- Email: [email protected]
EFFECT OF COLD ON BLEEDING
399
plead " was under appeal and the accused was subsequently found "
guilty ", exemplifies the vulnerability of this position and suggests that the whole prob-
not
anyone in lem deserves the attention of the National Council for
Civil Liberties. London N.W.3.
BARBARA ROBB Chairman, AEGIS (Aid for the Elderly in Government Institutions.)
that 0-6 g. would certainly have a maximal clinical effect if the clinical effect depends exclusively on inhibition of the release reaction of platelets stimulated by adrenaline. A preliminary analysis of one trial in progress does not suggest that aspirin, 0-6 g. daily, has a beneficial effect There is, however, on the particular situation studied. one report 11 of a high aspirin dose having an effect in rabbits while a lower dose had none. Accordingly, a reconsideration of aspirin dose-levels became important, since it might be argued empirically that a drug should be given in as high a dose as is safe and tolerable.
EFFECT OF COLD ON BLEEDING
SiR,-The letter of Dr. Kattlove and Professor Alexander1 is an important contribution to understanding of the cold-tolerance test for haemostasis, in which a small wound is exposed to different temperatures.2 A decrease from 25°C to 16°C resulted in significant prolongation of the bleeding-time and increased blood-loss, similar to the effect of chilling both the incision site and the surrounding skin.3Theoretically, any one of the factors contributing to haemostasis could be affected by cold-platelets as well as vascular or plasma components. From their observations, Kattlove and Alexander conclude that platelet aggregation is inhibited by cold, and that this could account for the prolonged bleeding-time when the site of the incision is chilled. That plasma factors are affected as well is suggested by at least two other observations. Firstly, the in-vivo cold-tolerance test shows abnormal bleeding patterns in patients with congenital coagulation-factor deficiencies but with normal platelets.33 (The patterns are different from those obtained from patients with thrombocytopenia.) Secondly, while studying the influence of temperature on coagulation tests, we found that the tests of plasma coagulation factors (prothrombin-time, recalcification-time, partial thromboplastin-time) became highly abnormal when they were performed at lower temperatures. These observations suggest that plasma factors as well as platelet aggregation are affected by low temperatures. More obscure is the effect of cold on vascular components of haemostasis, but we should like to mention the interesting finding that, in patients with von Willebrand’s disease, bleeding increases
A. H. SUTOR A. RUPRECHT W. KÜNZER W. SCHENCK.
TWO IN-VIVO STUDIES COMPARING HIGH AND LOW ASPIRIN DOSAGE SIR,-Ever since the ingestion of aspirin was reported to influence hsemostasis in normal people 5 and to alter platelet function profoundly when tested in vitro,6 it has
repeatedly been suggested that aspirin might have a prophylactic effect on thrombosis. Several trials are in progress and more may be planned, so two small studies were undertaken to try to establish an appropriate dose of aspirin. When 0-15 g. of aspirin was given to adults it caused complete inhibition of the adrenaline-induced release reaction of platelets tested in vitro. Thus it can be argued
5.
Kattlove, H., Alexander, B. Lancet, 1970, ii, 1359. Sutor, A. H., Bowie, E. J. W., Owen, Ch. A., Jr. Blut, 1971, 22, 27. Sutor, A. H., Bowie, E. J. W., Owen, Ch. A., Jr. Lancet, 1970, ii, 1084. Sutor, A. H., Ruprecht, A., Schenck, W., Altemeyer, K.-H., Karitzky, D., Schreiber, R., Künzer, W. Unpublished. Weiss, H. J., Aledort, L. M., Kockwa, S. J. clin. Invest. 1968, 47,
6. 7.
Zucker, M. B., Peterson, J. Proc. Soc. exp. Biol. Med. 1968,127,547. O’Brien, J. R., Finch, W., Clark, E. J. clin. Path. 1970, 23, 522.
4.
