Hamostaseologie最新文献

Immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cells are novel therapeutic strategies that enhance anticancer immunity by activating or engineering cancer-targeting T cells. The resulting hyperinflammation carries several side effects, ranging from autoimmune-like symptoms to cytokine release syndrome (CRS), with potentially severe consequences. Recent findings indicate that ICIs increase the risk of venous and arterial thromboembolic adverse events. Patients with prior VTE might be at higher risk of developing new events under ICI while other risk factors vary across studies. So far, data on CAR T-linked coagulopathies are limited. Hypofibrinogenemia in the presence of CRS is the most commonly observed dysregulation of hemostatic parameters. A rare but particularly severe adverse event is the development of disseminated intravascular coagulation activation, which can occur in the setting of CRS and may be linked to immune effector cell-associated hemophagocytic lymphohistiocytosis. While the increasing number of studies on thromboembolic complications and coagulation alterations under ICIs and CAR T therapies are concerning, these results might be influenced by the retrospective study design and the heterogeneous patient populations. Importantly, numerous promising new T cell-based immunotherapies are currently under investigation for various cancers and are expected to become very prominent therapy options in the near future. Therefore, coagulopathies and thrombosis under T cell-directed immuno- and anti-cancer therapies is important. Our review provides an overview of the current understanding of ICI- and CAR T-associated thromboembolism. We discuss pathogenic mechanisms of inflammation-associated coagulation activation and explore potential biomarkers for VTE.

The hemostatic system and cancer display a tight interconnection, and hemostatic imbalance frequently occurs in patients with cancer. While extensive knowledge about thrombotic risk has been generated, less is known about bleeding risk and associated risk factors. However, bleeding risk is of high significance as patients with cancer frequently receive therapeutic anticoagulation for various indications and/or are candidates for primary thromboprophylaxis. The risk of bleeding in patients with cancer is variable and difficult to assess in clinical practice. Certain clinical settings such as hospitalization, specific underlying risk factors (e.g., tumor type), and medications (e.g., anticoagulation) can contribute to the individual bleeding risk of a patient with cancer. In addition, some dynamic factors such as platelet count or kidney function have an impact. Particularly, data on baseline risk of bleeding are lacking to allow for risk assessment in cancer patients without anticoagulation. In contrast, risk assessment models for the prediction of bleeding events in cancer patients receiving anticoagulation have been developed; however, these have yet to be validated. The recognition of the importance of bleeding risk in cancer patients is growing, leading to an increasing number of studies investigating and reporting bleeding complications. As study designs and reporting of bleeding events vary, it is challenging to offer a clear synthesis of evidence. In this narrative review, we provide an overview of currently available data about incidence, risk factors, and clinical impact of bleeding events in patients with cancer, and critically review risk assessment models for bleeding in cancer patients during anticoagulant therapy.

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.

Wolfgang mondorf, frankfurt: DHR -2025, WAS GIBT ES NEUES?: Die DHR-Webseite (www.pei.de/DE/regulation/melden/dhr/dhr-node.html) beinhaltet neben fünf Publikationen, die letzte von 2020, einen Jahresbericht 2022/2023. Die Daten aus 2023 sind als vorläufig gekennzeichnet. Veröffentlicht sind die Anzahlen gemeldeter Fälle (Hämophilie A/B nach Schweregrad, von Willebrand Syndrom Typ 3 und andere, seltene Faktoren und Hemmkörper bei Kindern und Erwachsenen), sowie der Verbrauch bis 2022. Klinisch relevante Daten, wie z.B. Blutungen, die Teil der Einzelmeldung sind, finden sich nicht.

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.

