1474

proportion of children with serious social as well as visual problems,in whom one might expect a lesser effect of genetic counselling. Inparticular, as Phillips and colleagues show in one of their examples,the marriage of individuals with hereditary blindness would not beexpected in itself to increase the population frequency of thesedisorders, but rather to redistribute cases from the sighted to theblind population. A comparable situation was pointed out fordiabetics many years ago by Prof. J. H. Edwards.

Finally, it seems both unfortunate and irrelevant to juxtapose theproblem of world population with that of hereditary blindness.Quite apart from the fact that populations are close to static andbirth rates falling in most developed countries where geneticcounselling is widely available, it seems entirely wrong to associatefamilies with responsibility for this more general issue, and to imbuethem with some special "procreative instinct" that is in any waydifferent from normal.We would suggest that more effective prevention of hereditary

blindness will depend on attempting not only to change attitudes ofaffected individuals but also to increase the general awareness of andinvolvement by ophthalmologists in genetic counselling, on

developing a more general network of specialist clinics of the typerun by Phillips and by ourselves, and on the development ofeffective tests of prevention, both prenatal and in the detection ofcarriers.

Section of Medical Genetics,Department of Medicine,Welsh National School of Medicine,Cardiff CF4 4KN

Paediatric Department,Royal Devon and Exeter Hospital

PETER S. HARPER

MARY VOWLES

PREOPERATIVE PREDICTION OF POSTOPERATIVEDEEP-VEIN THROMBOSIS

SrR,-Dr Shah and colleagues (May 1, p. 10 15) raise several pointsabout our paper (Feb. 20, p. 409), our findings apparently differingfrom their unpublished results. They question our use of visualinspection to choose a cut-off point (175) identifying 90% of patientsin deep-vein thrombosis (DVT). It is certainly possible to calculatethis cut-off point: for example, if a normal distribution is assumed,the cut-off point in study 1 is 173. The 95% confidence intervalsinclude our cut-off point of 170 in study 2, and account for any "lackof reproducibility" between study 1 and study 2. We gave 95%confidence intervals for our combined data in our paper.Shah et al. report a lower frequency ofDVT in the patients (10/56,

18%) compared with ours (39/104, 37.5%. Both frequencies fallwithin the wide range reported (10-42%).’ This variation probablyreflects different characteristics of patient groups: we stated that thehigh frequency of DVT in our group probably reflected our selectionof patients undergoing major procedures (laparotomy under generalanaesthesia lasting at least 45 min). Shah et al. report age and

overweight to be poor discriminants of DVT, in contrast to ourfindings. However, we find it difficult to see how any firmconclusions can be reached from their study, in which only 10patients had DVT. Several other studies have shown that age andobesity are risk associations not only for DVT2-4 but also

pulmonary embolism. 5Shah et al. suggest that we should have used routine venography

to diagnose DVT in our study of selective prophylaxis withheparin, rather than 125I-fibrinogen scanning. We are aware of theirstudy which suggests that scanning becomes less sensitive with timeafter operation. Nevertheless, the scanning technique we used

1. Kakkar VV Prevention of venous thrombembolism. Clin Haematol 1981, 10: 543-82.2. Clayton JK, An derson JA, McNicol GP Preoperative prediction of postoperative deep

vein thrombosis Br Med J 1976; ii: 910-12.

3 Kakkar VV, Howe CT, Nicolaides AN, Renney JTG, Clarke MB Deep veinthrombosis of the leg—is there a "high risk" group. Am J Surg 1970, 120: 527-30

4. Nicolaides AN, Irving D. Clinical factors and the risk of deep venous thrombosis In:Nicolaides AN ed. Thromboembolism Aetiology, advances in prevention and

management Lancaster M.T.P Press, 1975 193-2045 Hume M, Sevitt S, Thomas DP Venous thrombosis and pulmonary embolism

