NORMAL APTT IN A PATIENT WITH A PERSISTENT ACQUIRED FACTOR XI INHIBITOR.
A 55 year-old white male (MR) with documented normal hemostatic tests at our institution for 14 years, was admitted for a laminectomy. His pre-operative APTT and prothrombin time activity (Q) were again normal. A prolonged APTT of 58 seconds (21-31 N) and Q of 18% (> . 70% N) was noted on the 14th post-operative day; patient had received I unit PRBC during surgery.Mixtures of pooled normal plasma (NPP) incubated with MR’ s plasma (301, 37° C) yielded normal APTTs with as little as 20% NPP in these mixtures, suggesting a plasma factor(s) deficiency. Factor XI level was undetectable with normal values of factors Vlll-C, IX and XII. A factor XI level of 7% was found in incubated mixtures (60’ , 37° C) of equal parts of NPP + MR’ s plasma as compared to 70% in NPP + buffer and < 1% in MR’ s native plasma + buffer, indicating the presence of an inhibitor in MR’ s plasma. Infusion of 1540 ml of FFP (22 ml/kg) to the patient resulted in an APTT of 28 seconds and a Q of 36% with a persistent undetectable XI (expected ∿ 45%). The in-vivo lack of response to FFP was also suggestive of an inhibitor.Additional in-vitro tests showed that the response of MR’ s plasma was no different from that of NPP with the addition of increasing dilutions of human brain thromboplastin, differentiating this inhibitor from the Lupus type anticoagulant. The severely reduced Q was due to severe temporary reductions in factors II (20%), V (34%), Vll/X (2%) and X (20%) without any evidence of hepatocellular dysfunction or vitamin K deficiency. Fibrinogen, thrombin time, FSP, platelet counts and bleeding times remained normal throughout.There was no external evidence of bleeding after the first operation at any site, despite 1M injections and venepunctures. MR was reoperated on day 15 for a cauda equina hematoma; adequate intra and 72 hour post-operative management was with 1 U FFP Q 6 hourly and Amicar; this was associated with a normal PTT, Q %35% and undetectable XI, but without generalized bleeding. Discontinuation of this regimen resulted in onset of bleeding from drainage tubes only, without bleeding from the rest of the incision. Reinstitution of I U FFP Q 12 hourly and Amicar resulted in a prompt cessation of bleeding. Patient had no evidence for an autoimmune disease, dyspro-teinemia or any other illness. The potential role of the 1 unit of PRBC transfused cannot be discounted. Further data on this inhibitor will be presented.