Alterations in von Willebrand Factor Levels in Patients with Malaria: A Systematic Review and Meta-Analysis of Disease Severity

Background and Objectives: Elevated von Willebrand factor (vWF) levels have been reported in malaria, but their relationship with disease severity remains unclear. This study aimed to compare vWF levels between Plasmodium-infected and uninfected individuals and assess changes in severe infections. Materials and Methods: The systematic review was registered in PROSPERO (CRD42024558479). A comprehensive search across six databases identified studies reporting vWF levels in malaria. A meta-analysis was conducted using a random-effects model, with standardized mean difference (SMD) as the effect measure due to varying measurement units. Heterogeneity was assessed using the I-2 statistic. Results: Of 1647 identified records, 26 studies met the inclusion criteria. The meta-analysis showed significantly higher vWF levels in Plasmodium-infected individuals compared to uninfected controls (p < 0.001, SMD: 2.689 [95% CI 1.362; 4.017], I-2: 98.1%, 12 studies, 3109 participants). However, no significant difference was found between severe and less severe cases (p = 0.051, SMD: 3.551 [95% CI -0.007; 7.109], I-2: 99.3%, 8 studies, 1453 participants). Conclusions: vWF levels are significantly elevated in individuals with Plasmodium infections, indicating a potential role in malaria pathophysiology. Although levels tend to be higher in severe cases, current evidence is insufficient to support vWF as a reliable marker for disease severity. Further prospective and well-controlled studies are needed to validate its diagnostic and prognostic value in malaria management.