Thromb Haemost 2019; 119(01): 117-127
DOI: 10.1055/s-0038-1676348
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

Low Concentrations of Recombinant Factor VIIa May Improve the Impaired Thrombin Generation of Glanzmann Thrombasthenia Patients

Sarina Levy-Mendelovich
1  Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2  The Israeli National Hemophilia Center and Thrombosis Unit, Sheba Medical Center, Tel Hashomer, Israel
3  The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel
,
Tamara Levy
1  Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Ivan Budnik
4  Department of Pathophysiology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
,
Assaf Arie Barg
1  Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2  The Israeli National Hemophilia Center and Thrombosis Unit, Sheba Medical Center, Tel Hashomer, Israel
3  The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel
,
Nurit Rosenberg
1  Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2  The Israeli National Hemophilia Center and Thrombosis Unit, Sheba Medical Center, Tel Hashomer, Israel
3  The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel
,
Uri Seligsohn
1  Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2  The Israeli National Hemophilia Center and Thrombosis Unit, Sheba Medical Center, Tel Hashomer, Israel
3  The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel
,
Gili Kenet
1  Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2  The Israeli National Hemophilia Center and Thrombosis Unit, Sheba Medical Center, Tel Hashomer, Israel
3  The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel
,
Tami Livnat
1  Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2  The Israeli National Hemophilia Center and Thrombosis Unit, Sheba Medical Center, Tel Hashomer, Israel
3  The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel
› Author Affiliations
Further Information

Publication History

30 July 2018

13 October 2018

Publication Date:
31 December 2018 (online)

Abstract

Introduction Glanzmann thrombasthenia (GT) is a rare bleeding disorder. The disease is caused by the lack or dysfunction of platelet membrane glycoprotein IIb/IIIa (integrin αIIbβ3) which is essential for platelet aggregation. Bleeding episodes are usually managed by platelet transfusions. Recombinant activated factor VII (rFVIIa) is a common adjunct or alternative treatment option.

Objective This article evaluates GT patients' response to increasing concentrations of rFVIIa using an ex vivo thrombin generation assay to elaborate the knowledge in which rFVIIa treats a platelet dysfunction for bleeding episodes and preoperative management.

Materials and Methods Twenty-four GT patients in a non-bleeding state were enrolled into the study. Thrombin generation was measured in platelet-rich plasma (PRP) in the presence of 0.7 to 7.0 µg/mL rFVIIa. Clinical data of rFVIIa used to treat GT patients' bleeding episodes was collected, and patients' follow-up course was documented.

Results Thrombin generation was significantly decreased in GT patients compared with controls. An individual response to rFVIIa spiking was noted in GT patients' PRP. In the majority of patients, a significant improvement in thrombin generation was already demonstrated with low concentrations (0.7 µg/mL) of rFVIIa.

Conclusion Thrombin generation is improved in the majority of GT patients following ex vivo spiking with rFVIIa. The magnitude of this improvement is individual and was noted at low concentrations of rFVIIa. There is a need for a prospective clinical trial to find the optimal doses or rFVIIa for treatment of GT patients.

Note

This work was performed in partial fulfilment of the MD thesis requirements of the Sackler Faculty of Medicine, Tel Aviv University.