Low
Dosage
on
Collagen Response
The release reaction induced by collagen may be a more physiological process than that induced by adrenaline, and differences have been reported.9 Accordingly, seven healthy volunteers aged 23 to 42, four males and three females, who had ingested no aspirin for at least a week were tested, and their platelets were shown to give a normal vigorous response to collagen. Three were then given a low dose of aspirin, 0-6 g. every night, and four were given a high dose, 1-5 g. at night and 0-9 g. in the morning (i.e., 2-4 g. daily). The aggregation of their platelet-rich plasma was tested daily with a standard strong suspension of tendon extract,lO here called collagen. The daily aspirin ingestion and the tests were continued until a steady state was reached-i.e., until it was reasonably certain that no
TABLE I-COLLAGEN SLOPE ON A HIGH AND LOW DOSE OF ASPIRIN*
when the incision site is chilled.
Universitäts-Kinderklinik, 78 Freiburg, Germany.
1. 2. 3.
Effect of High and
2169.
* "
Initial " is reading obtained before ingesting aspirin. Day 1, 2, &c., indicates the number of days after beginning ingesting aspirin on which the platelets were tested.
greater inhibition would occur. All seven volunteers were then rested for 10 days, when their response to collagen was retested to check that it had returned to the pretreatment level. The tests were then repeated after each volunteer had been transferred to the other aspirin dosage level; thus all seven were tested on the high and low
dosage regimen. The results of " slope " 1° are reported in table high figure indicates brisk aggregation. 1.
2.
I.
A
Comparing the two resting figures at least 14 days apart, it will be seen once again 11 that each volunteer tends to have a personally characteristic response. The average result on the 2nd day on aspirin is similar that on the 1st day; thus the result is apparently maximal at once and there is no evidence at either dose-level of a cumulative effect.12
to
Peterson, J., Zucker, M. B. Thromb. Diath. hœmorrh. 1970, 23, 148. Valdorf-Hansen, J. F., Zucker, M. B. Am. J. Physiol. (in the press). O’Brien, T. R., Heywood, J. B., Heady, J. A. Thromb. Diath. hœmorrh. 1966, 16, 752. 11 O’Brien, J. R. Coagulation, 1968, 1, 311. 12. Atac, A., Spagnolo, M., Zucker, M. B. Proc. Soc. exp. Biol. Med. 1970, 133, 1331.
8. 9. 10.
plead " was under appeal and the accused was subsequently found "
guilty ", exemplifies the vulnerability of this position and suggests that the whole prob-
not
anyone in lem deserves the attention of the National Council for
Civil Liberties. London N.W.3.
BARBARA ROBB Chairman, AEGIS (Aid for the Elderly in Government Institutions.)
that 0-6 g. would certainly have a maximal clinical effect if the clinical effect depends exclusively on inhibition of the release reaction of platelets stimulated by adrenaline. A preliminary analysis of one trial in progress does not suggest that aspirin, 0-6 g. daily, has a beneficial effect There is, however, on the particular situation studied. one report 11 of a high aspirin dose having an effect in rabbits while a lower dose had none. Accordingly, a reconsideration of aspirin dose-levels became important, since it might be argued empirically that a drug should be given in as high a dose as is safe and tolerable.
EFFECT OF COLD ON BLEEDING
SiR,-The letter of Dr. Kattlove and Professor Alexander1 is an important contribution to understanding of the cold-tolerance test for haemostasis, in which a small wound is exposed to different temperatures.2 A decrease from 25°C to 16°C resulted in significant prolongation of the bleeding-time and increased blood-loss, similar to the effect of chilling both the incision site and the surrounding skin.3Theoretically, any one of the factors contributing to haemostasis could be affected by cold-platelets as well as vascular or plasma components. From their observations, Kattlove and Alexander conclude that platelet aggregation is inhibited by cold, and that this could account for the prolonged bleeding-time when the site of the incision is chilled. That plasma factors are affected as well is suggested by at least two other observations. Firstly, the in-vivo cold-tolerance test shows abnormal bleeding patterns in patients with congenital coagulation-factor deficiencies but with normal platelets.33 (The patterns are different from those obtained from patients with thrombocytopenia.) Secondly, while studying the influence of temperature on coagulation tests, we found that the tests of plasma coagulation factors (prothrombin-time, recalcification-time, partial thromboplastin-time) became highly abnormal when they were performed at lower temperatures. These observations suggest that plasma factors as well as platelet aggregation are affected by low temperatures. More obscure is the effect of cold on vascular components of haemostasis, but we should like to mention the interesting finding that, in patients with von Willebrand’s disease, bleeding increases
