Letter: HL-A antigens in lymphatic leukaemia.
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Biomedical subjects
Publications and source records attributed to F R Davey.
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An autoantibody was found on the red cells of a patient who had never been transfused previously, but was ill with metastatic adenocarcinoma. The patient's blood group was A1. In addition, the patient's serum and the eluate from the patient's red cells agglutinated A1 but not A2, B, and O red cells. This auto-A1 antibody was reactive at a wide thermal range and was inactivated by dithiothreitol, suggesting the presence of an IgM immunoglobulin. Moreover, the antibody was not associated with a hemolytic anemia.
Over a 6-year period, 866 cases were analyzed for disputed parentage. In 194 cases (22%), the alleged father was excluded as the biological father. One hundred and eight-one cases (93%) were direct exclusions, and 13 cases (7%) were indirect exclusions. Ninety-two percent of falsely accused men were identified by typing for HLA antigens alone. Exclusions based solely on red cell data occurred in 8 percent of the cases. When only HLA testing was performed, 177 of 362 (43%) cases had a probability of paternity of greater than or equal to 95 percent. When both HLA and red cell typings were performed, 110 of 160 (69%) cases had a probability of paternity of greater than or equal to 95 percent. No significant differences in the proportion of exclusions or proportion of alleged fathers with a probability of paternity of greater than or equal to 95 percent were observed between Caucasians or blacks. We conclude that typing for HLA antigens provides the most powerful data for excluding or including an alleged father. However, typing for red cell antigens adds significant data in excluding a falsely accused man and in determining the probability of paternity at a critical level (greater than or equal to 95%). In addition, the current study suggests that additional assays are needed to identify genetic characteristics of cases with probability of paternity less than 95 percent.
Possible associations between location of residence and acute leukemia risk were investigated in a study of 610 newly diagnosed patients, aged 18-79 y, and 618 population controls. There was an association between ever living within 5 miles (8 km) of an industrial plant and leukemia risk, with adjusted odds ratios (ORs) of 1.4 (95% confidence interval [95% CI] = 1.0-1.9) for all acute leukemias combined, 1.4 (95% CI = 1.0-2.0) for acute myeloid leukemia, and 1.7 (95% CI = 1.0-2.7) for acute lymphocytic leukemia. Odds ratios increased with decreasing distance from industrial sites, but a gradient with duration of residence was seen only among those less than age 60 who had lived within a mile of any industry. Suggestive associations were also observed for residence near specific industries, but the number of individuals living near any one industry was small.
A variety of hemostatic abnormalities has been reported in patients following open-heart surgery. Since surgery itself may induce changes in the coagulation system, the analyses of postoperative coagulation assays in the bleeding patients may be extremely difficult to interpret without an understanding of the coagulation dynamics in the nonhemorrhagic postoperative patients. Thus, we studied the pattern of change in several coagulation assays performed on 36 consecutive patients before and during the first two postoperative weeks. Approximately one third of the patients has some clotting abnormality before surgery. Shortened prothrombin time (PT) and activated partial thromboplastin time (APTT) were observed within the first three postoperative days. Only following warfarin therapy (initiated on the third postoperative day) was significant prolongation of PT and APTT observed. During the 14 postoperative days, fibrinogen levels and fibrinogen degradation products progressively increased without prolongation of the thrombin time or decrease in the euglobulin clot lysis time. On the first postoperative day, the platelet count and platelet adhesiveness values were significantly less than before surgery (p less than 0.01 and p less than 0.05). Over the following two weeks, the platelet count and platelet adhesiveness returned to normal. Although there was slight lengthening of the Ivy bleeding time on the first postoperative day, this assay was never abnormal. Thus, we conclude that the following cardiopulmonary bypass there is (1) probably activation of circulating procoagulants, (2) progressive increase in fibrinogen levels, (3) activation to the fibrinolytic system, and (4) transient thrombocytopenia with a superimposed platelet defect.
Myeloma gamma globulins have been reported to interfere with fibrinogen-fibrin conversion. A patient with multiple myeloma is described with a gamma globulin IgG1lambda concentration of 11 g per dl, prolonged thrombin time and poor clot retraction. Purified gamma globulin from the patient's serum and from normal serum caused prolongation of the thrombin time and reptilase clotting time assays in both normal plasma and in solutions of bovine fibrinogen. In addition, fibrin clots formed during the thrombin time assays were found to be ultrastructurally abnormal. This data suggests that the interaction of gamma globulin in the polymerization of fibrin may, in at least some cases, be due to nonspecific protein interaction.
Platelet glass bead retention by the Salzman and infusion pump techniques were compared in 36 control individuals, 10 patients with von Willebrand's syndrome and four patients with thrombocytopathies. No significant differences between the results of the two assays were observed. Eleven percent or less of the control individuals had diminished platelet glass bead retention. The mean percentage platelet retention of the von Willebrand's group and the thrombocytopathy group was less than the mean platelet retention of the control group. However, at least 50 percent of the patients with von Willebrand's syndrome had normal platelet retention by both methods. In the thrombocytopathy group, glass bead retention was more consistently diminished. Although an inverse correlation existed between the duration of bleeding time and the platelet retention assays, consistently diminished platelet retention results were observed only when the bleeding time was 18 minutes or longer. It has been concluded by us that while the glass bead retention assays may be helpful in characterizing certain types of platelet disorders, they are not useful screening assays in the diagnosis of von Willebrand's syndrome.
The automated-activated coagulation time, manual-activated coagulation time and the activated partial thromboplastin time were compared to the whole blood clotting time in the measurement of hypocoagulation of heparinized blood. The normal ranges and degree of reproducibility were determined for each clotting assay. Each method was examined for its sensitivity to various concentrations of heparin. In addition, blood samples from patients treated with heparin were assayed by all four methods and their results were compared. The results indicated that the manual-activated clotting time correlated best with the whole blood clotting time, was sensitive to low concentrations of heparin, formed a discernible clot within a convenient time period in blood containing high concentrations of heparin, was reproducible and was easily performed.