Search

A young Italian man (A.P.) has a lifelong history of bleeding from gums and mucocutaneous tissue. Electron microscopy showed a wide diversity of platelet size including giant forms. In citrated platelet-rich plasma (PRP), platelet aggregation induced by adenosine diphosphate (ADP) and other agonists was much reduced. Both secretion and clot retraction were normal. The aggregation of washed platelets with ADP was improved but remained subnormal, as was aggregation with collagen and thrombin. Fibrinogen-binding was analyzed by flow cytometry using platelets in whole blood or PRP and was markedly decreased. Crossed immunoelectrophoresis of Triton X-100 extracts of (A.P.) platelets showed that GP IIb-IIIa levels were 40% to 50% of normal. Glycoprotein (GP) IIb and GP IIIa were of usual migration in sodium dodecyl sulfate- polyacrylamide gel electrophoresis, but their labeling was much reduced during lactoperoxidase-catalyzed iodination. Binding to (A.P.) platelets of four different 125I-labeled monoclonal antibodies to GP IIb-IIIa complexes was reduced to 12% to 20% of normal levels. However, when the patient's platelets were stimulated with alpha-thrombin, monoclonal antibody binding showed the same increase (approximately 20,000 sites) as normal platelets. Both flow cytometry and immunocytochemical studies showed that the distribution of residual surface GP IIb-IIIa within the total (A.P.) platelet population was heterogeneous and not related to platelet size. Staining of ultrathin sections confirmed the presence of an internal pool of GP IIb-IIIa. Monoclonal antibodies to other membrane glycoproteins bound normally to (A.P.) platelets. The patient has a selective deficiency of the surface pool of GP IIb-IIIa complexes that is manifested clinically by a mild Glanzmann's thrombasthenia-like syndrome.

Studies of space-time clustering of cases of childhood leukaemia have yielded equivocal results. This might be because the disease has a long and variable latent period, in which case the usual statistical tests for such clustering are inappropriate. A new statistical method is described which allows for such latent periods. For each patient, periods of "susceptibility" and "infectivity" are defined in which it is assumed he respectively "caught" and could "transmit" the disease. The measure of clustering is taken as the number of patients who were in the "right" place at the "right" time to "catch" the disease from another patient. This test is applied to childhood acute lymphoblastic leukaemia (death before age 6) in Greater London in the period 1952-65. Cases are postulated to be "susceptible" at various times before clinical onset of leukaemia, including in utero, and "infective" at various times around onset. Their effective "contacts" at these times are defined as circles of radius up to 4 km around their places of residence at these times. Slight evidence of clustering was found associated with certain of the defined times and distances, but the degree of clustering was small and could reasonably be attributed to chance. It is suggested, however, that this method of analysis might usefully be applied to other sets of such data. No evidence was found to add to our previously reported finding of space-time clustering of the dates and places of birth of children with leukaemia.

1. Complement-fixing antibody was found to develop in a patient suffering from acute disseminated lupus erythematosus, who received treatment with ACTH.2. Bioassay experiments showed that this antibody had no antihormone properties.3. Further experiments with different batches of ACTH, and with the organic residue left after extraction of ACTH, suggested that the antibody was produced in response to the injection of a pituitary impurity.4. Neither complement-fixing antibodies to significant titre, nor precipitins could be demonstrated in the sera of nine other patients undergoing ACTH therapy. Total doses given varied from 520 to 9000 mg.

Inhibition of division of blast cells is common in untreated acute leukaemia of childhood. During relapse, while a patient is on maintenance therapy, the proportion of blast cells in cyclic division increases.

FOLLOWING the report of McGinnis et al. that the red cells of fifteen out of forty patients with leukaemia tested by them had a diminution of I antigen1, we tested red cells from fifteen patients with acute leukaemia using anti-I sera from the following three persons: (a) a group A patient with M. pneumoniae infection whose serum was obtained at the time of a transient rise of her cold agglutinin titre to 128 at 4° C; (b) a group A patient with the chronic cold agglutinin syndrome who had a cold agglutinin titre of 1,024 at 4° C; and (c) a healthy donor of group Ai who had a cold agglutinin titre of 8 at 4° C. These sera were used after neutralization of isoagglutinin anti-B with group B substance.

