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The recent introduction of self-treatment has dramatically improved the management of severe haemophilia A and B (Christmas disease), and most sufferers in Britain can now inject themselves intravenously with factor VIII or IX con centrate whenever they suspect bleeding.1 This change in management has reduced dependence on hospital treatment, increased social independence and morale,2 and possibly will delay, if not prevent, the development of chronic haemophilic arthropathy.8 The potential effect, however, of this advance on employment prospects has yet to be determined. In previous studies on the employment of haemophiliacs4 6 the reported incidence of unemployment varied from 18% to 35% compared with a national unemployment rate of around 7%. It might be expected that improved treatment would increase employment prospects and help offset the approximate cost of ?2000 a patient a year for purchasing blood product concentrate. We describe a study of the factors that currently affect the employment prospects of the haemophiliac, together with an assessment of the impact of self-treatment.

Summary. 23 obligate carriers of mild and severe haemophilia A and 26 normal females were bled on three occasions, and their plasmas assayed for procoagulant factor VIII (VIIIC), factor VIII related antigen (VIIIRAg) and factor VIII clotting antigen (VIIICAg). A comparison of the ratios VIIIC/VIIIRAg and VIIICAg/VIIIRAg indicated that, although the two ratios gave the same proportional misclassification of carriers as normals (four of 23), the latter ratio showed greater discriminatory power when an unequal variances predictive method was used to calculate likelihood ratios (for carrier status). This greater power was shown to be due to a greater reproducibility between visits for the VIIICAg/VIIIRAg ratio. Discrimination was considerably better when the median of the three median values for each variable was analysed, compared to the median value obtained at the first visit. There was also no statistical difference between VIIICAg/VIIIRAg (or VIIIC/VIIIRAg) ratios obtained from carriers of severe compared to mild haemophilia.

Aortic and mitral valve replacement in a patient with severe haemophilia A. P. D. Meagher, K. A. Rickard, J. G. Richards and D. K. Baird, Aust. N.Z. J. Med., 1981, 11, pp. 7679. A forty-nine year old man with severe Haemophilia A developed left ventricular failure as a complication of valvular heart disease. On November 26th, 1979, open heart surgery was performed and both the aortic and mitral valves were replaced with porcine heterografts Replacement therapy in the form of Factor Vlll concentrates maintained the Factor Vlll coagulant level at 100% until ten days post-operatively and a total dose of 116,600 units were given The patient described is the first haemophiliac to undergo open heart surgery in Australia and the first reported case in the world to have had a successful double valve graft With the current availability of factor Vlll concentrates, elective surgical procedures are being performed more frequently. Such procedures require careful pre-operative planning and post-operative monitoring of replacement therapy to ensure satisfactory haemostasis. Although haemostatic defects may occur after open heart surgery, this case report illustrates that the haemostatic problems of open heart surgery and haemophilia can be prevented by pre-operative planning and meticulous postoperative monitoring of replacement therapy

Percutaneous transcatheter arterial embolization was performed in a case of severe haemophilia A to control haemorrhage secondary to renal trauma. The treatment proved to be life-saving. Eighteen months follow-up revealed no evidence of hypertension, renal failure or infection.

4935 bleeding episodes in 75 adolescents with severe haemophilia A and without inhibitors to Factor VIII were studied during 5 years 1973-1977 6726 Factor VIII transfusions were given. 1.22 transfusions per bleed given in 1973 rose to 1.39 transfusions per bleed in 1977. 1.20 transfusions per bleed were given to 10 year olds which rose to 1.47 at 15 years. 745 bleeding episodes needed retransfusion within 24 hours. Iliopsoas (61% of bleeds) and retroperitoneal (58% of bleeds) were the sites needing most retransfusions wichin 24 hours. Total transfusions per bleed were most frequent in retroperitoneal (3.6) and iliopsoas (2.5) bleeds. On 181 occasions bleeds occurred into more than one site simultaneously and required 221 transfusions for complete resolution. Multiple bleeds involving the thigh (1.4) and upper arm (1.4) required most transfusions per bleeding episode.Conclusions are that adolescent transfusion requirements peak at 15 years. Bleeds into the psoas and retroperitoneum may benefit from higher initial doses of Factor VIII and multiple bleeds require no more initial therapy than single bleeds.

