George had a phone conversation with a reference lab colleague who generated protein S levels on a patient specimen: free and total protein S concentrations over 70%, clot-based protein S activity less than 1%. PT normal, PTT prolonged by about 15 seconds. DRVVT prolonged, not shortened by platelet phospholipid-rich reagent. What could account for these findings, and what would you do next?
Added on 3-29-18: My colleague ran a thrombin time; the result was normal, and also found that two addition specimens from the same facility had similar results. Does this change your assessment? Geo.
From Dean Willett, Precision
From Dean Willett, Precision BioLogic:
Lupus anticoagulants are known interferences in PS activity tests. I wouldn’t rule out the possibility that this is what’s going on in that sample. APCR is also an interferant but wouldn’t typically have an effect on the PTT. Here’s an old reference:
I might suggest they try running their LA positive control for the various protein S tests to see if they observe a similar pattern.
I would investigate for
I would investigate for presence of a DOAC; probably not dabigatran as the TT was normal; I would suggest rivaroxaban or apixaban. Typical scenario: patient has thrombosis and is put on anticoagulant therapy. Then decision to investigate the reason after this has happened. Many ‘thrombophilia’ assays may be affected. Some recommended reading: Favaloro EJ, Lippi G. Laboratory testing in the era of direct or non-vitamin K antagonist oral anticoagulants: a practical guide to measuring their activity and avoiding diagnostic errors. Semin Thromb Hemost. 2015;41:208–27, also Favaloro EJ, Pasalic L, Curnow J, Lippi G. Laboratory monitoring or measurement of direct oral anticoagulants (DOACs): advantages, limitations and future challenges. Curr Drug Metab. 2017;18:598–608, and more, Gosselin RC, Adcock DM, Bates SM, Douxfils J, Favaloro EJ, Gouin-Thibault I, Guillermo C, Kawai Y, Lindhoff-Last E, Kitchen S. International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost. 2018;118:437–50.
The sample might be
The sample might be contaminated by silica (maybe from pro-coagulation tube for serum sample). On the one hand, contact activation pathway was activated and contact factors were consumed, therefore APTT and DRVVT were prolonged; on the other hand, coagulation factors were commonly activated (including factor V), The coagulation time of the clot-based protein S test was shortened significantly, as the time is inversely proportional to the protein S activity, so the result of protein S was less than 1%.