From Ali Sadeghi-Khomami: Hi George, I read Dave McGlasson’s paper with great interest. In brief, his case had the following results:
|PTT 2 h 37°C incubation||>200s|
|Platelet neutralization (PNP)||Positive|
|Kaolin clotting time (KCT)||>200s|
- The article didn’t mention anything about a prolonged PT mix but just PTT have done that way.
- The PNP positive, could be a false positive due to factor V release from platelets.
- Later follow up: DRVVT screen and confirm both positive
- Staclot-LA negative, no data provided other than result on your site.
In my opinion the laboratory diagnosis must be lupus anticoagulant (LA) because the phospholipid dependency of results using the dilute Russell viper venom time (DRVVT) and KCT confirmed it. The PNP result could be considered a false positive in this case due to factor V release from platelets. However, the clinical diagnosis with the patient suffering from bleeding is not in line with typical thrombotic complications of LA. Sometimes clinical symptoms could be covered by another cause, like coincidence of a factor V inhibitor and LA.
The patient was suffering from infection, which could cause transient LA-like antibodies. Also the patient was on Keflex, which could be considered a vitamin K antagonist, especially in patients with liver disease.
I have a question for you or Dave from page 120, column 1: factors 2, 8, 9, 10, 11 and 12 were all normal. Factor 5 was missing. Factor assays were one-stage assays based on PT (F2, 5, 10) or PTT (F8 9, 11, 12). How could one-stage clot-based factor assays be done when inhibitors (specific or non-specific inhibitors) are present? I am surprised to see other factors were assayed as normal when the PTT and PT were both prolonged.
Thanks to Ali for this in-depth analysis. George sent his question on to Dave who responded below.
I found Ali’s comments warranted a response; remember this was 1990. We didn’t have D-dimers then, nor the Staclot-LA. The DRVVT screen was available but not the DRVVT confirm assay. That came later and when it did we tested stored aliquots for LA. A factor V deficiency or factor V inhibitor will prolong the DRVVT and make the results spurious. However, I have no knowledge of a factor V deficiency or inhibitor causing a positive Staclot-LA. The correction by the platelets of the PNP actually gave us the idea to give the patient platelet concentrate. This was based on an old paper by Chediak that described a patient with a factor V inhibitor not responding to FFP but when given platelets the bleeding came under control. The platelet factor V is apparently a little different isometrically and worked its magic.
I did talk about a PT mixing study on pg 1 column 3. However we did not do an incubated PT mix. As we demonstrated in table 1, the factor V deficiency caused the positive PNP results, not the factor V inhibitor. This persisted throughout the patient’s life as revealed in subsequent work-ups.
Your issue about the one-stage factor assays is valid. We were initially unable to performany factor assays. They were all less than 1% activity. The specimens were sent to Dr. Shapiro’s reference lab in Philadelphia and they came up with the FV inhibitor of >1220 Bethesda units. Subsequent specimens revealed that all of the other factor assays were within normal limits.
I will find an article from Lab Medicine a few years ago that also suggested a PNP positive with a factor V inhibitor might cause a subject to clot, but this has never happened and is an artifact. That is why the PNP test has been replaced by better confirmatory assays such as the DRVVT confirm and the Staclot-LA. We could produce a positive PNP starting at about 23% activity of FV.
Thanks very much George and Dave for your follow up.
Thanks very much George and Dave for your follow up.
Gentlemen I forgot to add the article by J Chediak on the co
Gentlemen I forgot to add the article by J Chediak on the controlling of a FV inhibitor with platelet transfusions. Chediak J, Ashenhurst JB, Garlick I, Desser RK. Successful management of bleeding in a patient with factor V inhibitor by platelet transfusions. Blood 1980;56:835-41.
George and Ali, I went back and found the articles in Lab Me
George and Ali, I went back and found the articles in Lab Medicine and some more data on this subject. We actually used this subject’s specimen in a wet workshop at the International Antiphospholipid Conference in San Antonio in 1992. The participants used different screening assays and confirmatory test to identify unknown plasma specimens. When using this subject’s plasma and the PNP assay, everyone determined that a lupus anticoagulant (LA) was present. When the Staclot-LA was used, the results for the presence of an LA were negative. We later determined that this subject developed IgG and IgA anticardiolipin antibodies approximately 2 years after our original paper was published. This may relate to the presence of an LA. However, the FV deficiency with a very low presence to non-existent evidence of an inhibitor persisted throughout the rest of the patient’s lifespan. Articles are Wang L, Nguyen AND. Acquired factor V inhibitor with lupus-like features. Lab Med. 2002;551-552 and McGlasson DL. Platelet-Neutralization Procedure and FV inhibitors Lab Med. 2002;669.