In oral and maxillo-facial surgery, the application of the Nd-YAG laser may be considered as a standard method in the treatment of patient suffering from hemorrhagic diathesis. ACKERMANN (1984) re-portet his experiences of more than 1000 treatments in oral surgery during the last 10 years, executed in cooperation with the Munich Centre of Haemophilia. In his studies, the indication of laser-coagulation diseases (Haemophilia A and B), infirmity of thrombocytes (Thrombastenia, Thrombocytopenia, disorders of the function of thrombocytes) and the more exceptional vascular bleeding diseases. Postoperative bleeding was reported in 10% of the cases and therefore lies within the known limit. In most cases an ambulant treatment with local anaesthesia was possible. Only for patients with severe Haemophilia A with a remaining activity of factor VIII below 1% as well as in cases of inhibitors against factor VIII a stay in hospital for 1 or 2 days was necessary. Also the laser coagulation in anticoa-gulated patients has been successfully used. Ackerraann’s clinical studies show that the Nd-YAG-laser is a remarkable alternative to the classical methods of treatment, considering especially the possibility to avoid the problem of transferred plasma proteins during surgical treatment.

Eighty-two boys with severe haemophilia A who spent some time at Lord Mayor Treloar College during 1973-7 were studied. All episodes of bleeding that occurred during term time were recorded, along with the number of transfusions. The bleeding frequency among these boys, most of them aged 10-17 years, increased steadily from 8,31 episodes/100 days in 1973 to 12,63 episodes/100 days in 1977. At the same time there was a steady fall in bleeding frequency with age. Altogether 24% of bleeding episodes were into the elbow joint, 22% into the knee, and 15% into the ankle. As the boys grew older the proportion of bleeding episodes in the legs declined and that in the arms increased. The overall results reflect the fact that special schools now see only the severest cases of haemophilia. The pattern of bleeding during adolescence suggests that concepts of management of arm bleeding need modifying.

The results of total knee replacement in five patients aged between 22 and 37 with severe haemophilia A or B are described. All patients had been managed conservatively without success. Frequent bleeds, severe pain and limitation of movement were the indications for operation. Despite close haematological surveillance, bleeding problems occurred in three of the patients and large quantities of plasma concentrates were required. Review of the patients over a period of 25 to 48 months after operation showed dramatic lessening of pain and maintenance of a satisfactory range of movement. The frequency of haemarthrosis diminished markedly and the requirements for factor concentrate in the years after operation fell substantially. Two patients returned to employment. Total knee replacement led to marked clinical improvement in all the patients, but the long-term results are not yet known.

SummaryA young male haemophiliac child is here described in whom intracerebral haemorrhage required craniotomy and the subsequent insertion of a ventriculo-peritoneal shunt. These procedures can now be attempted in severe haemophilia A because of the ease in clotting factor replacement therapy.

One hundred and thirty-seven knee bleeds treated with an initial dose of 11-16 units of factor VIII/kg have been reviewed in an attempt to find the predictive factors for bleeds requiring retransfusion. Thirty-two bleeds (23.4%) were retransfused within 48 hours because of extension of bleeding or poor progress. Fifty-nine per cent of bleeds which were retransfused presented with pain and 72% were tender at presentation. These figures contrasted with those for bleeds which were not retransfused of 30% and 45%. The difference in each case is significant. Forty-seven per cent of retransfused bleeds presented with less than 50% of normal movement against 12% who were not retransfused. This difference was also highly significant. It is suggested that knee bleeds presenting with pain, tenderness and/or more than 50% restriction of movement should be considered for higher initial doses of factor VIII.

Summary. Between August 1973 and May 1979, 18 patients suffering from severe haemophilia A underwent synovectomy for recurrent haemarthroses, resistant to medical management. A total of 23 joints (11 knees and 12 elbows) were subjected to operation, five patients undergoing two synovectomies on different joints. Post-operative follow-up period ranged from 12 to 58 months for elbow synovectomy and from 29 to 76 months for knee synovectomy. All patients experienced fewer haemarthroses, the average number of bleeding episodes per joint over a 12 month period being reduced from 19 to 3 for knee joints, and from 24 to 3 for elbow joints. This improvement was apparent in the immediate post-operative year and maintained thereafter. Over the same follow-up period nine of the 11 knee joints were found to have lost an average 42° mobility. Following elbow synovectomy five out of 12 patients lost an average of 28° mobility; six patients gained an average 11° mobility. The post-operative complication rate was high for knee synovectomy, 54% suffering haemorrhage despite haemostatic factor VIII levels. For elbow synovectomy the rate was much lower, 75% of operations being uncomplicated. The average in-patient time for knee operation was 75 d, and for the elbow 19 d. We conclude that synovectomy of the knee joint is to be avoided when other means of reducing bleeding episodes are available, whereas elbow synovectomy retains a useful role in the treatment of recurrent haemarthroses which do not respond to clotting factor prophylaxis.

