Introduction: von Willebrand disease (VWD) is the common bleeding disorder with a clinically relevant bleeding prevalence of 1:10,000. von Willebrand disease patients lack both von Willebrand factor (VWF) and factor VIII (FVIII), which are critical for normal haemostasis. The conventional treatment for VWD includes desmopressin and replacement therapy with plasma derived FVIII with VWF concentrates or recombinant VWF. Development of alloantibodies is a rare occurrence, there is a paucity in the literature of treatment modalities in these patients. Not many reports are available in literature on the efficacy of emicizumab in VWD patients with or without alloantibodies to VWF. Aim:To do systematic review of literature on emicizumab in VWD and report our experience of emicizumab in two patients of VWD Methods: We used electronic search engines till May 2021 in 'Google scholar' and 'PubMed' , to collect the case reports or case series on use of emicizumab for management of VWD. Two of our severe VWD patients were successfully treated with emicizumab. A systematic review was performed and the results discussed. Results:The electronic search revealed six case reports using emicizumab for treatment of VWD. Two were in vitro studies and four in patients with VWD type 3 disease.In vitro studies and in VWD patients on emicizumab, showed improvement in thrombin generation and fibrin formation. Among four patients, three had alloantibodies to VWD and one was negative. All these patients were treated with emicizumab for 6-12 m. After starting emicizumab, none of them had spontaneous bleeding requiring treatment. During treatment with emicizumab, one patient had trauma-associated soft tissue hematoma, which was treated with rFVIIa and another patient had bleeding following dental exfoliation treated with Humate P. We treated two of our VWD patients one with and one without inhibitors with emicizumab after failure of other therapies.Both the patients showed marked improvement and continued to remain well and free of bleeding episodes. None of the patients had any thrombosis or thrombotic microangiopathy (TMA) during treatment with emicizumab.

Introduction Factor replacement therapy in treatment of haemophilia A is complicated by the production of neutralising antibodies known as inhibitors. The formation of inhibitors is multifactorial being associated with both genetic and environmental factors. Aim To document the prevalence of inhibitors in severe haemophilia in the community where most patients receive only infrequent episodic replacement therapy and evaluate the factors which could be contributing to it. Methods Community based camps were conducted in different parts of the country. Patients were assessed through a structured questionnaire and blood samples were obtained for laboratory evaluation of inhibitors and defined immunological parameters. Results Inhibitors were present in 87/447 (19.5%) of the evaluated patients. High‐titre inhibitor (>5 Bethesda Units [BU]) was identified in 31 (35.6%) patients. HLA DRB1‐13‐positive cases (RR = 2.04; 95% CI 1.06‐3.911; P = 0.033) had an increased risk of inhibitor formation which was retained in the high‐titre subset. A decreased risk of inhibitor formation was noted with heterozygous IL4‐590 C/T allele (RR = 0.22; 95% CI 0.108‐0.442: P = 0.000). There were no significant correlations between any of the evaluated environmental factors and the development of inhibitors in this study. Conclusion The overall prevalence of inhibitors in patients with severe haemophilia A is similar to that reported among patients receiving regular replacement therapy. The data from this study, limited by its retrospective and cross‐sectional study design, would suggest that genetic rather than environmental are more likely to impact the development of inhibitors.

ABSTRACT:The clinical presentations of hypopituitarism in the middle aged and elderly people differ from adolescents and young adults. The symptoms are non-specific with variable duration of onset and they may present with altered sensorium, psychiatric manifestations or metabolic abnormalities. Thus offering a diagnostic challenge for the clinician. Metabolic abnormalities offers a clue to their early diagnosis and hence prompt treatment.