Journal of Thrombosis and Haemostasis最新文献

Background: Managing unfractionated heparin (UFH) during percutaneous mechanical circulatory support (PMCS) for cardiogenic shock (CS) is challenging due potential discrepancies between coagulation tests.

Objectives: To study the causes and consequences of discrepancies between anti-Xa and activated partial thromboplastin time (APTT) for UFH-monitoring during micro-axial flow pump support (Impella™) for CS.

Patients/methods: We assessed patients in CS supported with Impella™ in two tertiary care centres over 62 months. UFH was titrated based on anti-Xa levels with parallel APTT measurements. In-range anti-Xa levels were considered between 0.20-0.30IU/mL or 0.31-0.50IU/mL and corresponding APTT levels were 40-55s and 56-80s, respectively. Pearson correlation was calculated between anti-Xa and APTT. Samples with in-range anti-Xa but prolonged APTT were analyzed for abnormalities in INR (≥1.5) and/or fibrinogen (<1.5g/l). Mortality during Impella™ support was then compared in those with and without additional coagulation abnormalities (Chi-square test).

Results: Correlation between anti-Xa and APTT was weak (r=0.50, p<0.001, N=2447). When anti-Xa in range (N=1914 samples), 24% had short, 52% had in-range, and 24% had prolonged corresponding APTT. Of 57 patients with prolonged APTT, 28 had abnormal same-day INR and/or fibrinogen, whereas 29 had normal fibrinogen and INR. Mortality was higher in patients with abnormal INR and/or fibrinogen compared to those with normal fibrinogen and INR (32% vs. 10%; p=0.043).

Conclusions: Anti-Xa/APTT-discrepancies are frequent during pMCS for CS, highlighting the importance of a multiple testing strategy. Outcomes of patients with prolonged APTT was related to the presence of abnormal INR and/or fibrinogen, suggesting serious concomitant underlying disease.

Background: Limited data exists on persons with rare bleeding disorders (RBDs) possessing a heterozygous genotype, as most studies focus on bi-allelic genotypes and more severe coagulation factor deficiencies. A growing body of evidence suggests that persons with a heterozygous genotype experience clinically relevant bleeding symptoms.

Objectives: Explore the incidence of bleeding symptoms and postoperative bleeding in persons with a heterozygous genotype.

Patients/methods: This cross-sectional sub-study of the Rare Bleeding Disorders in the Netherlands study (2017-2019) included persons with rare coagulation factor deficiencies and disorders of fibrinolysis with a heterozygous or bi-allelic genotype. Clinical data and laboratory samples were collected during a single study visit along with questionnaires.

Results: Eighty-six persons with a heterozygous genotype and fifty-five with a bi-allelic genotype were included. Median factor activity levels in persons with a heterozygous genotype approached 50% with considerable heterogeneity (range: 11-93%). In 75%, persons with a heterozygous genotype reported bleeding severity of grade II or III. Female specific bleeding was common. In total, 425 surgical procedures were performed. Persons with a heterozygous genotype were less likely to receive periprocedural treatment, and omission of periprocedural treatment was associated with postoperative bleeding in procedures with intermediate-high bleeding risk. Postoperative bleeding was comparable for persons with a heterozygous genotype (35%; 59/171) and a bi-allelic genotype (35%; 86/247, p=.926).

Conclusions: In our RBD population, the majority of persons possessing a heterozygous genotype exhibited spontaneous bleeding symptoms. Especially in intermediate-high risk procedures, a proactive approach to periprocedural hemostatic treatment in persons with a heterozygous genotype seems beneficial.

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is thought to result from incomplete resolution of vascular obstruction following acute pulmonary embolism (PE). However, at least 25% of CTEPH patients do not have a documented episode of acute venous thromboembolism (VTE). We hypothesized that patients without a VTE in their past medical history have different clinical and radiological characteristics compared to CTEPH patients with previous acute VTE.

Methods: Baseline data and history of VTE were retrospectively retrieved from the charts of all CTEPH patients included between 2014-2022 in the Amsterdam UMC CTEPH registry. CT pulmonary angiography, right heart catheterization and pulmonary function tests were performed in all patients. Subsegmental disease was defined by the presence of a contrast defect in the pulmonary arterial vessels after the first arterial branch division.

Results: A total of 262 CTEPH patients were included; 47 patients (18%) did not have previous acute VTE. Baseline radiological assessment showed that subsegmental disease was more frequent in patients without previous VTE (n=16/43; 35%, 95%CI: 22-49) compared to patients with previous VTE (n= 27/214; 13% (95%CI: 9.0-18), OR: 2.6 (95% CI: 1.2-5.7). The patients without previous VTE were less frequently assigned to pulmonary endarterectomy (PEA) compared to patients with acute VTE (30%, (95% CI: 18-44) versus 56%, (95% CI: 49-62); OR: 0.5 (95% CI: 0.2-0.9). Comorbidities, pulmonary function and hemodynamics were not different.

Conclusion: CTEPH patients without previous VTE, had more distally located disease on imaging compared to CTEPH patients with previous VTE and were less often subjected to PEA.

Monitoring unfractionated heparin (UFH) to ensure effective anticoagulation may be performed using anti-factor Xa activity (anti-Xa) instead of the activated partial thromboplastin time. However, in patients who have been treated with oral factor Xa (FXa) inhibitors (apixaban, rivaroxaban, and edoxaban) while switching to UFH therapy, there is a risk that these oral anti-FXa drugs could interfere with UFH calibrated anti-Xa monitoring. This may lead to inappropriate anticoagulation management. This report of the ISTH Subcommittee on Control of Anticoagulation summarizes the evidence on the risk of interference from previous treatment with oral FXa inhibitors and UFH anti-Xa after heparin initiation. This communication provides pragmatic recommendations for UFH initiation and management with anti-Xa monitoring after switching from oral FXa inhibitors.

Background: The management of recurrent venous thromboembolism (VTE) despite anticoagulant treatment in patients with cancer is uncertain. To address this, we used data from the Hokusai VTE Cancer trial, which compared edoxaban with dalteparin to treat cancer-associated VTE.

Methods: In this post-hoc analysis, we characterized and evaluated anticoagulant treatment strategies during and after on-treatment recurrent VTE, including the type and dose of anticoagulant. All patients with adjudicated on-treatment recurrent VTE within 12 months after randomization were included. Outcomes were second recurrent VTE and major bleeding within 3 months after the first recurrent VTE.

Results: A total of 67 patients developed on-treatment recurrent VTE while receiving therapeutic-dose edoxaban (31%), therapeutic-dose low-molecular-weight heparin (LMWH) (34%), maintenance-dose LMWH (21%), or other therapies (14%). After the recurrent event, 28 patients (42%) received an increased dose, 35 (52%) a comparable dose, and 4 (6%) a reduced dose or stopped anticoagulants. Common treatment regimens included supratherapeutic-dose LMWH (21%), therapeutic-dose LMWH (51%), DOAC (16%), or another treatment strategy (12%). In the 3 months after recurrent VTE, 6 (9%) patients had a second recurrence, and 7 (10%) had major bleeding.

Conclusions: Treatment strategies for recurrent VTE in patients with cancer are heterogeneous. The risk of a second recurrence and major bleeding are considerable. More studies are needed to determine the optimal treatment strategy for recurrent cancer-associated thrombosis.