Hanna K de Jong1, Chris M Parry2, Thomas W van der Vaart3, Liesbeth M Kager4, Stannie J van den Ende3, Rapeephan R Maude5, Lalith Wijedoru5, Aniruddha Ghose6, Mohammed U Hassan6, Mohammed A Hossain6, Arjan M Dondorp7, Steve Baker8, M Abul Faiz9, Joost C M Meijers10, W Joost Wiersinga11. 1. Department of Internal Medicine, Division of Infectious Diseases, and Center for Experimental Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Meibergdreef 9, Room G2-130, 1105 AZ Amsterdam, The Netherlands. Electronic address: h.k.dejong@amc.nl. 2. Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. 3rd Floor, 60th Anniversary Chalermprakiat Building, 420/6 Ratchawithi Rd., Ratchathewi District, Bangkok 10400, Thailand; Center for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford, UK. Old Road, Headington, Oxford OX3 7LE, United Kingdom; Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK. Pembroke Place, Liverpool L3 5QA, United Kingdom. Electronic address: cmparry@liverpool.ac.uk. 3. Department of Internal Medicine, Division of Infectious Diseases, and Center for Experimental Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Meibergdreef 9, Room G2-130, 1105 AZ Amsterdam, The Netherlands. 4. Department of Internal Medicine, Division of Infectious Diseases, and Center for Experimental Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Meibergdreef 9, Room G2-130, 1105 AZ Amsterdam, The Netherlands. Electronic address: L.M.Kager@nwz.nl. 5. Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. 3rd Floor, 60th Anniversary Chalermprakiat Building, 420/6 Ratchawithi Rd., Ratchathewi District, Bangkok 10400, Thailand. 6. Chittagong Medical College Hospital, Chittagong, Bangladesh. 7. Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. 3rd Floor, 60th Anniversary Chalermprakiat Building, 420/6 Ratchawithi Rd., Ratchathewi District, Bangkok 10400, Thailand; Centre for Specialized Care and Research, Chittagong, Bangladesh. Electronic address: arjen@tropmedres.ac. 8. Center for Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford, UK. Old Road, Headington, Oxford OX3 7LE, United Kingdom; Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Vietnam. Electronic address: sbaker@oucru.org. 9. Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. 3rd Floor, 60th Anniversary Chalermprakiat Building, 420/6 Ratchawithi Rd., Ratchathewi District, Bangkok 10400, Thailand; Centre for Specialized Care and Research, Chittagong, Bangladesh. 10. Department of Experimental Vascular Medicine and Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. Meibergdreef 9, Room G2-130, 1105 AZ Amsterdam, The Netherlands. Electronic address: j.c.meijers@amc.uva.nl. 11. Department of Internal Medicine, Division of Infectious Diseases, and Center for Experimental Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Meibergdreef 9, Room G2-130, 1105 AZ Amsterdam, The Netherlands. Electronic address: w.j.wiersinga@amc.nl.
Abstract
OBJECTIVES: Typhoid fever caused by Salmonella Typhi remains a major burden worldwide. Gastrointestinal bleeding can be seen in up to 10 percent of patients and may be fatal. The coagulopathy, which may be the driver of this severe complication in patients with typhoid fever, however is ill defined. The aim of this study was to evaluate the activation of coagulation, anticoagulation, and fibrinolysis in patients with acute typhoid fever. METHODS: Parameters of coagulation and fibrinolysis were measured in 28 hospitalized patients with culture-confirmed or PCR-confirmed typhoid fever and compared to 38 age- and sex-matched healthy volunteers. RESULTS: Patients demonstrated activation of the coagulation system, as reflected by elevated in vitro thrombin generation and high plasma levels of fibrinogen, D-dimer and prothrombin fragment F1 + 2 in concert with consumption of coagulation factors resulting in a prolonged prothrombin-time and activated-partial-thromboplastin-time. Concurrently, the anticoagulant proteins, protein C and antithrombin, were significantly lower in comparison to healthy controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis and a marked activation of endothelial cells. The extent of coagulation activation was associated with the course of the disease, repeated testing during convalescence showed a return toward normal values. CONCLUSIONS: Activation of coagulation is an important clinical feature of typhoid fever and is associated with severity of disease.
OBJECTIVES:Typhoid fever caused by Salmonella Typhi remains a major burden worldwide. Gastrointestinal bleeding can be seen in up to 10 percent of patients and may be fatal. The coagulopathy, which may be the driver of this severe complication in patients with typhoid fever, however is ill defined. The aim of this study was to evaluate the activation of coagulation, anticoagulation, and fibrinolysis in patients with acute typhoid fever. METHODS: Parameters of coagulation and fibrinolysis were measured in 28 hospitalized patients with culture-confirmed or PCR-confirmed typhoid fever and compared to 38 age- and sex-matched healthy volunteers. RESULTS:Patients demonstrated activation of the coagulation system, as reflected by elevated in vitro thrombin generation and high plasma levels of fibrinogen, D-dimer and prothrombin fragment F1 + 2 in concert with consumption of coagulation factors resulting in a prolonged prothrombin-time and activated-partial-thromboplastin-time. Concurrently, the anticoagulant proteins, protein C and antithrombin, were significantly lower in comparison to healthy controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis and a marked activation of endothelial cells. The extent of coagulation activation was associated with the course of the disease, repeated testing during convalescence showed a return toward normal values. CONCLUSIONS: Activation of coagulation is an important clinical feature of typhoid fever and is associated with severity of disease.
Authors: Bastiaan W Haak; Hanna K de Jong; Sarantos Kostidis; Martin Giera; Rapeephan R Maude; Rasheda Samad; Lalith Wijedoru; Aniruddha Ghose; Mohammed Abul Faiz; Christopher M Parry; W Joost Wiersinga Journal: Open Forum Infect Dis Date: 2020-06-26 Impact factor: 3.835