From Lori Pinelli, Glens Falls Hospital: Hello George. Our current prothrombin time (PT) mixing time procedure only includes running the initial 1:1 mix along with the patient and the normal pooled plasma (NPP). Twice in the past year, I have been asked to perform an incubated PT mix in addition to the initial analysis. Both patients had normal activated partial thromboplastin times (aPTTs, PTTs) and elevated PTs. They were both factor VII deficient and corrected upon addition of NPP. I was asked to perform the incubated mix to rule out an inhibitor. Are there time/heat dependent Factor VII inhibitors? Should I be routinely performing the incubated mix for PT correction studies? Thank you!
Hi, Lori, and thank you for your question. I farmed it to several colleagues who have mixing study expertise, and so far have received responses from Dave McGlasson andDr. Larry Smith. I anticipate additional responses, however meanwhile, both Larry and Dave confirmed my opinion that there is no value in performing an incubated PT mixing study.
To summarize their comments, if both the PT and PTT are prolonged, perform only the PTT mixing study. If the immediate mix corrects, perform the incubated PTT mixing study to determine if a specific inhibitor, usually anti-factor VIII, is present. Anti-factor VIII is an IgG antibody that may require 37°C incubation to be detected. Additionally, some weak lupus anticoagulants (LAs) don’t show up until after incubation.
If only the PT is prolonged, the likelihood of an LA is low. The phospholipid concentration of the PT reagent exceeds the phospholipid concentration of the PTT reagent and is consequently less sensitive to LA. According to both Larry and Dave, the greatest likelihood is a factor VII deficiency, as you have found. This requires no incubation.
In the past, anti-factor II (prothrombin) and anti-factor V antibodies would be detected in patients who had been treated with bovine thrombin based fibrin glue in a prior surgical procedure. The antibodies arose as cross-reaction to the bovine thrombin and could generate severe bleeding as they neutralized most available factor V and prothrombin. We see fewer of these antibodies now as distributors have switched to human thrombin, though there may still be some around. The anti-factor II and anti-factor V antibodies could be detected in either the PTT and in the PT mixing study without incubation. Dave McGlasson told of a patient whose anti-factor V antibody was triggered by Keflex antibiotic therapy and who experienced severe hemorrhage.
Finally, Larry Smith suggests that when the PTT is normal and the PT is prolonged, avoid the PT mixing study altogether and go straight to a factor VII assay for the best and most timely results! Please watch this post, it is likely to attract additional comments. Geo.