- Email: [email protected]
COATS' DISEASE
690 most potent ’21 24 and of factors known to increase oxyhaemoglobin dissociation, and hence tissue oxygen uptake,22 25 carbon dioxide is the most powerful and easily adjustable. Nature has arranged that the chief end-product of metabolism is its primary regulator.
carbon dioxide is the
Johnstone about the diagnosis and treatment of their cases, and her comment on Dr. Quick’s letter follows.-ED. L.
SIR,-Dr. Quick has, I believe, confused two problems hxmophilic bleeding. So-called sponInstitute of Clinical Research, Middlesex Hospital Medical School, taneous bleeding such as that causing haemarthroses, BRYAN BROOM. London, W.1. hxmatomata, or haematuria is frequently controlled by blood concentrations of factor vill between 5 and 20% of COATS’ DISEASE normal. Such bleeding is probably from trivial breaches SIR,-Iread with interest your annotation of Aug. 17 in the vascular system and, as Dr. Quick says, does not concerning the articles by the late Dr. Woods and myself. occur in the mildly affected patient. In the severely You referred to two patients with the adult form of the affected patient this type of bleeding is usually well disease in whom hypercholestersemia was present. controlled by plasma infusions. Bleeding after major Actually, the paper described five adult cases. Lipid trauma does, however, occur in the mildly affected patient studies were performed on four of these patients, and in and the blood concentration of factor vill required for its each hypercholesteraemia was present. control is much higher than can ever be obtained by Further, citing that Coats held the deposition of plasma infusion. cholesterol to result from haemorrhage, you implied that Case 1, recorded by Livingstone and Johnstone, was a we regard hypercholesterasmia as a primary factor in both mildly affected patient with 7-8% of factor vni in his blood. the adult and juvenile forms of the disease. Such an We had not expected much difficulty in preventing postimplication is, of course, unwarranted, since there is no operative bleeding. Using human A.H.G. and plasma, blood concentrations of factor vni constantly above 16% of normal hypercholesteraemia in the juvenile cases. Wilmer Institute, were probably maintained for 14 days. Yet despite this treatJohns Hopkins Hospital, ment he had 4 quite serious episodes of bleeding. Case 3 was JAMES R. DUKE. Baltimore, Maryland. in the control of
mildly affected, with a natural factor-vm concentration of 30% normal. The records of these two cases together were taken to indicate that the blood concentration of factor-vin should be above 40% of normal in the postoperative period following tonsillectomy. For other operations somewhat lower levels may suffice. Dr. Quick does not apparently believe that the bleeding which follows serious trauma in a hxmophilic patient is any more difficult to control than spontaneous bleeding. This has not been our experience. The use of plasma for the control of bleeding after major surgery exposes the severely affected patient to a now quite unjustifiable risk. Occasional patients with an unusual response to plasma may do well, but in many cases the postoperative period will be interrupted by annoying or dangerous bleeding. Given concentrates in adequate doses, healing will be normal after most major operations in all but those patients who have circulating anticoagulants.
very
TONSILLECTOMY IN PATIENTS WITH COAGULATION DEFECTS
SiR,-Mr. Livingstone and Dr. Johnstone (Aug. 24) emphasise the surgical importance of recognising mild bleeders so as to be forewarned for postoperative bleeding. One of the chief aims of our laboratory has been to detect and characterise coagulation defects in mild bleeding states. Comparing the results of Livingstone and Johnstone with those of our laboratory, several striking discrepancies are observed. One is the level of factor vill required to maintain adequate haemostasis. They state that a level of 40% of normal is needed throughout postoperative healing. In contrast, our observation has been that a hxmophiliac with a factor-vm concentration of 1-5-4% is a mild bleeder, very rarely has haemarthrosis, and may have long periods in which the bleeding tendency is subclinica1.26 Successful control of bleeding is often achieved after raising the concentration of factor vni to 5 % by means of fresh frozen plasma transfusion. Your contributors’ diagnosis of prothrombin deficiency in case 2 is puzzling. The normal one-stage prothrombin is reported as 14 minutes 8 seconds and that of the patient as 17 minutes 14 seconds. This is obviously an error. If the figures were 14 and 17 seconds respectively, it is improbable that the bleeding would be due to a deficiency of prothrombin. As shown previously, hypoprothrombinmmia is sensitively detected by the one-stage prothrombintime test and can be quantitatively measured with a slight modification-namely, by addition of a small amount of ncri-ti
serum tn
thf nlnomn 27
Marquette University, Milwaukee, Wisconsin.