58 patients with ALL were studied at intervals during two years of maintenance chemotherapy. All patients received the same induction and cranial irradiation and were then randomized into two groups. Group C (Continuous) received daily drugs and Group I tIntermittent) were given drugs for five days followed by 16 days without drugs in successive cycles. Patients in both groups received the same total drug dose. Blood neutrophils counts were lower in Group I and fell after each course of drugs whereas neutrophil counts remained relatively constant in Group C. Lymphocyte counts, PHA responsiveness and serum immunoglobulin levels were significantly lower in Group C compared with Group I at all times tested during the study. The incidence of serious infections was higher in Group C (11/34 patients) than in Group I (4/24 patients). In most cases the onset of infection was preceded by a period of extreme lymphopenia (<0.4×109/1). Intermittent chemotherapy is therefore less suppressive of lymphocyte population size and function than continuous chemotherapy.

Samples of blood and marrow from 94 newly diagnosed children with ALL were investigated for the presence of cell ‘membrane markers’. Four types of ALL were recognised: Group I (75%) common ALL (anti ALL+, Greaves et al. 1977), Group II (12%) T cell, Group III (2%) B cell, Group IV (11%) ‘null’ cell. The white cell count at diagnosis was >20×109/1 in 36% of children in Group I but in over 90% of children in the other groups. Massive mediastinal enlargement was a feature of Group II (9/11 patients) and Group IV (4/10,patients). Remission induction was easier in Groups I and II, than III or IV.Preliminary follow up shows that the initial white cell count influences prognosis in common ALL (Group I) but that children in Group I with a high white cell count have a relatively better prognosis (median complete remission 86 weeks) than children in Group II (median complete remission duration 30 weeks).ReferenceM F Greaves et al., 1977. Membrane phenotyping: diagnosis, monitoring and classification of acute ‘lymphoid’ leukaemia in Immunodiagnosis of Leukaemias and Lymphomas. Verlag Munich, 1977.

WE have shown1that the clotting time of platelet-rich plasma (PRP) is progressively shortened by incubation at 37° C with a suspension of kaolin, and that this reflects a progressive increase in availability of platelet factor 3 (PF3) as well as activation of the plasma clotting system. Since maximal acceleration of clotting by kaolin was only achieved when platelets and plasma were activated to-together, it seemed likely that a plasma component was required for the reaction of platelets with kaolin. In order to determine whether a plasma coagulation factor was concerned in this reaction, investigations were carried out on the PRP of patients with a series of congenital coagulation defects. Equal volumes (0.1 ml.) of PRP and kaolin (5 mg per ml. of buffered saline, pH 7.3) were incubated at 37° C for 20 min and then recalcified with 0.1 ml. of 0.025 M calcium chloride, 0.1 ml. of a partially purified preparation of the deficient factor (or of buffered saline) being added in each case immediately before or after incubation with the kaolin. In the cases of factor-XII and factor-XI deficiency, activation product (prepared by the method of Nossel2) was used in place of the respective purified factors. Factors V and VIII were prepared by ammonium sulphate precipitation from barium sulphate-adsorbed platelet-poor oxalated normal plasma and factors VII, IX and X by adsorption of normal serum on to barium sulphate and subsequent elution into 5 per cent trisodium citrate. The fibrinogen reagent used (kindly provided by the Blood Products Laboratory of the Lister Institute) was prepared from fresh plasma by the method of Kekwick and Mackay3and was 66 per cent clottable; it also contained plasminogen and some factor VIII and anti-von Willebrand activity.

BLOOD platelets from patients with thrombasthenia do not adhere to glass in either a whole blood system or in a platelet-rich plasma system to which adenosine diphosphate (ADP) has been added, and they fail to adhere to each other in the presence of ADP, noradrenaline, thrombin, or connective tissue extract1,2. The electrophoretic mobility of thrombasthenic platelets has been shown to be normal3, but hitherto the changes in mobility which normally occur in the presence of aggregating agents4have not been studied in thrombasthenia.