Argatroban Affects Fibrinogen Assay (January 5)
Kim Kinney asks, “We have a patient on argatroban and it is severely falsely decreasing his fibrinogen level. What is recommended and what do other institutions do to handle the issue? Beckman now has QFA thrombin, which was designed for this issue along with heparin, but we have yet to move to it.”
George’s reply: Argatroban and direct thrombin inhibitors (DTIs) lepirudin (Refludan), bivalirudin (Angiomax), and the recently released dabigatran (Pradaxa), like heparin, prolong the thrombin time. Since the Clauss functional fibrinogen assay is based upon the thrombin time, the DTIs interfere. Given the known variability of the Clauss and the onset of dabigatran, I think we’ll all have to switch to an immunoassay.
QFA Fibrinogen Assay (January 8)
Dave McGlasson gave a further response to Kim Kinney’s January 5 question about argatroban affecting the results of the Clauss fibrinogen assay.
“I had a study subject who was on Argatroban and who had disparate fibrinogen levels: the derived fibrinogen was normal but the Fib-C result was below 100 mg/dL. We conferred with Beckman/IL and switched to the Hemosil QFA thrombin reagent. The QFA reagent has 100 NIH units/mL vs. 35 units/mL in the Fib C. We found that this did make a difference on monitoring subjects on Argatroban.”
RVV and Hemophilia (January 12)
Vilas Hiremath at United Labs asked: “I have spiked hemophilic plasma with RVV. The TEG shows that an 81-minute R-value is corrected to 3.2 minutes. Your comment please.”
George responds: Russell viper venom activates coagulation at the level of factor X, bypassing the requirement for normal factor VIII activity. Factor deficiencies that prolong the RVV assay are factors X, V, prothrombin (II), and fibrinogen (if severely deficient). We don’t use the RVV much these days, but we do use the dilute Russell viper venom time test (DRVVT) routinely as a screening and confirmatory test for lupus anticoagulant.
Hepatitis A Testing (January 13)
Mark Lesage, Lab Manager at Skyline Hospital sent in this question: “We currently do a total hepatitis A antibody and if that is positive we reflex to the hepatitis A IgM antibody. Is there a single test that would determine immunity?”
George replied that Mark’s approach is the correct one, as there is no assay for the IgG antibody.
Heparin Calibrator Set (January 14)
From JK Henrickson at Beckman-Coulter: “We have several customers who want to perform the ex vivo heparin therapeutic range study for their partial thromboplastin time (PTT) heparin assay, however, their institution does not have these types of patients very often. Is there a commercial source for heparinized plasmas, specifically unfractionated heparin?”
George answers: To establish a therapeutic range using the ex vivo (Brill-Edwards) method, the laboratory must assay at least 50 specimens from patients on unfractionated heparin (UFH) whose prothrombin times (PTs) are normal, plus 20 normal specimens. For smaller acute care facilities, it is difficult to locate 50 or more specimens that meet this criterion, yet we are required to run the curve with each change in reagent, reagent lot number, or instrument.
Unfortunately, none of the commercial vendors has developed a set of UFH plasmas. The best advice I have heard is to review PTT specimens daily, select the ones with prolonged PTTs and normal PTs, aliquot and freeze. Hopefully, over a year’s time the laboratory would accumulate enough specimens to run the curve, but they would need to continue this practice indefinitely.
An alternative, which I suspect you have discussed with your clients, is to bypass the PTT altogether and just set up the anti-Xa heparin assay, which is more accurate and reproducible.