Chronic murine schistosomiasis causes aberrant hemostasis

TY - JOUR

T1 - Chronic murine schistosomiasis causes aberrant hemostasis

AU - Hewitson, James Philip

AU - Greenman, Joanna

AU - Moss, Lucie

AU - Chakraborty, Shinjini

AU - Whitehead, Bradley

AU - Palmfedt, johan

AU - Nejsum, Peter

AU - Hitchcock, Ian Stuart

N1 - © 2024 International Society for Experimental Hematology. Published by Elsevier Inc.

PY - 2025/2/1

Y1 - 2025/2/1

N2 - Background: Schistosomiasis afflicts >250 million people worldwide, leading to an annual loss of >3 million disability adjusted life years. Schistosoma mansoni causes intestinal schistosomiasis with parasite eggs either transversing intestinal tissue or lodging within the liver and other organs, causing intestinal hemorrhage and liver pathology. Large (~1cm) adult worms survive for years within blood vessels, but we lack a clear understanding of their impact on hemostasis. Objectives: We used a chronic mouse model of schistosomiasis to determine the impact on platelet numbers, phenotype and function. Methods: Hemostatic function was assessed by platelet phenotyping (flow cytometry and proteomics), whole blood aggregometry and longitudinal coagulometry. Results: Whilst platelets from schistosome-infected mice lack elevated surface P-selectin and activated αIIbβ3, unbiased proteomic analysis reveals infection-induced increases in MHC-I, IgM and IgG antibodies, and complement components. Whole blood from schistosome-infected mice spontaneously aggregates in the absence of exogenous agonists. Conversely, prothrombin and activated partial thromboplastin times are prolonged at the chronic stage of infection (10-12 weeks). Conclusions: A mouse model of S. mansoni infection shows wide-ranging changes in hemostatic function which may have clinically relevant implications for populations in endemic regions.

AB - Background: Schistosomiasis afflicts >250 million people worldwide, leading to an annual loss of >3 million disability adjusted life years. Schistosoma mansoni causes intestinal schistosomiasis with parasite eggs either transversing intestinal tissue or lodging within the liver and other organs, causing intestinal hemorrhage and liver pathology. Large (~1cm) adult worms survive for years within blood vessels, but we lack a clear understanding of their impact on hemostasis. Objectives: We used a chronic mouse model of schistosomiasis to determine the impact on platelet numbers, phenotype and function. Methods: Hemostatic function was assessed by platelet phenotyping (flow cytometry and proteomics), whole blood aggregometry and longitudinal coagulometry. Results: Whilst platelets from schistosome-infected mice lack elevated surface P-selectin and activated αIIbβ3, unbiased proteomic analysis reveals infection-induced increases in MHC-I, IgM and IgG antibodies, and complement components. Whole blood from schistosome-infected mice spontaneously aggregates in the absence of exogenous agonists. Conversely, prothrombin and activated partial thromboplastin times are prolonged at the chronic stage of infection (10-12 weeks). Conclusions: A mouse model of S. mansoni infection shows wide-ranging changes in hemostatic function which may have clinically relevant implications for populations in endemic regions.

U2 - 10.1016/j.exphem.2024.104689

DO - 10.1016/j.exphem.2024.104689

M3 - Article

SN - 0301-472X

VL - 142

JO - Experimental Haematology

JF - Experimental Haematology

M1 - 104689

ER -