Hamostaseologie最新文献

Patients with cancer are at increased risk of venous thromboembolism (VTE). Treatment of VTE remains challenging due to a significant risk of both VTE recurrence and bleeding compared with patients without underlying malignancy. Moreover, patients with cancer often present with several comorbidities such as tumor- or treatment-induced bone marrow failure, renal impairment, and extensive concomitant anticancer or supportive medication, resulting in potential drug-drug interactions. Further challenging circumstances include gastrointestinal (GI) disorders, in the context of a GI intraluminal tumor itself, GI surgery, or systemic therapy-induced GI toxicity. However, treatment options and study data in the management of cancer-associated thrombosis (CAT) have expanded over the last few years. As a result, it is becoming increasingly important to assess the patient's individual risk of bleeding and its comorbidities, and the patient's personal preferences. Prospectively, further therapeutic strategies such as factor XIa inhibitors are under clinical investigation. The aim of our narrative review is to summarize the current literature on therapy options for CAT, including common treatment situations encountered in the management of patients with cancer.

Over the past two decades, the incidence of cancer-associated thrombosis (CAT) has increased. It is nowadays a common and often serious complication among patients with cancer. Although medical thromboprophylaxis is recommended for most surgical and nonsurgical cancer patients, it has been infrequently used in ambulatory patients with cancer because of the burden of treatment and concerns about bleeding. However, various risk assessment scores are now available and randomized placebo-controlled trials have established the efficacy of low-molecular-weight heparin or the direct oral Xa inhibitors rivaroxaban and apixaban in ambulatory patients with cancer at high risk of venous thromboembolism (VTE). This review provides an overview of (1) primary thromboprophylaxis in the setting of hospitalized surgical and medical patients, (2) extended thromboprophylaxis after hospital discharge, (3) performance of risk assessment tools for CAT, and (4) primary thromboprophylaxis in ambulatory patients with cancer. The aim is to provide support to physicians in identifying ambulatory patients with cancer at high VTE risk who benefit most from medical thromboprophylaxis according to current recommendations from international guidelines.

Introduction:  Platelets greatly contribute to cardiovascular diseases. We sought to explore the association of platelet counts with infarct size and outcome in patients presenting with acute ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention (PPCI).

Methods and results:  In this retrospective study, we grouped 1,198 STEMI patients into tertiles (T) based on platelet count on admission: T1 = 102-206 [10⁹ platelets/L] (n = 402), T2 = 207-259 [10⁹ platelets/L] (n = 396), and T3 = 260-921 [10⁹ platelets/L] (n = 400). Primary endpoint was 1-year all-cause mortality. Patients with highest platelet counts on admission showed the greatest area at risk and infarct size: area at risk (median) was 22.0% (interquartile range [IQR]: 12.0-39.8%) in T1, 21.0% (IQR: 11.0-37.1%) in T2, and 26.0% (IQR: 14.9-45.0%) of the left ventricle in T3 (p = 0.003); final infarct sizes after 7 to 14 days were as follows: 10.0% (IQR: 2.0-21.0%) in T1, 9.0% (IQR: 2.0-20.7%) in T2, and 12.0% (IQR: 3.0-27.3%) of the left ventricle in T3 (p = 0.015) as serial imaging revealed. At 1 year, 16 all-cause deaths occurred in T1, 5 in T2, and 22 in T3 (log-rank test, p = 0.006). After adjustment, T1 and T3 were associated with all-cause 1-year mortality (T1: hazard ratio [HR] = 3.40, 95% confidence interval [CI] = 1.23-9.54, p = 0.02; T3: HR = 3.55, 95% CI = 1.23-9.78, p = 0.01) compared with T2. At 5 years, all-cause mortality remained numerically higher in the T1 and T3.

Conclusions:  In patients with STEMI undergoing PPCI, low and high blood platelet levels on admission were associated with increased long-term mortality (Fig. 1).

Tissue factor (TF) is a transmembrane protein essential for hemostasis. Different forms of active TF circulate in the blood, either as a component of blood cells and extracellular vesicles (EVs) or as a soluble plasma protein. Accumulating experimental and clinical evidence suggests that TF plays an important role in thrombosis. Many in-house and commercially available assays have been developed to measure TF-dependent procoagulant activity or antigen in blood and have shown promising results for the prediction of disease outcomes or the occurrence of thrombosis events in diseases such as cancer or infectious coagulopathies. This review addresses the different assays that have been published for measuring circulating TF antigen and/or activity in whole blood, cell-free plasma, and EVs and discusses the main preanalytical and analytical parameters that impact results and their interpretation, highlighting their strengths and limitations. In the recent decade, EVTF assays have been significantly developed. Among them, functional assays that use a blocking anti-TF antibody or immunocapture to measure EVTF activity have higher specificity and sensitivity than antigen assays. However, there is still a high variability between assays. Standardization and automatization are prerequisites for the measurement of EVTF in clinical laboratories.

Arterial (ATE) and venous (VTE) thromboembolic complications are common causes of morbidity and mortality in BCR-ABL-negative myeloproliferative neoplasms (MPNs). However, there are few studies that include all MPN subtypes and focus on both MPN-associated ATE and VTE. In our single-center retrospective study of 832 MPN patients, a total of 180 first thromboembolic events occurred during a median follow-up of 6.6 years (range: 0-37.6 years), of which 105 were VTE and 75 were ATE. The probability of a vascular event at the end of the follow-up period was 36.2%, and the incidence rate for all first ATE/VTE was 2.43% patient/year. The most frequent VTE localizations were deep vein thrombosis with or without pulmonary embolism (incidence rate: 0.59% patient/year), while strokes were the most frequent ATE with an incidence rate of 0.32% patient/year. When comparing the group of patients with ATE/VTE (n = 180) and the group without such an event (n = 652) using multivariate Cox regression analyses, patients with polycythemia vera (hazard ratio [HR]: 1.660; [95% confidence interval [CI] 1.206, 2.286]) had a significantly higher risk of a thromboembolic event than the other MPN subtypes. In contrast, patients with a CALR mutation had a significantly lower risk of thromboembolism compared with JAK2-mutated MPN patients (HR: 0.346; [95% CI: 0.172, 0.699]). In summary, a high incidence of MPN-associated VTE and ATE was observed in our retrospective study. While PV patients or generally JAK2-mutated MPN patients had a significantly increased risk of such vascular events, this risk was reduced in CALR-mutated MPN patients.

During routine treatment, plasma samples of patients with hemophilia A or acquired hemophilia A are frequently analyzed for the presence of FVIII-specific antibodies. While only inhibitory antibodies can be detected by the Bethesda assay, inhibitory and non-inhibitory antibodies can be detected by ELISA. However, plasma samples of patients frequently contain endogenous or substituted FVIII, hence interfering with both types of analyses. One option for the inactivation of FVIII is heat denaturation, which unfortunately has been shown to lead to high background signals complicating the discrimination of negative and positive plasma samples. In the current study, we developed a method of acid denaturation for FVIII-containing plasma samples that can help identify samples containing FVIII-specific antibodies and compared the effects of heat and acid denaturation on the detection of FVIII-antibody interactions in a monoclonal setting. The aim of our study was to establish an analysis that allows safer treatment decisions in the context of tolerance to FVIII.