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NORMAL T-CELL SUBSET RATIOS IN PATIENTS WITH SEVERE HAEMOPHILIA A TREATED WITH CRYOPRECIPITATE
461 enhanced sperm
motility
has clinical
significance
awaits further
SYMPATHETIC ACTIVITY IN BENIGN FAMILIAL
investigation.
TREMOR
C. Y. HONG B. N. CHIANG
Departments of Medicine and Biochemistry, National Yang-Ming Medical College; and Taiwan Veterans General Hospital, Taipei, Taiwan, Republic of China
J. KU Y. H. WEI
NORMAL T-CELL SUBSET RATIOS IN PATIENTS WITH SEVERE HAEMOPHILIA A TREATED WITH CRYOPRECIPITATE
SIR,-Studies in symptom-free patients with haemophilia A treated with commercial concentrates have revealed T-helper to of healthy controls and of T-suppressor cell ratios lower than those 1-3 patients treated with cryoprecipitate. The significance of altered T-cell ratios is not known. They have been attributed both to the unknown acquired immunodeficiency syndrome (AIDS) agent and to properties ofthe purified concentrate itself. Altered ratios are also seen in patients treated with locally produced plasma products, mostly concentrates, in areas of evidently low endemicity of
AIDS.4-66
Finland is self-sufficient in the production of coagulation factor products from voluntary, non-paid donors. Two cases of AIDS in homosexual men have been observed in the population (4’88 million). Only small pool (eight donors) cryoprecipitate is used in the treatment of adult patients with haemophilia A, von Willebrand’s disease, and factor XIII deficiency. We have assayed T-cell subsets in 24 patients with severe haemophilia A (mean age 33±11 years). The group represents onequarter of the 106 patients with severe disease in Finland. The average amount of cryoprecipitate used for the past five years was 52 000 U per year (range 10 400 to 137 600). The percentage of OKT3, OKT4, and OKT11-positive cells were determined by an indirect immunofluorescence with commercial antisera (Ortho Diagnostic Systems [table]). The control group consisted of 37 healthy male blood donors (mean age 27±3 years).
to explain why blockade of beta-2 in the treatment of benign is useful peripheral adrenoceptors familial tremor (BFT), as discussed in your Nov 26 editorial. Because a similar tremor, tremor, is readily affected by sympathetic activity, we measured endogenous plasma adrenaline and noradrenaline in patients with BFT. Ten patients with BFT (eight male), who were examined by one of us (M. O’B.), were studied. The mean age was 50 years (range 19-75). One patient was on propranolol and primidone but took no medication on the day of study. The remaining nine patients were on no medication. Ten control patients (nine male) were recruited from the outpatient department. The mean age was 47 years (range 16-69). One patient had chronic bronchitis and the remainder were dermatology patients on topical treatment only. There was no significant difference between the two groups in smoking history, history of alcohol intake, weight, or height. Blood was samplesfrom an indwelling venous catheter after each subject had rested supine for 20-min and again after standing for 10 min. After each blood sample heart rate and blood pressure were recorded. Catecholamines were assayed by a radioenzymatic method.3All measurements were made by the same observer using the same equipment. Significance was tested by the Wilcoxon rank-
SiR,-Our findings may help
physiological
sum test. 50r
T-CELL SUBSETS IN HAEMOPHILIACS USING CRYOPRECIPITATE
Effect of posture
T-cell subset ratios were normal in patients with severe haemophilia A treated with Finnish cryoprecipitate. None of the patients had an inverted ratio. The T-helper/T-suppressor ratio did not correlate with the age, yearly amount of cryoprecipitate used, or
IgG level. It seems that lympocyte abnormalities are characteristic not of haemophilia patients in general but of those on concentrate accept that the altered T-cell subset ratios in with concentrates are not necessarily caused treated haemophiliacs by the AIDS agent, we have to presume that they are caused by unknown properties of large-pool factor VIII concentrates. treatment.
If
we
Finnish Red Cross Blood Transfusion Service, SF-00310 Helsinki 31, Finland
VESA P. O. RASI JUKKA L. K. KOISTINEN C. MARTINA LOHMAN OLLI J. SILVENNOINEN
MM, Ratnoff OD, Scillan JJ, Jones PK, Schachter B. Impaired cellmediated immunity in patients with classic hemophilia. N Engl J Med 1983; 308:
1. Ledermann
79-83.
