188 suffered no side-effects. Haemolysis has also been described with intermediate-purity 4,5 and high-purity concentrate,6 and appears to be due to the accumulation in vivo of the infused-blood-group allo-agglutinins. In all cases reported the haemolysis was moderate, and regressed spontaneously when treatment with A.H.F. was stopped. The risk of a high allo-agglutinin titre or the presence of hasmolysins in cryoprecipitate or concentrate could be avoided by screening the individual donations of plasma or, in the instance of concentrate, possibly by preparing it from pools of plasma selected in proportion to the normal distribution of the ABO groups or by neutralising alloagglutinins with A and B blood-group substances. This problem is being examined at the Blood Products Laboratory, where the factor-vm concentrate given to the above patient was prepared. Hæmophilia Centre, Royal Free Hospital, G. P. TAMAGNINI Pond Street, KATHARINE M. DORMANDY. London NW3 2QG.

probably a very effective prosthesis, but somewhat embarrassing if it should burst while walking through the pigeons in the churchyard! Regional Cancer Registry, Queen Elizabeth Medical Centre, Birmingham B15 2TH.

JUNE MARCHANT.

FACTOR-VIII CONCENTRATE IN HÆMOPHILIA

SIR,-Cecilia Cronin (June 7, p. 1303) draws attention to the possible need to consider the ABO blood-group of the patient when large quantities of factor vm either as cryoprecipitate or concentrate have to be given, because of the allo-agglutinins that these preparations may contain. The following case is of interest in this context: A 34-year-old man with severe haemophilia (factor vm less than 1%) underwent arthrodesis of the left shoulder under cover of intermediate-potency facior-viu concentrate. Haemostasis was satisfactory during surgery, and to maintain the level of factor vm above 30% he required eight-hourly infusions of 1000 units of A.H.F. for twelve days. The wound healed rapidly and the stitches were removed on the fourteenth day under cover of cryoprecipitate. While he was receiving A.H.F. hmmoglobin dropped steadily from

Blood Products Laboratory, Lister Institute of Preventive

Medicine, Elstree, Hertfordshire.

concentrate, the patient’s 12-5 to 7-6 g. per dl., the

D. ELLIS W. D’A. MAYCOCK.

PROTHROMBIN-COMPLEX CONCENTRATES IN LIVER DISEASE SIR,-Reports from the United States have warned us of the hazards of thromboembolism associated with commercial prothrombin-complex concentrates.7,8 Although such complications have not been reported with the products used in Europe, one is happy to accept the encouraging conclusions of Dr Green and his colleagues (June 14, p. 1311) that factor-vn-rich concentrates can be safely used in high-risk patients with liver failure. We should like to report our experience with other preparations, providing additional laboratory evidence that their use is not accompanied by signs of activation of the coagulation system.

’Prothromplex’ (Immuno AG, Vienna), a freeze-dried containing 25 units per ml. of factors n, ix, and x, has been used by us since 1973 in patients with liver disease who needed biopsy, laparoscopy, or portacaval shunts and had prolonged prothrombin-time (r.T.) (patientplasma/normal-plasma ratio > 1.3) and/or prolonged partial thromboplastin-time (P.T.T.) (ratio > 1 ’2). Although there was no instance of abnormal bleeding, complete correction of coagulation tests was usually not achieved at a dosage of 25 units per kg. Therefore, a factor-vn concentrate recently made available by the same manufacturers has been given (25 units per ml.) to patients in whom administration of prothromplex was not followed by complete correction of the abnormal coagulation screening-tests. The results obtained in four patients with chronic liver disease submitted to biopsy or laparoscopy are shown in the accompanying table. The abnormality of P.T., P.T.T., and ’Normotest ’ (N.T.) usually persisted after the infusion of prothromplex. The subsequent administration of factorvn concentrate achieved a complete correction of P.T. and concentrate

Laboratory findings during treatment with A.H.F. concentrate rose to 16%, and the peripheral blood film showed increasing rouleaux formation, spherocytosis, and polychromasia (see accompanying figure). The osmotic fragility was greatly increased and the total bilirubin rose to 1-8 mg. per 100 ml. with a conjugated bilirubin of 0-3 mg. per 100 ml. The direct

reticulocyte-count

antiglobulin

test

(D.A.T.)

was

positive owing

to

complement

on

the surface of the red cells. The patient’s blood-group was A rhesus-positive, the titre of anti-B agglutinins was 32; no anti-A and no hsemolysins were detected. The titres of saline allo-agglutinins anti-A and anti-B in several batches of dissolved A.H.F. concentrate used in this patient were 32 and 16 respectively. No IgG antibodies were. detected. His haemoglobin rose spontaneously after infusions of A.H.F. concentrate were stopped. .

During the early trials of treatment with Cohn fraction I degree of hsemolysis was a constant feature in patients of blood-groups A and B,1-3 while patients of blood-group 0 a

McMillan, C. W., Diamond, L. K., Surgenor, D. M. New Engl. J. Med. 1961, 265, 224. 2. Newcombe, T. F., Walston, M. E. J. Am. med. Ass. 1963, 185, 628. 3. Maider, M. J., Shulman, N. R. Am. J. Med. 1966, 41, 56. 1.

After the infusion of each concentrate, there was no of platelet-count, plasma-fibrinogen, factors v and VIII, and serum F.D.P. P.T.T., however,

N.T.

significant change 4.

5. 6. 7. 8.

Schorr, J. H., Ballard, M. S., Radel, E., Yu, M. Transfusion, 1966, 6, 522. Johnson, A. H., Karpatkin, M. H., Newman, J. Br. J. Hœmat. 1971, 21, 21. Rosati, L. A., Barnes, B., Oberman, H. A. Transfusion, 1970, 10, 139. Kasper, C. K. New Engl. J. Med. 1973, 289, 160. Blatt, P. M., Lundblad, R. L., Kingdon, H. S., MacLean, G., Roberts, H. R. Ann. intern. Med. 1974, 81, 766.