From Joyce Low: We have a patient with a prolonged prothrombin time (PT) and normal partial thromboplastin time (APTT, PTT). He bled, but factor levels were all normal. He’s an 84 year old man here for pacemaker insertion. PT was 19s (Neoplastine; reference interval 11–15s ), PTT 31s (Actin FS RI 25–35s), thrombin time, fibrinogen, and platelets normal. Patient developed a hematoma and infection at pacemaker insertion site. Pacemaker subsequently removed with bleeding that required 3 fresh frozen plasma twice.
PT mix showed partial correction to 16s but did not become normal. Incubating the mix for 2 h did not show a time dependent inhibitor. Extrinsic factors were all normal between 80-106%; II=106%, V=80%, VII=91%, X= 89%. We later found factor VIII to be >300% and factor IX 164% on the initial specimen. The von Willebrand factor was also very high.
Because of the Fritsma Factor post about FVII Padua, the PT was repeated using Innovin and was still prolonged at 16s (RI 9–12s when we used to use Innovin years ago). Liver enzymes normal, albumin borderline low. In lupus anticoagulant assays, RVV was normal but TTI (tissue thromboplastin inhibition with diluted Innovin) ratio was 2.0 and mix ratio 1.3. (Note from George, Joyce’s message appears to be truncated at this point).
Hi, Joyce, this one is a stumper. I ran it past my colleague Dave McGlasson this morning and we couldn’t reach a definitive answer. I suspect that there is an anti-factor V inhibitor and Dave agrees (sort of). These arise in patients who have had prior surgery in which the surgeon used bovine thrombin-based fibrin glue (Tisseal) to help seal the surgical field. Bovine thrombin triggers formation of both factor II and factor V inhibitors, often together. Fibrin glue is now made using synthetic human thrombin so it no longer generates inhibitors, but your patient may have been exposed back in the late 90s or early 2000s.
Of course, you will ask why, with an inhibitor present, the factor V level is 80% and the PTT normal? Here my conclusion grows weaker, but one possibility is that his platelets are becoming activated, perhaps in vitro after collection, and secreting factor V that escapes the inhibitor. Also, the PT reagent may be more sensitive to the factor V level than the PTT. It’s a stretcher, but the best I can come up with. I’ll be looking for help on this one!