Modification of the Bethesda assay for factor VIII or IX inhibitors to improve efficiency.

A factor IX inhibitor was assayed by using a modification of the Bethesda assay for factor VIII inhibitors. The incubation time was shortened to 15 min. A screening method using the activated partial thromboplastin time was used after sample incubation to determine the correct dilution of the patient's plasma to assay for residual factor IX activity prior to determining the inhibitor titer, thereby significantly reducing the number of factor assays needed. This screening method was also shown to be applicable to assaying a factor VIII inhibitor.

The effect of a sulfated polysaccharide on antithrombin III.

A major naturally occurring inhibitor of blood is AT-III. We have investigated the potentiation of AT-III inhibition of factors Xa, IIa, and plasmin by the heparinoid substance SP-54. Both coagulation and amidolytic methods were used. SP-54 potentiated AT-III inhibition of factors Xa and IIa in the absence of heparin. When heparin was present, potentiation of inhibition of factor Xa usually occurred, but not of factor IIa. SP-54 also potentiated the AT-III inhibition of plasmin action. Laurell immunoelectrophoresis showed no changes in AT-III in the presence of SP-54. In view of the recent importance placed on the role of AT-III and factor Xa in thrombogenesis, an oral agent which potentiates AT-III activity can have important implications for thrombotic therapy.

Intermediate syndrome of platelet dysfunction.

We studied eight patients with intermittent bleeding episodes usually following trauma and associated with the ingestion of medicine known to interfere with platelet function. All patients had a normal or minimally prolonged baseline bleeding time. All had a normal platelet count, glass bead retention test, and platelet serotonin content and a variable pattern of abnormalities in prothrombin consumption and platelet factor 3 availability. However, all showed abnormal platelet aggregation reactions using epinephrine, adenosine diphosphate, and collagen. Following the administration of 975 mg aspirin, our patients' bleeding times became prolonged to a greater extent than the bleeding times of normal controls (range 13 to greater than 20 min). Review of the literature showed approximately 5% of "normal" controls had findings similar to those we report. We believe we are describing a group of individuals with an intermediate form of platelet dysfunction. Although their bleeding diathesis is not as severe as that of patients with platelet dysfunction syndromes previoulsy described, they do bleed significantly when subjected to trauma following the ingestion of drugs such as aspirin. We propose that this defect is common and should be screened for. The aspirin tolerance test is a simple test for detecting these patients.