Prothrombin and β2-glycoprotein I frequently contribute to antiphospholipid antibody interactions with phospholipids and the generation of abnormal waveform profiles in coagulation assays

Zuowei Su; Tomonori Izumi; Thomas L. Ortel

doi:10.1160/TH02-09-0052

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(02): 218-226
DOI: 10.1160/TH02-09-0052

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Prothrombin and β₂-glycoprotein I frequently contribute to antiphospholipid antibody interactions with phospholipids and the generation of abnormal waveform profiles in coagulation assays

Zuowei Su

¹Division of Hematology, Department of Medicine, and the Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA

,

Tomonori Izumi^*

¹Division of Hematology, Department of Medicine, and the Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA

,

Thomas L. Ortel

¹Division of Hematology, Department of Medicine, and the Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA

› Author Affiliations

Abstract

Summary

Transmittance waveforms are generated during clot formation on photo-optical coagulation analyzers. We previously showed that 61.5% of patients with antiphospholipid antibodies (APLA) exhibited a negative deflection in the pre-coagulation phase of the prothrombin time (PT slope 1). The current studies investigated the ‘molecular basis’ of this abnormal parameter. We found that the negative PT slope 1 is IgG-mediated and is not dependent on the presence of fibrinogen or thrombin activity. We also found that IgG from most of the patients required a specific thromboplastin and the presence of prothrombin or β₂-glycoprotein I (β₂GPI) to produce an abnormal IgG waveform assay. In addition, the abnormal IgG waveform required cofactor binding to phospholipids when β₂GPI was the cofactor, and annexin V could partially block this interaction. In conclusion, these results showed that the interactions of IgG with phospholipids via β₂GPI or prothrombin constitute the core mechanisms of the abnormal waveforms.

Keywords

Antiphospholipid antibodies - prothrombin - β₂-glycoprotein I - transmittance waveforms

Full Text

References

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