Sustained Survival Benefit of Emicizumab and Postponed Immunosuppression in Acquired Hemophilia A.

Acquired hemophilia A (AHA) is a severe bleeding disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII). Standard treatment involves immunosuppressive therapy (IST), which carries a significant risk of serious infections, the leading cause of death in AHA patients. The GTH-AHA-EMI study investigated the use of emicizumab to prevent bleeding during the first 12 weeks of management while postponing IST.

Implications of the API-CAT Trial for Extended Secondary Prophylaxis of Cancer-associated Venous Thromboembolism: Guidance from an Expert Panel.

Venous thromboembolism (VTE) is an increasingly frequent complication of solid tumors and hematological malignancies, significantly contributing to morbidity and mortality. In patients with acute cancer-associated VTE, therapeutic anticoagulation with direct oral factor Xa inhibitors (DXIs) or low-molecular-weight heparin (LMWH) for 3 to 6 months is recommended by clinical practice guidelines based on randomized controlled trials. Although extended secondary VTE prophylaxis should be considered in patients with persisting active cancer, the type, intensity, and duration of continued anticoagulation have not been rigorously studied until recently.

Impact of anesthesia type on postoperative pain and outcomes in primary hip and knee arthroplasty: a retrospective register analysis.

Background: This study explores the effects of single-sided spinal versus general anesthesia on patients undergoing hip and knee arthroplasty within a fast-track surgery environment. Although many studies suggest better outcomes with neuraxial anesthesia in lower extremity joint replacement, its benefits in fast-track surgery remain unclear.

Methods: A retrospective analysis was performed on data derived from 283 patients.

Changes in Hemophilia Treatment in the Eastern Part of Germany between 2015 and 2021-Data from the Kompetenznetz Hämorrhagische Diathese Ost (KHDO).

Introduction:  Treatment options for patients with hemophilia (PWH) have changed substantially in the last years. This study aimed to compare hemophilia treatment in the eastern part of Germany in 2021 with data from 2015.

Methods:  Substitution diaries and patient records of PWH from 2021 were collected in 13 hemophilia centers from the "Kompetenznetz Hämorrhagische Diathese Ost" (KHDO) and compared with 2015.

Efficacy of emicizumab in patients with severe haemophilia A without factor VIII inhibitors in Germany: evaluation of real-life data documented by the smart medication eDiary.

Background: Systematically documented data on real-world use of emicizumab, a bispecific antibody factor (F)VIII mimetic, are still lacking in people with severe haemophilia A (PwSHA). Smart medication, a real-time, online platform, monitors treatment administration and outcomes for people with haemophilia A in Germany.

Objective: To evaluate annualised bleeding rates (ABRs) and annualised joint bleeding rates (AJBRs), using data documented in the smart medication eDiary, for PwSHA receiving emicizumab.

Expert Opinion for Defining a Severe Bleeding Phenotype to Guide Prophylaxis in Patients with Nonsevere Hemophilia.

Prophylaxis is the standard of care for patients with severe hemophilia, patients with moderate hemophilia, or those with another congenital bleeding disorder that is associated with a severe bleeding phenotype and/or a high risk of spontaneous life-threatening bleeding. Patients with nonsevere hemophilia (factor VIII [FVIII] ≥ 1%) may also have a bleeding phenotype that requires prophylaxis. To date, however, there are no clear criteria as to when prophylaxis is indicated in these patients.

Emicizumab versus immunosuppressive therapy for the management of acquired hemophilia A.

Background: Acquired hemophilia A (AHA) is an autoimmune bleeding disorder caused by neutralizing antibodies against coagulation factor VIII. Immunosuppressive therapy (IST) is standard of care to eradicate autoantibody production and protect from further bleeding but carries a risk of severe infection and mortality in frail patients with AHA. Recently, emicizumab has been studied for its potential to reduce the need for early and aggressive IST.

Imbalance of the von Willebrand Factor - ADAMTS-13 axis in patients with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S).

Background: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an ultra-rare, autosomal-dominant small vessel disease caused by loss-of-function variants in the gene TREX1. Recently, elevated serum levels of von Willebrand Factor Antigen (vWF-Ag) pointed to an underlying endotheliopathy, and microvascular ischemia was suggested to contribute to the neurodegeneration in RVCL-S. Aim of this study was to further elucidate the endotheliopathy in RVCL-S.

Patient perspective on living with mild hemophilia in Germany: results from a nationwide survey.

Introduction: The disease burden and bleeding risk of patients with mild hemophilia may be underestimated. Their health-related quality of life (QoL) may be negatively impacted by insufficient treatment and bleed-related joint damage connected to a potentially delayed diagnosis.

Aim: This study aims to gain information on the care reality and QoL of patients aged ≥12 years with mild hemophilia in Germany.

Measurement of recombinant porcine factor VIII in patients with congenital haemophilia A and inhibitors in the presence of emicizumab.

