[Impact of COVID-19 Pandemic on Medical Care of Patients with Inherited Bleeding Disorders].

Background And Objectives: Chronic diseases, such as inherited bleeding disorders (IBD) are often associated with high costs of medical care. COVID-19 containment measures, including isolation and triage, led to restrictions in the health care of chronically ill patients. The aim of the present study was to investigate the effects of the COVID-19 pandemic on the health care of IBD patients.

Impact of COVID-19 pandemic on mental health of patients with inherited bleeding disorders in Germany.

Background: The worldwide pandemic spread of SARS-CoV-2 can lead to either respiratory infection or containment-associated isolation with possible higher impact on chronic diseases such as inherited bleeding disorders (IBD). The aim of the study was to evaluate the impact of COVID-19 on patients and caregivers of IBD patients regarding their concerns and worries related to own health, access to treatment and availability of factor concentrates and their experiences related to medical care.

Methods: Multicentre, cross-sectional study evaluating the impact of COVID-19 on mental health of IBD patients.

Practical Guidance of the GTH Haemophilia Board on the Use of Emicizumab in Patients with Haemophilia A.

Emicizumab has been approved for bleeding prophylaxis in patients with haemophilia A (PWHAs) with or without inhibitors. Because of substantial differences between factor VIII (FVIII) and Emicizumab, the 'Ständige Kommission Hämophilie' of the German, Austrian, Swiss Society for Thrombosis and Haemostasis Research (GTH) established a practical guidance for the use of Emicizumab in PWHAs. A systematic literature research was conducted in PubMed.

Smart Medication ™, an Electronic Diary for Surveillance of Haemophilia Home Care and Optimization of Resource Distribution.

This report describes the technical features and potential advantages of the application of electronic haemophilia treatment diary and an evaluation of real-life electronic treatment data collected from haemophilia patients. Since 2012, a total of 663 patients from 30 German haemophilia treatment centres (HTCs) have used the device. Data of nine HTCs were merged for real-life data analysis.

Identification of Thiols in Yellow Onion (Allium cepa L.) Using Solvent Vented Large Volume Injection GC-MS.

Thiols are often highly odor active molecules and as such can significantly contribute to aroma while being present at extremely low concentrations. This paper details the identification of thiols in yellow onion juice by solvent extraction followed by thiol enrichment using a mercuric agarose gel column. Due to the inherent thermal instability and low concentrations of thiols in onion, chromatographic analysis utilized larger volume solvent elimination injections.

[Therapy of inherited diseases of platelet function. Interdisciplinary S2K guideline of the Permanent Paediatric Committee of the Society of Thrombosis and Haemostasis Research (GTH e. V.)].

Inherited disorders of platelet function are a heterogeneous group. For optimal prevention and management of bleeding, classification and diagnosis of the underlying defect are highly recommended. An interdisciplinary guideline for a diagnostic approach has been published (AWMF # 086-003 S2K; Hämostaseologie 2014; 34: 201-212).

Early orthopaedic challenges in haemophilia patients and therapeutic approach.

Introduction: There is growing evidence that subclinical joint bleeding early in life may lead to subtle changes in joint function, gait, and muscle development in young children with haemophilia. The early identification of such changes provides an opportunity for clinicians to intervene before irreversible structural changes occur.

Materials And Methods: We have undertaken motion analysis of the knee in 273 children (mean age 9.

Addition of in-vitro generated endothelial microparticles to von-Willebrand plasma improves primary and secondary hemostasis.

Increased endothelial microparticles (EMP) as markers for endothelial activation have been associated with worse outcomes in clinical prothrombotic situations. The procoagulant properties of EMP can be attributed to the expression of phospholipids, tissue factor and von-Willebrand factor on their surface. We therefore investigated whether addition of in-vitro generated EMP modifies hemostasis in plasma from patients with severe von-Willebrand disease (VWD).

Increased amounts of von Willebrand factor are bound to microparticles after infusion of desmopressin.

Effects of desmopressin (DDAVP) in platelet disorders and primary haemostasis cannot be attributed solely to the increase in FVIII/VWF (von Willebrand factor), as VWF/FVIII concentrates have no effect in these circumstances. Microparticles (MP) can support haemostasis by expression of phospholipids, tissue factor and VWF on their surface. We hypothesized that significant amounts of VWF are bound to MP after DDAVP administration and that consequently depletion of MP should influence VWF:Ag and VWF:RCo plasma levels.

Successful long-time treatment with mycophenolate-mofetil in a child with acquired factor VIII inhibitor.

Unlabelled: Here, we report about a boy (age: 18 years) who developed an acquired factor VIII inhibitor at the age of 9 years. He presented with bleeding in his right ankle, multiple haematomas and a high-titer factor VIII type II inhibitor (400 BU).

Therapy: He received treatment with MMF (CellCept®), dexamethasone-immunoglobulin pulses, and rituximab together with high dose FVIII (Hannover protocol).

Mode of action of pulegone on the urinary bladder of F344 rats.

Essential oils from mint plants, including peppermint and pennyroyal oils, are used at low levels as flavoring agents in various foods and beverages. Pulegone is a component of these oils. In a 2-year bioassay, oral administration of pulegone slightly increased the urothelial tumor incidence in female rats.

Prioritisation in haemophilia A: a qualitative study of stakeholder attitudes and preferences.

To learn more about prioritisation in the health care system, we performed an exploratory qualitative study on haemophilia A. The aim was to generate haemophilia disease-specific criteria and to learn more about reasoning in the decision-making process. The 40 participants (patients, relatives, physicians, nurses) were asked in semi-structured interviews about their experiences regarding the German health care system in general and the management of haemophilia A.