Oxford University Press, 1970 56-61

detects most postoperative thrombi found at necropsy. Ó

Furthermore a study of heparin prevention of DVT, whichcombined routine bilateral ascending venography 6 days after

surgery with 125I-fibrinogen scanning, found similar frequencies ofDVT in heparin and control groups with the two diagnosticmethods (venography, 13% vs 27%; scanning, 12% vs 27%).7 Webelieve it as valid to use scanning as venography when studyingheparin prophylaxis of DVT in the 6 days after general surgery.From the patient’s viewpoint, scanning is preferable for screening,since venography is invasive, painful, and may induce DVT.Shah et al. cited two studies in which heparin delayed the onset of

DVT. These studies were on patients undergoing hip surgery, inwhom scanning was continued for several days after heparin hadbeen stopped. Do general surgical patients, protected from DVT bylow-dose heparin while in hospital, acquire DVT after they go homeand their heparin is stopped? We do not know, because of thepractical difficulties of studying this (scanning at home, or

readmission for venography). The rationale for using low-doseheparin to reduce the incidence of DVT after general surgery restson two trials which claimed to show reduction in "fatal pulmonaryembolism".8,9 This endpoint is subjective and neither study wasdouble-blind. One study included a control group but gives noinformation on duration offollow-up.8 The other study followed uppatients for 30 days but had no control group.9 To resolve thequestion, we believe that a study of low-dose heparin and totalmortality is required. 10 Sevitt and Gallagher’ 1 were able to showthat anticoagulants significantly reduced total mortality by studyinga group at high risk of DVT and pulmonary embolism-the old andinjured. We suggest that our index, which identifies another highrisk group-the old and fat-could be used to select general surgicalpatients for studies of DVT prophylaxis and total mortality.University Departments of Medicineand Surgery,

Glasgow Royal Infirmary,Glasgow G4 0SFand Department of Statistics,

University of Glasgow

G. D. O. LOWED. C. CARTERC. R. M. PRENTICE

PROTAMINE VERSUS ANGIOGENESIS

SIR,-Your June 5 editorial reflects some of the paradoxes ofmodern medical communication. While you have been able tocomment on this "new" concept within ten days of its publication inNature you do not refer to the equally interesting and extensivework of O’Meara and his co-workers, given good coverage in TheLancet less than twenty years ago. 1 Folkman and Taylor’s work welldeserves comment, but it would be a pity if the concept were tobecome associated solely with their names at the expense of thepioneering work of O’Meara.His "cancer coagulative factor" andits antagonism with protamine is basically the same concept as thatnow being investigated so elegantly.

Finally, to avoid the indignity of being hoist with my own petard,I should say that, while I believe Professor O’Meara’s work to beoriginal, I have no absolute proof that he did not himself draw onsome earlier, forgotten work.

University Department of Surgery,Welsh National School of Medicine,Cardiff CF4 4XN L. E. HUGHES

6 Morris GK, Mitchell JRA Evaluataion of 125 I-fibrigogen test for venous thrombosisin patients with hip fractures, comparison between isotope scanning and necropsyfindings Br Med J 1977, i: 264-66

7 Immelman EJ, Jeffery P, Benatar SR, et al Failure of low-dose heparin to preventsignificant thromboembolic complications in high-risk surgical patients interim

report of prospective trial. Br Med J 1979, i: 1447-508. International Multicentre Trial Prevention of fatal postoperative pulmonary

embolism by low doses of heparin Lancet 1975, ii: 45-519. Gruber UF, Saldeen T, Brokop T, et al Incidences of fatal postoperative pulmonary

embolism after prophylaxis with dextran 70 and low-dose heparin-an internationalmulticentre study. Br Med J 1980, 280: 69-72

10. Prentice C, Lowe G, Forbes CD. Preventing postoperative thromboembolism Br MedJ 1979, ii: 128

11 Sevitt S, Gallagher NG Prevention of venous thrombosis and pulmonary embolism ininjured patients Lancet 1959, ii: 981-89

1 O’Meara RAQ, O’Halloran MJ Protamine derivatives in the treatment of advancedcancer of the breast Lancet 1963, ii: 613-14