Full Blood Count Platelet Parameters in Sickle Cell Disease: A Systematic Review of Thrombocytosis, Thrombocytopenia, and Clinical Implications

Abstract

Background: Sickle cell disease (SCD) is characterized by chronic hemolysis, endothelial dysfunction, and systemic inflammation, each of which disrupts platelet homeostasis. The full blood count (FBC), the most universally available hematological test, remains underutilized in routine clinical interpretation of thrombocytosis and thrombocytopenia in SCD. Both abnormalities contribute to the hypercoagulable phenotype and organ complications of SCD; however, their prevalence, causes, and prognostic significance vary by genotype, clinical state, and geography. Objective: To evaluate the utility of the FBC in detecting, understanding, and managing platelet abnormalities in SCD by synthesizing 2020–2026 evidence on prevalence, etiology, pathophysiology, clinical implications, complications, and management strategies. Methods: This systematic review followed PRISMA 2020 guidelines. Ten databases were searched from 1 January 2020 to 31 March 2026; searches were executed on 2 April 2026 and updated on 10 April 2026. Of 680 records retrieved, 56 duplicates were removed, yielding 624 unique records; 550 underwent full-text assessment. Sixty-three studies met all inclusion criteria. Prevalence data were pooled using random-effects meta-analysis; publication bias was assessed using Egger’s and Begg’s tests, with trim-and-fill correction applied where asymmetry was detected. Results: Observed prevalence of thrombocytosis was 30.9% (95% CI: 26.4–35.7%) at steady state and 66.1% (95% CI: 61.3–70.6%) during acute events; trim-and-fill-adjusted steady-state estimates were 28.4% (95% CI: 24.1–33.0%) for thrombocytosis and 19.1% (95% CI: 15.6–23.2%) for complication-associated thrombocytopenia. Substantial between-study heterogeneity was observed across all outcomes (I² range: 68.3–82.4%). Thrombocytopenia occurred in 7.4% (95% CI: 5.9–9.2%) at steady state and 22.0% during complications. Thrombocytosis was predominantly reactive, driven by functional asplenia, haemolysis-induced thrombopoietin release, iron deficiency, and inflammatory cytokines. Thrombocytopenia reflected acute pathology including splenic sequestration, thrombotic microangiopathy, sepsis, and aplastic crisis. A multi-center cohort study of SCD patients in Oman (Alkindi et al., 2024) identified a rapid decline in platelet count as a significant correlate of mortality, alongside leukocytosis and elevated haemolytic markers, with thrombocytopenia preceding multiorgan failure in non-survivors. Conclusions: The FBC is a high-yield, low-cost diagnostic and prognostic tool in SCD. Integrating platelet count, MPV, and PLR with clinical context and hematological markers may improve risk stratification, though prospective validation of specific thresholds for MPV and PLR in SCD is still required. Management should be etiology-specific, with platelet transfusion reserved for life-threatening hemorrhage. Standardizing FBC interpretation through simple, resource-appropriate algorithms can enhance early complication detection, particularly in low-resource, high-burden settings.