ARMAND
J. QUICK.
*** We apologise to Mr. Livingstone and Dr. Johnstone for introducing the errors in their paper. The prothrombin-times to which Professor Quick refers were in fact 14-8 seconds (normal) and 17-4 seconds (patient). Dr. Rosemary Biggs advised Mr. Livingstone and Dr. Gibbs,
F. A., Gibbs, E. L., Lennox, W. G. Amer. J. Physiol. 1935 111, 557. Kety, S. S., Schmidt, C. F. J. clin. Invest. 1948, 27, 484. 25. Bohr, C., Hasselbach, K. A., Krogh, A. Skand. Arch. Physiol. 1904 17, 104. 26. Quick, A. J. Amer. J. med. Sci. 1962, 244, 535. 27. Quick, A. J., Hussey, C. V. Lancet, 1962, i, 173. 23.
24.
Dr. Quick’s comment on the prothrombin-time in case 2 raises a problem in the interpretation of technique. We base the diagnosis of prothrombin deficiency on the twostage method. If the results of the two-stage and the one-stage methods as they are carried out in our laboratory are compared, the one-stage method shows little abnormality for prothrombin values (two-stage) above 30% of normal. This is a constant finding in our laboratory in all patients who have prothrombin deficiency but normal concentrations of factors v, VII, and x. It is our experience that patients with prothrombin levels below 40% may bleed following major trauma. This experience consists in the past observation of bleeding in such patients and its control by adequate therapy. Since case 2 had prothrombin deficiency (two-stage) of an order which we should expect to predispose to traumatic bleeding, since 3 other members of his family had similar defects, since no other abnormality could be found, and since bleeding was prevented after tonsillectomy by giving a concentrate containing prothrombin, we made a diagnosis of prothrombin deficiency. Unfortunately I must disagree with Dr. Quick. The one-stage prothrombin-time as we use it is invaluable for the detection and assessment of deficiencies of factors v, vil, or x but has proved insensitive to prothrombin
deficiency. Medical Research Council Blood Coagulation Research Unit, Churchill Hospital, Oxford.
ROSEMARY BIGGS.
carbon dioxide is the
Johnstone about the diagnosis and treatment of their cases, and her comment on Dr. Quick’s letter follows.-ED. L.
SIR,-Dr. Quick has, I believe, confused two problems hxmophilic bleeding. So-called sponInstitute of Clinical Research, Middlesex Hospital Medical School, taneous bleeding such as that causing haemarthroses, BRYAN BROOM. London, W.1. hxmatomata, or haematuria is frequently controlled by blood concentrations of factor vill between 5 and 20% of COATS’ DISEASE normal. Such bleeding is probably from trivial breaches SIR,-Iread with interest your annotation of Aug. 17 in the vascular system and, as Dr. Quick says, does not concerning the articles by the late Dr. Woods and myself. occur in the mildly affected patient. In the severely You referred to two patients with the adult form of the affected patient this type of bleeding is usually well disease in whom hypercholestersemia was present. controlled by plasma infusions. Bleeding after major Actually, the paper described five adult cases. Lipid trauma does, however, occur in the mildly affected patient studies were performed on four of these patients, and in and the blood concentration of factor vill required for its each hypercholesteraemia was present. control is much higher than can ever be obtained by Further, citing that Coats held the deposition of plasma infusion. cholesterol to result from haemorrhage, you implied that Case 1, recorded by Livingstone and Johnstone, was a we regard hypercholesterasmia as a primary factor in both mildly affected patient with 7-8% of factor vni in his blood. the adult and juvenile forms of the disease. Such an We had not expected much difficulty in preventing postimplication is, of course, unwarranted, since there is no operative bleeding. Using human A.H.G. and plasma, blood concentrations of factor vni constantly above 16% of normal hypercholesteraemia in the juvenile cases. Wilmer Institute, were probably maintained for 14 days. Yet despite this treatJohns Hopkins Hospital, ment he had 4 quite serious episodes of bleeding. Case 3 was JAMES R. DUKE. Baltimore, Maryland. in the control of
mildly affected, with a natural factor-vm concentration of 30% normal. The records of these two cases together were taken to indicate that the blood concentration of factor-vin should be above 40% of normal in the postoperative period following tonsillectomy. For other operations somewhat lower levels may suffice. Dr. Quick does not apparently believe that the bleeding which follows serious trauma in a hxmophilic patient is any more difficult to control than spontaneous bleeding. This has not been our experience. The use of plasma for the control of bleeding after major surgery exposes the severely affected patient to a now quite unjustifiable risk. Occasional patients with an unusual response to plasma may do well, but in many cases the postoperative period will be interrupted by annoying or dangerous bleeding. Given concentrates in adequate doses, healing will be normal after most major operations in all but those patients who have circulating anticoagulants.
