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Notes: Summary. The overall purpose of the “Decade Plan” published in 1992 was to do everything possible to make effective treatment available to people with haemophilia throughout the world. In 1990 it was estimated that there were 350,000 individuals with haemophilia worldwide, with 80% or 280,000 without treatment. By the year 2020 this may have reached the figure 440,000, or the population of Jerusalem. Earlier this century Carroll Birch reported a series of 113 patients where 82 died before their 15th year, and only six survived beyond 40. Thus as Jones has pointed out for the developing world this is a paediatric problem for the WFH to face now. The examples described in this paper illustrating the WFH programmes and the committment of many people from the 88 member organisations worldwide as well as the doctors and scientists shows what can be done through cooperation. There is no doubt that these achievements are capitalising from the unique quality of WFH from the beginning, that is a membership which includes both those with haemophilia and their families, and those with an interest in treating haemophilia.

Notes: Abstract Whole-rock samples of the Merensky Unit were analysed for major elements, Cu, Ni, Cr, Co, Eu, Th, U, Cs, and the platinum-group elements Pt, Pd, Rh, Ir and Au. There is a sympathetic variation of Cu, Ni, Co, and S throughout the sequence. Th and U abundances are highest around the Merensky Reef, and their distribution in the rest of the unit reflects the amount of mesostasis. Eu distribution is governed by primary plagioclase. Pt, Pd, Rh, Ir and Au (PM) are concentrated in the Merensky Reef. The relative proportions throughout the unit are Ir〈Rh〈Pd⪕Au〈Pt. Au, Pd, Pt are depleted upwards in the plagioclase-rich part of the unit. Except for Ir, the PM correlate with Th and U at lower PM levels. The PM are highly intercorrelated and there is considerable variation in the individual ratios. The distribution of trace elements in the Merensky Unit was governed by the growth rates of the primary silicates. At low abundances the PM behave as incompatible elements, together with late S. At higher concentrations the primary S content controls PM abundances. Residual liquid compositions computed from a marginal-facies analysis show parallel FeO and SiO2 enrichment trends; interaction of these trends resulted in the Merensky Reef and its attendant mineralization.

Notes: Abstract This whole rock and silicate mineral study focuses on the genesis of the Merensky reef sequence, as well as the footwall and hanging wall norites at an area of Rustenburg Platinum Mines in a demonstrably normal (undisturbed) environment. Continuous sampling provides major and trace element variations and mineral compositions and allows an evaluation of the post- liquidus processes which affected the sequence. Following the formation of liquidus phases three stages are envisaged to have modified the rocks. These are (a) migration of fluid during early compaction of cumulates, (b) circulation of fluids within the crystal mush, and (c) reaction and solidification of trapped liquid. Liquidus compositions are nowhere preserved in the sequence. A strong link is demonstrated between orthopyroxene compositions (e.g. Mg# and TiO2) and the incompatible trace element content of the whole rocks. The final amount of trapped liquid is shown to have been variable but never exceeded 10%. Calculated liquidus (pre-equilibration) orthopyroxene compositions show an up- sequence progression of evolving compositions from the footwall norite to the hanging wall norite. Initial Sr isotopic values do not support a simple magma mixing model by which radiogenic Main Zone magma mixes with that of the Critical Zone at the level of the Merensky reef. There is evidence that the hanging wall norite formed from a much more evolved magma. These conclusions have implications for the distribution and origin of the PGE-enriched Merensky reef package.

Notes: Objective To review the obstetric problems, pregnancy outcome and management of carriers of haemophilia.Design Retrospective review of haemophilia and maternity unit records.Setting Haemophilia Comprehensive Care Centre.Participants Thirty-two carriers of haemophilia (24 haemophilia A, eight haemophilia B) who had their obstetric care at the Royal Free Hospital over a 10-year period (1985–1995).Main outcome measures Uptake and results of prenatal diagnosis, changes in factor levels during pregnancy, effect of knowledge of fetal gender on obstetric management and neonatal outcome, and maternal haemorrhagic complications.Results There were 82 pregnancies and 32 resulted in miscarriage or social abortion. The option of prenatal diagnosis was taken up in only 35% (17/48) of pregnancies. There were five affected male fetuses diagnosed prenatally but only three women opted for termination of the pregnancy. Knowledge of fetal gender was unavailable to the attending obstetrician in 46% (21/46) of pregnancies. A fetal scalp electrode was applied in eight, fetal blood sampling was performed in four, and ventouse delivery was conducted in one of these pregnancies. No adverse effects were reported from the first two procedures, but the ventouse delivery was associated with a huge cephalhaematoma requiring blood transfusion. On the other hand, in five cases fetal blood sampling was withheld because fetal gender was unknown. Four of the eight caesarean sections performed might have been avoided if the gender had been known. The incidence of primary and secondary postpartum haemorrhage was high, 22% (including two cases with massive haemorrhage) and 11%, respectively.Conclusion Carriers of haemophilia A and B require special obstetric care with close liaison with the haemophilia centre, and management guidelines should be available and observed. Knowledge of fetal gender is very valuable for management in labour and should be determined antenatally even if the mother declines prenatal diagnosis.

