Shed mediastinal blood transfusion in open heart surgery

1078

Urine collection from disposable considered a reliable screening test. Royal Oldham Hospital, Oldham OL1 2JH, UK

nappies

could

at

best be

I. BLUMENTHAL

CM, Oguro JE, Fine BP, Martinez AB. The prevalence of bacteriuria in full-term and premature newbom infants. J Pediat 1973, 82: 125-32.

1. Edelmann

Postoperative delirium and plasma tryptophan

u. Mean

Urinary Albumin Concentrøtlon (nig/1)

Bland-Altman plot of

urinary albumin.

filterpaper versus whole urine gave a bias (mean difference) of - 0-33 ± 2 SD) of + 2-7 to

mg/l with limits of agreement (mean difference 3-3mg/I.

SIR,-Dr van der Mast and her colleagues (Oct 5, p 851) report a correlation between decreased tryptophan concentrations in plasma and the development of post-cardiotomy delirium. We can suggest an explanation. Blood transfusions during or after surgery lead to a significant increase in neopterin.1 Neopterin is formed upon stimulation with interferon-y and is a marker for activated cellular irnmunity.2 In parallel with the formation of neopterin, tryptophan is degraded by indoleamine-2,3-dioxygenase induced by interferon-y.3,4Furthermore, immunostimulation by interleukin-2 also leads to increased neopterin formation and tryptophan degradation in vivo.5 We propose that immunostimulation, caused, for example, by blood transfusion, during the operation leads to reduced plasma tryptophan levels via the induction of indoleamine-2,3-dioxygenase

by interferon-y.

-

Unit for Metabolic Medicine,

Guy’s Hospital, UMDS, London SE1 9RT, UK

VITAS DARGIS ROBERT CHEN DAVID BROWN GIANCARLO VIBERTI HARRY KEEN JAMES WALKER

1. Viberti GC, Jarrett RJ, Mahmud U, Hill RD, Argyropoulos A, Keen H. Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1982; i 1430-32. 2. Close CF. Sex, diabetes duration and microalbuminuna m type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1987; 30: 508A. 3. Feldt-Rasmussen B, Mathiesen ER, Deckert T. Effect of two years strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetics. Lancet 1986; ii: 1300-04. 4. Cohen DL, Close CF, Viberti GC. The variability of overnight albumin excretion in insulin-dependent diabetic and normal subjects. Diabetic Med 1987; 4: 437-40. 5. Nathan DM, Rosenbaum G, Protasowicki VD. Single void samples can be used to estimate quantitative microalbuminuria. Diabetes Care 1987; 10: 414-18. 6. Pathology specimens through the post. J Med Defence Union 1988; 4: 26. 7. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; i: 307-10.

SjR,—Urine microscopy in general practice has the advantage that specimens can be looked at in the fresh state. Despite their limitations white cell counts are a useful screen for urinary infection.The compact, disc-shaped ’Lensman’ microscope, based on folded optics, may be ideal for this task since it is easier to use, is truly portable, and fits easily into a medical bag.2 Its two magnifications (80 x and 200 x ) preclude its use for the detection of bacteria. 84 Kidbrooke Grove, London SE3 0LG, UK

NIGEL MASTERS

RK, Ditchbum JS. A study of microscopical and chemical tests for the rapid diagnosis of urinary tract infections. Br J Gen Pract 1990; 40: 406-08. 2. Dunning K, Masters NJ. The Lensman microscope. In: Royal College of General 1. Ditchbum

Practitioners reference book. London RCGP, 1991: 559-60.

SIR,-Dr Ahmad and colleagues show that urine collection from disposable nappies is more convenient and cheaper than adhesive bags. They are, however, incorrect in implying that urine infections can be correctly identified. The criterion of more than 105 colony-forming units/ml was derived by Kass from midstream urine specimens of adult women. Such a definition is inappropriate in the context of the collection methods used by Ahmad and colleagues.! To confirm the diagnosis made on a bag or nappy specimen a suprapubic or catheter sample would still be required.

Institute for Medical Chemistry and Biochemistry, University of Innsbruck, A-6020 Innsbruck, Austria

GÜNTER WEISS ERNST R. WERNER GABRIELE WERNER-FELMAYER HELMUT WACHTER

1 Wachter H, Fuchs D, Hausen A, et al. Are conditions linked with T-cell stimulation necessary for progressive HTLV-III infection? Lancet 1986; i: 97. 2. Wachter H, Fuchs D, Hausen A, et al. Neopterin as a marker for activation of cellular immunity: Immunologic basis and clinical application. Adv Clin Chem 1989; 27: 81-141. 3. Werner ER, Werner-Felmayer G, Fuchs D, et al. Parallel induction of tetrahydrobiopterin biosynthesis and indoleamine 2,3-dioxygenase activity in human cells and cell lines by interferon-gamma Biochem J 1989; 262: 861-66. 4 Werner-Felmayer G, Werner ER, Fuchs D, et al. Characteristics of interferon induced tryptophan metabolism in human cells in vitro. Biochim Biophys Acta 1989, 1012: 140-47. 5. Brown RR, Lee CM, Kohler PC, et al. Altered tryptophan and neopterin metabolism in cancer patients treated with recombinant interleukin 2. Cancer Res 1989; 49: 4941-44.

