Factor VIII inhibitors in haemophiliacs: a single-centre experience over 34 years, 1964-97.

A retrospective study of the natural history of factor VIII inhibitors in haemophilia A patients experienced in a single comprehensive haemophilia centre over three decades is reported. 431 haemophilia A patients of all severities have been followed-up for a total of 5626 patient-years. The frequency of inhibitors was 10% in the severe haemophilia A patients and 37% occurred in children <10 years. The majority of the patients received several products before developing the inhibitors. 59% of patients had <50 exposure days and 48% were high responders (>5 BU). An 8-year (1987-95) inhibitor-free period was seen during which all previously untreated patients were treated with an intermediate-purity factor VIII concentrate. A moderate haemophiliac with a missense mutation that has not been described in association with inhibitor is reported. Six HIV-positive patients preserved their antibody response to factor VIII even at the advanced stage of their disease.

Wear testing of materials and surfaces for total knee replacement.

A simple wear test was investigated for evaluating the wear and damage of material pairs when used in total knee replacement. The test consisted of an axially loaded metallic femoral indentor and a reciprocating ultrahigh molecular weight polyethylene (UHMWPE) flat disk that represented the tibial component. A number of variables were studied including the effect of conformity by varying the radii of the femoral surface, distilled water or serum as a lubricant, different femoral materials, and different types of UHMWPE. In general, the different morphologies of the surface wear of the UHMWPE were similar to those seen on retrieved total knee replacements. Increased conformity with a cylindrical indentor gave a reduced wear rate initially, compared with that of the lower conformity spherical indentor. However, the wear rates were similar subsequent to this initial wearing in phase. Transfer films of UHMWPE were observed on the cobalt-chrome indentors for both serum and distilled water lubrication, although this film was more extensive for distilled water. The lowest wear rate was observed when oxidized zirconium was used on the femoral side, which was attributed to greater wettability, surface hardness, and immunity to oxidative wear. Tests using cobalt-chrome femoral cylinders and different grades of UHMWPE showed different wear rates. Of these PEs, GUR 415 showed less wear than both RCH 1000 and UHMWPE containing numerous fusion defects. For the latter, wear was attributed to a fatigue mechanism, although in most cases it was associated with surface phenomena rather than subsurface cracking. However, in some specimens of UHMWPE subsurface crack propagations occurred with defects. The test method is discussed in relation to its applicability to the evaluation and comparison of bearing materials and surfaces, with particular application to total knee replacements.

Polyethylene wear in unicondylar knee prostheses. 106 retrieved Marmor, PCA, and St Georg tibial components compared.

106 unicondylar knee replacement tibial components were retrieved and analyzed for the amount and type of polyethylene wear. Three different designs were retrieved which had essentially the same femorotibial conformity. Each design showed a characteristic failure pattern. The polyethylene of PCA tibial components showed serious delamination after only short durations, as a result of heat pressing. St Georg sledge prostheses showed some delamination after 4 years' duration due to sub-surface cracks which were initiated by fusion defects in the polyethylene; metal backing of the components did not affect delamination of this prosthesis. The Marmor designs showed the least wear, with shiny depressions and surface pitting; no delamination was observed in the Marmor prosthesis. Molecular weight determination by gel permeation chromatography and analysis of crystallinity using Fourier transformation infra-red spectroscopy demonstrated that St George polyethylene had higher molecular weight and crystallinity than Marmor polyethylene. In some of the components investigated, crystallinity and molecular weight of the polyethylene were reduced under the wear track when compared with the unworn polyethylene. Since fusion defects may cause delamination of polyethylene we urge manufacturers to reduce the number of such defects.

Clinical experience with polyelectrolyte-fractionated porcine factor VIII concentrate in the treatment of hemophiliacs with antibodies to factor VIII.

Circulating antibodies to factor VIII (anti-VIII, "inhibitors") occurring in patients with hemophilia neutralize porcine factor VIII less readily than human factor VIII in vitro. Over an 18-mo period, 8 patients with anti-VIII were treated with 45 courses (297 infusions) of polyelectrolyte-fractionated porcine factor VIII concentrate (PE porcine VIII). Where no anti-PE porcine VIII was detectable, mean post-infusion rise in plasma factor VIII was 1.29 U/dl/units infused/kg. Above 13 Old Oxford units of anti-PE porcine VIII and 48 Bethesda units of anti-human VIII, there were no postinfusion rises in plasma factor VIII. Where postinfusion rises were detected, clinical responses were good and conventional methods could be used to guide dosage. Ten percent of infusions were followed by febrile reactions, but these were usually mild and decreased in frequency and severity with increasing exposure. Multiple and prolonged courses of therapy were given to some patients without evidence of loss of clinical or laboratory efficacy. PE porcine VIII could provoke anamnestic rises of anti-VIII in susceptible patients, but appeared to have a lower immunogenic potential than human VIII. PE porcine VIII is a rational and effective therapeutic alternative for patients with anti-VIII, particularly those with intermediate level inhibitors who cannot be managed effectively using human factor VIII.