A. H. SUTOR A. RUPRECHT W. KÜNZER W. SCHENCK.
TWO IN-VIVO STUDIES COMPARING HIGH AND LOW ASPIRIN DOSAGE SIR,-Ever since the ingestion of aspirin was reported to influence hsemostasis in normal people 5 and to alter platelet function profoundly when tested in vitro,6 it has
repeatedly been suggested that aspirin might have a prophylactic effect on thrombosis. Several trials are in progress and more may be planned, so two small studies were undertaken to try to establish an appropriate dose of aspirin. When 0-15 g. of aspirin was given to adults it caused complete inhibition of the adrenaline-induced release reaction of platelets tested in vitro. Thus it can be argued
5.
Kattlove, H., Alexander, B. Lancet, 1970, ii, 1359. Sutor, A. H., Bowie, E. J. W., Owen, Ch. A., Jr. Blut, 1971, 22, 27. Sutor, A. H., Bowie, E. J. W., Owen, Ch. A., Jr. Lancet, 1970, ii, 1084. Sutor, A. H., Ruprecht, A., Schenck, W., Altemeyer, K.-H., Karitzky, D., Schreiber, R., Künzer, W. Unpublished. Weiss, H. J., Aledort, L. M., Kockwa, S. J. clin. Invest. 1968, 47,
6. 7.
Zucker, M. B., Peterson, J. Proc. Soc. exp. Biol. Med. 1968,127,547. O’Brien, J. R., Finch, W., Clark, E. J. clin. Path. 1970, 23, 522.
4.
Low
Dosage
on
Collagen Response
The release reaction induced by collagen may be a more physiological process than that induced by adrenaline, and differences have been reported.9 Accordingly, seven healthy volunteers aged 23 to 42, four males and three females, who had ingested no aspirin for at least a week were tested, and their platelets were shown to give a normal vigorous response to collagen. Three were then given a low dose of aspirin, 0-6 g. every night, and four were given a high dose, 1-5 g. at night and 0-9 g. in the morning (i.e., 2-4 g. daily). The aggregation of their platelet-rich plasma was tested daily with a standard strong suspension of tendon extract,lO here called collagen. The daily aspirin ingestion and the tests were continued until a steady state was reached-i.e., until it was reasonably certain that no
TABLE I-COLLAGEN SLOPE ON A HIGH AND LOW DOSE OF ASPIRIN*
when the incision site is chilled.
Universitäts-Kinderklinik, 78 Freiburg, Germany.
1. 2. 3.
Effect of High and
2169.
* "
Initial " is reading obtained before ingesting aspirin. Day 1, 2, &c., indicates the number of days after beginning ingesting aspirin on which the platelets were tested.
greater inhibition would occur. All seven volunteers were then rested for 10 days, when their response to collagen was retested to check that it had returned to the pretreatment level. The tests were then repeated after each volunteer had been transferred to the other aspirin dosage level; thus all seven were tested on the high and low
dosage regimen. The results of " slope " 1° are reported in table high figure indicates brisk aggregation. 1.
2.
I.
A
Comparing the two resting figures at least 14 days apart, it will be seen once again 11 that each volunteer tends to have a personally characteristic response. The average result on the 2nd day on aspirin is similar that on the 1st day; thus the result is apparently maximal at once and there is no evidence at either dose-level of a cumulative effect.12
to
Peterson, J., Zucker, M. B. Thromb. Diath. hœmorrh. 1970, 23, 148. Valdorf-Hansen, J. F., Zucker, M. B. Am. J. Physiol. (in the press). O’Brien, T. R., Heywood, J. B., Heady, J. A. Thromb. Diath. hœmorrh. 1966, 16, 752. 11 O’Brien, J. R. Coagulation, 1968, 1, 311. 12. Atac, A., Spagnolo, M., Zucker, M. B. Proc. Soc. exp. Biol. Med. 1970, 133, 1331.
8. 9. 10.