Introduction: Recombinant porcine factor VIII (rpFVIII) is a treatment option for break-through bleeds in patients with congenital haemophilia A with inhibitors (CHAwI) on emicizumab. However, there are limited data about the measurement of rpFVIII in the presence of emicizumab.

Aim: To analyse whether rpFVIII can be measured with a chromogenic assay with bovine component (bCSA) in plasma from CHAwI on emicizumab treatment.

Recombinant porcine factor VIII in patients with congenital haemophilia A with inhibitors undergoing surgery: Phase 3, single-arm, open-label study.

Introduction: Recombinant porcine factor VIII (rpFVIII; susoctocog alfa) is predicted to provide functional FVIII activity in patients with congenital haemophilia A with inhibitors (CHAWI).

Aims: To evaluate the efficacy and safety of rpFVIII in patients with CHAWI undergoing invasive procedures.

Methods: This phase 3, multicentre, single-arm, open-label study (NCT02895945) enrolled males aged 12-75 years with severe/moderately severe CHAWI who required surgical/invasive procedures.

Emicizumab for the Treatment of Acquired Hemophilia A: Consensus Recommendations from the GTH-AHA Working Group.

Background:  Acquired hemophilia A (AHA) is a severe bleeding disorder caused by autoantibodies against coagulation factor VIII (FVIII). Standard treatment consists of bleeding control with bypassing agents and immunosuppressive therapy. Emicizumab is a bispecific antibody that mimics the function of activated FVIII irrespective of the presence of neutralizing antibodies.

Emicizumab prophylaxis in patients with acquired haemophilia A (GTH-AHA-EMI): an open-label, single-arm, multicentre, phase 2 study.

Background: Acquired haemophilia A is caused by neutralising autoantibodies against coagulation factor VIII, leading to severe bleeding. Standard treatment involves immunosuppressive therapy, which is associated with adverse events and mortality in the frail population of patients with acquired haemophilia A. This study investigated whether emicizumab, a factor VIIIa mimetic antibody, protects patients with acquired haemophilia A from bleeding and allows deferral of immunosuppression during the first 12 weeks after diagnosis.

Outcomes After Decompressive Surgery for Severe Cerebral Venous Sinus Thrombosis Associated or Not Associated with Vaccine-Induced Immune Thrombosis with Thrombocytopenia: A Multicenter Cohort Study.

Background: Clinical observations indicated that vaccine-induced immune thrombosis with thrombocytopenia (VITT)-associated cerebral venous sinus thrombosis (CVST) often has a space-occupying effect and thus necessitates decompressive surgery (DS). While comparing with non-VITT CVST, this study explored whether VITT-associated CVST exhibits a more fulminant clinical course, different perioperative and intensive care unit management, and worse long-term outcome.

Methods: This multicenter, retrospective cohort study collected patient data from 12 tertiary centers to address priorly formulated hypotheses concerning the clinical course, the perioperative management with related complications, extracerebral complications, and the functional outcome (modified Rankin Scale) in patients with VITT-associated and non-VITT CVST, both with DS.

Weight-adjusted dosing of tinzaparin for thromboprophylaxis in obese medical patients.

Background: The optimal dose of tinzaparin for prophylaxis in obese medical patients is not well defined.

Objectives: To evaluate the anti-Xa activity in obese medical patients on tinzaparin prophylaxis adjusted for actual bodyweight.

Methods: Patients with a body mass index of ≥30 kg/m treated with 50 IU/kg tinzaparin once daily were prospectively included.

Influencing Factors and Differences in Born Aggregometry in Specialized Hemostaseological Centers: Results of a Multicenter Laboratory Comparison.

 Light transmission aggregometry (LTA) is regarded as the gold standard in platelet function diagnostics. However, there is a relevant degree of interlaboratory variability in practical applications.  The aim of the present study was to develop a practicable laboratory comparison on LTA and to analyze differences and influencing factors in regard to standardization in five specialized hemostaseological centers.

Targets of autoantibodies in acquired hemophilia A are not restricted to factor VIII: data from the GTH-AH 01/2010 study.

The root cause of autoantibody formation against factor VIII (FVIII) in acquired hemophilia A (AHA) remains unclear. We aimed to assess whether AHA is exclusively associated with autoantibodies toward FVIII or whether patients also produce increased levels of autoantibodies against other targets. A case-control study was performed enrolling patients with AHA and age-matched controls.

[Coagulation diagnostics in the clinical routine-part 2 : Monitoring of anticoagulation treatment, new-onset thrombocytopenia and thrombophilia].

Monitoring of vitamin K antagonist treatment with the international normalized ratio (INR) is obligatory, whereas this only applies to direct oral anticoagulants (DOAC) or low molecular weight heparin in the context of selected clinical scenarios. For DOAC the focus is on the determination of trough and peak plasma levels of the drug but for low molecular weight heparins the focus is on anti-Xa activity. The timing of blood sampling in relation to drug intake is essential for the interpretation of the results.