Shed mediastinal blood transfusion in open heart surgery SiR,—In your Aug 17 editorial you question the efficacy of shed mediastinal blood (SMB) transfusion after open heart surgery. We disagree with many of your opinions. You begin by saying "successful cardiac surgery depends heavily on the use of blood and blood products". In fact, a recent study by Goodnough and colleagues1 demonstrated that blood use in cardiac surgery (both red cells and components) varies greatly between centres and is not related to operative result. Even in complex surgery, blood use can be kept to a minimum when conservation methods are used.2 You correctly point out that reinfusion of large volumes of SMB can be associated with mild coagulopathy. However, in most cases transfusion volumes are small (less than 1000 ml). Neither we nor other advocates of SMB transfusion believe that it is a substitute for proper surgical haemostasis or re-exploration of the bleeding patient. When massive bleeding occurs because of coagulopathy, we believe that SMB transfusion reduces red cell requirements, although component therapy may also be indicated. Studies at both Johns Hopkins and the Cleveland Clinic did not reveal any alteration of clotting or increased use of blood components when SMB was given.3.4 The concerns you raise about the possibility of infection are unsubstantiated, and in no study has transfusion of this blood been associated with an increased risk of surgical infection. The time limit for re-infusion was arbitrarily established to conform with recommendations for other types of blood salvage.

1079

With respect to efficacy, three of the four studies you cite support the transfusion of SMB. We have reviewed 477 consecutive adults having both coronary and valve surgery. Of these, 277 (58%) were transfused with SMB. Since we transfuse this blood only when patients shed more than 250 ml over 4 h, these patients had higher blood loss (1400 ml before chest tube removal) than the 200 patients who were not given SMB (900 ml). Despite their increased blood loss, the 277 patients who received SMB needed less postoperative transfusion (mean= 0-9 unit red cells) than did the other patients (mean= 1-6 units red cells). The average transfusion volume of SMB was 500 ml. You present the dilemma that patients who bleed small amounts do not need their SMB and in those with high blood loss SMB return may be unsafe. Even if one accepts these two groups, there is a third-those in whom the amount of blood loss allows the effective and safe return of SMB. It is this group that has been investigated in the clinical studes of SMB use, and clinical practice should be based on these data rather than on your unsubstantiated, theoretical concerns. We would welcome data supporting these reservations, but in their absence, we believe that SMB transfusion continues to have an important part, by reducing the transfusion of homologous blood, in a comprehensive blood conservation programme for patients having cardiac surgery. Division of Cardiothoracic Surgery, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA

ROBERT L. THURER MARK A. POPOVSKY ROBERT G. JOHNSON

Goodnough LT, Johnston MF, Toy PT. The variability of transfusion practice in coronary artery bypass surgery, Transfusion Medicine Academic Award Group. JAMA 1991; 265: 86-90. 2. Salzman EW, Weinstein MJ, Weintraub RM, et al. Treatment with desmopressin acetate to reduce blood loss after cardiac surgery a double-blind randomized trial. 1.

N Engl J Med 1986; 314: 1402-06. 3. Schaff HV, Hauer JM, Bell WR, et al. Retransfusion of shed mediastinal blood following cardiac surgery: a prospective study. J Thorac Cardiovasc Surg 1978; 75: 632-41. 4. Thurer RL, Lytle BW, Cosgrove DM, Loop FD. Autotransfusion following cardiac surgery: a randomized, prospective study. Ann Thorac Surg 1979; 27: 500-07. 5. Johnson RG. Postoperative salvage: autologous blood transfusion, current issues. Arlington: American Association of Blood Banks, 1988: 57-65.

changes that constitute the hypercoagulable state

Haemostatic

SIR,-In the Northwick Park Heart Study (NPHS), a high factor VII coagulant activity (VII) is associated with an increased risk of coronary heart disease (CHD). The possibility that a high VII indicates a hypercoagulable state now receives support from the demonstration of a positive association between VIIc and the plasma concentration of Fl+2 activation peptide (Fl +2), which is released when prothrombin is converted to thrombin by factor Xa. When plasma VII and F I + 23 were measured five times in 63 men with CHD and each patient’s results were averaged, the correlation was 0.26 (95% CI 0-01-0-47; p 0-04). In the second study (NPHS II) the correlation between single determinations of each variable in 955 healthy middle-aged men aged 50-60 was 0-11 (95% CI 005-017; p=00009). The demonstration of these correlations is encouraging, bearing in mind the "damping" effect of the anticoagulant system (antithrombin III and protein C) on the intermediate steps linking factor VII activity with thrombin =

