Abstract Number: PB0053
Meeting: ISTH 2021 Congress
Theme: Coagulation and Natural Anticoagulants » Coagulation Factors and Inhibitors
Background: Patients with lower-leg cast immobilization and knee arthroscopy patients are at high risk of venous thromboembolism (VTE), despite low-molecular-weight-heparin as prophylaxis. Improved prophylactic strategies are needed for which knowledge on the underlying mechanism of VTE in these patients is essential. For this it is of interest to what extent thrombin generation is affected by lower-leg trauma and knee arthroscopy.
Aims: To measure the effect of (1) lower-leg trauma and (2) knee arthroscopy on thrombin generation.
Methods: Blood samples were collected from POT-CAST (Prevention Of Thrombosis after Lower Leg Plaster Cast) and POT-KAST (Prevention Of Thrombosis after Knee Arthroscopy) trials. Blood draw took place shortly after lower-leg trauma and within four hours before/after knee arthroscopy. A selection of patients who did not develop VTE were selected for current analyses: 89 patients with lower-leg injury and 88 knee arthroscopy patients. Thrombin generation was measured using thrombomodulin-modified CAT (Calibrated Automated Thrombography). Furthermore, plasma levels of thrombin-antithrombin complexes, prothrombin fragment 1+2 and fibrinopeptide A were measured in a smaller subset of patients by commercially available enzyme-linked immunosorbent assays.
Aim 1: lower-leg injured patients were compared with preoperative measurements of arthroscopy patients (controls), resulting in mean differences (or mean ratios if ln-retransformed).
Aim 2: pre- and postoperative measurements in arthroscopy patients were compared, resulting in paired mean changes.
Results: Ex vivo thrombin generating potential and in vivo activation of coagulation were elevated after lower leg trauma (Table 1). Ex vivo thrombin generating potential and in vivo activation of coagulation did not change after knee arthroscopy (Table 2).
| Lower-leg injury (N=89), mean (SD) | No lower-leg injury (N=88), mean (SD) | Mean difference/ratio (95%CI)† | Adj. mean difference/ratio (95%CI)†* | |
| ETP (nM IIa*min) | 566.0 (202.2) | 451.4 (239.4) | 114.6 (48.8 to 180.3) | 120.0 (55.0 to 185.1) |
| Thrombin peak (nM IIa) | 152.3 (59.4) | 117.3 (67.4) | 35.0 (16.1 to 53.8) | 36.6 (17.8 to 55.3) |
| Lag time (min) | 2.0 (0.5) | 2.1 (0.6) | -0.1 (-0.3 to 0.0) | -0.1 (-0.3 to 0.0) |
| Velocity index (nM IIa/min) | 72.8 (33.8) | 55.7 (37.5) | 17.0 (6.4 to 27.6) | 18.0 (7.4 to 28.6) |
| In vivo markers of coagulation activation | (N=67) | (N=28) | ||
| TAT complexes (μg/l)‡ | 5.7 (4.8 to 6.7) | 2.3 (2.1 to 2.5) | 2.5 (1.9 to 3.2) † | 2.3 (1.7 to 3.0) † |
| Prothrombin fragment 1+2 (pmol/l)‡ | 260.7 (231.2 to 294.0) | 242.7 (218.6 to 269.3) | 1.1 (0.9 to 1.3) † | 1.0 (0.8 to 1.2) † |
| Fibrinopeptide A (ng/ml) | 143.9 (91.5) | 95.1 (64.3) | 48.8 (11.0 to 86.7) | 43.8 (5.9 to 81.8) |
| ETP: endogenous thrombin potential; TAT: thrombin-antithrombin complexes. *Adjusted for age, sex, Body Mass Index (BMI) and comorbidities. † Mean ratios are denoted in the table with this symbol and in italics. ‡ TAT and F1+2 were not normally distributed and therefore ln-retransformed, resulting in geometric means with 95%CIs and mean ratios. |
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Aim 1: Thrombin generation parameters and plasma levels of associated parameters in patients with lower-leg injury compared to patients without lower-leg injury.
| Preoperative (N=88), mean (SD) | Postoperative (N=85)*, mean (SD) | Paired mean change (95%CI) | |
| ETP (nM IIa*min) | 451.4 (239.4) | 473.1 (260.9) | 28.7 (-4.1 to 61.5) |
| Thrombin peak (nM IIa) | 117.3 (67.4) | 121.0 (72.0) | 5.0 (-4.0 to 13.9) |
| Lag time (min) | 2.1 (0.6) | 2.0 (0.5) | -0.1 (-0.2 to 0.0) |
| Velocity index (nM IIa/min) | 55.7 (37.5) | 58.7 (42.1) | 3.2 (-2.0 to 8.3) |
| In vivo markers of coagulation activation | (N=28) | (N=28) | |
| TAT complexes (μg/l)† | 2.3 (2.1 to 2.5) | 2.1 (1.9 to 2.3) | -0.2 (-0.5 to 0.2) |
| Prothrombin fragment 1+2 (pmol/l)† | 242.7 (218.6 to 269.3) | 226.6 (201.4 to 255.1) | -14.9 (-38.4 to 8.5) |
| Fibrinopeptide A (ng/ml) | 95.1 (64.3) | 101.2 (64.0) | 6.1 (-20.8 to 33.1) |
| ETP: endogenous thrombin potential; TAT: thrombin-antithrombin complexes. * Thrombin generation was not measured in the postoperative samples of three patients due to lack of plasma (N=2) or inadequate sample quality (N=1). † TAT and F1+2 were not normally distributed and therefore ln-retransformed, resulting in geometric means with 95%CIs. |
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Aim 2: Pre- and postoperative plasma levels of thrombin generation parameters and plasma levels of associated parameters in patients who underwent knee arthroscopy.
Conclusions: Lower-leg injury is associated with an enhanced ex vivo thrombin generating potential and in vivo thrombin generation, while knee arthroscopy has no effect on ex vivo thrombin generation, and surprisingly does not result in in vivo activation of coagulation. The pathogenesis of VTE therefore may be different for these patient groups.
To cite this abstract in AMA style:
Touw CE, Nemeth B, van Adrichem R, Lijfering W, van Hylckama Vlieg A, Nelissen R, Lisman T, Cannegieter S. The Effect of Lower-leg Trauma and Knee Arthroscopy on Thrombin Generation [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/the-effect-of-lower-leg-trauma-and-knee-arthroscopy-on-thrombin-generation/. Accessed November 29, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-effect-of-lower-leg-trauma-and-knee-arthroscopy-on-thrombin-generation/