Although the possibility of spontaneous remission and a delayed benefit from prior therapy cannot be excluded in this small group of patients, pulsed high-dose treatment with dexamethasone may provide a low-cost therapeutic option with minimal side effects in patients with refractory idiopathic thrombocytopenic purpura.

The availability of safe replacement clotting factor concentrates together with effective antiviral drugs to treat human immunodeficiency and hepatitis C viruses and the provision of care at designated haemophilia treatment centres have resulted in a new phenomenon in haemophilia management - the ageing patient. Today, increasing numbers of persons with haemophilia (PWH) are middle-aged and older, and they face the same age-related health issues as the general population. The impact of these risks on PWH is unclear, however, and there is a paucity of information about how to manage comorbidities in this patient population. This review focuses on five comorbidities that uniquely affect older PWH: cardiovascular disease, liver disease, cancer, renal disease and joint disease. Available research is summarized and potential management approaches are suggested.

A B S T R A C T Human factor VIII froml nornmals anid hemophiliacs was partially purified by ethaniol and polyethylene glycol precipitations. Final purification was achieved by gel filtration on 2 or 4%Xc agarose or ion1 exchange chromatography on diethylaminoethyl cellulose. Comparable amounts of highly purified protein were obtained from normal and hemophilic plasma following the agarose chromatographv step. Highly purified factor VIII was not dissociated by 6 -MI guanidine hydrochloride or 1% sodium dodecyl sulfate. However, when reduced by P-mercaptoethanol and analyzed by sodium dodecyl sulfate polvacrylamide gel electrophoresis, a single subunit species with an estimiiated 19-5,000 molecular weight was found for both normcal an(d hemiiophilic factor VIII. By sedimiientation equilibrium analysis, the normal factor V-III subunit was homogeneous and had an estimated nmolecular wveight of 202,000. The subunit polypeptides from niormal or hemoplilic factor VIII contained carbohy\drate. Each was homogeneous by isoelectric focusing. Immilllunodiffusion of purified normal and hemoplhilic factor VIII against rabbit aintiserum to purified normiial liuman factor VIII slhowed a single line of precipitationi. V-erv low concenitr-ations of purified humiian thrombin initially increased the activitv of normal factor VIII about threefold and tlhen progressively destroyed activity by 3 h. Only-minimal activation occurred with hemiiophilic factor VIII. Both the activation and inactivation of normal alnd hemo-

Neither normal nor hemophilic factor VIII protein enters a 5% sosium dodecyl sulfate gel; on reduction, however, a single 195 000-molecular-weight peptide is observed. Hemophilic and normal factor VIII contain carbohydrate and appear identical in subunit molecular weight, electrical charge, and major antigenic determinants. Thrombin activation and inactivation of factor VIII does not detectably change the subunit molecular weight. Trypsin causes similar activity changes and obviously cleaves the factor VIII subunit. Human plasmin destroys factor VIII procoagulant activity and degrades the factor VIII subunit to 103 000-, 88 000-, and 17 000-molecular-weight peptides. Both normal and hemophilic factor VIII as well as thrombin-inactivated factor VIII support ristocetin-induced platelet aggregation. Purified factor VIII chromatographed on 4% agarose in 1.0 M sodium chloride shows no dissociation of the procoagulant activity from the void volume protein. Gel chromatography on 4% agarose in 0.25 M calcium chloride results in a procoagulant activity peak removed from the void volume protein; both peaks contain protein which does not enter a 5% SDS gel, but on reduction a 195 000-molecular-weight subunit band is observed for each. Both the void volume protein peak and the procoagulant activity peak from the 0.25 M calcium chloride-agarose gel column support ristocetin-induced platelet aggregation. After removal of calcium, a small amount of procoagulant activity is present only in the void volume peak. These data suggest that both the procoagulant and von Willebrand activities are on the same molecule. Thus our previous conclusion remains the same: human factor VIII is a large glycoprotein composed of identical 195 000-molecular-weight subunits jointed by disulfide bonds and is responsible for both antihemophilic and von Willebrand activities in human plasma.