Translating Vascular Biology into Clinical Benefit: A Critical Narrative Review of Sickle Cell Thromboinflammation in West Africa

Abstract

Sickle cell disease is a systemic vasculopathy in which intravascular haemolysis, endothelial activation, leukocyte and platelet recruitment, and coagulation activation operate as a single self-reinforcing process now commonly described as thromboinflammation. Most of the mechanistic architecture supporting this description has been assembled in transgenic murine models and in cohorts recruited in high-income settings, whereas the largest affected population lives in West Africa. This review critically examines whether the dominant thromboinflammatory framework is supported by, and useful for, evidence generated in West African populations, and identifies where translation has failed. Literature was identified through structured searching of biomedical and open-access scholarly indexes, supplemented by backward and forward citation searching and by examination of authoritative institutional material, with a final search date of 22 June 2026. The synthesis is organised around mechanistic domains, the regional empirical record, population-level modifiers, clinical endpoints and translational interventions rather than around individual studies. Three findings emerge. First, the West African evidence base is dominated by cross-sectional case–control comparisons of circulating markers, principally soluble adhesion molecules, angiogenic factors, global coagulation assays and haem-scavenging proteins. These studies consistently reproduce the direction of effect reported elsewhere but rarely link markers to prospectively adjudicated clinical events, so their prognostic value remains untested locally. Second, the region’s distinctive biological context, including endemic malaria, high haemoglobin C carriage, variable alpha-thalassaemia co-inheritance and marked survivorship bias in hospital cohorts, plausibly modifies the thromboinflammatory phenotype in ways that neither the murine literature nor high-income cohorts capture. Third, venous thromboembolism, the endpoint most directly predicted by the framework, is almost unmeasured in the region, while the intervention with the strongest local evidence for modifying the axis is hydroxycarbamide, whose uptake remains low. Confidence in mechanism-based prognostication in West African populations is presently limited. Priorities include longitudinal biomarker cohorts anchored to adjudicated endpoints, deliberate measurement of thrombotic outcomes, and evaluation of whether inexpensive composite haematological indices can substitute for specialised assays.