A case report of acquired Haemophilia A: A rare medical emergency.

Acquired Haemophilia A (AHA) is a rare potentially lifethreatening bleeding disorder caused by the presence of autoantibodies against coagulation factors. It is usually characterised by severe spontaneous haemorrhage, which can lead to high morbidity and mortality. The diagnosis is often challenging. Treatment requires vigilant and accurate laboratory investigations, control of bleeding episodes, and eradication of inhibitors using bypassing agents and/or immunosuppressive agents. Hereby, we present a case report of unusual bleeding episodes with isolated raised activated partial thromboplastin time (APTT).

[Comprehensive identification of compensatory mutations in rifampicin-resistant Mycobacterium tuberculosis strains].

Objective: To comprehensively identify compensatory mutations in rpoA, rpoB and rpoC genes of rifampicin-resistant Mycobacterium tuberculosis (RIF-r MTB) and to evaluate the effect of rifampicin-resistant mutation type and lineage background on occurrence of compensatory mutations. Methods: Published MTB whole genome sequencing data were searched and downloaded. RIF-r MTB was identified through known rifampicin-resistant mutations. Based on parallel evolutionary patterns, we identified putative compensatory mutations in the phylogenetic tree and calculated proportions of accumulating compensatory mutations in each rifampicin-resistant mutations' type and lineage background of RIF-r MTB. Statistic significance was analyzed by chi-square test. Results: A total of 8 453 global MTB whole genome sequencing data were downloaded form ENA (covering 12 countries), including 1 749 RIF-r MTB. Based on phylogenetic analysis, we totally identified 60 putative compensatory mutations (6 in rpoA gene, 16 in rpoB gene and 38 in rpoC gene), 11 of which were newly reported. RIF-R strains carrying rpoB S450L (41.7%, 279/669) had a significant higher chance to accumulate compensatory mutations than strains with other rpoB mutations (8.0%, 31/388, χ(2)=378.5, P<0.000 1). In addition, RIF-R strains from lineage 2 (34.0%, 223/656) had a significant higher chance to accumulate compensatory mutations than strains from other lineages [lineage1: 4.7%(2/43), 2/43, lineage3: 12.5%(4/32), 4/32, lineage4: 15.1%(78/517), 78/517; χ(2)=238.5, P<0.000 1]. Conclusions: Our study comprehensively identified putative rifampicin-resistant compensatory mutations of rifampicin resistance. RIF-R strains carrying rpoB S450L mutation or from lineage 2 had a significantly higher chance to accumulate compensatory mutations than strains either with other rpoB mutations or from other lineages.