Haemophilia and the forbidden abdomen.

Abdominal surgery became routinely possible over a hundred years ago, after the introduction of general anaesthesia and sterile procedures. Abdominal surgery for haemophiliacs had to wait another 60 or 70 years for adequate control of haemostasis. This paper traces its gradual achievement from the 1920s to the 1970s through a series of reports of appendectomies, gastric and intestinal operations, gall bladder operations and splenectomies in patients with haemophilia of varying degrees of severity. A short-lived flurry of interest in splenectomy as a proposed treatment for haemophilia is also mentioned.

Relation of simple clotting tests to clotting factor levels in liver disease.

The prothrombin time with Manchester and ox thromboplastins, the 'P & P' test of Owren and Aas, the partial thromboplastin time, the thrombin time and assays for factors II, V, VII, VIII:C, IX and X were performed by one observer in 18 patients with liver disease and 27 normal subjects; the prothrombin time and partial thromboplastin time were also carried out on another 28 similar patients by various observers. Routine liver function tests were measured in all patients. The prothrombin time with Manchester thromboplastin was well correlated with other clotting tests, and performing the other tests did not add to the information. Discriminant function analysis confirmed that clotting tests did not distinguish between different types of liver disease. Correlations between clotting tests and liver function tests reflected liver cell damage but were also influenced by acute phase reactions.

Oral anticoagulant control with a chromogenic substrate: calibration, precision and cost.

Prothrombin time ratios, and bioassays and chromogenic (S2222) assays for factors VII and X, were obtained on 23 newly anticoagulated patients and 23 patients on long term oral anticoagulants. Factor levels were plotted against prothrombin time ratios. For factor VII, a different relationship was apparent for newly anticoagulated and for stabilized patients by both assay methods, but for factor X the same relationship was found. Chromogenic factor-X levels were calibrated against prothrombin time, and a prescribing exercise showed reasonable agreement between doses based on prothrombin time ratios and on assays for both clinical groups; factor-VII levels could not be used because of the different relationship between newly anti-coagulated and long-term patients. Despite the high precision of reading the chromogenic end point, chromogenic assays were not more precise than bioassays. With S2222, the cost of automated anticoagulant control would be more expensive than control by manual prothrombin times.

Calculating the dose of factor VIII in the management of haemophilia.

Three methods of calculating the dose of factor VIII have been compared. A simple formula based on body weight has been found satisfactory for cryoprecipitate and freeze-dried concentrate; but where body fluid build departs markedly from average, height should probably also be taken into account. Modifications for children are noted.

The ICTH/WFH study of the partial thromboplastin time in mild haemophilia.

A study has been carried out in two stages to compare the sensitivity of different Partial Thromboplastin Time (P.T.T.) methods to partial deficiencies of factor VIII. In Stage 1, 63 laboratories throughout the world compared their own methods with a reference method, all using samples of the same three mild haemophilic plasmas. Wide variation was found between laboratories using the same method, especially for those methods which were not well standardised. There was fairly good agreement for the reference method. All methods correctly diagnosed the three mild haemophilic plasmas, but their factor VIII levels were rather low. Stage 2 was restricted to seven laboratories in Great Britain, comparing seven well-standardised commercial methods and the same reference method. A much wider range of abnormal plasmas was tested, and a variety of normal ones. P.T.T.'s for all plasmas (factor VIII levels from 5 to 58 iu/dL) fell outside the normal range by all methods, with a few exceptions. It was not possible to rank the methods in any order.

The stability of the WHO reference thromboplastin NIBS & C 67/40.

The International Reference Preparation of human brain thromboplastin coded 67/40 has been thought to show evidence of instability. The evidence is discussed and is not thought to be strong; but it is suggested that it would be wise to replace 67/40 with a new preparation of human brain, both for this reason and because 67/40 is in a form (like Thrombotest) in which few workers seem to use human brain. A 'plain' preparation would be more appropriate; and a freeze-dried sample of BCT is recommended as the successor preparation. The opportunity should be taken also to replace the corresponding ox and rabbit preparations. In the collaborative study which would be required it would then be desirable to test in parallel line the three old and the three new preparations. The relative sensitivities of the old preparations could be compared with those found in earlier studies to obtain further evidence on the stability of 67/40; if stability were confirmed, the new preparations should be calibrated against it, but if not, the new human material should receive a calibration constant of 1.0 and the new ox and rabbit materials calibrated against that. The types of evidence available for monitoring the long-term stability of a thromboplastin are discussed.

Antithrombin activities in childhood malnutrition.

Antithrombin activities in 30 severely malnourished children and 40 normal children were estimated in clotting tests by thrombin neutralisation as anti-Xa and by a heparin antithrombin assay; and by immunodiffusion as alpha 2-globulin and alpha 1-antitrypsin. The patients' mean alpha 2-globulin was severely depressed, and there were less marked depletions in mean values for thrombin neutralisation, anti-Xa, and in the heparin antithrombin assay (which showed the flat curve thought to reflect a thrombotic tendency). The alpha 1-antitrypsin values were normal. The findings support the concept of antithrombin as the summation of alpha 2-globulin and alpha 1-antitrypsin (with alpha 2-macroglobulin); and the low values may be related to the high incidence of thrombosis reported in childhood malnutrition, although it was not seen in these patients.

Home treatment in haemophilia: clinical, social and economic advantages.

Twenty-eight severely affected haemophiliacs were observed for 3 months under treatment as hospital out-patients and for the subsequent 9 months while treating themselves at home. Delay in receiving treatment and financial costs were both clearly reduced by home treatment, the patients recovered from individual bleeds more quickly and reported a greater sense of personal freedom and independence. The amount of treatment required did not materially change and no untoward effects were noted; the use of analgesics tended to be less.

Classification of von Willebrand's disease.

The classification of von Willebrand's disease should be based primarily on the mode of inheritance: thus, the main division would between autosomal dominant and autosomal recessive types. Phenotypic subdivisions within these major types may then be possible. A subgroup of the dominant type seems to be well defined by increased electrophoretic mobility of the VIII-related antigen.

An artificial 'haemophilic' plasma for one-stage factor-VIII assay.

An 'artificial' plasma for one-stage factor-VIII assays is made by incubating human plasma with EDTA, to destroy factor VIII, and afterwards removing the anticoagulant by dialysis. Bovine factor V is then added to a given level. In the assay, contact activation is controlled by adding contact product. It was confirmed that factor-VIII activity was destroyed and that the EDTA was freely dialysable. The fibrinogen in the treated plasma clotted normally with thrombin. Likely variation in the factor-V activity was found not to be critical. The concentration of fibrinogen and other factors was adequate. Variation between batches was small. The artificial plasma yielded assay results closely comparable to haemophilic plasma in samples with factor-VIII activities in the range 0.01--20.0 iu/ml; the mean results in the artificial system were estimated to be 0.997 x those in haemophilic plasma, with a 95% confidence interval of 0.901--1.103. Biological variability in individual assays was smaller in the artificial system than when haemophilic plasma was used. Instability at the bench was more often detected in the artificial system than in haemophilic plasma assays, but the effect was eliminated from the results by obtaining duplicated readings in a balanced order.