Prothrombin and beta 2-glycoprotein I frequently contribute to antiphospholipid antibody interactions with phospholipids and the generation of abnormal waveform profiles in coagulation assays.
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 beta(2)-glycoprotein I beta(2) GPI) to produce an abnormal IgG wave-form assay. In addition, the abnormal IgG waveform required cofactor binding to phospholipids when beta(2) GPI was the cofactor, and annexin V could partially block this interaction. In conclusion, these results showed that the interactions of IgG with phospholipids via beta(2) GPI or prothrombin constitute the core mechanisms of the abnormal waveforms.
Su
Zuowei
Z
Division of Hematology, Department of Medicine, Duke University Medical Center, Durham, N.C. 27710, USA.
Izumi
Tomonori
T
Ortel
Thomas L
TL
D017152:Antibodies, Antiphospholipid / Q000378:metabolism*; D001780:Blood Coagulation Tests; D001798:Blood Proteins / Q000378:metabolism; D016022:Case-Control Studies; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology / Q000502:physiology; D008051:Lipid Bilayers; D010743:Phospholipids / Q000378:metabolism*; D020033:Protein Isoforms / Q000502:physiology; D011516:Prothrombin / Q000378:metabolism*; D011517:Prothrombin Time; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D001798:Blood Proteins; D006023:Glycoproteins; D007074:Immunoglobulin G; D008051:Lipid Bilayers; D010743:Phospholipids; D020033:Protein Isoforms; D053482:beta 2-Glycoprotein I; D011516:Prothrombin