DDAVP fraction I-0 was prepared from a plasma pool derived from 80 blood donors who had received DDAVP and tranexamic acid. A control fraction I-0 was prepared from a plasma pool from the same group of blood donors under identical conditions except for the drug treatment. The DDAVP plasma pool as well as the DDAVP fraction I-0 contained 2–3 times as much VIII:C as the controls. VIIIR:Ag increased to a lesser extent. No difference in stability of VIII:C was seen. In vivo studies showed that infusion of the DDAVP fraction I-0 to 3 patients with severe haemophilia A (

A 15-year-old boy with severe haemophilia A and circulating antibodies to factor VIII, developed a pseudotumour with osteolysis of the tibia. He made a complete recovery following what seemed to be a spontaneous inward rupture of the cyst wall.

DURING an investigation of sera from about 200 polytransfused individuals (collected at the City of Stockholm Blood Transfusion Centre), one serum (from patient B. N.) was found which formed precipitates with 230 (93.9 per cent) of 245 sera from unrelated individuals living in the Stockholm area. This patient suffers from severe haemophilia A and has received forty-five transfusions since 1943. The method used for demonstrating this isoprecipitin is a gel diffusion on microscope slides as described elsewhere1.

A total of 164 unrelated patients with severe haemophilia A were screened for partial inversions of the factor VIII (F8) gene resulting from recombination between the intronic F8A gene and one or other of two homologous upstream A gene sequences. Inversions were found in 69 (42%) patients. Most inversions (90%) involved the distal rather than the proximal A gene. This unique mutational mechanism is estimated to occur with a frequency of 7.2 x 10(-6) per gene per gamete per generation. Although two patients with an inversion possessed inhibitors (antibodies) against factor VIII, possession of inhibitors did not appear to be associated disproportionately with inversion-type mutations.

Objective: A cost analysis model was developed to compare annual cost of prophylaxis with activated prothrombin complex concentrate (aPCC) vs. on-demand therapy with activated recombinant factor VII (rFVIIa) in severe haemophilia A patients with inhibitors for the Spanish National Health System (NHS). Methods: Model inputs were drug cost for prophylaxis (aPCC) and for on-demand treatment (rFVIIa or aPCC); bleeding episodes management (excluding bypassing agent cost); surgical costs and disease management (excluding bleeding episodes). Annual bleeding episodes treated on-demand was assumed to be 25, whereas breakthrough bleeds on prophylaxis was 8. Dose for prophylaxis was 75.72 U kg−1, three times per week. The total on-demand dose/bleeding episode was 679.66 μg kg−1 (rFVIIa) and 235.28 U kg−1 (aPCC). The average bleeding cost (€2998) considered different bleeding sites (62.5% joints, 28.6% muscles and soft tissues, 3.6% mucocutaneous tissues and 5.4% other areas). A 7.5% deduction was applied to ex-factory drug prices. Unitary costs (€2013) derived from local databases. Sensitivity analyses (SA) were performed. Results: Annual cost of aPCC prophylaxis (€524 358) was 16% lower than on-demand treatment with rFVIIa (€627 876). Yearly drug costs were €497 017 for aPCC (€73 166 for on-demand treatment and €423 850 for prophylaxis), and €548 870 for rFVIIa. Disease management cost (€2645 per year) and surgical procedures (€708 per year) were common for both strategies. In the SA prophylactic treatment led to savings between €26 225 and €-1 008 960. Conclusion: Prophylaxis with aPCC reduces number of bleeding episodes in severe haemophilia A patients with inhibitors. aPCC prophylaxis resulted in savings in excess of €100 000 per-patient per year, being 16% less costly than on-demand treatment with rFVIIa, for the Spanish NHS.

Summary Treatment adherence in adolescents with chronic diseases is around 50%, and failure is more common in preventive therapy. In haemophilia, contradictory results are reported by the published studies. The objective of this study was to evaluate adherence with factor VIII (FVIII) prophylaxis in Spanish patients with severe haemophilia A between age 6 and 20 years. Data were collected retrosp-ectively in the previous 2 years. The primary endpoint was the absolute adherence index (AAI), and the endpoints were related to clinical status, age, prophylaxis regimen, responsibility for factor administration and quality of life (QoL), assessed by the Haemo-QoL questionnaires. A total of 78 patients from 14 Spanish hospitals were recruited. Adherence ranged between −64.4 and 66.7 (mean −3.08). No differences were observed between children and adolescents (7.11 vs. 6.39; P = 0.809). A statistically significant association (P