- Email: [email protected]
CONCENTRATES OF CLOTTING-FACTOR IX
41
rough indication of the serum-albumin the test should a seriously injured or collapsed patient requires immediate and rapid resuscitation or where a patient facing extensive surgery and loss of blood has not had recent serum-protein measurements. If such a patient is tested and placed in groups 1 or 2, Hartmann’s or similar fluid may be given in equal volume with blood or plasma substitute with little risk of producing oedema if the c.v.p. is kept within safe limits. If the patient is placed in group 3, transfusions should be of colloid solutions only and controlled by careful monitoring of the c.v.p. As
a
be useful where
Department of Anæsthesia, North Tees General Hospital,
Hardwick, Stockton-on-Tees, Cleveland TS19 8PE
E. N. S. FRY
CONCENTRATES OF CLOTTING-FACTOR IX SIR,-Your leader (Nov. 1, p. 855) reviewing the clinical use of prothrombin-complex concentrates emphasised their potential use in the management of haemophiliacs with inhibitors to factor VIII.I-3 We have treated five severe haemophiliacs (factor vm 1%) who had factor-vm inhibitor with ’Fraction R’ (Immuno AG, Vienna), a new preparation of activated factors of the prothrombin complex (see accompanying table). The administration of fraction R was followed by clinical improvement in patients 1, 3, and 5. Failure in patient no. 2 was not surprising, since response to treatment of haematuria is known to be capricious even in haemophiliacs without inhibitor ; bleeding is likely to have subsided spontaneously in patient 4. There was a marked anamnestic rise of the inhibitor level in four patients, and its magnitude appeared similar to that observed in the same patients treated on previous occasions with factor-viii concentrates.4
Prothrombin-complex concentrates, therefore, are not less antigenic than factor-vni concentrates, and should not be used in the management of non-dangerous bleeding episodes to avoid an unnecessary rise of the inhibitor. They may be an additional weapon in life-endangering situations. However, a large infusion of high-potency factor-viii concentrates still appears the safest and most effective form of treatment in patients with lower inhibitor levels; this procedure must be
1. Kurczynski, E. M., Penner, J. A. New Engl. J. Med. 1974, 291, 164. 2. Sultan, Y., Bronet, J. C., Dehe, P. ibid. p. 1087. 3. Abilgaard, L. F., Britton, M., Roberts, R. Blood, 1974, 44, 933. 4. Ruggeri, Z. M., Mannucci, P. M., Allain, J. P., Frommel, D. Ann. N.Y. Acad. Sci. 1975, 240, 412.
accompanied by exchange transfusion or plasmapheresis 6 a cell separator in patients with high inhibitor levels.’
with
3rd Institute of Clinical Medicine.
hemophilia and Thrombosis Centre, Angelo Bianchi Bonomi, Via Pace 15, 20122 Milan,
Italy.
P. M. MANNUCCI R. BADER Z. M. RUGGERI
ECTOPIC PREGNANCY, HYDATIDIFORM MOLE AND CLOMIPHENE
SIR,-Weiss and Aboulafial seem to imply that clomiphene citrate may "cause" ectopic pregnancy and hydatidiform mole. The demonstration of an association is not the demonstration of a cause, and in this example it seems highly likely that clomiphene citrate is not an setiological factor in either condition. It is quite pointless citing the incidence of ectopic pregnancy in the general population and comparing this with reported incidences of patients taking clomiphene. The local incidence of ectopic pregnancy varies widely. In some parts of the world it is as high as 1 in every 28 live births. This should be considered when comparing different series. But much more important is the incidence of ectopic pregnancy in patients who have been investigated for infertility. We now realise that infertility is a multifactorial problem. It is not possible to divide patients into those with tubal problems only or those with ovulatory problems. The crude investigations we use at the moment may pick up gross abnormalities of tubal or ovarian function but almost certainly miss important minor disorders. There remains, for instance, a remarkable disparity between apparently regular ovulation and pregnancy, in the absence of any other demonstrated abnormality. There is an increased incidence of ectopic pregnancy in patients investigated for infertility, in some series as high as 1 in 42 cases investigated.2 Some of these patients will have tubal factors demonstrated but most will not. If anything the clomiphene group of patients seem to have a comparatively low incidence of ectopic gestation. The incidence of hydatidiform mole may be marginally increased. The frequency of hydatidiform mole in ectopic pregnancy where the tube is resected is 1-3%. A meaningful analysis would have to be based on the incidence of hydatidiform mole in patients who have had infertility investigations. 5. Capitanio, A , Coppola, R., Mannucci, P. M., Ruggeri, Z. M. in Proceedings of the IX Congress of the World Federation of Hæmophilia, p. 213. Amsterdam, 1974. 6. Allain, J. P., Roberts, H. R. in Handbook of Hemophilia; p. 655. Amsterdam, 1975. 1. Weiss, D. B., Aboulafia, Y Lancet, 1975, ii, 1094. 2. Grant, A. Clin. Obstet. Gynaec. 1962, 5, 861.
