title: The impact of thrombin generation and rotation thromboelastometry on assessment of severity of factor XI deficiency.
abstract: The phenotype of bleeding in patients with severe FXI deficiency is unpredictable and unlike other bleeding disorders, it is not directly correlated with levels of FXI. In this study we analyzed whether the global coagulation assays can serve as a clinical tool in predicting bleeding tendency in patients with severe FXI deficiency undergoing surgery, taking into account the large inter-individual variability of FXI levels and genotypes. Thrombin generation (TG) was measured in 39 platelet-poor plasma with or without tissue factor (TF) and in the presence or absence of corn trypsin inhibitor (CTI). Rotation thromboelastometry (ROTEM) was performed with fresh whole blood of 26 patients applying NATEM and INTEM tests. TG induced by recalcification can distinguish between bleeding and non-bleeding patients with severe FXI deficiency particularly among those with FXI activity of 2-20IU/dl. The addition of TF or TF and CTI to the TG assay masked the ability to differentiate between XI activity, genotype as well as bleeding and non-bleeding patients. ROTEM assays failed to distinguish bleeding from non-bleeding patients but could do so between different FXI activity levels and genotypes. In conclusion, in the current study we found a sensitive tool to distinguish between bleeding and non-bleeding patients. In order to recommend TG as a predictive tool for treatment tailoring, a larger patient group is required.
authors.affiliation: National Hemophilia Center and Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Tami
authors.initials: T
authors.lastname: Livnat
authors.affiliation: National Hemophilia Center and Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Boris
authors.initials: B
authors.lastname: Shenkman
authors.affiliation: National Hemophilia Center and Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Martinowitz
authors.affiliation: Coagulation Laboratory, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Ariella
authors.initials: A
authors.lastname: Zivelin
authors.affiliation: National Hemophilia Center and Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Rima
authors.initials: R
authors.lastname: Dardik
authors.affiliation: Coagulation Laboratory, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Ilia
authors.initials: I
authors.lastname: Tamarin
authors.affiliation: Coagulation Laboratory, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Mansharov
authors.affiliation: Department of Pathophysiology, Sechenov First Moscow State Medical University, Moscow, Russia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Budnik
authors.affiliation: National Hemophilia Center and Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: ophiras@sheba.health.gov.il.
authors.forename: Ophira
authors.initials: O
authors.lastname: Salomon
mesh_terms: D003937:Diagnosis, Differential; D005172:Factor XI / Q000032:analysis; D005173:Factor XI Deficiency / Q000097:blood* / Q000150:complications / Q000175:diagnosis*; D006470:Hemorrhage / Q000097:blood* / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013916:Thrombelastography / Q000379:methods*; D013917:Thrombin / Q000032:analysis*
chemical_list: D005172:Factor XI; D013917:Thrombin
keywords: factor XI deficiency; thrombin generation; thromboelastometry