An Acquired Inhibitor To Coagulation Factor II

A 77 year old woman with symptoms of GI tract bleeding, haematuria, bruising and profuse bleeding after dental extraction was found to have a prolonged thrombin time (>90 secs) but normal reptilase time and fibrinogen level. Both prothrombin time and KCCT were prolonged to greater than twice normal values. She had no previous history of bleeding problems and no drug history apart from analgesics.

On investigation of citrated plasma samples an antithrombin III level as measured in a chromogenic heparin cofactor assay of 607% was found but measured immunologically of 120%. Upon chromatography on Ultragel AcA44 two peaks of antithrombin activity were observed one eluting in the position of normal antithrombin III immunologically. The activity of this fraction differed according to whether the antithrombin assay was a progressive type or heparin cofactor. The other much larger peak eluted in this second peak off AcA44 and the activity was not susceptible to heparin. The activity in this peak was pooled and chromatographed on DEAE Sephacel. It eluted in 0.0175 M Na (P) pH 6.8 as a single peak coincident with antithrombin activity. On SDS electrophoresis a single band was obtained. This fraction corresponds to IgG. Less than 10% of the activity was eluted with 0.08 M (P) pH 6.6 in the fraction containing IgG and IgA.

The purified IgG directly inhibited thrombin. When added to normal plasma and prothrombin measured using activated factor Xa, complete loss of prothrombin was observed at dilutions of the inhibitor corresponding to 25% of that found in the patient plasma. The inhibitor had no effect on the rate of generation of factor Xa in normal plasma (S2222) as initiated by thromboplastin nor on the activity of purified factor Xa. The evidence suggests that this is the first report of an acquired inhibitor specific for factor II.