Elevated VWF with normal ADAMTS13 in pediatric sickle cell disease: links to crises and ischemic stroke

Sickle cell disease (SCD) remains a significant health care challenge associated with high burden or morbidity and mortality in sub-Saharan Africa, often resulting from vaso-occlusion and ischemic stroke. In under-resourced communities, inaccessibility of magnetic resonance imaging and computed tomography scanning complicates screening; therefore, there is a need for hematological assays as accessible cost-effective alternatives to bridge the gap. This cross-sectional study involving 80 pediatric patients with SCD and 32 healthy controls focused on the von Willebrand factor (VWF)-a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) axis, considered to be involved in vaso-occlusion and ischemia in SCD. Using hematological assays, the study evaluated full blood count (FBC), VWF antigen (VWF:Ag), VWF activity (VWF:Act), and ADAMTS13 antigen levels in patients with SCD and healthy controls. The study revealed elevated neutrophil counts coupled with reduced red blood cell (RBC) counts, lower hemoglobin levels, elevated nucleated RBCs, and lower platelet counts in pediatric SCD phenotypes compared with those in healthy controls. VOC was associated with elevated VWF:Ag, normal VWF:Act, and normal ADAMTS13 antigen, whereas ischemic stroke cases showed no significant differences in VWF:Ag, VWF:Act, and ADAMTS13 antigen levels compared with those in the healthy controls. Compared with healthy controls, patients with SCD in steady state had elevated ADAMTS13 antigen levels. These findings indicate chronic inflammation and hemolysis, likely sustained by neutrophil-linked proinflammatory mediators, might be involved in the dysregulation of the VWF-ADAMTS13 axis, increasing the risk of vaso-occlusion. Therefore, FBC, VWF:Ag, VWF:Act, and ADAMTS13 antigen may be used for risk stratification and the early diagnosis of pediatric SCD complications.