Associations Among Disseminated Intravascular Coagulation, Thrombocytopenia Cytokines/Chemokines and Genetic Polymorphisms of Toll-Like Receptor 2/4 in Chinese Patients with Sepsis

Abstract

Shaowei Jiang,1 Jing Ma,2 Shan Ye,3 Connor Meaney,4 Timothy Evan Moore,4 Shuming Pan,1 Chengjin Gao1 1Department of Emergency, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China; 2Department of Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China; 3Department of Internal Medicine, Shanghai Songnan Community Health Service Center, Shanghai, 200092, People’s Republic of China; 4Division of Rheumatology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, 84132, USACorrespondence: Chengjin Gao; Shuming Pan Email [email protected]; [email protected](s): Toll-like receptors (TLRs) on platelets have been extensively studied. Both TLR2 and TLR4 have been shown to augment platelet activation and alter its function from a hemostatic regulator to an immune sentinel. However, few studies have investigated the relationship between genetic polymorphisms in TLR2, TLR4 and platelets. We investigated whether genetic polymorphisms of TLR2 and TLR4 were related to thrombocytopenia and coagulation failure in Chinese patients with sepsis.Basic Methods: Adult Chinese patients with sepsis in the intensive care unit of a university medical center were monitored for up to 28 days. Thrombocytopenia and disseminated intravascular coagulation (DIC), diagnosed using Japanese Association for Acute Medicine (JAAM) criteria, were observed as the primary outcomes. Single-nucleotide polymorphisms (SNPs) in TLR2 (rs111200466, rs5743708) and TLR4 (rs11536889, rs145801336, rs11536896, rs7869402) in patients with sepsis were detected by polymerase chain reaction. The data were analyzed using chi-square and rank sum tests.Results: The genotype of TLR2 (rs111200466) (Del/Del) was associated with the initial DIC. The genotype of TLR4 (rs11536889) (C/C&C/G) was associated with initial DIC, DIC onset during hospitalization and platelet counts. Furthermore, both DIC and platelet counts were associated with cytokines and chemokines, especially the IL10.Conclusion: Our results demonstrate that in Chinese sepsis patients, the rs111200466 SNP in TLR2 and rs11536889 SNP in TLR4 are associated with thrombocytopenia and DIC, with potential effects on the TLR4 pathways of platelets.Keywords: sepsis, disseminated intravascular coagulation, TLR2/4, genetic polymorphisms

Keywords

• sepsis
• disseminated intravascular coagulation
• tlr2/4
• genetic polymorphisms