899 PROLACTIN SECRETION IN XYY MALES
50)
report in-
creased plasma-prolactin levels in three 47, XYY
SIR,-Dr Price and colleagues (July 1,
men at a
p.
security hospital. In a similar French institution, we did a T.R.H. test on six dangerous, mentally ill patients of 47, XYY chromosome constitution.’ These patients, aged 19-33 years and 176-197 cm in height, had not been receiving neuroleptic treatment for 2 months. Four had normal basic prolactin levels (7-5-10 ng/ml) and two a raised level of plasma-protein by radioimmunoassay (’Prolactin RIA’, C.I.S.). After injection of 200 g of T.R.H., the prolactin response was positive in five cases and negative in one.’ Basal plasma-prolactin concentrations (ng/ml) were: 55.0, 475, 7.5, 70, 90, and 10-0. Thus in this small series of patients, no definite relationship could be established between prolactin secretion and 47, XYY constitution. maximum
Service de Sûreté, Centre Hospitalier Spécialisé, 33410 Cadilac-sur-Garonne, France
M. BENEZECH
Laboratoire de Cytogénétique, Centre de Transfusion Sanguine, 73011 Chambéry
B. NOËL
DEXTRAN OR HEPARIN?
of Mr Powley (July 29, p. 261) and Mr Davies (Sept. 30, p. 732) prompt me to respond to their criticism of low-dose heparin prophylaxis. I agree that to deny adult surgical patients some form of prophylaxis is irresponsible and that dextran 70 is much less widely used than subcutaneous heparin for prophylaxis. However, Davies’ statement that "the efficacy of 1 litre of dextran given intravenously after induction of anaesthesia was established in a large multicentre double-blind controlled clinical trial" is not accurate; the trial was not double-blind nor were its results statistically significant. A symposium sponsored by the International Committee on Thrombosis and Hasmostasis, held in Leuven on July 19, discussed the design of several clinical trials. The Cardiff trial was presented in detail by Davies. It became evident that the trial was not double-blind, since the anoesthetist could easily recognise the difference between the two solutions simply by inverting the bottle, and therefore easily choose to give or not to give dextran 70; this resulted in a substantial number of patients who did not receive a dextran infusion. This trial also failed to provide information regarding the comparability of the groups with respect to factors known to influence the occurrence of the thromboembolic complications. Prof. M. Vessey (Oxford) also pointed out that the difference in the frequency of fatal pulmonary embolism in the two groups (i.e., 7 patients in the saline group and 1 in the dextran group) is not statistically significant when a two-tail analysis is used. The details of these discussions will be published. During the past 4 years, thirty-one trials have assessed the value of low-dose heparin prophylaxis in patients undergoing a variety of surgical operations. This experience, based on several thousand patients, is different from the misleading information presented in Davies’ table outlining the advantages and disadvantages of dextran and heparin. These trials show
SIR,--The
comments
the full doses of heparin needed to treat patients with thromboembolic disease. (e) No evidence has ever been presented that thrombi formed in vivo in the presence of dextran are more easily lysed by the patient’s own fibrinolytic system. (f) Before the cost of these two methods of prevention can be compared, the efficacy of dextran prophylaxis in preventing deaths due to fatal pulmonary embolism must be demonstrated. It also remains to be determined whether a single dextran infusion or three or more infusions will be required to produce a protective effect. to receive
Powley claims that surgeons in busy peripheral hospitals are offering routine heparin prophylaxis. Data on heparin sales point to the contrary. In 1974, only three firms, compared with seven in 1978, were marketing heparin specifically prepared for prophylactic use. Furthermore, Department of Health data on heparin usage in England, Wales, and Northern Ireland for 1975/76, 1976/77, and 1977/78 indicate that heparin usage has increased by approximately 15% per year during this period. Certainly Powley’s solution is simple and does not require any nursing supervision. But, however attractive and appealing a device may be, it remains useless unless its efficacy, in preventing deaths due to fatal pulmonary embolism, has been not
demonstrated. I hope that these misleading letters will not hinder the wider adoption of low-dose heparin prophylaxis.
