Abstract Number: PB1920
Meeting: ISTH 2020 Congress
Theme: Thrombotic Microangiopathies » Antiphospholipid Syndrome
Background: Despite strict anticoagulant treatment, a proportion of patients with antiphospholipid syndrome (APS) experiences recurrent thrombotic episodes. Treatment with anticoagulants has two main effects: it reduces thrombin generation and, as a consequence, attenuates thrombin-mediated anti-fibrinolytic effects, thereby enhancing endogenous fibrinolysis.
Aims: To evaluate the anticoagulant and profibrinolytic responses to warfarin and activated protein C (APC) in patients with APS.
Methods: Twenty-three APS patients (20 triple and 3 double aPL-positive) and 26 aPL-negative patients under stable warfarin treatment, along with 20 healthy controls, were studied. Anticoagulation was measured by thrombin generation assay and fibrinolytic resistance as the lysis time of plasma clots by rt-PA. The two assays were also performed after addition of APC. PAI-1 levels were determined by ELISA, and myeloperoxidase (MPO) by chromogenic assays.
Results: Warfarin treatment induced a strong reduction of thrombin generation in both aPL-positive and aPL-negative patients, peak thrombin activity being even lower in the former (table 1). Using a clot lysis assay that is very sensitive to thrombin generation, we found longer lysis time in aPL-positive group. This fibrinolysis impairment could not be explained by PAI-1 levels, which, surprisingly, were lower in aPL-positive patients. The latter, moreover, showed a strong resistance to the anticoagulant and even more so to the profibrinolytic effect of APC addition to plasma. Finally, MPO, a marker of neutrophil activation and NETosis, was significantly increased in aPL-positive group.
Conclusions: In APS patients, the marked inhibition of thrombin generation induced by warfarin treatment is not accompanied by the expected enhancement of fibrinolysis, notwithstanding the lower levels of PAI-1. This phenomenon, along with the strong resistance to the profibrinolytic effect of APC, may contribute to recurrent thrombosis in APS patients under warfarin treatment. The role of neutrophil activation in fibrinolysis impairment warrants further investigation.
| aPL-positive (n=23) | aPL-negative (n=26) | P (aPL+ vs aPL-) | Healthy controls (n=20) | |
| ETP (nMxmin) | 287 (129-534) | 344 (253-500) | n.s. | 1078 (950-1242) |
| Peak thrombin (nM) | 25 (7.9-64) | 60 (38-104) | 0.041 | 178 (133-255) |
| Lysis time (min) | 67 (64-74) | 52 (42-59) | <0.0001 | 76 (69-83) |
| PAI-1 (ng/ml) | 28 (23-47) | 62 (47-74) | 0.0008 | 38 (22-54) |
| APC-induced ETP reduction (%) | 27 (10-100) | 100 (57-100) | 0.002 | 52 (42-59) |
| APC-induced lysis time reduction (%) | 9.0 (5.7-15) | 33 (21-54) | <0.0001 | 36 (32-47) |
| MPO (mOD) | 160 (87-500) | 85 (60-136) | 0.048 | 68 (38-81) |
[Table 1. Anticoagulant and profibrinolytic responses (median & IQR) in patients under warfarin treatment]
To cite this abstract in AMA style:
Ammollo CT, Semeraro F, Bison E, Banzato A, Pengo V, Colucci M. Patients with Antiphospholipid Syndrome Display a Marked Resistance to the Profibrinolytic Activity of Anticoagulants [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/patients-with-antiphospholipid-syndrome-display-a-marked-resistance-to-the-profibrinolytic-activity-of-anticoagulants/. Accessed September 29, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/patients-with-antiphospholipid-syndrome-display-a-marked-resistance-to-the-profibrinolytic-activity-of-anticoagulants/