A review of the scientific and literary accomplishments of Professor R.G. Macfarlane CBE, FRS.

This article gives an account of some of the pioneer work of Professor R.G. Macfarlane CBE, FRS in haemostasis and fibrinolysis.

Studies on a monoclonal antibody to human factor viii coagulant activity, with a description of a facile two-site factor VIII coagulant antigen assay.

IgG was purified from the ascites tumor fluid obtained from mice injected with a monoclonal cell line secreting antibody that inhibited VIII:C. With a modified Bethesda assay method (18 hr, 4 degrees C), the titer of the purified IgG was 14,000 U/mg. In a fluid-phase IRMA for VIII:CAg utilizing the Fab fragment prepared from the monoclonal IgG, two high-titer human anti-VIII:C inhibitors (IgG fractions) showed no demonstrable competition for the monoclonal VIII:CAg binding site.

A bleeding disorder due to deficiency of alpha 2-antiplasmin.

A deficiency of alpha 2-antiplasmin has been identified in a female patient with severe and frequent bleeding episodes. Routine coagulation and platelet assays of the patient's plasma were within normal limits. However, abnormally rapid whole blood or dilute plasma clot lysis times and an abnormal FXIII test in which clots were lysed in the presence of urea or saline suggested an abnormal fibrinolytic system.

Coagulative interventions during angiography.

Incident to his routine diagnostic and interventional activities, the angiographer is becoming increasingly involved in the manipulation of blood clotting factors. Since the field of hemostasis generally extends beyond the sphere of conventional angiographic training, an analysis of selected angiographic aspects was undertaken. This paper reviews and summarizes the fundamentals of coagulation, and appropriate methods for manipulating coagulation during angiography, particularly via heparin and protamine sulfate.

Identification of platelet receptors for bovine von Willebrand factor on human platelets by a new platelet receptor test.

A new test for the quantitation of platelet receptor activity for bovine von Willebrand factor in human platelet extracts is described. The test is based on the competition for the von Willebrand factor occurring between platelets, an antibody against von Willebrand factor, and platelet extracts containing the von Willebrand receptor. Bovine von Willebrand factor aggregates human platelets directly.

Characterization of a new mode of defective ristocetin-induced platelet aggregation.

A patient with a reduced response to the platelet-aggregating agent ristocetin and a prolonged bleeding time was found to have an abnormally high level of vWf as measured by Laurell immunoelectrophoresis. Characterization of the patient's vWf by disc-gel electrophoresis and crossed immunoelectrophoresis showed it to be indistinguishable from vWf isolated from normal plasma. The specific activity of the purified vWf in supporting RIPA was the same for both patient and normal vWf.

The effect of naturally occurring antibodies to factor VIII on an immunoradiometric assay for factor VIII coagulant antigen. Observation on a cross-reacting material-positive (CRM+) hemophiliac with a factor VIII inhibit.

An IRMA for VIII:CAg was performed on plasma samples from 13 hemophilic and four nonhemophilic subjects, containing naturally occurring antibodies against factor VIII. The VIII:C binding ligand was an iodinated Fab fraction of a high-titer factor VIII antibody arising in a hemophiliac. Since the IRMA is an equilibrium binding assay, the inclusion of an antibody against VIII:C in the test system would be expected to compete with the ligand for the available antigenic sites on the VII:C molecule: the higher the titer of the antibody expressed in BIU, the greater the degree of inhibition of the IRMA measuring VIII:CAg.

Bioequivalence of subcutaneous calcium and sodium heparins.

The bioequivalence of subcutaneous porcine calcium and sodium heparins was studied in 48 normal male subjects randomly assigned to 1 of 4 study groups. Each subject received a single subcutaneous injection of 15,000 U of calcium heparin or 1 of 3 sodium heparins. Serial coagulation studies (Lee-White clotting time, activated partial thromboplastin time, thrombin calcium clotting time, and heparin level) were performed over 10 hr.

The action of immobilized thrombin on factor VIII, fibrinogen and a synthetic tripeptide.

Bovine thrombin was insolubilized by attachment to cyanogen bromide-activated Sepharose (Sepharose-thrombin) or to activated (Affi-Gel 10) agarose containing a 10 A long arm (Affi-Gel-thrombin). Coupling in both instances approximated 7,000 units of thrombin per ml packed gel as determined by 125I-thrombin incorporation. The thrombin beads hydrolyzed the synthetic tripeptide Bz-Phe-Val-Arg-pNA (S-2160) at different rates, with the Sepharose-thrombin more active (220 esterase units per ml) than Affi-Gel thrombin (20.

The Passovoy defect: further characterization of a hereditary hemorrhagic diathesis.

We studied a coagulation abnormality present in 12 members of five kindreds who bruised easily and bled excessively after minor trauma. Their activated partial thromboplastin times were between 32 and 39 seconds (normal, 22.8 to 28.

Number, location and severity of coronary arterial changes in steelhead trout (Salmo gairdnerii).

Steelhead trout (Salmo gairdnerii) were taken at three stages of sexual maturity to study their coronary arteries for arteriosclerotic lesions. At least 18 sections from the glutaraldehyde- and osmium-fixed arteries were obtained from each fish. Fish in the middle of the spawning migration and sexually mature fish at the spawning ground had lesions in about 20% of the arterial sections.