even
Thrombosis Research Unit,
King’s College Hospital Medical School, London SE5 8RX
V. V. KAKKAR
SIR,-Mr Davies (Sept. 30, p. 732) states "It is widely held that to deny adult surgical patients some form of prophylaxis is irresponsible". Although he does not specifically declare himself for this policy, his remarks will add support to the philosophy of such treatment. May I make a plea against this type of blanket principle in treatment, which, I think, will bring the use of prophylactic heparin or dextran into disrepute. Despite the improved diagnosis of both deep-vein thrombosis and pulmonary embolism, I think few surgeons would deny that fatal pulmonary embolism now is much less common on well-run units that it was a quarter of a century ago. This must surely be due to a much better control of infection by improved surgical technique and antibiotics and also to the disappearance of the old butcher type of surgeon who tore at tissues and left hasmatomas, often infected. Some of the trials for prophylactic heparin have been on very selective groups of patients such as the elderly who have undergone trauma, and it is not logical to translate experience in limited groups to all surgery. We should be seeking, not to encourage indiscriminate use of prophylactic anticoagulation, but to identify patients in whom it is less dangerous and to find those in whom it increases the postoperative morbity. I think we shall discover that infection and tissue damage, whether by the surgeon or trauma, are the most important factors in producing unwanted intravascular coagulation and its
sequelar. General
Hospital, Birmingham B4 6NH
GEORGE T. WATTS
that:
(a) Low-dose heparin does not require monitoring. (b) The frequency of bleeding in general surgical patients receiving low doses of subcutaneous heparin is 7.7 compared with the 5.6 in the control group and not as great as 27*? as suggested by Davies. (c) Anti-thrombm-III depletion has never been observed in patients on
low-dose
s.c.
heparin.
(d) The only contraindication to low-dose heparin prophylaxis is a history of haemorrhagic disorders or bleeding diathesis; the other contraindications listed in the table are applicable only to patients who are 1. Benezech, M., Croizet, M.,
Belabas, M., Mathieu, C., Mathieu, P., Noël, B., Ferret-Bouin, P. Ann. Endocr., 1978, 39, 89.
SIR,-In his letter comparing dextran with heparin, Mr Davies does not stress sufficiently the risk of severe anaphylactoid reaction to dextran. We have seen a fatal reaction to this agent. A healthy 41-year-old ex-nurse with a history of deepvenous thrombosis but no allergies was admitted for sterilisation. Before anaesthesia was induced a prophylactic infusion of dextran 70 was started. After approximately 50 ml had been given over 2 min the patient collapsed, became cyanosed and pulseless, and had a convulsion. The infusion was stopped and the seizure controlled with intravenous diazepam. Despite
50)
report in-
creased plasma-prolactin levels in three 47, XYY
SIR,-Dr Price and colleagues (July 1,
men at a
p.
security hospital. In a similar French institution, we did a T.R.H. test on six dangerous, mentally ill patients of 47, XYY chromosome constitution.’ These patients, aged 19-33 years and 176-197 cm in height, had not been receiving neuroleptic treatment for 2 months. Four had normal basic prolactin levels (7-5-10 ng/ml) and two a raised level of plasma-protein by radioimmunoassay (’Prolactin RIA’, C.I.S.). After injection of 200 g of T.R.H., the prolactin response was positive in five cases and negative in one.’ Basal plasma-prolactin concentrations (ng/ml) were: 55.0, 475, 7.5, 70, 90, and 10-0. Thus in this small series of patients, no definite relationship could be established between prolactin secretion and 47, XYY constitution. maximum
Service de Sûreté, Centre Hospitalier Spécialisé, 33410 Cadilac-sur-Garonne, France
M. BENEZECH
Laboratoire de Cytogénétique, Centre de Transfusion Sanguine, 73011 Chambéry
B. NOËL
DEXTRAN OR HEPARIN?
