Patients with the Antiphospholipid Syndrome (APLS) Show Hypercoagulability Due to Hypofibrinolysis and Increased Fibrin Generation, but Thrombin Generation Is Variable
Authors: Curnow Jennifer L , Morel-Kopp Marie-Christine , Rojas Ninfa , Aboud Margaret , Ward Christopher 
Published: October 2019

We have previously demonstrated hypercoagulability utilizing a global haemostatic assay, the Overall Haemostatic Potential (OHP) in a heterogenous population of patients with a demonstrable lupus anticoagulant. Our aim in this study was to determine whether the OHP assay demonstrated a persistent hypercoagulable state in a well-defined prospective population with APLS and whether global assays were able to predict the occurrence of thrombotic complications. Informed consent was obtained and blood was collected on three occasions, three months apart from 54 patients with APLS, recruited from Haematology clinics at Royal North Shore Hospital, Sydney, Australia between May 2005 and November 2007. Clinical data was collected including history of prior and subsequent thrombotic events. Two control groups consisted of 200 healthy blood donors and 20 patients with autoimmune disorders, but no history of thrombosis. Assays performed were PT, INR, APTT, FVIIIc, lupus anticoagulant assay (LAC), anticardiolipin antibodies (ACLA), b2-glycoprotein1 antibodies (B2GP1), a thrombin generation assay (Calibrated Automated Thrombogram, CAT) and the OHP assay which utilizes thrombin (0.03 IU/ml) and rt-PA (350 ng/ml) to trigger fibrin generation and fibrinolysis, respectively, in platelet poor plasma. Change in optical density in microtitre wells is measured over 60 minutes. Statistical analysis involved calculation of means, SD, T-tests and paired T-tests utilizing SPSS v16.0. Fifty percent of APLS patients were male, compared with 10% of the autoimmune control group. APLS had been diagnosed on the basis of persistent antiphospholipid antibodies and at least one thrombotic event: VTE (n=46), ATE (n=6) or recurrent late miscarriage (n=2). Number of thrombotic events prior to study entry ranged form 1 to 6 per patient, with 49/66 events unprovoked. Samples from APLS patients on anticoagulation (OAC, n=35) were analysed separately from those not anticoagulated (n=19). Global assay results for samples collected at different time points were stable, with no significant differences on paired T-test. APLS patients had significantly shorter PT, higher fibrinogen, increased fibrin generation and reduced fibrinolysis parameters (p<0.001), compared with healthy donors. The autoimmune control group also showed hypercoagulable OHP parameters compared with healthy donors (p<0.001), with assay results comparable to those in APLS patients, not on OAC. The only thrombin generation assay parameter significantly increased in APLS patients, not on OAC, compared with controls was peak thrombin (266 vs 298 nM, p=0.016). However thrombin generation was significantly suppressed in those on OAC (p<0.001). Only one patient had recurrent DVT during the study. The OHP assay identifies a hypercoagulable state in APLS patients with reduced fibrinolysis and increased fibrin generation, even when anticoagulated. The calibrated automated thrombogram (CAT) showed increased peak thrombin generation in APLS patients not on OAC but endogenous thrombin potential (ETP) was not significantly elevated. Thrombin generation was suppressed by OAC therapy. These global assays show differential results in patients with APLS. More prolonged follow up will be necessary to determine whether the assays predict recurrent thrombotic events and are useful in risk stratification of APLS patients.