Inhibitor-immunology-study. Evaluation of inhibitor development in haemophilia B.

Unlabelled: The development of inhibitors in haemophilia B is one of the most important complications of replacement therapy, affecting mortality and morbidity. Inhibitor development is based on complex immunological factors, and to date, only little is known about its underlying mechanisms. Here, we present first results of the haemophilia B group of our Inhibitor-Immunology study.

The mutation N528S in the von Willebrand factor (VWF) propeptide causes defective multimerization and storage of VWF.

We characterized a consanguineous Turkish family suffering from von Willebrand disease (VWD) with significant mucocutaneous and joint bleeding. The relative reduction of large plasma von Willebrand factor (VWF) multimers and the absent VWF triplet structure was consistent with type 2A (phenotype IIC) VWD. Surprisingly, platelet VWF was completely deficient of multimers beyond the VWF protomer, suggesting defective alpha-granular storage of larger multimers.

Inhibitor-Immunology-Study. Different HLA-types seem to be involved in the inhibitor development in haemophilia A.

Unlabelled: The development of inhibitors is one of the most important complications of replacement therapy in haemophilia, affecting mortality and morbidity. Inhibitor development is based on complex immunological factors. Cytokines and their receptors, T-cell receptors, and the Major Histocompatibility Complex may play important roles in the development of inhibitors.

Popliteal venous thrombosis in juvenile arthritis with Baker cysts: report of 3 cases.

Three pediatric patients with different illnesses leading to knee arthritis and large Baker cysts and additional calf swelling are reported. Calf swelling was due to true popliteal venous thrombosis and not to the much more common cause of pseudothrombophlebitis. Careful ultrasound examination can differentiate these two causes of calf swelling.

Spectrum of molecular defects and mutation detection rate in patients with mild and moderate hemophilia A.

The amount of residual F8 (FVIII:C) determines the clinical severity of hemophilia A. Recently, we showed that the mutation detection rate in severely affected male patients (FVIII:C<1% of normal) is virtually 100% when testing for the common intron 22-/intron 1- inversions and big deletions, followed by genomic sequencing of the F8 gene. Here we report on the spectrum of mutations and their distribution throughout the F8 gene sequence in 135 patients with moderate (n=23) or mild (n=112) hemophilia A.

Retention test Homburg to monitor the adhesive properties of von Willebrand factor after substitution or desmopressin therapy.

To diagnose von Willebrand disease (vWD) and to monitor drug efficacy, several tests have been established that are not, however, focused on the platelet adhesion properties of von Willebrand factor (vWF). The new platelet retention test Homburg (RTH) is characterized by a nonthrombogenic filter that retains platelets from blood when it is pressed through this filter. It was the aim of this study to examine the capability of this test to monitor the adhesive properties of vWF after its substitution in vWD or its release by desmopressin infusion.

Spectrum of molecular defects and mutation detection rate in patients with severe hemophilia A.

Hemophilia A is the most frequently occurring X-linked bleeding disorder, affecting one to two out of 10,000 males worldwide. Various types of mutations in the F8 gene are causative for this condition. It is well known that the most common mutation in severely affected patients is the intron 22 inversion, which accounts for about 45% of cases with F8 residual activity of less than 1%.

[Platelet retention test Homburg (RTH) and drug monitoring of platelet adhesive properties of von Willebrand factor].

Platelet plug formation is initiated by the process of platelet adhesion, mainly mediated by the von Wille-brand factor (VWF). Therefore, apart from established criteria the platelet adhesion property is a further criterion to determine VWF e. g.

Health status and health-related quality of life of children with haemophilia from six West European countries.

A multicentre, international, cross-sectional study was carried out in the frame of field testing of the first haemophilia-specific quality-of-life (QoL) questionnaire (Haemo-QoL). The aim of this paper is to describe health status and health care and their impact on QoL in haemophilic children in Western Europe. Children aged 4-16 years with severe haemophilia without inhibitors were enrolled by 20 centres in France, Germany, Italy, the Netherlands, Spain and the United Kingdom.

The deletion polymorphism in the angiotensin-converting enzyme gene is a moderate risk factor for venous thromboembolism.

ACE displays potent vasoconstrictive effects, attenuation of fibrinolysis, and platelet activation and aggregation, thus possibly promoting venous thromboembolism (VTE). The ACE gene contains an insertion (I) or deletion (D) polymorphism accounting for 50% of the variation in serum ACE concentration. To evaluate the role of the I/D polymorphism in VTE, its prevalence was determined in 931 patients with VTE and 432 blood donors.

Recurrent pulmonary embolism in a 13-year-old male homozygous for the prothrombin G20210A mutation combined with protein S deficiency and increased lipoprotein (a).

We report the case of a 13-year-old male presenting with recurrent symptoms of respiratory distress after a trauma of the lower limb. Pulmonary symptoms had been misinterpreted for several weeks and only marked symptoms of deep venous (DVT) and caval vein thrombosis later prompted the correct diagnosis of DVT and embolic events and subsequently a successful thrombolytic therapy. The case reported here shows a diagnostic pitfall of pulmonary embolism in an adolescent.

Prevalence of a 23bp insertion in exon 3 of the endothelial cell protein C receptor gene in venous thrombophilia.

Background: The endothelial cell protein C receptor (EPCR) enhances protein C activation by the thrombin-thrombomodulin complex. As evidence is accumulating that EPCR is an important component of the protein C anticoagulant pathway, polymorphisms in the EPCR gene might be candidate risk factors predisposing to venous thromboembolism (VTE). Recently, a 23bp insertion in exon 3 of the EPCR gene has been identified, which duplicates the preceding 23 bases and results in a STOP codon downstream from the insertion point.