Hamostaseologie最新文献

This review summarizes the rationale and current data on the use of thrombopoietin receptor agonists (TPO-RAs) for treating severe thrombocytopenia in infants, children, and adolescents. It focuses on substances that have been approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for pediatric patients. Romiplostim and eltrombopag are already established as second-line treatment for persistent or chronic immune thrombocytopenia (ITP). As in adults, TPO-RAs are currently also evaluated in severe aplastic anemia (SAA), chemotherapy-induced thrombocytopenia (CIT), myelodysplastic syndromes (MDS), and poor engraftment after hematopoietic stem cell transplantation in pediatric and adolescent patients. Moreover, studies on the implication of TPO-RA in treating rare inherited thrombocytopenias, such as Wiskott-Aldrich syndrome (WAS), congenital amegakaryocytic thrombocytopenia (CAMT), or MYH9-associated thrombocytopenia, deserve future attention. Current developments include testing of avatrombopag and lusutrombopag that are approved for the treatment of thrombocytopenia associated with chronic liver disease (CLD) in adult patients. In pediatric and adolescent medicine, we expect in the near future a broader use of TPO-RAs as first-line treatment in primary ITP, thereby considering immunomodulatory effects that increase the rate of sustained remission off-treatment, and a selective use in rare inherited thrombocytopenias based on current clinical trials.

Patients with an unexplained mild to moderate bleeding tendency are diagnosed with bleeding disorder of unknown cause (BDUC), a classification reached after ruling out other mild to moderate bleeding disorders (MBD) including von Willebrand disease (VWD), platelet function defects (PFDs), coagulation factor deficiencies (CFDs), and non-hemostatic causes for bleeding. This review outlines our diagnostic approach to BDUC, a diagnosis of exclusion, drawing on current guidelines and insights from the Vienna Bleeding Biobank (VIBB). According to guidelines, we diagnose VWD based on VWF antigen and/or activity levels ≤50 IU/dL, with repeated VWF testing if VWF levels are <80 IU/dL. This has been introduced in our clinical routine after our findings of diagnostically relevant fluctuations of VWF levels in a high proportion of MBD patients. PFDs are identified through repeated abnormalities in light transmission aggregometry (LTA), flow cytometric mepacrine fluorescence, and glycoprotein expression analysis. Nevertheless, we experience diagnostic challenges with regard to reproducibility and unspecific alterations of LTA. For factor (F) VIII and FIX deficiency, a cutoff of 50% is utilized to ensure detection of mild hemophilia A or B. We apply established cutoffs for other rare CFD being aware that these do not clearly reflect the causal role of the bleeding tendency. Investigations into very rare bleeding disorders due to hyperfibrinolysis or increase in natural anticoagulants are limited to cases with a notable family history or distinct bleeding phenotypes considering cost-effectiveness. While the pathogenesis of BDUC remains unknown, further explorations of this intriguing area may reveal new mechanisms and therapeutic targets.

Splanchnic vein thrombosis (SVT) is a rare type of venous thromboembolism occurring within the splanchnic venous system. Portal vein thrombosis is the most common presentation, while Budd-Chiari syndrome is the least common. Liver cirrhosis and abdominal solid cancer are the main local risk factors for SVT, whereas myeloproliferative neoplasms are the predominant systemic risk factors. Signs and symptoms of SVT are nonspecific and include abdominal pain, gastrointestinal bleeding, and ascites. Asymptomatic SVT is not uncommon, and the majority would be detected incidentally on routine abdominal imaging performed for the follow-up of liver diseases and tumors. The management of SVT aims to prevent thrombus progression, promote vessel recanalization, and prevent recurrent venous thromboembolism. Anticoagulation should be started early in order to increase the chances of vessel recanalization and reduce the risk of portal hypertension-related complications. Direct oral anticoagulants have been included in recent guidelines, as alternatives to vitamin K antagonists, after clinical stability has been reached; however, caution is required in patients with liver or kidney dysfunction. Treatment duration is based on the presence (or absence) and type (transient vs. permanent) of risk factors. This narrative review aims to summarize the latest evidence on SVT, with a particular focus on the anticoagulant treatment in special categories of patients (e.g., liver cirrhosis, solid cancer, myeloproliferative neoplasms, pancreatitis, incidentally detected SVT, Budd-Chiari syndrome, and chronic SVT).

