Abnormalities of hemostasis in sickle cell patients and predisposition to thrombotic risk: a systematic review and...

Sickle cell disease is a hemoglobinopathy characterized by alterations in the components of hemostasis. Despite efforts and individual and multiple studies carried out to understand the pathophysiology of the disease, particularly regarding abnormalities of hemostasis and coagulation, questions remain. This meta-analysis aimed to evaluate the studies linking inflammatory, coagulation, and fibrinolysis abnormalities in sickle cell patients, putting them in an intrinsic state of hypercoagulability and predisposing them to thrombotic risk.

The systematic review of databases and search engines was conducted over 24 years (2000-2024) and worldwide according to the reporting guidelines of PRISMA and the Cochrane Handbook. The research articles listed were searched in the PubMed and Web of Science databases. Only case-control articles were retained. Data were extracted from the articles and analyzed using the statistical software R version 4.3.2. The standardized mean difference (SMD) was used to assess the extent of the disease on the different parameters studied. Heterogeneity across individual studies was assessed using Higgins's inconsistency Q statistics and reported as I² and p-value. ROBINS-E was used to assess the risk of bias in the included studies.

303 studies were initially identified; after the elimination of duplicates and of works not meeting the objective of the study, 17 studies were finally included for meta-analyses. The standardized mean difference (SMD) using the common effect model is 0.79 [0.58, 1.00] for prothrombin time for 5 studies analyzed (p < 0.01), 0.26 [0.06, 0.46] for fibrinogen for 6 studies analyzed (p < 0.01), and 0.87 [0.62, 1.11] for D-dimer for 6 studies analyzed (p < 0.01); thus reflecting the strong influence of sickle cell disease on the production of Prothrombin, fibrinogen and D-dimer when compared to normal controls. For protein C, the SMD with the common effect model is -1.32 [-1.54, -1.09] for 5 studies analyzed (p < 0.01), and for protein S, it is -1.45 [-1.69, -1.22] for 5 studies analyzed (p < 0.01); thus reflecting a significant negative influence of sickle cell disease on protein C and protein S production when compared to normal controls. Finally, the SMD for antithrombin using the common effect model is 0.66 [0.35, 0.98] for 5 studies analyzed (p < 0.01), thus reflecting the strong influence of sickle cell disease on the production of antithrombin when compared to normal controls.

Analyses performed from these studies reported a large influence of sickle cell disease on the inflammatory, coagulation, fibrinolysis, and natural anticoagulant system when compared to normal controls, assessed by a SMD that ranged from moderate to large. These results provide more information on research related to coagulation abnormalities in sickle cell disease and will help improve patient care.