Effect of activated recombinant human factor 7 (Niastase) on laboratory testing of inhibitors of factors VIII and IX.
Activated recombinant human factor VIIa (rFVIIa) has been used as a hemostatic agent in patients with hemophilia and acquired inhibitors. Other indications for rFVIIa may include liver disease, warfarin sodium (Coumadin) overdose, or trauma. Monitoring patients on this treatment with standard laboratory testing is problematic. Bleeding risk does not correlate well with the prothrombin time (PT) or the activated partial thromboplastin time (aPTT) during therapy with rFVIIa. In addition, there is no identifiable literature on the effect of rFVIIa on assays of inhibitors in this patient group. Monitoring inhibitors may be important during interventions aimed at acutely reducing inhibitor levels, such as during plasma exchange or protein adsorption. We performed factor assays and evaluated inhibitor levels in plasma from 3 patients with deficiencies in FVIII (2 patients) or FIX (1 patient) and inhibitors (titer range, 5.8-17.4 Bethesda units) before and after adding rFVIIa (range, 0.25-8 microg/mL) in vitro. Additionally, we performed assays of factors of both intrinsic and extrinsic systems to determine the impact of rFVIIa on these tests. We found that both factor levels and inhibitor titers from patients with hemophilia A or B could be measured accurately, even in the presence of suprapharmacologic doses of rFVIIa (8 microg/mL). We also obtained accurate measurements for other assays of the intrinsic coagulation system (FXI and FXII) based on the aPTT. Conversely, we found that assays of the extrinsic system based on the PT (FII, FV, and FX) produced results that were unreliable. FVII results were very high but reproducible. These results suggest that assays based on the PT are inaccurate and should be avoided during FVIIa treatment. Conversely, FVIII and FIX levels and inhibitor titers can be accurately monitored in hemophilia patients receiving rFVIIa according to results of aPTT-based coagulation tests.
Keeney
M
M
London Health Sciences Centre, London, Ontario, Canada.
Allan
D S
DS
Lohmann
R C
RC
Yee
I H Chin
IH
D000906:Antibodies / Q000097:blood*; D019411:Clinical Laboratory Techniques; D016903:Drug Monitoring / Q000379:methods / Q000592:standards; D005164:Factor IX / Q000276:immunology*; D005167:Factor VII / Q000494:pharmacology*; D005169:Factor VIII / Q000276:immunology*; D015942:Factor VIIa; D005174:Factor XII; D006467:Hemophilia A / Q000097:blood / Q000276:immunology; D002836:Hemophilia B / Q000097:blood / Q000276:immunology; D006801:Humans; D010314:Partial Thromboplastin Time; D011994:Recombinant Proteins / Q000494:pharmacology
D000906:Antibodies; D011994:Recombinant Proteins; D005167:Factor VII; D005169:Factor VIII; D005164:Factor IX; D005174:Factor XII; C103587:recombinant FVIIa; D015942:Factor VIIa