Adrenocorticotrophic hormone and platelet stickiness

Journal of the neurological Sciences

151

Elsevier Publishing Company, Amsterdam - Printed in The Netherlands

Short Reports

Adrenocorticotrophic hormone and platelet stickiness INTRODUCTION

Recent communications have confirmed the report by NATHANSON AND SAVITSKY (1954) that the blood platelets of patients with multiple sclerosis show a greater tendency to adhere to glass surfaces than do those of normal subjects, or patients with other chronic neurological disorders (CAsPARY et al. 1965; WRIGrIT et al. 1965). Many neurologists consider A C T H to have a place in the management of multiple sclerosis and that it is more likely to be efficacious in the case of recent onset or relapse, a situation in which platelet stickiness is most often increased. As we have been unable to find any studies of the effect of A C T H on platelet adhesiveness, the purpose of this communication is to report observations in a small series of patients and controls who received a standard infusion of ACTH. MATERIALS AND METHODS

Opportunity to undertake this study presented itself during investigations into adrenal function in asthma and multiple sclerosis which will be the subject of an independent report. The 14 subjects of the study included 10 with multiple sclerosis. Of these, 3 had fresh symptoms and signs of less than one month's duration. The controls comprised two asthmatics, one young man with a spontaneous pontine haemorrhage (initially admitted with a diagnosis of multiple sclerosis) and a healthy volunteer. Each patient was admitted to hospital. None had received steroid therapy previously. The infusion was given into an antecubital vein starting at 9.30 a.m. using 30 units of corticotrophin (Cortrophin, Organon) in 500 ml of normal saline. The corticotrophin was obtained as a lyophilized powder and stored in a deep freeze until required. The infusion was regulated to deliver at least 25 units of corticotrophin in 8 hours. Blood samples for determinations of platelet stickiness were collected before setting up the drip and seven hours after commencement. They were taken by clean venepuncture using a 21-gauge needle and 20 ml siliconed syringe; 18 ml blood were gently transferred to a siliconed bottle containing 2 ml 3.8 ~o trisodium citrate and mixed by inversion. Platelet adhesiveness was measured using a modification of WRmHTS (1941) technique. Within 15-30 min of obtaining the sample, 2 ml citrated blood were pipetted into a 25 ml conical flask ('Quickfit') which was held horizontally by a stopper fastened to a base plate. This was rotated for 30 rain at 4 rev./min by a synchronous electric motor. Platelet counts were made before and after rotation J. neurol. Sci. (1967) 4:151-153

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using a modification of NYGAARD'S method (HELEEM 1960), 600-1000 platelets being counted under phase contrast at 400 x magnification.

RESULTS AND DISCUSSION

Table 1 shows the mean platelet counts and the adhesive platelets, expressed as a percentage of the initial counts, before and after infusion of A C T H . I f the patients with multiple sclerosis are considered, it will be seen that there was no significant TABLE

1

PLATELET STICKINESS IN PATIENTS AND CONTROLS BEFORE AND AFTER

Before A C T H

Patients Controls

ACTH ADMINISTRATION

After A C T H

mean initial platelet count ( × 10 s)

mean percent adhesive platelets

mean initial platelet count ( × 10 a)

mean percent adhesive platelets

mean change in adhesion (%)

243.5 4- 54.2 232.0 -- 17.0

45.8 ± 7.1 43.5 4- 7.3

249.3 -4- 26.8 263.6 4- 71.0

45.5 4- 9.0 39.0 4- 4.7

--0.2 --4.5

All figures given with their standard deviations. difference in initial platelet counts in the two sets of observations, neither was there any consistent effect of the infusion on platelet stickiness. This applied equally to the acute cases and to the remainder. However, the present material is limited particularly with regard to patients suffering from acute relapses. The apparent reduction in stickiness in the controls was, in large measure, due to the findings in one asthmatic subject. In a previous publication (WRIGHT et al. 1965), in which platelet studies were carried out on patients receiving A C T H , it was the authors' impression that adhesiveness was uninfluenced by therapy. The present results would be in accord with this view. Clearly, only the effects of A C T H that would be evident within hours have been considered. It is, however, the opinion of some neurologists that clinical improvement may be perceived within hours of administering A C T H in circumstances that make this unlikely to be fortuitous (MILLER 1964). Moreover, adrenal secretions are known to have in v i t r o an immediate effect on platelets, both noradrenaline and adrenaline producing aggregation of platelet suspensions (MITCHELL AND SHARP 1964). Delayed effects of A C T H on platelet stickiness will require separate investigation but it is likely that these will be more difficult to distinguish from variations due to the course of the disease. The pathogenetic significance, if any, of the observation in vitro of increased glassadhesiveness of platelets is, at present, obscure and in relation to multiple sclerosis has been discussed fully by FIELD AND CASPARY (1964). Indeed, the mechanism of increased stickiness is itself far from clear. At present, it is quite possible that changes in platelet properties are of secondary, rather than primary significance and may be the consequenceof other disturbances, e.g. in clotting factors or plasma lipids (THOMPSON 1966). Similarly, the mode of action of A C T H in multiple sclerosis is purely conjectural J. neurol. Sci. (1967) 4:151-153

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at present, and its effects are usually attributed to antiphlogistic properties. This study is unable to furnish any evidence for the hypothesis that the action o f A C T H might be mediated by modification o f platelet stickiness.

SUMMARY The administration o f an A C T H infusion in a small series o f patients with multiple sclerosis has not influenced platelet adhesiveness.

ACKNOWLEDGEMENTS The author wishes to t h a n k Dr. E. J. Field for help and encouragement and also Professor H e n r y Miller, whose patients were studied. Medical Research Council Demyelinating Research Unit, and Department of Neurology, Royal Victoria Infirmary and University, Newcastle upon Tyne (Great Britain)

P. MILLAC

REFERENCES CASPARY,E. A., J. PRINEAS,H. MILLERANDE. J. FIELD(1965) Lancet, ii: 1108. FIELD,E. J. ANDE. A. CASPARY(1964)Lancet, ii: 876. HELLEM,A. J. (1960 Scand. J. Clin. Lab. Invest., Suppl. 57: 12. MILLER,H. (1964)Practitioner, 192: 62. MITCHELL,J. R. A. ANDA. A. SHARP(1964) Brit. J. Haematol., 10: 78. NATHANSON,M. ANDJ. P. SAVITSKY(1954) Bull. N.Y. Acad. Med., 28 : 462. THOMPSON,R. H. S. (1964) Proc. roy. Soc. Med., 59: 269. WRIGHT,H. P. (1941) J. Path. Bact., 53 : 255. WRIGHT,H. P., R. H. S. THOMPSONANDK. J. ZILKHA(1965) Lancet, ii: 1109. (Received 23 July, 1966) J. neuroLSci. (1967) 4:151-153

Ontogenesis of paradoxical sleep in the human newborn INTRODUCTION I n 1957, two years after the discovery by ASERINSKY AND KLEITMAN (1955) o f a period o f multiple eye-movements during sleep, DEMENT AND KLEITMAN drew attention to the fast cortical activity in the L E G which characterizes this period o f sleep and showed that in men it is closely related to dreaming. The localisation in the reticular nuclei o f the pons of the structures responsible for This study was supported by the Scientific Medical Research Foundation of Belgium, by the 'Fondation Reine Elisabeth de Belgique', and the grant USAF (EOAR) 61(052)-949. J. neurol. Sci. (1967) 4:153-157