The mode of action of sugammadex on coagulation.

OBJECTIVE: To explore the mode of action (MoA) by which sugammadex interferes with coagulation. MATERIALS AND METHODS: The effect of sugammadex on various steps in the coagulation cascade including thrombin generation, factor Xa activity, and factor Xa generation was explored in human plasma. RESULTS: Sugammadex did not affect a conventional thrombin generation test (TGT), while it prolongs activated partial thromboplastin time (APTT) and prothrombin time (PT). However, a customized TGT with PT reagent revealed sugammadex effects. In addition, sugammadex prolonged a one-step prothrombinase-induced clotting time (PiCT) using human factor Xa. Furthermore, sugammadex interfered with factor Xa generation induced by an intrinsic and not by an extrinsic activator, nor by Russell's viper venom factor X (RVV-X). CONCLUSION: Adapted, rather than standard, experiments show that sugammadex is likely to decrease factor Xa activity in the common pathway and activation of factor X specifically in the intrinsic pathway.

Diagnostic possibilities of specific fibrin(ogen) degradation products in relation to venous thromboembolism.

The exclusion of deep venous thrombosis (DVT) in the elderly is hampered by low specificity in clinical decision of D-dimer assays in older patients. To reduce false-positive results, we evaluated specific fibrin(ogen) degradation product assays for their contribution in the diagnosis of DVT. In a post-hoc study with outpatients suspected for DVT, we evaluated the elastase-specific fibrinogen (fibrinogen elastase degradation product, FgEDP) and D-E-specific fibrin (fibrin degradation product, FbDP) degradation product assays in relation to DVT. Results were combined with five D-dimer assays as ratio, with a specific focus on age-dependency. In 437 patients (DVT prevalence 39%), FgEDP correlated with D-dimer in DVT-negative patients (P<0.001), but not in DVT-positive patients (P > 0.55). FbDP results correlated with D-dimer in both groups (P<0.001). The values of the area under the curve of the receiver operating characteristic curve for both assays were lower than D-dimer. Using the ratios, only in the fourth age quartile D-dimer/FgEDP ratios had diagnostic value with lower number needed to test (1.8-12.7) as compared to D-dimer less than 500 µg/l alone (5.4-102). The D-dimer/FbDP ratios in DVT-negative elderly patients increased to a plateau by increasing D-dimer. In DVT-positive patients, these ratios were near constant for increasing values of D-dimer. In elderly patients, the D-dimer/FgEDP ratios may improve the number of patients in whom DVT could be excluded. The D-dimer/FbDP ratios showed differences in composition of fibrin degradation products between DVT-negative and DVT-positive patients and between young and old DVT-negative patients.

Strongly increased levels of fibrinogen elastase degradation products in patients with ischemic stroke.

Ischemic stroke is associated with leucocyte activation. Activated leucocytes release elastase, an enzyme that can degrade fibrinogen. Fibrinogen elastase degradation products (FgEDP) may serve as a specific marker of elastase proteolytic activity. In a case-control study of 111 ischemic stroke patients and 119 controls, significantly higher FgEDP levels were observed in cases than in controls, both in the acute phase and in the convalescent phase. Results were only slightly affected by adjustment for cardiovascular risk factors, C-reactive protein and fibrinogen. Our findings suggest that FgEDP might be involved in the pathogenesis of stroke.