Novel, bedside, tissue factor-dependent clotting assay permits improved assessment of combination antithrombotic and antiplatelet therapy.

BACKGROUND: Because optimal use of combinations of antiplatelet and antithrombotic drugs requires improved methods for assessment of therapeutic efficacy, we developed an assay designed to increase sensitivity that is based on initiation of clotting by tissue factor in minimally altered whole blood. METHODS AND RESULTS: Blood samples were obtained from healthy subjects, and the contact pathway of coagulation was inhibited with corn trypsin inhibitor (a specific factor XIIa inhibitor without effect on other coagulation factors). Clotting was initiated with relipidated tissue factor and detected with a Hemochron ACT instrument. Results were reproducible with samples from 25 healthy volunteers (mean time to clot, 125+/-17 seconds). Blood was also exposed to pharmacological concentrations of antithrombotic and antiplatelet agents in vitro. Heparin (0.25 anti-IIa/Xa U/mL) prolonged the time to clot by 2.4-fold (172 seconds, P:<0.05); hirudin (1.0 anti-IIa U/mL), by 3-fold (250 seconds P:<0.05); and enoxaparin (0.6 anti-Xa U/mL), by 2 -fold (123 seconds, P:<0.05). Additive effects of antiplatelet agents were readily detectable with both heparin and hirudin. Thus, addition of 3 microg/mL abciximab to 1.0 anti-IIa/Xa U/mL heparin and to 1.0 anti-IIa U/mL hirudin further prolonged the times to clot by 140 and 67 seconds, respectively (P:<0.05 for each). Addition of abciximab to enoxaparin did not further prolong the time to clot (increment, 13 seconds; P:=NS). CONCLUSIONS: The assay developed should facilitate improved dose selection, titration, and monitoring of combination antithrombotic and antiplatelet treatment regimens.

Risk assessment for HIV infection: validation study of a computer-assisted preliminary screen.

Development has been undertaken for microcomputer software intended to assess individual risk for HIV infection by analyzing personal case histories pertinent to drug abuse, receptive blood transfusion, and sexual behavior. The software performs interactive confidential interviews of individuals desiring expert assistance when deciding whether to commit to an antibody test. In the first phase of a validation study, 87 subjects responded to the computer interview. For each subject, human immunodeficiency virus (HIV) antibody status was on clinical record. This sample included 70 subjects, 29 of whom were HIV seropositive, recruited from the clientele of an AIDS antibody testing and counseling facility. In this phase, the software accurately assessed 28 of 29 seropositives (96.6%) to be at risk for HIV. The second phase was based upon participation of an additional 74 subjects who were undergraduates at the University of Oklahoma. In this presumed low-risk sample, 55 members reported never having previously tested for HIV antibodies. Seven members (12.7%) of the untested group were declared at risk in the course of receiving confidential computer screen advice. Of these 7, there were 3 members (42.9%) who were motivated by the computer to voluntarily seek HIV antibody testing. Of the 7 declared at risk, 2 members (3.9%) were among the 51 seronegative subjects classified as heterosexuals without specific and identified risks. All Phase II subjects seeking follow-up antibody tests were found seronegative.