very
TONSILLECTOMY IN PATIENTS WITH COAGULATION DEFECTS
SiR,-Mr. Livingstone and Dr. Johnstone (Aug. 24) emphasise the surgical importance of recognising mild bleeders so as to be forewarned for postoperative bleeding. One of the chief aims of our laboratory has been to detect and characterise coagulation defects in mild bleeding states. Comparing the results of Livingstone and Johnstone with those of our laboratory, several striking discrepancies are observed. One is the level of factor vill required to maintain adequate haemostasis. They state that a level of 40% of normal is needed throughout postoperative healing. In contrast, our observation has been that a hxmophiliac with a factor-vm concentration of 1-5-4% is a mild bleeder, very rarely has haemarthrosis, and may have long periods in which the bleeding tendency is subclinica1.26 Successful control of bleeding is often achieved after raising the concentration of factor vni to 5 % by means of fresh frozen plasma transfusion. Your contributors’ diagnosis of prothrombin deficiency in case 2 is puzzling. The normal one-stage prothrombin is reported as 14 minutes 8 seconds and that of the patient as 17 minutes 14 seconds. This is obviously an error. If the figures were 14 and 17 seconds respectively, it is improbable that the bleeding would be due to a deficiency of prothrombin. As shown previously, hypoprothrombinmmia is sensitively detected by the one-stage prothrombintime test and can be quantitatively measured with a slight modification-namely, by addition of a small amount of ncri-ti
serum tn
thf nlnomn 27
Marquette University, Milwaukee, Wisconsin.
ARMAND
J. QUICK.
*** We apologise to Mr. Livingstone and Dr. Johnstone for introducing the errors in their paper. The prothrombin-times to which Professor Quick refers were in fact 14-8 seconds (normal) and 17-4 seconds (patient). Dr. Rosemary Biggs advised Mr. Livingstone and Dr. Gibbs,
F. A., Gibbs, E. L., Lennox, W. G. Amer. J. Physiol. 1935 111, 557. Kety, S. S., Schmidt, C. F. J. clin. Invest. 1948, 27, 484. 25. Bohr, C., Hasselbach, K. A., Krogh, A. Skand. Arch. Physiol. 1904 17, 104. 26. Quick, A. J. Amer. J. med. Sci. 1962, 244, 535. 27. Quick, A. J., Hussey, C. V. Lancet, 1962, i, 173. 23.
24.
Dr. Quick’s comment on the prothrombin-time in case 2 raises a problem in the interpretation of technique. We base the diagnosis of prothrombin deficiency on the twostage method. If the results of the two-stage and the one-stage methods as they are carried out in our laboratory are compared, the one-stage method shows little abnormality for prothrombin values (two-stage) above 30% of normal. This is a constant finding in our laboratory in all patients who have prothrombin deficiency but normal concentrations of factors v, VII, and x. It is our experience that patients with prothrombin levels below 40% may bleed following major trauma. This experience consists in the past observation of bleeding in such patients and its control by adequate therapy. Since case 2 had prothrombin deficiency (two-stage) of an order which we should expect to predispose to traumatic bleeding, since 3 other members of his family had similar defects, since no other abnormality could be found, and since bleeding was prevented after tonsillectomy by giving a concentrate containing prothrombin, we made a diagnosis of prothrombin deficiency. Unfortunately I must disagree with Dr. Quick. The one-stage prothrombin-time as we use it is invaluable for the detection and assessment of deficiencies of factors v, vil, or x but has proved insensitive to prothrombin
deficiency. Medical Research Council Blood Coagulation Research Unit, Churchill Hospital, Oxford.
ROSEMARY BIGGS.