From Jasmina Ahluwalia, MD: Hello George, We use the IL vWF Antigen (VWF:Ag) and vWF Ristocetin Cofactor (VWF:RCo) activity kits on the ACL TOP 500 analyser.
Lately, I have noticed that in nearly 5% of the samples tested we have VWF:RCo activity levels that are much higher than the antigen levels. We have repeat tested after a time interval and the results are pretty much the same. We recently ran the tests on a 28 year old for menorrhagia and the instrument reported VWF:Ag levels of 218% and 215% and VWF:RCo levels of 320% and 446% when tested after an interval of a month. These are values at the higher end but lower antigen than activity levels have been seen in the 30-40% ranges also. I would be keen to know if other people have encountered this. Thanks. Jasmina
Hello, Jasmina, and thank you for your question. I presume you have brought your observation to your Werfen representative. Werfen may have some inside information about the assay. Meanwhile, I shared your questions with Kathy Jacobs, Chronolog Corporation, and with Dean Willett, Precision BioLogic.
Kathy responded: Hi George, Very nice to hear from you again in this New Year! Regarding high VWF:RCo activity and and its resultant reduction of the VWF:Ag/VWF:RCo ratio, I am attaching a reference (below) where this was seen with patients who have liver disease–very interesting reading on the subject of high levels. The old NCCLS (now CLSI) Guideline H-51A, Vol. 22 No. 20 lists a number of conditions where mild to marked increases in the levels of VWF:RCo and VWF:Ag have been observed. These are liver disease, uremia, vasculitis, severe atherosclerosis, acute and chronic inflammatory states, physical stress and in premenopausal and postmenopausal women taking synthetic or conjugated estrogen.
Dean provided additional information about assay interferences, which are not necessarily confined to a single kit manufacturer. He presumes the assay Jasmina uses is available only outside the US. Results may become falsely elevated by human anti-bovine IgG antibodies (HABIA), paraprotein, hemoglobin (hemolysis) greater than 500 mg/dL, lipids above 1300 mg/dL, bilirubin over 18 mg/dL, triglycerides above 1020 mg/dL, and rheumatoid factor levels greater than 940 IU/mL. If a patient has been treated using mouse monoclonal antibodies, they may develop human anti-mouse antibodies (HAMA) that interfere in these assays. The IL-Werfen assays, like many, incorporate HAMA blocking agents to alleviate this concern.
I’ve send inquiries to additional experts, including some Werfen executives, and hope for further information. Meanwhile, tap or click here for the article that Kathy Jacobs provided: Lisman T, Bongers TN, Adelmeijer J, et al. Elevated levels of von Willebrand factor in cirrhosis support platelet adhesion despite reduced functional capacity. Hepatology 2006;44:53-61.