Fibrinogenemia and Factor Assays

Here is a question I can’t answer, from Pam Owens at Tricore Laboratory in Albuquerque

Hi, George. We are wondering at what point will an abnormally high fibrinogen start shortening the times of clot-based tests like factor assays. Specimens with low fibrinogens get some correction from the factor deficient plasma, but what about patients with a high fibrinogen level?

Hi, Pam. After a couple of days of literature searching, I’ve concluded there are no published data supporting our conventional wisdom that fibrinogenemia shortens the PTT and renders it less sensitive to coagulation factor deficiencies or to heparin therapy. Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants; American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2008;133:142-59S use the familiar term heparin resistance. Heparin resistance, they say, is when patients require unusually high doses of heparin to achieve a therapeutic PTT. They blame, among other things, factor VIII and fibrinogen elevation, citing their own data in Levine MN, Hirsh J, Gent M, et al. A randomized trial comparing activated thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin. Arch Intern Med. 1994;154: 49-56. The only other reference I found was Edson JR, Krivit W, White JG. Kaolin partial thromboplastin time: high levels of procoagulants producing short clotting times or masking deficiencies of other procoagulants or low concentrations of anticoagulants. J Lab Clin Med 1967; 70:463-70. The title looks promising but I’ve not been able to get my hands on a copy of this 42 year-old document so far.

I also looked up Cunningham MT, Brandt JT, Chandler WL, et al. Quality assurance in hemostasis: The perspective from the College of American Pathologists proficiency testing program. Semin Thromb Haemost 2007;33: 250-8, which confirms startlingly high CVs for the PT, PTT, and factor assays from the beginning of the CAP proficiency program, but does not address fibrinogenemia or factor VIII levels.

So, although we all agree fibrinogenemia shortens our clot-based assays and interferes with factor or heparin assays, we have little data to back our claim, and no data telling us how much fibrinogen has to be present. I suspect also that fibrinogen activity may affect diverse reagents differently. Perhaps one of our participants has more information, or someone can run a study. Geo.