DIABETIC RETINOPATHY: A SELF-SUSTAINING PROCESS

939

used rTPA as a second-dose thrombolytic agent in 14 patients, 5 of whom had recent exposure to streptokinase, 7 to APSAC, and 2 to rTPA. There were no allergic reactions. Thus one of the main

advantages of rTPA over APSAC is its freedom from allergic potential, making second-dose thrombolytic therapy feasible and

preventing the loss of myocardium which follows reocclusion. Regional Medical Cardiology Centre, Royal Victoria Hospital, Belfast BT12 6BA

A. J. MCNEILL A. A. J. ADGEY

HD, Noms RM, Brown MA, et al. Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction. N Engl J Med 1987; 317: 850-55. 2. Been M, De Bono DP, Muir AL, Boulton FE, Hillis WS, Homung R. Coronary thrombolysis with intravenous anisoylated plasminogen-streptokinase complex BRL 26921. Br Heart J 1985; 53: 253-59. 3. GISSI Study Group. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; i: 397-401. 1 White

PROPHYLACTIC LOW-DOSE ASPIRIN AND DIPYRIDAMOLE IN PREGNANCY

SIR,—The letter by Professor Elder and his colleagues (Feb 20, 410) suggests a beneficial effect of prophylactic low-dose aspirin in pregnant patients at risk of intrauterine growth retardation (IUGR) and fetal loss due to inadequate uteroplacental blood flow. In 1987 we reported comparable results in a controlled study of low-dose aspirin combined with dipyridamole.! Including the 24 patients described previously we have now treated 37 women with plain aspirin 1 mg/kg (usually 60-80 mg) and 75 mg dipyridamole three times daily from 16 to 34 weeks’ gestation. Compliance was assessed by measurement of thrombininduced production of malondialdehyde by platelets.! All women had had at least two pregnancies beyond 20 weeks’ duration complicated by severe IUGR and placental infarction, without any other complication of pregnancy or significant associated disease (table). Only 15 (18%) of the 83 pregnancies that had gone beyond 20 weeks had resulted in live births. In contrast to Elder’s patients, none of our women had had pre-eclampsia or established systemic lupus erythematosus (SLE), although lupus anticoagulant with elevated anti-cardiolipin antibody titres was demonstrated in 2 of them. 4 women had borderline essential hypertension and were prescribed methyldopa, but no other treatment was given except oral iron supplements, and diets were unrestricted. The 37 patients have now completed 44 pregnancies on aspirin-dipyridamole prophylaxis. 39 (93%) of 42 pregnancies proceeding beyond 20 weeks have resulted in live births at a median duration of pregnancy of 37 (range 27-40) weeks (table). Low birthweight (below 10th centile) occurred in 12%, a much lower frequency than expected.12 There was one obvious failure, in a healthy gravida 3, para 2, who had repeated IUGR and fetal death in the second trimester; she was delivered at 25 weeks’ gestation of a 170 g fetus (below 2.3rd centile) with an extensively infarcted placenta. The two other fetal deaths were due to abruptio placentae (27 weeks’, 950 g) and to premature rupture of membranes and intrauterine infection (33 weeks, 2150 g). p

No maternal

observed,

nor

or

neonatal

haemorrhage complications

were

any other adverse effects attributable to low-dose

aspirin/dipyridamole. Unlike Elder and colleagues’ patients, of whom 38 % had SLE an unspecified number had renal disease, our patients had no significant underlying disease. The good results obtained in both groups suggest that prophylactic antiplatelet therapy corrects the postulated uteroplacental vascular prostacyclin-platelet thromboxane imbalance3 irrespective of its underlying cause. This effect may be due mainly to low-dose aspirin; the contribution of dipyridamole remains disputed.4 The two studies show sufficient promise to justify a large, controlled clinical trial; and the application of low-dose aspirin, with or without dipyridamole, in general obstetric practice should await the results of such a trial. and

Institute of Obstetrics and Gynaecology, Erasmus University Medical School, PO Box 1738, Rotterdam, Netherlands