RH, Casper JT, et al. T-lymphocyte subpopulations in patients with classic hemophilia treated with cryoprecipitate and lyophilized concentrates. N Engl J Med 1983; 308: 83-86. 3. Goldsmith JC, Moseley PL, Monick M, Brady M, Hunninghake GW. T-lymphocyte subpopulation abnormalities in apparently healthy patients with hemophilia. Ann Intern Med 1983; 98: 294-96. 4. Ludlam CA, Carr R, Veitch SE, Steel CM. Disordered immune regulation in haemophiliacs not exposed to commercial factor VIII. Lancet 1983; i: 1226. 5. Rickard KA, Joshua DE, Campbell J, Wearne A, Hodgson J, Kronenberg H. Absence of AIDS in haemophiliacs in Australia treated from an entirely voluntary blood donor system. Lancet 1983; ii: 50-51. 6. Froebel KS, Madhok R, Forbs CD, Lennie SE, Lowe GDO, Sturrock RD. Immunological abnormalities in haemophilia: are they caused by American factor VIII concentrate? Br Med J 1983; 287: 1091-93. 2. Menitove JE, Aster
on
the
plasma adrenaline and noradrenaline.
Horizontal lines show the mean±SD.
There was no significant difference in the noradrenaline levels between the two groups (see figure). In the control group the supine plasma adrenaline was 0 -19::tO’07 nmol/l (mean±SD), similar to the normal reference range for our laboratory.4 This rose to 0-23.tO-08 nmol/1 on standing. In the BFT group the corresponding values were 0 - 43--tO - 11 and 0 -48::tO’13, both significantly higher than control values (p<0-001). Since adrenaline is derived almost solely from the adrenal medulla the raised levels in the BFT group suggest an increased secretion by the gland. The alternative possibility-a reduced clearance rate-was not tested. The raised levels in the BFT group were still within the normal physiological range, which has an 2 upper limit of approximately 2 nmol/1 during severe exercise.2 Therefore it is difficult to attribute the abnormality of BFT solely to the increased levels of adrenaline, particularly since there was some overlap in levels between the two groups. However, endogenous adrenaline appears to have significant beta-2 agonist properties, even though not normally present in sufficient quantities to have
plasma
CD, Foley TH, Owen DAL, McAllister RG. Peripheral &bgr;-adrenergic receptors concerned with tremor. Clin Sci 1967; 33: 53-65. 2. Warren JB, Dalton N. A comparison of the bronchodilator and vasopressor effects of exercise levels of adrenaline in man. Clin Sci 1983; 64: 475-79. 3. Peuler JD, Johnson GA. Simultaneous single isotope radioenzymatic assay of plasma noradrenaline, adrenaline and dopamine. Life Sci 1977; 21: 625-36. 4. Trompeter RS, Dalton N, Turner C. Plasma adrenaline in diagnosis of phaeochromocytoma in a child. Lancet 1982; i: 518. 1. Marsden
5.
Cryer PE. Isotope-derivative measurements of plasma norepinephrine and epinephrine in man. Diabetes
1976; 25:
1071-82.
motility
has clinical
significance
awaits further
SYMPATHETIC ACTIVITY IN BENIGN FAMILIAL
investigation.
TREMOR
C. Y. HONG B. N. CHIANG
Departments of Medicine and Biochemistry, National Yang-Ming Medical College; and Taiwan Veterans General Hospital, Taipei, Taiwan, Republic of China
J. KU Y. H. WEI
NORMAL T-CELL SUBSET RATIOS IN PATIENTS WITH SEVERE HAEMOPHILIA A TREATED WITH CRYOPRECIPITATE
SIR,-Studies in symptom-free patients with haemophilia A treated with commercial concentrates have revealed T-helper to of healthy controls and of T-suppressor cell ratios lower than those 1-3 patients treated with cryoprecipitate. The significance of altered T-cell ratios is not known. They have been attributed both to the unknown acquired immunodeficiency syndrome (AIDS) agent and to properties ofthe purified concentrate itself. Altered ratios are also seen in patients treated with locally produced plasma products, mostly concentrates, in areas of evidently low endemicity of
AIDS.4-66
Finland is self-sufficient in the production of coagulation factor products from voluntary, non-paid donors. Two cases of AIDS in homosexual men have been observed in the population (4’88 million). Only small pool (eight donors) cryoprecipitate is used in the treatment of adult patients with haemophilia A, von Willebrand’s disease, and factor XIII deficiency. We have assayed T-cell subsets in 24 patients with severe haemophilia A (mean age 33±11 years). The group represents onequarter of the 106 patients with severe disease in Finland. The average amount of cryoprecipitate used for the past five years was 52 000 U per year (range 10 400 to 137 600). The percentage of OKT3, OKT4, and OKT11-positive cells were determined by an indirect immunofluorescence with commercial antisera (Ortho Diagnostic Systems [table]). The control group consisted of 37 healthy male blood donors (mean age 27±3 years).