of Mr Powley (July 29, p. 261) and Mr Davies (Sept. 30, p. 732) prompt me to respond to their criticism of low-dose heparin prophylaxis. I agree that to deny adult surgical patients some form of prophylaxis is irresponsible and that dextran 70 is much less widely used than subcutaneous heparin for prophylaxis. However, Davies’ statement that "the efficacy of 1 litre of dextran given intravenously after induction of anaesthesia was established in a large multicentre double-blind controlled clinical trial" is not accurate; the trial was not double-blind nor were its results statistically significant. A symposium sponsored by the International Committee on Thrombosis and Hasmostasis, held in Leuven on July 19, discussed the design of several clinical trials. The Cardiff trial was presented in detail by Davies. It became evident that the trial was not double-blind, since the anoesthetist could easily recognise the difference between the two solutions simply by inverting the bottle, and therefore easily choose to give or not to give dextran 70; this resulted in a substantial number of patients who did not receive a dextran infusion. This trial also failed to provide information regarding the comparability of the groups with respect to factors known to influence the occurrence of the thromboembolic complications. Prof. M. Vessey (Oxford) also pointed out that the difference in the frequency of fatal pulmonary embolism in the two groups (i.e., 7 patients in the saline group and 1 in the dextran group) is not statistically significant when a two-tail analysis is used. The details of these discussions will be published. During the past 4 years, thirty-one trials have assessed the value of low-dose heparin prophylaxis in patients undergoing a variety of surgical operations. This experience, based on several thousand patients, is different from the misleading information presented in Davies’ table outlining the advantages and disadvantages of dextran and heparin. These trials show
SIR,--The
comments
the full doses of heparin needed to treat patients with thromboembolic disease. (e) No evidence has ever been presented that thrombi formed in vivo in the presence of dextran are more easily lysed by the patient’s own fibrinolytic system. (f) Before the cost of these two methods of prevention can be compared, the efficacy of dextran prophylaxis in preventing deaths due to fatal pulmonary embolism must be demonstrated. It also remains to be determined whether a single dextran infusion or three or more infusions will be required to produce a protective effect. to receive
Powley claims that surgeons in busy peripheral hospitals are offering routine heparin prophylaxis. Data on heparin sales point to the contrary. In 1974, only three firms, compared with seven in 1978, were marketing heparin specifically prepared for prophylactic use. Furthermore, Department of Health data on heparin usage in England, Wales, and Northern Ireland for 1975/76, 1976/77, and 1977/78 indicate that heparin usage has increased by approximately 15% per year during this period. Certainly Powley’s solution is simple and does not require any nursing supervision. But, however attractive and appealing a device may be, it remains useless unless its efficacy, in preventing deaths due to fatal pulmonary embolism, has been not
demonstrated. I hope that these misleading letters will not hinder the wider adoption of low-dose heparin prophylaxis.
even
Thrombosis Research Unit,
King’s College Hospital Medical School, London SE5 8RX
V. V. KAKKAR
SIR,-Mr Davies (Sept. 30, p. 732) states "It is widely held that to deny adult surgical patients some form of prophylaxis is irresponsible". Although he does not specifically declare himself for this policy, his remarks will add support to the philosophy of such treatment. May I make a plea against this type of blanket principle in treatment, which, I think, will bring the use of prophylactic heparin or dextran into disrepute. Despite the improved diagnosis of both deep-vein thrombosis and pulmonary embolism, I think few surgeons would deny that fatal pulmonary embolism now is much less common on well-run units that it was a quarter of a century ago. This must surely be due to a much better control of infection by improved surgical technique and antibiotics and also to the disappearance of the old butcher type of surgeon who tore at tissues and left hasmatomas, often infected. Some of the trials for prophylactic heparin have been on very selective groups of patients such as the elderly who have undergone trauma, and it is not logical to translate experience in limited groups to all surgery. We should be seeking, not to encourage indiscriminate use of prophylactic anticoagulation, but to identify patients in whom it is less dangerous and to find those in whom it increases the postoperative morbity. I think we shall discover that infection and tissue damage, whether by the surgeon or trauma, are the most important factors in producing unwanted intravascular coagulation and its
sequelar. General
Hospital, Birmingham B4 6NH
GEORGE T. WATTS
that:
(a) Low-dose heparin does not require monitoring. (b) The frequency of bleeding in general surgical patients receiving low doses of subcutaneous heparin is 7.7 compared with the 5.6 in the control group and not as great as 27*? as suggested by Davies. (c) Anti-thrombm-III depletion has never been observed in patients on
low-dose
s.c.
heparin.
(d) The only contraindication to low-dose heparin prophylaxis is a history of haemorrhagic disorders or bleeding diathesis; the other contraindications listed in the table are applicable only to patients who are 1. Benezech, M., Croizet, M.,
Belabas, M., Mathieu, C., Mathieu, P., Noël, B., Ferret-Bouin, P. Ann. Endocr., 1978, 39, 89.
SIR,-In his letter comparing dextran with heparin, Mr Davies does not stress sufficiently the risk of severe anaphylactoid reaction to dextran. We have seen a fatal reaction to this agent. A healthy 41-year-old ex-nurse with a history of deepvenous thrombosis but no allergies was admitted for sterilisation. Before anaesthesia was induced a prophylactic infusion of dextran 70 was started. After approximately 50 ml had been given over 2 min the patient collapsed, became cyanosed and pulseless, and had a convulsion. The infusion was stopped and the seizure controlled with intravenous diazepam. Despite
