Heterogeneity of the APC-resistance phenomenon.

Abstract

We developed an amidolytic assay for the determination of APC-resistance by inhibition of factor Xa (F Xa) generation, expecting it to be a result of factor VIIIa (F VIIIa) inactivation. Thirty-nine samples were tested with the proposed assay and compared to an APTT-based assay performed using the APC-resistance kit (Chromogenix, Mölndal, Sweden). In both assays APC was added at the last stage of the reaction together with CaCl2. The response to APC was calculated as a ratio of absorbances (or of clotting times) of a sample tested with or without APC and as the amount of F VIII activity generated in the presence of APC. An APC-ratio less than 2.0 and residual F VIII activity over 55% indicated APC-resistance. The results demonstrated that APC-response was heterogenic and dependent on the assay used for the determination. Only 1/3 of the tested samples were resistant in both APTT-based and in amidolytic assays. A number of samples developed an adequate decrease in F VIII activity, but the APC-resistance was still registered by the APTT-based assay. Other samples had a sufficient APC-response in APTT-based assay, in spite of diminished inactivation of F VIIIa. The obtained data presented the response to APC as a complex process with a chain of reactions. It indicated that poor degradation of coagulation factors may not be sufficient for its development.

• Authors: M Bokarewa, M Blombäck
• Journal: Thrombosis research (Thromb Res) Vol. 75 Issue 4 Pg. 395-400 (Aug 15 1994) ISSN: 0049-3848 [Print] United States
• PMID: 7997977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Protein C
• Factor VIII
• Factor Xa

Topics

• Adult
• Amides (metabolism)
• Drug Resistance (physiology)
• Factor VIII (metabolism)
• Factor Xa (biosynthesis)
• Female
• Humans
• Middle Aged
• Partial Thromboplastin Time
• Protein C (metabolism)