease in intravenous drug users, as well as on the prevalence of intravenous drug use among selected VTE patients. Two reviewers independently selected the articles and appraised their quality. A random-effect meta-analysis was performed to pool risks across studies.

Results

We included 18 studies with a total of 7691 patients. The overall prevalence of VTE among PWID was 29% (95%CI: 19–40%). Among patients diagnosed with VTE, 15% (95%CI: 10–20%) were PWID. Similar rates were confirmed in more recent studies published in the past decade, although these studies are often based on the general population from higher-risk areas. Reported rates of chronic venous disease ranged between 58% and 61%. The majority of the included studies had a low to moderate quality of evidence. We could not exclude a selection bias in the studies in geographical regions with high intravenous drug use prevalence.

Conclusion

VTE and chronic venous disease appear to be common and understudied complications of injective drug use. National programs for PWID patients should also focus on early and late VTE-associated complications.

Summary/background

Native Ecoli-Asparaginase (NEA)-containing regimens is an integral part of the ALL-treatment protocol for pediatric and young adults. By observation, polyethylene glycol-asparaginase (PEG-a) recipients have experienced heightened rates of thrombosis. We conducted a meta-analysis investigating which ASP formulation, instigated thrombosis more intensely. We examined potential risk factors and whether LMWH intervention influence VTE prevention.

Methods

209 studies were reviewed and analyzed. 18 PEG-a- and 15 NEA-containing studies are selected. Of these, 23 Non-LMWH and 10 LMWH thromboprophylaxis interventions are used for VTE rates comparison. One single-center and four comparative studies sought to determine the impact of LMWH on VTE prevention.

Results

The combined data set indicated a significantly higher proportion of VTE incidences in the PEG-a population compared to the NEA recipients. The non-LMWH study data showed a significantly higher proportion of VTE incidences in the PEG-a recipients. In the LMWH-containing data, PEG-a recipients had only slightly higher VTE outcome. LMWH has a favorable effect on VTE prevention as shown by the Forest plot. ASPs exposure and age ≥10 years ranked high-risk for VTE.

Conclusion

PEG-a- compared to NEA-treated adult patients are at significantly higher risk of developing VTE. LMWH demonstrated a protective effect on VTE prevention.

Background

Chronic obstructive pulmonary disease (COPD) and infections are risk factors for venous thromboembolism (VTE), but the reasons behind the associations are not fully known. Few studies have investigated whether lung function and respiratory symptoms in individuals without COPD are associated with VTE.

Objectives

To study the incidence of VTE in individuals without COPD and other major VTE risk factors, in relation to baseline lung function and respiratory symptoms, through a 44-year follow-up prospective cohort study.

Methods

As part of a health screening program, a total of 20,253 men and 7361 women underwent a baseline examination from 1974 to 1992, including a spirometry test and a self-administered questionnaire about respiratory symptoms, e.g., chronic bronchitis, cough, phlegm, and dyspnoea. Lung function was assessed through quartiles of forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC). Through linkage with national registers, all individuals were followed for incidence of VTE.

Results

Respiratory symptoms (cough and dyspnoea) at baseline were associated with an increased risk of incident VTE in women after adjustments for age, height, BMI, smoking status, varicose veins, and FEV1/FVC. The adjusted hazard ratio in relation to chronic bronchitis was 1.57 (95% confidence interval 1.17–2.11). Poor lung function was not associated with an increased risk of VTE after adjustments for potential confounders.

Conclusion

Women with respiratory symptoms of cough and dyspnoea without COPD have an increased risk of VTE, independent of lung function and major VTE risk factors. Further studies are needed to confirm the association and to study the clinical applicability of the results.

Background

Critically ill COVID-19 patients are at risk for venous thromboembolism (VTE). Therefore, they receive thromboprophylaxis and, when appropriate, therapeutic unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). To monitor heparins in COVID-19 disease, whole-blood rotational thromboelastometry (ROTEM) may be a promising alternative to the aPTT and anti-Xa assays.

Objective

To evaluate the ROTEM INTEM/HEPTEM ratios in mechanically ventilated COVID-19 patients treated with UFH and therapeutic LMWH.

Material and methods

A subcohort of mechanically ventilated COVID-19 patients of the prospective Maastricht Intensive Care Covid (MaastrICCht) cohort was studied. Anti-Xa, aPTT, and ROTEM measurements following treatment with UFH or therapeutic dose of LMWH (nadroparin) were evaluated using uni- and multivariable linear regression analysis and receiver operating characteristics.

Results

A total of 98 patients were included, of which 82 were treated with UFH and 16 with therapeutic LMWH. ROTEM-measured INTEM/HEPTEM CT ratio was higher in patients using UFH (1.4 [1.3–1.4]) compared to patients treated with LMWH (1.0 [1.0–1.1], p < 0.001). Both the aPTT and anti-Xa were associated with the CT ratio. However, the β-regression coefficient (95%CI) was significantly higher in patients on UFH (0.31 (0.001–0.62)) compared to therapeutic LMWH (0.09 (0.05–0.13)) for comparison with the anti-Xa assay. Furthermore, ROC analysis demonstrated an area under the curve for detecting UFH of 0.936(0.849–1.00), 0.851(0.702–1.000), and 0.645(0.465–0.826) for the CT ratio, aPTT, and anti-Xa, respectively.

Conclusion

The ROTEM INTEM/HEPTEM CT ratio appears a promising tool to guide anticoagulant therapy in ICU patients with COVID-19 disease, but associations with clinical endpoints are currently lacking.