Children with cancer have an increased risk for venous thromboembolic events (VTEs) compared to the healthy pediatric population. VTE rates in children with cancer vary among cancer types. Other VTE risk factors include central venous catheters and cancer therapies. VTE diagnosis relies on objective radiological imaging, and management to this date typically involves anticoagulant therapy. Low-molecular-weight heparins (LMWHs) are the most common choice. Evidence for primary VTE prevention is conflicting, and antithrombin replacement, LMWH, or apixaban have been studied. Recently, direct oral anticoagulants such as rivaroxaban or dabigatran were investigated for VTE treatment, showing promise in efficacy and safety. However, bleeding risks in this population need careful consideration, especially periprocedurally or with treatment-related thrombocytopenia. Prediction tools for VTE require adaptation for pediatric cancer patients. Progress in understanding and managing VTE in children with cancer is significant, with ongoing trials and real-world data contributing to improved strategies.

Cancer-associated thrombosis (CAT) is a common clinical problem in the treatment of cancer patients posing some unique challenges. These include the need to balance between the risk of recurrent thromboembolic events and bleeding complications in the individual cancer patient. A frequently encountered dilemma is the need for long-term anticoagulation in the setting of active malignancy. Until now, optimal duration, intensity, and type of anticoagulation in cancer patients remain an area of ongoing debate. In this case-based review, we present several challenging clinical scenarios and provide guidance on management. For optimal treatment results, CAT generally requires a multidisciplinary approach including specialists for thrombosis and hemostasis as well as hematology and oncology. Individual patient preferences should always be taken into account, especially in clinical situations with weak treatment evidence.

Chronic high-altitude hypoxia is associated with reduced platelet count, but it is unclear whether the decrease in platelet count is due to impaired production or increased clearance. This study examines how hypoxia affects platelet production and apoptosis and elucidates the impact of glycoprotein Ibα-von Willebrand factor interaction on platelets in rats using a hypobaric hypoxia chamber. The results showed that the number of megakaryocytes increased under hypoxia; however, the levels of differentiation and polyploidy decreased, while those of apoptosis increased. Platelet production did not reduce according to the reticulated platelet percentage, while platelet apoptosis enhanced; these results suggest that increased platelet clearance was the main reason behind platelet reduction. Our previous microarray results indicated that glycoprotein Ibα (GPIbα) expression increased under hypoxia, which was a protein involved in platelet clearance; therefore, we examined the interaction of platelet GPIbα with the von Willebrand factor (vWF) both in vivo and in vitro to explore the effect of this process on platelets and whether it is related to platelet apoptosis. Under hypoxia, the stronger interaction between GPIbα and vWF promoted platelet apoptosis; inhibiting this interaction reduced platelet apoptosis and increased platelet counts. Platelet reduction is associated with apoptosis induced by the interaction between GPIbα and vWF.

High neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of subclinical inflammation and have been associated with prognosis and mortality in many diseases. In this study, we evaluated the comparative value of NLR and PLR in identifying high mortality risk in patients hospitalized with acute pulmonary thromboembolism (PTE), and their relationship with the anatomical burden of thrombus.Patients who were followed up due to PTE were evaluated retrospectively. NLR and PLR were calculated from complete blood counts. The thrombus burden was assessed by the Qanadli score; based on the patients' archival computed tomography angiography images. Mortality prediction was based on an algorithm using the Pulmonary Embolism Severity Index, echocardiographic findings, and troponin levels.Three hundred-two PTE patients were included in the study. Median NLR, PLR, and Qanadli score values were higher in nonsurvivors, with NLR (8.4 [2.2-18.9]) vs. (3.1 [0.4-13.1]), PLR (317 [87.6-525.3]) vs. (124.4 [30-476.3]), and Qanadli scores (21 [3-26]) vs. (9 [1-28]), respectively (p < 0.001). We showed that setting a threshold value of >4.45 for NLR and >151.59 for PLR significantly predicts the high mortality-risk group. In the receiver operating characteristic analysis, when the threshold value for the Qanadli score distinguishing between low-risk and high-risk disease was set at 15.5, the sensitivity was calculated as 98.8% and the specificity was 94.9% (p = 0.001).This study showed that NLR, PLR, and Qanadli scores can provide essential contributions to the clinician's determination of the anatomical burden of thrombus and disease severity in PTE patients.