Abstract Number: PB0413
Meeting: ISTH 2021 Congress
Theme: Fibrinogen, Fibrinolysis and Proteolysis » Fibrinolytic Factors and Inhibitors
Background: Despite thromboprophylaxis, patients with lower-leg cast immobilization and patients undergoing knee arthroscopy are at high risk of venous thromboembolism (VTE). Hence, exploration of new preventive strategies is necessary. For this, it is of interest to what extent the natural anticoagulant and fibrinolytic systems contribute to VTE.
Aims: To measure the effect of (1) lower-leg trauma and (2) knee arthroscopy on plasma levels of natural anticoagulant and fibrinolytic factors.
Methods: Plasma samples were provided by participants of the POT-CAST (Prevention Of Thrombosis after Lower Leg Plaster Cast) and POT-KAST (Prevention Of Thrombosis after Knee Arthroscopy) trials. Samples were collected upon lower-leg trauma and before/after arthroscopy (<4 hours), respectively. Clot lysis time (CLT) was measured in in a selection of patients who did not develop VTE (lower-leg trauma N=289, arthroscopy N=293) by monitoring plasma clot formation and subsequent lysis in the presence of exogenous tPA. Plasma levels of antithrombin, free protein S, protein C, plasmin-alpha-2-antiplasmin complexes, plasminogen activator inhibitor-1, t-PA and D-dimer were quantified in subsets of these patients. For aim 1, measurements in lower-leg injury patients were compared with preoperative measurements of arthroscopy patients (controls), expressed as mean differences (or mean ratios if ln-retransformed) and adjusted for age, sex, BMI and comorbidities. For aim 2, pre- and postoperative measurements of arthroscopy patients were compared, i.e., paired mean changes.
Results: Ex vivo fibrinolytic potential was elevated in lower-leg injured and knee arthroscopy patients, however, in vivo activation of fibrinolysis was not affected. Plasma levels of antithrombin increased moderately after lower-leg trauma, while anticoagulant factors decreased following knee arthroscopy.
| Lower-leg injury, number of patients | Lower-leg injury, mean (SD) | No lower-leg injury, number of patients | No lower-leg injury, mean (SD) | Mean difference/ratio (95%CI)† | Adj. mean difference/ratio (95%CI)†* | |
| Antithrombin (%) | 89 | 113.6 (13.1) | 88 | 109.6 (10.6) | 4.0 (0.5 to 7.6) | 4.8 (1.2 to 8.4) |
| Free protein S (%) | 89 | 102.6 (20.5) | 88 | 103.6 (17.9) | -0.9 (-6.7 to 4.8) | -1.6 (-7.1 to 3.9) |
| Protein C (%) | 89 | 123.7 (24.1) | 88 | 125.6 (21.4) | -1.9 (-8.6 to 4.9) | -0.8 (-7.3 to 5.7) |
| Clot lysis time (min) | 289 | 70.0 (15.7) | 293 | 77.8 (23.7) | -7.7 (-11.0 to -4.5) | -5.1 (-8.2 to -2.0) |
| D-dimer ‡ | 289 | 714.5 (631.8 to 807.9) | 293 | 234.4 (211.9 to 259.4) | 3.0 (2.6 to 3.6) † | 3.0 (2.6 to 3.5) † |
| PAP complexes (ng/ml) ‡ | 67 | 296.1 (269.5 to 325.4) | 28 | 254.0 (203.0 to 317.9) | 1.2 (0.9 to 1.4) † | 1.1 (0.9 to 1.4) † |
| tPA (ng/ml) | 67 | 6.2 (2.9) | 28 | 7.3 (5.4) | -1.1 (-2.8 to 0.6) | -1.4 (-3.1 to 0.3) |
| PAI-1 (ng/ml) ‡ | 67 | 1.1 (0.9 to 1.3) | 28 | 1.1 (0.8 to 1.6) | -0.4 (-1.0 to 0.1) † | -0.6 (-1.1 to -0.1) † |
| PAP: plasmin-alpha-2-antiplasmin; tPA: tissue plasminogen activator; PAI-1: plasminogen activator inhibitor-1. * Adjusted for age, sex, body mass index and comorbidities. † Mean ratios are denoted in the table with this symbol and in italics. ‡ D-dimer, PAP and PAI-1 were not normally distributed and therefore ln-retransformed, resulting in geometric means with 95%CIs and mean ratios. |
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Aim 1: Natural anticoagulant factor levels, clot lysis time and fibrinolytic factor levels in patients with lower-leg injury compared with subjects without lower-leg injury.
| Number of patients* | Preoperative, mean (SD) | Postoperative, mean (SD) | Paired mean change (95%CI) | |
| Antithrombin (%) | 88 | 109.6 (10.6) | 101.7 (10.9) | -7.8 (-9.5 to -6.0) |
| Free protein S (%) | 88 | 103.6 (17.9) | 99.4 (17.8) | -4.3 (-5.8 to -2.7) |
| Protein C (%) | 88 | 125.6 (21.4) | 117.3 (20.3) | -7.9 (-9.4 to -6.4) |
| Clot lysis time (min) | 277 | 77.8 (23.7) | 65.1 (14.1) | -13.3 (-15.4 to -11.2) |
| D-dimer † | 277 | 231.8 (209.7 to 256.1) | 212.0 (193.5 to 232.3) | -56.1 (-101.3 to -11.0) |
| PAP complexes (ng/ml) †§ | 28 | 254.0 (203.0 to 317.9) | 247.9 (201.4 to 305.3) | -32.3 (-276.6 to 211.9) |
| tPA (ng/ml) | 28 | 7.3 (5.4) | 6.8 (5.6) | -0.4 (-3.3 to 2.4) |
| PAI-1 (ng/ml) † | 28 | 1.1 (0.8 to 1.6) | 0.8 (0.5 to 1.1) | -0.7 (-1.0 to -0.3) |
| PAP: plasmin-alpha-2-antiplasmin; tPA: tissue plasminogen activator; PAI-1: plasminogen activator inhibitor-1. * Due to lack of plasma or inadequate sample quality, anticoagulant factors were not measured in postoperative samples of three patients and clot lysis time was not measured in postoperative samples of 16 patients. † D-dimer, PAP and PAI-1 were not normally distributed and therefore ln-retransformed, resulting in geometric means with 95%CIs. |
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Aim 2: Pre- and postoperative natural anticoagulant factor levels, clot lysis time and fibrinolytic factor levels in patients who underwent knee arthroscopy.
Conclusions: Ex vivo fibrinolytic potential increases after lower-leg trauma and knee arthroscopy, which however does not lead to elevated in vivo fibrinolysis. Anticoagulant factor levels decrease after knee arthroscopy, while they are not clearly affected by lower-leg trauma.
To cite this abstract in AMA style:
Touw C, 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 the Natural Anticoagulant and Fibrinolytic Systems [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/the-effect-of-lower-leg-trauma-and-knee-arthroscopy-on-the-natural-anticoagulant-and-fibrinolytic-systems/. Accessed November 29, 2021.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-effect-of-lower-leg-trauma-and-knee-arthroscopy-on-the-natural-anticoagulant-and-fibrinolytic-systems/