From colleague and friend Kelly Townsend, Tricore Laboratories, Albuquerque: We periodically see elevated protein C activity results in our rheumatology patients. We’ve been wondering what might be leading to this finding. They do not all have positive LA, and in fact tend to have PTT‘s in the lower half of the reference interval (sometimes quite short). We use the Precision Biologic DRVV-based Cryochek Clot C kit for protein C activity, but saw the same thing when we were using the Stago StaClot protein C kit. We do not have the chromogenic protein C or the protein C antigen on our menu, so haven’t followed up on whether those results are also elevated.
Hi, Kelly, from Jong E, Van Gorp ECM, Levi M, Ten Cate H, Chapter 13: The crosstalk in inflammation and coagulation in in fectious disease and their roles in disseminated intravascular coagulation. In Kitchens CS, Kessler CM, Konkle BA, Consultative Hemostasis and Thrombosis, Third Edition, Elsevier, 2013 I learn that protein C becomes activated through upregulation of endothelial cell membrane thrombomodulin in inflammatory conditions. Since you are measuring protein C function with the Cryochek Cot C assay, I suspect the elevation may reflect activation, and not necessarily a protein C production increase. It would be interesting to measure protein C antigen to “confirm” this admittedly speculative idea. By the way, Dr. Kitchens’ text is my favorite clinical reference on all coagulation topics. This theory is partly confirmed in Dimitroulas T, Douglas KM, Panoulas VF, et al. Derangement of hemostasis in rheumatoid arthritis: association with demographic, inflammatory and metabolic factors. Clin Rheumatol. 2013; 32:1357–64. It appears from another publication, Xue M, March L, Sambrook PN, Jackson CJ. Differential regulation of matrix metalloproteinase 2 and matrix metalloproteinase 9 by activated protein C: relevance to inflammation in rheumatoid arthritis. Arthritis Rheum. 2007;56:2864–74, that activated protein C is antiinflammatory, though I’m really in over my head when it comes to metalloproteinase functions.
I hope this helps with your question, and I hope my answer attracts the attention of participants who understand the interplay of hemostasis and inflammation, and in particular, the role of metalloproteinases.