Notes: The haemostatic efficacy of a new highly purified factor IX concentrate, prepared by metal chelate affinity chromatography, was assessed in 13 patients with haemophilia B undergoing a variety of surgical operations. Four of the patients had developed post-operative thromboembolic complications following previous operations, when treated with a prothrombin complex concentrate. None of the patients in the present series developed any evidence of post-operative thrombotic complications. Effective haemostasis was achieved in all patients, with the exception of a surgical bleed in one case, and late post-operative bleeding in a second patient when the factor IX activity fell below 20iu/dl. The product is treated with a solvent-detergent process that destroys lipid-enveloped viruses, while the affinity chromatography process during manufacture removes in excess of 4 log10 of a non-lipid-enveloped virus. In follow-up studies, none of the patients has shown evidence of fresh infection from the concentrate, when assessed by virological markers. It is concluded that this high-purity concentrate (tradenane ‘Replenine’) is effective for the treatment of patients with haemophilia B who undergo surgical operations.

Notes: Summary. Diagnosis and therapy for the vast majority of haemophiliacs in the world remain beyond their reach. Health care costs for hemophilia replacement products keep rising. Global inequities for financing health care result in most hemophiliacs being undertreated. The transfusion-transmitted disease, factor VIII inhibitors, is common. Its predictability escapes detection. Management has progressed substantially and offers many therapeutic modalities. Programs for prophylaxis or immune tolerance induction are impossible for most patients. Thus, the challenge for haemophiliacs is to attain these goals.

Notes: Summary. Radiological and orthopaedic outcome in severe and moderate haemophilia A and B patients undergoing long-term prophylactic treatment were prospectively investigated focusing on the age of onset of prophylaxis and the number of joint bleedings prior to treatment. We report on 21 patients with severe and moderate haemophilia A and B receiving prophylactic treatment of between 3.1 and 16.1 year's duration. Three patient groups were evaluated according to the age at onset of prophylaxis. In group I prophylactic treatment was initiated in the first 2 years of life. Patients in group II received prophylaxis at the age of 3–6 years. Late-onset or secondary prophylactic treatment was started at the age of 6 years and above in seven patients (group III). All patients received virus-inactivated F VIII or F IX concentrates at dosages of 30–50 IU/kg body weight i.v. three times per week for those with haemophilia A and twice per week for those with haemophilia B. Elbow, knee and ankle joints were investigated at 3–4-yearly intervals according to the radiological and orthopaedic scores recommended by the World Federation of Haemophilia. The total number of joint bleedings before and after start of prophylaxis were recorded in all patients. In group I 7/8 patients had unaffected joints with constant radiological and orthopaedic scores of zero or 1, after a median of 11.25 years of prophylactic treatment. One patient in this group demonstrated mild radiological alterations (score 4). Patients in group II showed neither radiological nor orthopaedic alterations at study entry. Surprisingly, worsening joint scores could be detected despite ongoing prophylaxis after the 3-year interval (median orthopaedic score 4, median radiological score 8). Treatment group III already showed considerable joint damage at study entry with a median radiological score of 11 (0–33) and a median orthopaedic score of 4 (0–11). Despite prophylactic treatment, both radiological (median 19.5, range 2–47) and orthopaedic scores (median 8, range 2–12) deteriorated after 3 years. Prior to onset of prophylaxis, no or only one joint bleeding occurred in treatment group I. In group II, a median of six joint bleeds (range 1–8) was reported before prophylaxis was started. Patients in group III usually experienced a median of more than 10 joint haemorrhages (range 6–10 or more). Under prophylactic treatment the number of joint bleedings decreased significantly in group II and III. However, radiological and orthopaedic scores increased as a sign of progressing osteoarthropathic alterations in patients reporting more than five joint haemorrhages before onset of prophylaxis whereas no joint alterations could be assessed in patients with no or only one joint bleeding episode prior to prophylaxis. Even a small number of joint bleedings seems to cause irreversible osteoarthropathic alterations leading to haemophilic arthropathy. Once apparent, further progression of joint damage could not be arrested despite of prophylactic treatment (groups II and III). In order to prevent haemophilic arthropathy, effective prophylaxis should be started before or at least after the first joint bleeding in severe haemophilia A and B.