review · International Blood Research & Reviews
Sickle cell disease involves a self-reinforcing process of blood vessel damage, clotting activation, and inflammation termed thromboinflammation. Although this framework was primarily established through animal models and clinical cohorts in high-income settings, most affected individuals live in West Africa. A critical examination of regional research reveals that local studies mainly rely on cross-sectional case-control comparisons of circulating biomarkers. While these markers show changes consistent with global literature, they are rarely linked to prospectively confirmed clinical outcomes. Additionally, distinct regional factors, including endemic malaria, frequent haemoglobin C carriage, alpha-thalassaemia co-inheritance, and survivorship bias in hospital cohorts, substantially alter the disease presentation. Furthermore, direct outcomes such as venous thromboembolism remain largely unmeasured, and the uptake of hydroxycarbamide, the most strongly supported therapeutic intervention, remains limited.
Sickle cell disease affects millions of people, predominantly in West Africa. Because existing biological models derive from wealthy nations, local patient management risks relying on unverified prognostic markers. Clarifying how regional factors alter blood vessel inflammation helps clinicians and policymakers focus on validated treatments, improved outcome tracking, and relevant care standards tailored to the populations most burdened by the condition.
This work is at an early conceptual and evaluative stage. It identifies a translational need for diagnostic developers and clinical researchers to build longitudinal biomarker validation studies and investigate inexpensive composite haematological indices that can substitute for costly, specialised assays. Such tools could eventually aid healthcare providers in low-resource settings, though prospective clinical trials linking markers to adjudicated outcomes are needed before any viable clinical products or diagnostic workflows can emerge.
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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.
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DOI: 10.9734/ibrr/2026/v17i4399
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