production. The application of activation peptide assays to the investigation of coagulation factor deficiency states has provided a tentative explanation for the association between VII and FI +2’ Measurements immediately before and after correction of these deficiencies with purified or recombinant proteins revealed that the factor VII/tissue factor (TF) pathway is mainly responsible for basal in-vivo activation of factor IX, factor X, and prothrombin, with negligible direct contribution from the contact system (factor XII and factor XI)4,5 (and Bauer et al, unpublished). The strength of the procoagulant drive could be set in part by the activity state of the factor VII molecule and the number of exposed TF sites. Factor VII is cleaved by several haemostatic enzymes to its potent derivative, factor VIIa.6,7Both factor VII and factor VIla bind with

similar avidity to endogenous TF sites so that the extent of the procoagulant drive (and hence FJ +2 concentration) should be partly dependent upon the relative levels of factor VII and factor VIla in vivo. This ratio is also a determinant of plasma VII measured by the in-vitro bioassay. The significant correlation between plasma VIIc and FJ +2 concentration supports the notion that the extent of factor VIIactivation is involved in establishing the basal functional state of the coagulation mechanism. Studies of congenital coagulation factor deficiencies have also indicated that high levels of factor IXa generated by basal VII-TF activity are unable to convert factor X to Xa’ 4,5 We suspect, however, that when thrombotic stimuli accelerate factor VII-TF function the natural anticoagulant mechanisms are gradually overwhelmed. The resultant increased generation of factor Xa (by direct action of factor VII-TF on factor X) and thrombin leads to the formation of factor VIlla and an activated platelet surface with assembly of the factor VIlla-factor IXa-factor X complex. This chain of events releases the potential of circulating factor IXa for factor Xa generation, thereby boosting the conversion of prothrombin to thrombin and fibrinogen to fibrin. It appears possible that individuals with high levels of extrinsic pathway function are relatively close to a point at which the potential of their dormant but powerfully procoagulant intrinsic cascade is released by fissuring of a coronary artery plaque. This hypothesis could explain the association between a high VII and increased risk of CHD, and is currently being tested in NPHS II. MRC Epidemiology and Medical Care Unit, Northwick Park Hospital, Harrow HA1 3UJ, UK

G. J. MILLER H. C. WILKES T. W. MEADE

Charles A Dana Research Institute and Harvard-Thorndike Laboratory, Department of Medicine, Beth Israel Hospital, Boston, Massachusetts, USA

K. A. BAUER S. BARZEGAR R. D. ROSENBERG

1. Meade TW, Mellows S, Brozovic M, et al. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; i: 533-37. 2. Brozovic M, Stirling Y, Hamcks C, North WRS, Meade TW. Factor VII in an industrial population. Br J Haematol 1974; 28: 381-91. 3. Tietel JM, Bauer KA, Lau HK, Rosenberg RD. Studies on the prothrombin activation pathway utilizing radioimmunoassays for the fragment and thrombin-antithrombin complex. Blood 1982; 59: 1086-97. 4. Bauer KA, Kass BL, ten Cate H, Hawiger JJ, Rosenberg RD. Factor IX is activated in vivo by the tissue factor mechanism. Blood 1990; 76: 731-36. 5. Bauer KA, Kass BL, ten Cate H, Bednarek MA, Hawiger JJ, Rosenberg RD. Detection of factor X activation in humans. Blood 1989; 74: 2007-15. 6. Radcliffe R, Nemerson Y. Activation and control of factor VII by activated factor X and thrombin. J Biol Chem 1975; 250: 388-95. 7. Kisiel W, Fujikawa K, Davie EW. Activation of bovine factor VII (proconvertin) by factor XIIa (activated Hageman factor). Biochem 1977; 16: 4189-94.

F2/F1+2

Chromosome 11

uniparental isodisomy predisposing to embryonal neoplasms

SiR,—Wilms’ tumours are thought to arise from two events that result in the inactivation of both alleles of a tumour-suppressor locus on chromosome 1 lp. Although the first allelic inactivation might be constitutional (germline genotype) or somatic (postzygotic), the second event would always be somatic and thus specific to the tumour cell. The sequence of germ-line mutation followed by tumour-specific loss of the normal allele occurs with WT1, the tumour-predisposing gene at llpl3. The demonstration of tumour-specific loss of sequences confined to 1lpl5 in both adrenal carcinoma and Wilms’ tumour suggests that the two-event hypothesis also applies to a second locus at l 1p15.3.4Although the inactivation of one of these two 1 lp loci is probably necessary in the genesis of at least some Wilms’ tumours, it is not known whether inactivation of either of these loci is sufficient to cause

tumorigenesis. We describe molecular genetic analysis in a child previously for hemihypertrophy and congenital adrenal carcinoma and in whom Wilms’ tumour subsequently developed.s He had no family history of congenital anomalies or embryonal tumours, no other phenotypic abnormalities, and his constitutional GC-banded

reported