CC BY 4.0 · TH Open 2020; 04(01): e40-e44
DOI: 10.1055/s-0040-1705091
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Prothrombin Is Responsible for the Lupus Cofactor Phenomenon in a Patient with Lupus Anticoagulant/Hypoprothrombinemia Syndrome

Vittorio Pengo
1  Cardiology Clinic, Thrombosis Centre, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padova, Italy
,
Lorena Zardo
2  Castelfranco Veneto General Hospital - ULSS 2 Treviso, Treviso, Italy
,
Maria Grazia Cattini
1  Cardiology Clinic, Thrombosis Centre, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padova, Italy
,
Elisa Bison
1  Cardiology Clinic, Thrombosis Centre, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padova, Italy
,
Elena Pontara
1  Cardiology Clinic, Thrombosis Centre, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padova, Italy
,
Sara Altinier
3  Department of Laboratory Medicine, University Hospital of Padova, Padova, Italy
,
Chunyan Cheng
1  Cardiology Clinic, Thrombosis Centre, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padova, Italy
,
Gentian Denas
1  Cardiology Clinic, Thrombosis Centre, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padova, Italy
› Author Affiliations
Further Information

Publication History

11 October 2019

22 January 2020

Publication Date:
09 March 2020 (online)

  

Abstract

Lupus anticoagulant is a misnomer as it is commonly associated with thromboembolic events. In few cases, the name retains its literal meaning when it characterizes patients with a bleeding disorder. We describe a patient with lupus anticoagulant, hypoprothrombinemia, and major bleeding (lupus anticoagulant/hypoprothrombinemia syndrome). Immunological studies revealed a huge amount of circulating monoclonal immunoglobulin M lambda (IgMλ) antiphosphatidylserine/prothrombin antibodies (14,400 U/mL). Affinity purified monoclonal antibodies (440 U/mL) prolonged the coagulation time of normal plasma by 12.2 seconds (diluted Russell viper venom time) and 25.5 seconds (silica clotting time). The original patient's plasma mixed 1:1 with normal plasma showed a marked prolongation of coagulation times (lupus cofactor) from a ratio of 2.94 to 5.23 in diluted Russel viper venom time and from 2.30 to 3.00 using the silica clotting time. Human prothrombin added to original patient's plasma caused a marked prolongation of coagulation times in diluted Russell viper venom test thus unequivocally explaining the lupus cofactor phenomenon. In conclusion, we have shown that lupus anticoagulant/hypoprothrombinemia syndrome is attributable to monoclonal IgMλ antibodies directed to phosphatidylserine/prothrombin and that prothrombin is the protein responsible for the observed lupus cofactor phenomenon.

Authors' Contribution

V.P. conceived and planned the study and took the lead in writing the manuscript. L.Z. performed the initial laboratory studies and provided patient's plasma and gave contribution to interpretation of data. M.G.C, E.B, E.P, and C.C. did the coagulation and immunological studies and contributed to interpretation of data. G.D. gave substantial contributions to interpretation of data and in writing the manuscript. All authors critically revised the manuscript and gave their approval to the final version.