A cross-sectional follow-up study of physical activity in adults with moderate and severe haemophilia.

AIM: To conduct a cross-sectional follow-up assessment of physical activity (PA) in people with moderate and severe haemophilia (PwMSH) from the Irish Personalised Approach to the Treatment of Haemophilia (iPATH) study. METHODS: Between June-December 2021, participants' PA was measured over one week using accelerometery, and was compared with their previously measured data from the original iPATH assessment. Self-awareness of PA and the impact of the Covid-19 pandemic on PA, pain, mobility and function were retrospectively examined using a survey. RESULTS: Of 30 participants who returned surveys [n = 19, severe (FVIII, <.01 IU/mL); n = 4, moderate (FVIII, .01-.05 IU/mL); n = 7, severe (FIX, <.01 IU/mL); age: 47 (36, 55) years], 28 completed accelerometery (follow-up time: 3 years). There were no significant differences in accelerometer PA (all p > .05), but achievement of World Health Organisation guidelines increased (67.9%-75.0%; p = .646). Increased self-awareness of PA was reported by 76.7%, and 66.7% reported desires to become more physically active. Compared to normal, most reported either no differences or lower levels of PA during lockdown restrictions. Self-reported PA increased for most when restrictions eased from April 2021 onwards. Beyond the pandemic, concerns included pain and access to exercise resources. CONCLUSION: Self-reported PA throughout the pandemic was variable, whilst there were no significant differences in objectively measured PA between assessment periods, despite reports of increased self-awareness and desires to be physically active at follow-up. Further qualitative research is needed to design personalised PA and health interventions, capturing perspectives of patients, their families, and multi-disciplinary haemophilia healthcare providers.

Plasma procurement and plasma product safety in light of the COVID-19 pandemic from the perspective of the plasma industry.

This review, written from the perspective of the plasma industry, discusses plasma procurement and plasma product safety in light of the COVID-19 pandemic. The COVID-19 pandemic impacted the whole world and, therefore, not unexpectedly, the pharmaceutical industry too. In spite of this, the plasma protein industry has continued to provide life saving therapies to critically ill patients. Moreover, companies have collected COVID convalescent plasma (CP) to support development of investigational therapies, for example, hyperimmune globulins to potentially treat SARS-CoV-2 infection, and collaborated with those collecting COVID CP for direct transfusion, which has been made available under emergency use in the United States. For plasma that is fractionated to become a therapy, general knowledge of coronaviruses and numerous new studies on the structure and function of SARS-CoV-2 provide reassurance that existing industry precautions, including donor selection, as well as virus inactivation and removal steps during the manufacturing process are sufficient to maintain the high standards of virus safety of plasma products. The pandemic also revealed the vulnerability and inadequacy of the current plasma ecosystem. There is a need for more plasma to be collected around the world to meet the growing need for safe and efficacious plasma-derived therapies. This requires outdated regulatory and policy restrictions to be realigned with current scientific evidence. More countries around the world should be in a position to contribute to global supply of plasma so that patients with life-threatening conditions - and often no alternative therapeutic solutions - have better access to care.

Clinical use of thrombin generation assays.

Determining patient's coagulation profile, i.e. detecting a bleeding tendency or the opposite, a thrombotic risk, is crucial for clinicians in many situations. Routine coagulation assays and even more specialized tests may not allow a relevant characterization of the hemostatic balance. In contrast, thrombin generation assay (TGA) is a global assay allowing the dynamic continuous and simultaneous recording of the combined effects of both thrombin generation and thrombin inactivation. TGA thus reflects the result of procoagulant and anticoagulant activities in blood and plasma. Because of this unique feature, TGA has been widely used in a wide array of settings from both research, clinical and pharmaceutical perspectives. This includes diagnosis, prognosis, prophylaxis, and treatment of inherited and acquired bleeding and thrombotic disorders. In addition, TGA has been shown to provide relevant information for the diagnosis of coagulopathies induced by infectious diseases, comprising also disturbance of the coagulation system in COVID-19, or for the assessment of early recurrence in breast cancer. This review article aims to document most clinical applications of TGA.

Recombinant ADAMTS13 reduces abnormally up-regulated von Willebrand factor in plasma from patients with severe COVID-19.

Thrombosis affecting the pulmonary and systemic vasculature is common during severe COVID-19 and causes adverse outcomes. Although thrombosis likely results from inflammatory activation of vascular cells, the mediators of thrombosis remain unconfirmed. In a cross-sectional cohort of 36 severe COVID-19 patients, we show that markedly increased plasma von Willebrand factor (VWF) levels were accompanied by a partial reduction in the VWF regulatory protease ADAMTS13. In all patients we find this VWF/ADAMTS13 imbalance to be associated with persistence of ultra-high-molecular-weight (UHMW) VWF multimers that are highly thrombogenic in some disease settings. Incubation of plasma samples from patients with severe COVID-19 with recombinant ADAMTS13 (rADAMTS13) substantially reduced the abnormally high VWF activity, reduced overall multimer size and depleted UHMW VWF multimers in a time and concentration dependent manner. Our data implicate disruption of normal VWF/ADAMTS13 homeostasis in the pathogenesis of severe COVID-19 and indicate that this can be reversed ex vivo by correction of low plasma ADAMTS13 levels. These findings suggest a potential therapeutic role for rADAMTS13 in helping restore haemostatic balance in COVID-19 patients.