to explain why blockade of beta-2 in the treatment of benign is useful peripheral adrenoceptors familial tremor (BFT), as discussed in your Nov 26 editorial. Because a similar tremor, tremor, is readily affected by sympathetic activity, we measured endogenous plasma adrenaline and noradrenaline in patients with BFT. Ten patients with BFT (eight male), who were examined by one of us (M. O’B.), were studied. The mean age was 50 years (range 19-75). One patient was on propranolol and primidone but took no medication on the day of study. The remaining nine patients were on no medication. Ten control patients (nine male) were recruited from the outpatient department. The mean age was 47 years (range 16-69). One patient had chronic bronchitis and the remainder were dermatology patients on topical treatment only. There was no significant difference between the two groups in smoking history, history of alcohol intake, weight, or height. Blood was samplesfrom an indwelling venous catheter after each subject had rested supine for 20-min and again after standing for 10 min. After each blood sample heart rate and blood pressure were recorded. Catecholamines were assayed by a radioenzymatic method.3All measurements were made by the same observer using the same equipment. Significance was tested by the Wilcoxon rank-
SiR,-Our findings may help
physiological
sum test. 50r
T-CELL SUBSETS IN HAEMOPHILIACS USING CRYOPRECIPITATE
Effect of posture
T-cell subset ratios were normal in patients with severe haemophilia A treated with Finnish cryoprecipitate. None of the patients had an inverted ratio. The T-helper/T-suppressor ratio did not correlate with the age, yearly amount of cryoprecipitate used, or
IgG level. It seems that lympocyte abnormalities are characteristic not of haemophilia patients in general but of those on concentrate accept that the altered T-cell subset ratios in with concentrates are not necessarily caused treated haemophiliacs by the AIDS agent, we have to presume that they are caused by unknown properties of large-pool factor VIII concentrates. treatment.
If
we
Finnish Red Cross Blood Transfusion Service, SF-00310 Helsinki 31, Finland
VESA P. O. RASI JUKKA L. K. KOISTINEN C. MARTINA LOHMAN OLLI J. SILVENNOINEN
MM, Ratnoff OD, Scillan JJ, Jones PK, Schachter B. Impaired cellmediated immunity in patients with classic hemophilia. N Engl J Med 1983; 308:
1. Ledermann
79-83.
RH, Casper JT, et al. T-lymphocyte subpopulations in patients with classic hemophilia treated with cryoprecipitate and lyophilized concentrates. N Engl J Med 1983; 308: 83-86. 3. Goldsmith JC, Moseley PL, Monick M, Brady M, Hunninghake GW. T-lymphocyte subpopulation abnormalities in apparently healthy patients with hemophilia. Ann Intern Med 1983; 98: 294-96. 4. Ludlam CA, Carr R, Veitch SE, Steel CM. Disordered immune regulation in haemophiliacs not exposed to commercial factor VIII. Lancet 1983; i: 1226. 5. Rickard KA, Joshua DE, Campbell J, Wearne A, Hodgson J, Kronenberg H. Absence of AIDS in haemophiliacs in Australia treated from an entirely voluntary blood donor system. Lancet 1983; ii: 50-51. 6. Froebel KS, Madhok R, Forbs CD, Lennie SE, Lowe GDO, Sturrock RD. Immunological abnormalities in haemophilia: are they caused by American factor VIII concentrate? Br Med J 1983; 287: 1091-93. 2. Menitove JE, Aster
on
the
plasma adrenaline and noradrenaline.
Horizontal lines show the mean±SD.
There was no significant difference in the noradrenaline levels between the two groups (see figure). In the control group the supine plasma adrenaline was 0 -19::tO’07 nmol/l (mean±SD), similar to the normal reference range for our laboratory.4 This rose to 0-23.tO-08 nmol/1 on standing. In the BFT group the corresponding values were 0 - 43--tO - 11 and 0 -48::tO’13, both significantly higher than control values (p<0-001). Since adrenaline is derived almost solely from the adrenal medulla the raised levels in the BFT group suggest an increased secretion by the gland. The alternative possibility-a reduced clearance rate-was not tested. The raised levels in the BFT group were still within the normal physiological range, which has an 2 upper limit of approximately 2 nmol/1 during severe exercise.2 Therefore it is difficult to attribute the abnormality of BFT solely to the increased levels of adrenaline, particularly since there was some overlap in levels between the two groups. However, endogenous adrenaline appears to have significant beta-2 agonist properties, even though not normally present in sufficient quantities to have
plasma
CD, Foley TH, Owen DAL, McAllister RG. Peripheral &bgr;-adrenergic receptors concerned with tremor. Clin Sci 1967; 33: 53-65. 2. Warren JB, Dalton N. A comparison of the bronchodilator and vasopressor effects of exercise levels of adrenaline in man. Clin Sci 1983; 64: 475-79. 3. Peuler JD, Johnson GA. Simultaneous single isotope radioenzymatic assay of plasma noradrenaline, adrenaline and dopamine. Life Sci 1977; 21: 625-36. 4. Trompeter RS, Dalton N, Turner C. Plasma adrenaline in diagnosis of phaeochromocytoma in a child. Lancet 1982; i: 518. 1. Marsden
5.
Cryer PE. Isotope-derivative measurements of plasma norepinephrine and epinephrine in man. Diabetes
1976; 25:
1071-82.