Cardio-oncology, a burgeoning subspecialty, addresses the complex interplay between cardiology and oncology, particularly in light of increased cardiovascular (CV) disease mortality in cancer patients. This review provides a comprehensive overview of cardio-oncology with a focus on the therapies used in hematological malignancies. We explore the bidirectional relationship between heart failure and cancer, emphasizing the need for collaborative care. The review discusses risk stratification, highlighting the importance of baseline CV risk assessment and personalized surveillance regimens. Primary and secondary prevention strategies, including pharmacological interventions, are outlined. The review also delves into the cardiotoxicity associated with hematological cancer therapies, focusing on anthracyclines, Bruton kinase inhibitors, BCR-ABL tyrosine kinase inhibitors, CAR-T cell therapy, immune checkpoint inhibitors, multiple myeloma treatments, and hematopoietic stem cell transplantation. We then highlight the high risk of venous and arterial thromboembolisms in cancer patients and the challenges of anticoagulation management in cardio-oncology. Finally, the review touches on the importance of long-term follow-up and appropriate screening in cancer survivors at high risk of CV morbidity and mortality, based on their CV risk profile and the type and dose of cardiotoxic therapies they received such as anthracyclines or high radiation doses.

Sepsis has been a major health problem for centuries and it is still the leading cause of hospital deaths. Several studies in the past decades have identified numerous biochemical abnormalities in severe cases, and many of these studies provide evidence of the perturbation of the hemostatic system. This can result in complications, such as disseminated intravascular coagulation that can lead to multiorgan failure. Nevertheless, large clinical studies have demonstrated that the simple approach of inhibiting the coagulation processes by any means fails to provide significant improvement in the survival of septic patients. A cause of this failure could be the fact that in sepsis the major clinical problems result not primarily from the presence of the infective agent or enhanced coagulation but from the complex dysregulated systemic host response to pathogens. If this overt reaction is not fully deciphered, appropriate interference is highly unlikely and any improvement by conventional therapeutic interventions would be limited. Cellular activation in sepsis can be targeted by novel approaches like inhibition of the heterotypic cellular interactions of blood cells by targeting surface receptors or posttranscriptional control of the hemostatic system by noncoding ribonucleic acid (RNA) molecules. Stable RNA molecules can affect the expression of several proteins. Thus, it can be anticipated that modulation of microRNA production would result in a multitude of effects that may be beneficial in septic cases. Here, we highlight some of the recent diagnostic possibilities and potential novel routes of the dysregulated host response.

Inherited platelet disorders (IPDs) represent a heterogeneous group of disorders that include both quantitative (thrombocytopenia or thrombocytosis) and qualitative (thrombocytopathy) defects. To gain better knowledge about the prevalence, pathogenesis, and clinical consequences of specific diseases, to improve diagnosis and treatment of patients with IPD, and to support translational research on a genetic, molecular, and physiological basis, the THROMKIDplus study group currently comprising 24 sites in Germany, Austria, and Switzerland decided to establish a patient registry with associated biomaterial banking for children. This registry is designed as a retrospective-prospective, multicenter observational study and supposed to launch in the second half of 2023. Blood smears, plasma, platelet pellets, and DNA of patients will be stored in certified biomaterial banks for future translational research projects. The main inclusion criteria are (1) diagnosis of or highly suspected IPD after assessment of a THROMKIDplus competence center and (2) patients aged 0 to 17 years. Initial and follow-up data on patient history, laboratory parameters, standardized documentation of bleeding tendency, and congenital defects are collected according to good clinical practice and current data protection acts by using the MARVIN platform, a broadly used data management system supported by the German Society for Pediatric Oncology Hematology (GPOH). The THROMKIDplus study group intends to enroll ∼200 patients retrospectively and an annual amount of ∼50 patients prospectively.