Immediate Coagulation Mornitoring In Anticoagulation Of Nephrotic Syndrome And Hemodialysis-dependent Patients

Background and Objective: Patients with nephrotic syndrome (NS) often have a hypercoagulable state, with high frequency of thromboembolic complications. Uremic patients usually suffer from coagulation disturbances, meanwhile, during hemodialysis (HD), contact of blood with artificial surfaces contributes to thrombogenesis. Thus, appropriate anticoagulation is crucial to prevent thromboembolism in nephrotic patients, to prevent extracorporeal blood clotting and to improve biocompatibility during HD. The Sonoclot signature provides a comprehensive overview of the clotting cascade. Previously, Sonoclot analysis has been used to monitor clot formation and guide blood component therapy. Some studies show that Sonoclot analysis can monitor accurate coagulable states and determine an appropriate heparin dose during HD. The present study is to investigate the coagulation parameters before and after the administration of 1) dalteparin sodium in NS patients to emphasize the importance of individualized anticoagulation under monitoring, 2) unfractionated heparins (UFH), dalteparin sodium or argatroban in HD patients to guide selection or application of anticoagulants for HD. Methods: (1) 18 NS patients were recruited, subcutaneously injected 5000IU of dalteparin sodium. Sonoclot parameters, including glass bead activated clotting time (gbACT), clot rate (CR) and platelet function (PF), were examined before injection, 4hr, 12hr and 24 hr later. Sonoclot parameters were also examined in 8 healthy volunteers without injecting dalteparin sodium. Based on CR decreased to normal after 4 hr or not, the patients were divided into anticoagulation effective-group and ineffective-group. Compare the clinical conditions and Sonoclot parameters between the two groups. (2) 13 HD patients and 5 HD patients with high risk of hemorrhage were recruited. Dalteparin sodium, 5000IU, was administered to 8 patients before HD in a single venous bolus. Whereas UFH was first intravenously injected 3000IU as a bolus, then with 1000IU/h speed in pump and ended 1 hr before HD. The 5 patients with risk of hemorrhage were injected with argatroban of an initial bolus of 8mg and then continuous infusion of 6mg/h and ended 15 min before HD. Blood was taken for Sonoclot analysis before initiation (0) and at the end of HD (4) from the arterial line, and from the arterial (2a) and venous (2v) line respectively 2 hr after injection.Results: (1) CD CR and PF but not gbACT increased in the patient group compared with the control group. (2) CR exceeded the normal range in all patients before treatment, and dropped to the lowest level after 4 hr, CR decreased to normal in 7 patients, CR decreased but still higher than normal in 11 patients. 12 hr later, CR exceeded normal range again in all patients, CR increased but lower than initial in 7 patients and higher than initial in 11 patients. (3) There was no significant difference of clinical parameters between the effective-group and the ineffective one. (2) ① All HD completed successfully, without coagulation and bleeding during and after HD. ② Sonoclot parameters dynamically changed during the HD process. ③UFH group, CR and PF after initiation of HD decreased significantly than before. There was no significance between CR2a and CR2v. ⑤ In Dalteparin sodium treated group, gbACT2a increased than gbACT of other points. CR of other points decreased than CR0. CR2v was greater than CR2a. There's no significance among PF of different points. ⑥Argatroban group, CR of 2hr later decreased than CR0, CR2v was lower than CR2a. There's no significance between CR4 and CR0, as well as gbACT, PF. Conclusion: (1) ① Sonoclot analyzer can be used for immediate monitoring the coagulable states of NS patients and for evaluating the anticoagulation efficacy of dalteparin sodium. ②After been treated with dalteparin sodium, the coagulation states depended on the individual's response to the anticoagulant. After being subcutaneously injected of 5000IU of dalteparin sodium once a day, more than half of the patients did not reach effective anticoagulation even at the peak efficacy. And the anticoagulation effect only persist in nearly one thirds of the patients after 12 hr. Furthermore, rebound of coagulation activation happened in some patients. Thus, anticoagulation treatment should be performed individually under monitoring. (2) ① Sonoclot analyzer can monitor the coagulable states and guide selection of anticoagulants for HD. ② UFH induced intensive anticoagulation during HD, so it is not a proper anticoagulant for patients with risk of hemorrhage. Dalteparin sodium, with little influence on PF, is still not suitable for patients with high-risk of hemorrhage because of superior anticoagulation effect in vivo than in vitro. Argatroban, with short elimination half-life and little influence on gbACT and PF, is an ideal anticoagulant for HD, especially for patients with high-risk of hemorrhage.