Jeffrey W Shupp1, Shannon M Prior2, Daniel Y Jo3, Lauren T Moffatt4, Kenneth G Mann5, Saulius Butenas6. 1. Department of Surgery, MedStar Washington Hospital Center, Washington, DC, United States. Electronic address: Jeffrey.W.Shupp@medstar.net. 2. University of Vermont, Department of Biochemistry, Burlington, VT, United States. Electronic address: smprior@uvm.edu. 3. Department of Surgery, MedStar Washington Hospital Center, Washington, DC, United States. Electronic address: Daniel.Y.Jo@medstar.net. 4. Department of Surgery, MedStar Washington Hospital Center, Washington, DC, United States. Electronic address: lauren.t.moffatt@medstar.net. 5. Haematologic Technologies, Inc., Essex Junction, VT, United States. Electronic address: haemtechken@gmail.com. 6. University of Vermont, Department of Biochemistry, Burlington, VT, United States. Electronic address: sbutenas@uvm.edu.
Abstract
INTRODUCTION: An elevated procoagulant activity observed in trauma patients is, in part, related to tissue factor (TF) located on blood cells and microparticles. However, analysis of trauma patient plasma indicates that there are other contributor(s) to the procoagulant activity. We hypothesize that factor (F)XIa and FIXa are responsible for an additional procoagulant activity in burn patients. METHODS: Multiple time-point plasma samples from 56 burn patients (total number of samples was 471; up to 20 time-points/patient collected in 3 weeks following admission) were evaluated in a thrombin generation assay using inhibitory antibodies to TF, FIXa and FXIa. RESULTS: Due to the limited volume of some samples, not all were analyzed for all three proteins. At admission, 10 of 53 patients (19%) had active TF, 53 of 55 (96%) had FXIa and 48 of 55 (87%) had FIXa in their plasma. 34 patients of 56 enrolled (61%) showed TF activity at one or more time-points. All patients had FXIa and 96% had FIXa at one or more time-points. Overall, TF was observed in 99 of 455 samples analyzed (22%), FXIa in 424 of 471 (90%) and FIXa in 244 of 471 (52%). The concentration of TF was relatively low and varied between 0 and 2.1pM, whereas that of FXIa was higher, exceeding 100pM in some samples. The majority of samples with FIXa had it at sub-nanomolar concentrations. No TF, FXIa and FIXa activity was detected in plasma from healthy individuals. CONCLUSIONS: For the first time reported, the majority of plasma samples from burn patients have active FXIa and FIXa, with a significant fraction of them having active TF. The concentration of all three proteins varies in a wide range.
INTRODUCTION: An elevated procoagulant activity observed in traumapatients is, in part, related to tissue factor (TF) located on blood cells and microparticles. However, analysis of traumapatient plasma indicates that there are other contributor(s) to the procoagulant activity. We hypothesize that factor (F)XIa and FIXa are responsible for an additional procoagulant activity in burn patients. METHODS: Multiple time-point plasma samples from 56 burn patients (total number of samples was 471; up to 20 time-points/patient collected in 3 weeks following admission) were evaluated in a thrombin generation assay using inhibitory antibodies to TF, FIXa and FXIa. RESULTS: Due to the limited volume of some samples, not all were analyzed for all three proteins. At admission, 10 of 53 patients (19%) had active TF, 53 of 55 (96%) had FXIa and 48 of 55 (87%) had FIXa in their plasma. 34 patients of 56 enrolled (61%) showed TF activity at one or more time-points. All patients had FXIa and 96% had FIXa at one or more time-points. Overall, TF was observed in 99 of 455 samples analyzed (22%), FXIa in 424 of 471 (90%) and FIXa in 244 of 471 (52%). The concentration of TF was relatively low and varied between 0 and 2.1pM, whereas that of FXIa was higher, exceeding 100pM in some samples. The majority of samples with FIXa had it at sub-nanomolar concentrations. No TF, FXIa and FIXa activity was detected in plasma from healthy individuals. CONCLUSIONS: For the first time reported, the majority of plasma samples from burn patients have active FXIa and FIXa, with a significant fraction of them having active TF. The concentration of all three proteins varies in a wide range.
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