Search

Introduction: Several well‐established clinical laboratory methods are available to measure von Willebrand factor (VWF) in plasma samples, but few data are available on their use for analysing recombinant VWF (rVWF). Aim: To evaluate how clinical diagnostic laboratories analyse rVWF and plasma‐derived VWF (pdVWF) spiked in vitro into VWF‐deficient plasma using quantitative protein and functional assays of VWF. Methods: Human VWF‐deficient plasma samples were spiked with rVWF (vonicog alfa; Takeda) or pdVWF/factor VIII (pdVWF/FVIII; antihemophilic factor/VWF complex [human], CSL Behring), each at final concentrations of 1.0, 0.6, 0.2, 0.1 IU/mL VWF:ristocetin cofactor activity (VWF:RCo) according to labelled VWF activity. The ISTH SSC secondary coagulation standard was used as a control. Participating laboratories received three sets of these blinded aliquots. Mean results per assay were compared with the expected potency based on the labelled VWF:RCo activity. Results: Among 39 laboratories, the most commonly established assay was VWF:RCo; 22 laboratories reported data from 2214 tests. Despite a trend to lower values, VWF:RCo activities for rVWF were in agreement with target concentrations (71%–109%), whereas VWF:platelet glycoprotein Ib (VWF:GpIb) and VWF collagen‐binding activity (VWF:CB) assays gave high recoveries (up to 132% and 127%, respectively). In contrast, pdVWF/FVIII was substantially underestimated by VWF:GpIb and VWF:CB assays (56%–86% recoveries), whereas the VWF:RCo assay gave recoveries of 47%–112% for pdVWF/FVIII. Conclusion: The results of VWF assays used in clinical laboratories differ between rVWF and pdVWF, particularly for VWF:GpIb and VWF:CB assays. These differences may arise from the higher multimeric structure of rVWF compared to pdVWF. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to examine physical activity (PA), physical fitness and cardiometabolic risk amongst people with moderate and severe haemophilia (PwMSH). Methods: The following domains were examined: PA (accelerometry); functional aerobic capacity (6‐Minute Walk Test); grip strength (dynamometry); balance (One Leg Stand Test); body composition (anthropometry and bioimpedance analysis); blood pressure; arterial stiffness; and cardiometabolic disorders. Results: A total of 53 PwMSH (44 years) and 33 controls (43 years; p =.679) were recruited. Compared to controls, PwMSH were significantly less active in moderate and vigorous PA parameters (all p <.05), and less physically fit indicated by 6‐Minute Walk distance (p <.0005), grip strength (p =.040) and balance (p <.0005). PwMSH had higher rates of abdominal adiposity compared to controls measured by waist circumference indices (all p <.05). Resting blood pressure and arterial stiffness were not significantly different (p =.797 and.818, respectively). With respect to overall PA, World Health Organisation recommended targets for adults were achieved by the majority of both groups (haemophilia: 72.9% vs. controls: 90.0%; p =.069). Importantly, the number of PwMSH who achieved guideline recommended PA via longer, sustained bouts of moderate–vigorous PA was significantly lower compared to controls (18.8% vs. 56.7%; p =.001). Lastly, clinically diagnosed hypertension, insulin resistance and hyperlipidaemia were more prevalent amongst PwMSH compared to controls. Conclusion: Low levels of PA and physical fitness, and significant rates of abdominal adiposity and hypertension may collectively influence the risk and severity of various cardiometabolic and/or musculoskeletal health issues amongst ageing PwMSH. Personalised multi‐disciplinary health interventions involving PA, dietary and health psychology input for PwMSH warrant future investigation. [ABSTRACT FROM AUTHOR]

Objectives: To establish the prevalence of pain and functional disability in Irish adults with moderate and severe haemophilia, and to examine demographic and lifestyle influences. Methods: Males ≥18 years with moderate or severe haemophilia participated. Pain and function were examined using the PROBE questionnaire. Results: Of 49 participants [median age 44 (IQR 32, 52) years], most had severe haemophilia (Factor VIII = 30; Factor IX = 13) and were on regular prophylaxis (88%). Those with moderate haemophilia (Factor VIII = 5; Factor IX = 1) treated on demand (12%). Acute (72%) and chronic pain (71%), functional difficulties (58%), and analgesic requirements (92%) were prevalent. Age was significantly associated with more advanced haemophilic arthropathy (p =.002), chronic pain (p =.029) and functional difficulties (p =.036). Adults who reported chronic pain commenced prophylaxis significantly later in life [32 (20, 51) vs. 8 (1, 23) years; p =.004]. Physical activity was significantly lower in those with functional difficulties (p <.05). A disparity between self‐perceived 'target joints' and clinically defined target joints was also identified (76% vs. 23%). Conclusion: Haemophilic arthropathy, pain and functional disability were prevalent amongst Irish adults with moderate and severe haemophilia. Age‐dependent lifestyle, analgesic and treatment influences on pain and function warrant further investigation. [ABSTRACT FROM AUTHOR]

Background and Objectives: Assessment of plasma quality often focuses on the common safety tests for minimizing the risk of transmitting blood‐borne pathogens. Little attention is paid to the possible quality attributes that ensure a consistent biochemical composition of plasma for fractionation. We therefore investigated the suitability of selected biochemical and haematological attributes that could be used as markers of plasma quality obtained by different separation and pre‐treatment procedures. Material and Methods: We characterized six plasma types, including source plasma, plasma recovered by classic means and in‐line filtered plasma, by determining the analytical attributes protein content, coagulation factors and markers of coagulation, contact and complement activation. Residual cell content and cell‐specific variables were also measured. Results: We found relevant differences between the plasma types in complement activation, as indicated by C3a measurements, while thrombin antithrombin complex values and, to a minor extent, activated factor XII concentrations indicated only moderate differences in activation levels of coagulation and contact systems. The most striking differences, however, were detected in residual cell content and concentrations of the platelet‐associated proteins, platelet factor 4 and β‐thromboglobulin. We showed that leucocyte reduction filters disrupt cells. This includes platelets, thereby releasing the platelet‐associated proteins platelet factor 4 and β‐thromboglobulin, and leucocytes as demonstrated by the release of elastase from polymorphonuclear leucocytes. Furthermore, the filtration processing of whole blood can lead to activation of the complement system. Conclusion: Our results show that biochemical and cellular surrogate markers are valuable discriminators of plasma types. [ABSTRACT FROM AUTHOR]