ABSTRACT
BACKGROUND: There is a large inter-individual variation in the efficacy of CD34+ cell mobilization and collection in healthy allogenic hematopoietic stem cell donors. Donor characteristics, blood cell counts, and factors related to mobilization and collection have previously been associated with blood CD34+ cell count or CD34+ cell yield after G-CSF mobilization and collection. Since the literature reporting associations is heterogeneous, we clarify the determinants of CD34+ count and yield in a scoping review. MATERIALS AND METHODS: Studies published between 2000 and 2023 were evaluated if they reported allogeneic donors undergoing G-CSF mobilization and peripheral blood stem cell collection (PBSC). Eligible studies assessed blood CD34+ cell count or CD34+ cell yield in the first PBSC collection after mobilization with 4 or 5 days of G-CSF treatment. Associations were recorded between these outcomes and donor factors (age, gender, weight, ethnicity), mobilization factors (G-CSF scheduling or dose), collection factors (venous access, processed blood volume) or laboratory factors (blood cell counts at baseline or after mobilization). RESULTS: The 52 studies each evaluated between 15 and 20,884 donors. 43 studies were retrospective, 33 assessed blood CD34+ cell counts and 39 assessed CD34+ cell yield from PBSC. Blood CD34+ cell counts consistently predicted CD34+ cell yield. Younger donors usually had higher blood CD34+ cell counts and CD34+ cell yield. Most studies that investigated the effect of donor ancestry found that non-European ancestry donors had higher blood CD34+ cell counts after mobilization and CD34+ cell yields from collection. CONCLUSIONS: There remains poor consensus about the best predictors of blood CD34+ cell counts and yield that requires further prospective study, particularly of the role of donor ancestry. The current focus on donor gender as a major predictor requires re-evaluation.
Subject(s)
Blood Coagulation Disorders , COVID-19 , COVID-19 Vaccines , Humans , SARS-CoV-2 , VaccinationABSTRACT
Hypodysfibrinogenemia (HD) is a heterogeneous disorder in which plasma fibrinogen antigen and function are both reduced but discordant. This report addresses the key clinical question of whether genetic analysis enables clinically useful subclassification of patients with HD. We report a new case and identify a further eight previously documented cases that have the laboratory features of HD but biallelic inheritance of quantitative and qualitative fibrinogen gene variants. The cases displayed both bleeding and thrombosis and sometimes had undetectable fibrinogen activity. In all cases, the predicted effect of the coinherited variants is reduced levels of circulating fibrinogen that is all dysfunctional. We propose the term pseudohomozygous dysfibrinogenemia for this subtype of recessively inherited HD that is distinct from the more commonly recognized monoallelic HD caused by a single fibrinogen gene variant.
ABSTRACT
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.
