A clinical audit of congenital thrombophilia investigation in tertiary practice

Background: The presumed cause of congenital thrombophilia can now be explained in similar to 50% of familial thrombosis cases following evaluation of a range of markers, primarily comprising factor V Leiden (FVL), activated protein C resistance (APCR), protein C (PC), protein S (PS) and antithrombin (AT). However, the effectiveness of such evaluations is largely determined by limiting improper investigations, either in inappropriate patients or at unsuitable timepoints. Aim: To evaluate clinical ordering patterns for a range of thrombophilia associated tests at a tertiary level public facility. Methods: Several independent audits into clinical requests for FVL, APCR, PC, PS, and AT testing were performed at our institution. Results: We identified a wide variety of clinical ordering background, although most requests related to 'thrombosis' or 'obstetric' indications. For FVL, the detection rate of heterozygotes continues to decline and is currently similar to 10% of investigations. For APCR, review of clinical requests and clinical notes indicated that around 36% of investigations occurred whilst patients were on anticoagulant therapy. For PC, PS and AT investigations, additional testing of samples that yielded low test results for PC, PS and/or AT indicated that an alarming 80% of these cases likely derived from patients on anticoagulant therapy. Conclusion: These results continue to reflect on poor patient or timing selection for congenital thrombophilia investigations that compromises the utility of these tests. In total, this would yield a very high rate of false positive identification for disorders that patients do not have, raising the question: are broadly based congenital thrombophilia investigations doing more harm than good?