RRML - Global clotting assays - monitoring the effect of by-passing agents in haemophilia patients with inhibitors

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Nr. 25(2)/2017 DOI:10.1515/rrlm-2017-0011

Research article

Global clotting assays - monitoring the effect of by-passing agents in haemophilia patients with inhibitors

Margit Șerban, Dan Poenaru, Laura Cernat, Delia Savescu, Jenel Pătrașcu, Wolfgang Schramm, Emilia Ursu, Delia Mihailov, Cristian Jinca, Ioana Ioniță, Smaranda Arghirescu

Correspondence should be addressed to: Margit Șerban

Abstract:

The development of FVIII/FIX inhibitor alloantibodies represents a severe complication requiring specific laboratory evaluation for establishing a life-saving therapy regimen. Our preliminary study aimed at elaborating a laboratory strategy for monitoring the effectiveness of Activated Prothrombin Complex Concentrate (APCC) and recombinant activated factor VII (rFVIIa) in haemophiliacs with inhibitors, by checking the reliability and clinical value of three complementary assays: clotting-time based coagulometry, thrombelastography (TEG) and thrombin generation assay (TGA). The investigations were performed on 7 patients with severe haemophilia A with high titer inhibitors treated for 12 episodes of severe bleedings, 5 of them for surgical interventions. After the administration of bypassing agents (BPAs) the clotting-time based assay brought changes only on prothrombin (p<0.01), potentially signaling a thrombotic risk, without any impact on the global hemostasis. TEG displayed prompt significant improvement only after rFVIIa (90µg/kg). TGA revealed significantly improved values for peak and velocity index, time to peak and start tail after both BPAs. Despite some disparities between biological hemostatic phenotype and clinical response to therapy, we concluded that TEG and TGA are the only current exploratory assays, expressing the quality of haemostatic control, representing a real support for a personalized, adapted therapy in hemophilia with inhibitors.

Keywords: haemophilia, inhibitors, TGA, TEG

Received: 7.9.2016
Accepted: 27.2.2017
Published: 31.3.2017

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Șerban M, Poenaru D, Cernat L, Savescu D, Pătrașcu J, Schramm W, et al. Global clotting assays - monitoring the effect of by-passing agents in haemophilia patients with inhibitors. Rev Romana Med Lab. 2017;25(2):135-43. DOI:10.1515/rrlm-2017-0011