Inhibition of annexin V binding to cardiolipin and thrombin generation in an unselected population with venous thrombosis.
OBJECTIVE
To examine the effect on annexin V binding to cardiolipin (CL) and in vitro thrombin generation by plasma samples from an unselected population of patients with confirmed venous thrombosis and matched controls. The prevalence of autoimmune antiphospholipid antibodies (aPL) was also determined.


METHODS
A total of 111 patients who presented to a single emergency room with symptoms suggestive of venous thromboembolic (VTE) disease were studied. In 34 patients the diagnosis of lower limb deep venous thrombosis (DVT) and/or pulmonary embolus (PE) was confirmed (VTE+ group). In the remaining 77 patients the diagnostic workup was negative (VTE- group). Plasma samples were collected prior to the initiation of anticoagulation and examined for IgG anticardiolipin (aCL), IgG anti-beta2-glycoprotein I (GPI), and IgG anti-prothrombin (aPT antibodies) by ELISA. In addition, the effect of individual patient and control plasma samples on annexin V binding to CL and on in vitro thrombin generation was determined by a competitive ELISA and a chromogenic assay, respectively.


RESULTS
The prevalence and levels of IgG aCL, anti-beta2-GPI, and aPT antibodies were similar in the VTE+ and VTE- groups. However, plasma samples from the VTE+ group caused a significant inhibition of in vitro thrombin generation (mean +/- SD Z score: -0.66 +/- 0.97 vs 0.26 +/- 1.46; p < 0.001) and a concurrent but less impressive inhibition of annexin V binding to CL (mean +/- SD Z score: -2.53 +/- 1.44 vs -2.05 +/- 1.61; p = 0.123). Upon analyzing a panel of clinical and laboratory variables, only age and inhibition of thrombin generation were significantly associated with VTE disease.


CONCLUSIONS
Our findings suggest that subtle abnormalities in annexin V physiology may contribute to the procoagulant state in patients with idiopathic venous thrombosis.
Hanly
John G
JG
Divisions of Rheumatology and Hematology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, 1341 Summer Street, Halifax, Nova Scotia, Canada B3H 4K4.
Smith
Stephanie A
SA
Anderson
David
D
D017304:Annexin A5 / Q000378:metabolism*; D017152:Antibodies, Antiphospholipid / Q000032:analysis* / Q000097:blood; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D001665:Binding Sites; D002308:Cardiolipins / Q000378:metabolism*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D011655:Pulmonary Embolism / Q000097:blood / Q000175:diagnosis*; D012016:Reference Values; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013917:Thrombin / Q000378:metabolism*; D020246:Venous Thrombosis / Q000097:blood / Q000175:diagnosis*
D017304:Annexin A5; D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D002308:Cardiolipins; D013917:Thrombin