EFFECT OF FRACTION R IN FIVE HAEMOPHILIACS WITH FACTOR-VIII
INHIBITORS
rough indication of the serum-albumin the test should a seriously injured or collapsed patient requires immediate and rapid resuscitation or where a patient facing extensive surgery and loss of blood has not had recent serum-protein measurements. If such a patient is tested and placed in groups 1 or 2, Hartmann’s or similar fluid may be given in equal volume with blood or plasma substitute with little risk of producing oedema if the c.v.p. is kept within safe limits. If the patient is placed in group 3, transfusions should be of colloid solutions only and controlled by careful monitoring of the c.v.p. As
a
be useful where
Department of Anæsthesia, North Tees General Hospital,
Hardwick, Stockton-on-Tees, Cleveland TS19 8PE
E. N. S. FRY
CONCENTRATES OF CLOTTING-FACTOR IX SIR,-Your leader (Nov. 1, p. 855) reviewing the clinical use of prothrombin-complex concentrates emphasised their potential use in the management of haemophiliacs with inhibitors to factor VIII.I-3 We have treated five severe haemophiliacs (factor vm 1%) who had factor-vm inhibitor with ’Fraction R’ (Immuno AG, Vienna), a new preparation of activated factors of the prothrombin complex (see accompanying table). The administration of fraction R was followed by clinical improvement in patients 1, 3, and 5. Failure in patient no. 2 was not surprising, since response to treatment of haematuria is known to be capricious even in haemophiliacs without inhibitor ; bleeding is likely to have subsided spontaneously in patient 4. There was a marked anamnestic rise of the inhibitor level in four patients, and its magnitude appeared similar to that observed in the same patients treated on previous occasions with factor-viii concentrates.4
Prothrombin-complex concentrates, therefore, are not less antigenic than factor-vni concentrates, and should not be used in the management of non-dangerous bleeding episodes to avoid an unnecessary rise of the inhibitor. They may be an additional weapon in life-endangering situations. However, a large infusion of high-potency factor-viii concentrates still appears the safest and most effective form of treatment in patients with lower inhibitor levels; this procedure must be
1. Kurczynski, E. M., Penner, J. A. New Engl. J. Med. 1974, 291, 164. 2. Sultan, Y., Bronet, J. C., Dehe, P. ibid. p. 1087. 3. Abilgaard, L. F., Britton, M., Roberts, R. Blood, 1974, 44, 933. 4. Ruggeri, Z. M., Mannucci, P. M., Allain, J. P., Frommel, D. Ann. N.Y. Acad. Sci. 1975, 240, 412.
accompanied by exchange transfusion or plasmapheresis 6 a cell separator in patients with high inhibitor levels.’
with
3rd Institute of Clinical Medicine.
hemophilia and Thrombosis Centre, Angelo Bianchi Bonomi, Via Pace 15, 20122 Milan,
Italy.
P. M. MANNUCCI R. BADER Z. M. RUGGERI
ECTOPIC PREGNANCY, HYDATIDIFORM MOLE AND CLOMIPHENE
SIR,-Weiss and Aboulafial seem to imply that clomiphene citrate may "cause" ectopic pregnancy and hydatidiform mole. The demonstration of an association is not the demonstration of a cause, and in this example it seems highly likely that clomiphene citrate is not an setiological factor in either condition. It is quite pointless citing the incidence of ectopic pregnancy in the general population and comparing this with reported incidences of patients taking clomiphene. The local incidence of ectopic pregnancy varies widely. In some parts of the world it is as high as 1 in every 28 live births. This should be considered when comparing different series. But much more important is the incidence of ectopic pregnancy in patients who have been investigated for infertility. We now realise that infertility is a multifactorial problem. It is not possible to divide patients into those with tubal problems only or those with ovulatory problems. The crude investigations we use at the moment may pick up gross abnormalities of tubal or ovarian function but almost certainly miss important minor disorders. There remains, for instance, a remarkable disparity between apparently regular ovulation and pregnancy, in the absence of any other demonstrated abnormality. There is an increased incidence of ectopic pregnancy in patients investigated for infertility, in some series as high as 1 in 42 cases investigated.2 Some of these patients will have tubal factors demonstrated but most will not. If anything the clomiphene group of patients seem to have a comparatively low incidence of ectopic gestation. The incidence of hydatidiform mole may be marginally increased. The frequency of hydatidiform mole in ectopic pregnancy where the tube is resected is 1-3%. A meaningful analysis would have to be based on the incidence of hydatidiform mole in patients who have had infertility investigations. 5. Capitanio, A , Coppola, R., Mannucci, P. M., Ruggeri, Z. M. in Proceedings of the IX Congress of the World Federation of Hæmophilia, p. 213. Amsterdam, 1974. 6. Allain, J. P., Roberts, H. R. in Handbook of Hemophilia; p. 655. Amsterdam, 1975. 1. Weiss, D. B., Aboulafia, Y Lancet, 1975, ii, 1094. 2. Grant, A. Clin. Obstet. Gynaec. 1962, 5, 861.
EFFECT OF FRACTION R IN FIVE HAEMOPHILIACS WITH FACTOR-VIII
INHIBITORS