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The article discusses a study conducted on a cohort of Pakistani patients with severe bleeding abnormalities including hematoma, epistaxis and prolonged wound bleeding, who were diagnosed with Bernard‐Soulier syndrome. According to the author, this disease is caused by defects to the platelet receptor for von Willebrand factor (VWF) and is accompanied by low platelet counts and impaired platelet agglutination after stimulation with ristocetin.

Combined coagulation factor VII (FVII) and factor X (FX) deficiency (combined FVII/FX deficiency) belongs to the group of bleeding disorders in which both factors show reduced plasma activity. It may arise from coincidental inheritance of separate coagulation factor deficiencies or a common cause as large deletions comprising both gene loci. The F7 and F10 genes are located on the long arm of chromosome 13. Here, we describe 10 cases with combined FVII/FX deficiency representing both genetic mechanisms of occurrence. Genetic analyses included direct sequencing of the F7 and F10 genes and MLPA (multiplex ligation-dependent probe amplification) for detection of heterozygous large deletions. In four patients, the combined deficiency was due to a large deletion within the terminal end of chromosome 13. In the remaining six cases the deficiency resulted from coincidental inheritance of different genetic alterations affecting both genes independently. In most cases, the genetic defects were heterozygous, presenting with prolonged PT, normal aPTT and mild or no bleeding symptoms. Only in one case compound heterozygous mutations were detected in the F10, resulting in prolonged aPTT and a more severe bleeding phenotype. To avoid a misdiagnosis of combined FVII/FX deficiency, analyses of single factor activities have to be performed in all cases with prolonged PT even if aPTT is normal. Genetic analyses are substantial for correct prediction of an inheritance pattern and a proper genetic counselling. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the new findings on the two late-diagnosed afibrinogenaemia patients.

Background: The number of implanted ventricular assist devices (VADs) has increased significantly recently. Bleeding, the most frequent complication, cannot be solely attributed to anticoagulation therapy. Acquired von Willebrand syndrome (AVWS) caused by increased shear stress is frequent in VAD patients and can increase the bleeding risk. The HeartMate III (HM III) is a novel left VAD featuring potential improvements over the HeartMate II., Methods and Results: In this study, we investigated the prevalence and onset of AVWS in 198 VAD patients. To our knowledge, this is the largest cohort of VAD patients whose longitudinal data on AVWS have been collected. We also analyzed whether AVWS is less severe in HM III patients than in HeartMate II patients. Because platelet dysfunction can raise the bleeding risk, we investigated platelet function in a subset of patients. In total, 198 VAD patients and 60 patients with heart transplants as controls were included in this study. The ratio of von Willebrand factor collagen binding capacity to von Willebrand factor:antigen, multimer analyses, and platelet function (especially secretion of α- and δ-granules) were investigated. All 198 VAD patients developed AVWS. As soon as the VAD was explanted, the AVWS disappeared within hours. AVWS was less severe in the HM III patients than in the HeartMate II patients. The HM III patients had fewer bleeding symptoms. In addition, VAD patients exhibited a platelet α- and δ-granule secretion defect., Conclusions: AVWS develops in VAD patients and may increase the bleeding risk. The HM III device causes less severe AVWS. Platelet secretion defects should be investigated in VAD patients because they also raise the bleeding risk., Clinical Trial Registration: https://www.drks.de/drks_web. Unique identifier: DRKS00000649., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Extracorporeal lung support and therapeutic anticoagulation are dogmatically linked for most clinicians in fear of clotting of the extracorporeal circuit. In the last decade, however, we have learned that bleeding complications in the course of extracorporeal membrane oxygenation (ECMO) therapy are common and not occasionally limiting or fatal. Even though international guidelines lowered the PTT-target values, ECMO therapy without anticoagulation has only been reported sporadically in case reports heretofore. This monocentric, observational study was designed to evaluate a protocol for venovenous ECMO therapy without additional anticoagulation. Patients without former thrombotic events solely received thrombosis prophylaxis with 40 mg subcutaneous enoxaparin per day like every critical care patient. After approval by the local ethics committee (Albert-Ludwigs-University Freiburg ethics committee, EK 513/14) all consecutive patients treated with venovenous ECMO therapy since introduction of the protocol have been identified. Digital charts of the patients have been evaluated with special regard to bleeding and thrombotic or embolic events or breakdown of the extracorporeal circuit. Sixty-one patients received venovenous ECMO therapy with prophylactic subcutaneous enoxaparin only. Median duration of ECMO therapy was 7 days (2-32). Overall 560 ECMO days have been observed. No system exchange because of thrombotic occlusion was necessary within the permitted 5 days run time of the centrifugal pump. Overall we identified thrombotic complications in four patients. In three of them centrifugal pump after a runtime of more than 5 days unexpectedly stopped completely because of thrombotic occlusion. In all cases pump exchange was performed promptly and patients did not incur hypoxic deficit. One other patient received substitution of blood products and coagulation factor concentrates because of severe bleeding and sustained myocardial infarction the day after. Only 18% of patients presented with essential clinical bleeding after 7 days of therapy. No fatal bleeding event and no intracranial hemorrhage was observed. Patients required only a third of blood product transfusion compared to published data. Venovenous ECMO therapy with prophylactic anticoagulation only was feasible in this study. It was not associated with an increased rate of system exchanges compared to regimes with therapeutic anticoagulation in registry data. It provides the potential to relevantly decrease the incidence of severe bleeding events and blood transfusion requirements. The apodictic adherence to anticoagulation in therapeutic dosage should be critically scrutinized in every patient., (© 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Venous thromboembolism [TE] is a multifactorial disease and protein C deficiency [PCD] constitutes a major risk factor. In the present study the prevalence of PCD and the clinical presentation at TE onset, including neonatal purpura fulminans, in a cohort of children are reported. In 367 unselected children (0·1-19 years) recruited between July 1996 and December 2013, a comprehensive thrombophilia screening was performed along with recording of anamnestic data. Twenty-five of 338 children (7·4%) had PCD. Mean age at first TE onset was 10 years (range 0·1-18). Leading thromboembolic manifestations were neonatal purpura fulminans (n = 5), TE of cerebral veins (n = 3), stroke (n = 2) deep veinthrombosis (DVT) of the leg (n = 10), DVT & pulmonary embolism (n = 2) and DVT & pelvic veins (n = 3). Concomitant risk factors for TE were identified in 12 patients, whereas 13 children spontaneously developed TE. A positive family history of DVT was found in 10 children. In this unselected cohort of paediatric patients with symptomatic TE the overall prevalence of PCD was 7·4%; 1·5% presented with neonatal purpura fulminans. Given its clinical implication for patients and family members, thrombophilia testing should be performed and the benefit of medical or educational interventions should be evaluated in this high-risk population., (© 2014 John Wiley & Sons Ltd.)