The Natural Coagulation Inhibitors, Inflammation, and Thrombotic Risk in Sickle Cell Patients in Cameroon, an Analytical Cross-Sectionnal Study

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Abstract

Introduction Thrombotic risk refers to the likelihood of a thrombus, or blood clot, forming in the vascular system, which can obstruct blood flow and cause serious complications. This risk is closely linked to the function of physiological coagulation inhibitors. The causes of thrombosis are multiple, including damage to the vascular wall caused by blood vessel injury, trauma, surgery, or vascular inflammation; these can initiate stasis, or slow blood flow, thus promoting blood cell aggregation and clot formation. These factors are encountered during several pathological processes, including sickle cell disease. This study aimed to evaluate physiological coagulation inhibitors and their association with inflammation and to deduce the thrombotic risk in patients with sickle cell disease. Materials and methods We conducted an analytical cross-sectional study over 1 year. The Bafoussam Regional Hospital served as the framework for this research. The study population consisted of homozygous sickle cell patients regularly followed in the hospital and recruited in the Hematology department. The collected blood samples were sent to the Hematology and Haemostasis laboratory. The analyses carried out were the hemogram by flow cytometry method, the determination of the activity of protein C, protein S, and Antithrombin with a coagulometer by magnetic method; and finally, the exploration of inflammation from CRP dosage by ultrasensitive method and the dosage of interleukin 6 by ELISA sandwich method. The data obtained were recorded in an Excel 2013 spreadsheet and analyzed using statistical software R version 4.1.1. Results 150 homozygous sickle cell patients were included in this study. Of these, 98 (65.34%) presented a thrombotic risk. A high frequency of anemia (94.7%) was reported. Moreover, 82.7% and 64.0%, respectively, of leucocytosis and thrombocytosis were reported. An elevation of inflammatory parameters was observed characterized by an elevation of CRP (100% of patients at risk versus none in the group without it); And a significantly higher median IL6 level in the group of patients at thrombotic risk (50.1 [28.7–76.6] (pg/ml)) compared to those without it (32.3 [14.1–44.4] pg/ml) ( p  = 0.001). A decrease in coagulation inhibitors was observed, notably a significant decrease in protein C in patients with thrombotic risk compared to those without, with respective proportions of 71.6% and 50% ( p  = 0.001). The median antithrombin level was 79.0% [77.0–92.0] in patients with thrombotic risk and 94.0% [84.0-102] in those without ( p  < 0.001). Patients at risk of thrombosis had a significant decrease in protein S (76.6% vs. 50% ( p  < 0.001)); the decrease in the latter was identified as a predictive factor of thrombotic risk during sickle cell disease (aOR = 1.5 [1.1;5.2]; p  = 0.04). Conclusion This study reports a significant frequency of thrombotic risk in the sickle cell population characterized by a decrease in physiological coagulation inhibitors. This highlights the need for a systematic exploration of these markers for the prevention of cardiovascular disease in this patient group.

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