H. C. S. WALLENBURG N. ROTMANS

Rotmans N. Prevention of recurrent idiopathic fetal growth retardation by low-dose aspirin and dipyridamole. Am J Obstet Gynecol 1987; 157: 1230-35. 2. Bakketeig LS, Hoffman HJ, Harley EE. The tendency to repeat gestational age and birthweight in successive births. Am JObstet Gynecol 1979; 135: 1086-1103. 3 Ylikorkala O, Makila U-M. Prostacyclin and thromboxane in gynecology and obstretrics. Am J Obstet Gynecol 1985; 152: 318-29. 4. FitzGerald GA Dipyridamole. N Engl J Med 1987; 316: 1247-57. 1

Wallenburg HCS,

DIABETIC RETINOPATHY: A SELF-SUSTAINING PROCESS

SIR,—Dr Petty and colleagues (Jan 30, p 208) describe stimulation of endothelial cell growth by sera from diabetic patients with retinopathy and suggest that diabetic metabolic disturbances are not central to the development of this disease. Their proposal is supported by the fact that successful pancreas transplantation with subsequent normoglycaemia neither reverses nor prevents the progression of diabetic retinopathy.l Evidently diabetic retinopathy becomes self-sustaining. The most plausible explanation is that its complex pathological changes are able to maintain production of vascular endothelial-cell proliferation factor even after pancreas transplantation. I particularly include those phenomena that lead to ischaemia, a stimulator2,3—such as powerful angiogenesis capillary

microangiopathy, venous anomalies, haemorrhages, microinfarcts, exudates, and vascular occlusive disease.’ Diabetic retinopathy is further characterised by fibrin deposition,sa powerful inducer of angiogenesis,6and fibrosis.7 The endothelial-cell proliferation factor described by Petty and colleagues is specific for vascular endothelial cells. That this factor may lead to formation of fibrotic tissue is further evidence in favour of the angiogenic hypothesis, according to which vascular endothelial cells give rise to fibroblastic cells during wound healing and fibrosis.8 Blood Diseases

Service,

Hôpital Paul-Brousse, 94800 Villejuif, France

JIRI T. BERANEK

OBSTETRIC HISTORY AND OUTCOME IN PREGNANCIES TREATED WITH LOW-DOSE ASPIRIN AND DIPYRIDAMOLE IN

37 WOMEN

RC, Goetz FC, Sutherland DER, et al. Progression of diabetic retinopathy after pancreas transplantation for insulin-dependent diabetes mellitus. N Engl J Med 1988; 318: 208-14. 2. Kumar S, West D, Shahabuddin S, et al. Angiogenesis factor from human myocardial infarcts. Lancet 1983; ii: 364-68. 3. Knighton DR, Silver IA, Hunt TK. Regulation of wound-healing angiogenesis: Effect of oxygen gradients and inspired oxygen concentration. Surgery 1981; 90: 262-70. 4 Naumann GOH, Apple DJ. Pathology of the eye. New York: Springer-Verlag, 1986. 5. Bannerjee RN, Sahni AL, Kumar V. Fibrinocoagulopathy in maturity onset diabetes mellitus and atherosclerosis. Thromb Diath Haemorrh 1973; 30: 123-32. 6. Dvorak HF, Harvey VS, Estrella P, Brown LF, McDonagh J, Dvorak AM. Fibrin containing gels induce angiogenesis. Lab Invest 1987; 57: 673-86. 7. Dvorak HF, Form DM, Manseau EJ, Smith BD. Pathogenesis of desmoplasia I: Immunofluorescence identification and localization of some structural proteins of line 1 and line 10 guinea pig tumors and of healing wounds. JNCI 1984; 73; 1195-211. 8. Beranek JT, Masseyeff R, Desmet VJ. Commentary Hyperplastic capillaries and their possible involvement in the pathogenesis of fibrosis. Histopaihology 1986; 10: 1. Ramsay

543-51.