Prothrombin conversion is accelerated in the antiphospholipid syndrome and insensitive to thrombomodulin by Romy M. W. Kremers, Stéphane Zuily, Hilde Kelchtermans,

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Presentation transcript:

Prothrombin conversion is accelerated in the antiphospholipid syndrome and insensitive to thrombomodulin by Romy M. W. Kremers, Stéphane Zuily, Hilde Kelchtermans, Tessa C. Peters, Saartje Bloemen, Véronique Regnault, H. Coenraad Hemker, Philip G. de Groot, Denis Wahl, and Bas de Laat BloodAdv Volume 2(11):1315-1324 June 12, 2018 © 2018 by The American Society of Hematology

Romy M. W. Kremers et al. Blood Adv 2018;2:1315-1324 © 2018 by The American Society of Hematology

TG in APS patients and controls. TG in APS patients and controls. Average TG curves are shown for healthy controls (dashed line) and APS patients (continuous line) at 1 (A) and 5 (B) pM TF. TG parameters lag time (C,E), time-to-peak (D,F), peak height (G,I), and ETP (H,J) were quantified for 1 and 5 pM TG curves, respectively. ***P < .001, **P < .01 according to a 2-sided Mann-Whitney U test. Romy M. W. Kremers et al. Blood Adv 2018;2:1315-1324 © 2018 by The American Society of Hematology

Prothrombin conversion in APS patients and controls. Prothrombin conversion in APS patients and controls. Average prothrombin conversion curves are shown for healthy controls (dashed line) and APS patients (continuous line) at 1 (A) and 5 (B) pM TF. Prothrombin conversion parameters for the total amount of prothrombin converted (PCtot; C,E) and maximum rate of prothrombin conversion (PCmax; D,F) were quantified for 1 and 5 pM TG curves, respectively. ***P < .001, **P < .01 according to a 2-sided Mann-Whitney U test. Romy M. W. Kremers et al. Blood Adv 2018;2:1315-1324 © 2018 by The American Society of Hematology

Thrombin decay capacity in APS patients and control subjects. Thrombin decay capacity in APS patients and control subjects. Thrombin decay capacity was assessed in healthy control subjects and APS patients without VKA therapy. No significant differences were detected between groups using a 2-sided Mann-Whitney U test. Romy M. W. Kremers et al. Blood Adv 2018;2:1315-1324 © 2018 by The American Society of Hematology

Thrombomodulin sensitivity of TG and thrombin dynamics in healthy subjects and APS patients with (blue) or without VKA treatment (red). Thrombomodulin sensitivity of TG and thrombin dynamics in healthy subjects and APS patients with (blue) or without VKA treatment (red). (A-C) The inhibition of TG (continuous line) by 20 nM TM (line with circle symbols) was measured in healthy controls (A) and APS patients without VKAs (B). The effect of TM was quantified as the percentage inhibition of TG peak height (C). (D-F) The inhibition of prothrombin conversion (continuous line) by 20 nM TM (line with circle symbols) was measured in healthy controls (D) and APS patients without VKAs (E). The effect of TM was quantified as the percentage inhibition of PCmax (F). (G-I) The inhibition of TG (continuous line) by 20 nM TM (line with circle symbols) was measured in controls on VKA (G) and APS patients on VKAs (H). The effect of TM was quantified as the percentage inhibition of TG peak height (I). (J-L) The inhibition of prothrombin conversion (continuous line) by 20 nM TM (line with circle symbols) was measured in controls on VKA (J) and APS patients on VKAs (K). The effect of TM was quantified as the percentage inhibition of PCmax (L). ***P < .001 compared with the control group using a 2-sided Mann-Whitney U test. Romy M. W. Kremers et al. Blood Adv 2018;2:1315-1324 © 2018 by The American Society of Hematology

TG and thrombin dynamics parameters measured at 5 pM TF in APS patients with and without prior thrombosis. TG and thrombin dynamics parameters measured at 5 pM TF in APS patients with and without prior thrombosis. TG peak height (A) and ETP (B) and total prothrombin conversion (C) and maximum rate of prothrombin conversion (D) were significantly higher in APS patients with prior thrombosis than in patients without a history of thrombosis. There was no difference between a history of venous thrombosis (green dots), arterial thrombosis (blue dots), or a combination of both (red dot). ROC curves were plotted for each of the variables. *P < .05 and **P < .01 compared with the control group using a 2-sided Mann-Whitney U test. Romy M. W. Kremers et al. Blood Adv 2018;2:1315-1324 © 2018 by The American Society of Hematology