Sex-specific hemostatic responses and alterations of Platelet Distribution Width (PDW) and D-dimer in mild COVID-19, Malaria, and co-infection in a tropical setting: A case-control study in Port Harcourt, Nigeria

In malaria-endemic tropical regions, overlapping coagulopathy in COVID-19 and malaria poses management challenges with potential sex differences. This STROBE-compliant case-control study evaluated sex-specific variations in platelet indices and assessed alterations of platelet distribution width (PDW) and D-dimer in mild cases. We studied 220 participants, 55 per group: healthy controls, malaria-positive, COVID-19-positive, and COVID-19 plus malaria co-infected, aged 20–65 years, balanced by sex (22 females and 33 males per group), conducted in Port Harcourt, Nigeria between November 2021 and March 2022. Platelet indices were measured using Sysmex XP-300 and D-dimer and fibrinogen by sandwich-ELISA. Data were analyzed using SAS 9.4 and JMP 14.3. PDW was significantly elevated in all infected groups versus controls: malaria 15.19 ± 1.47 fL, COVID-19 15.17 ± 1.51 fL, co-infection 15.58 ± 1.45 fL versus control 13.27 ± 1.20 fL; F = 25.850, p < 0.001. D-dimer was highest in co-infected group 552.80 ± 402.46 ng/mL; F = 2.816, p = 0.040. Two-way ANOVA showed no significant group×sex interaction for platelet indices but significant interactions for fibrinogen F = 18.42, p < 0.001 and D-dimer F = 3.14, p = 0.026. Sex-stratified analysis showed PDW higher in females in malaria p = 0.012 and co-infection p = 0.033, and D-dimer higher in males only in malaria p = 0.021. No significant correlations were observed between platelet indices and fibrinolytic markers. PDW was consistently elevated across mild infections and sex significantly modified fibrinolytic markers, indicating PDW and D-dimer are accessible indicators of hemostatic alterations in resource-limited tropical settings.