874 Uricaciduria is associated with an enzyme defect in purine synthesis, but the neurological manifestations have been unexplained. Schneider and Morgenstern2 examined the ultrastructure of platelets from a child with the disease and found them to have depolymerised microtubules. Since microtubules play a functional role in nervous tissue3 as they do in platelets, malfunctioning microtubules might explain the neurological signs of Lesch-Nyhan syndrome. You state that Chediak-Higashi syndrome seems to be as-
clotting-time was shortened, sometimes to two-thirds of its original value. Some of the collected reports, together with my observation, were reported in a previous letter !2 In all the clinical cases reported the doses of heparin were substantial and
sociated with defective microtubules, but you omit to say that defective platelet function is part of the disease both in man and cattle. 3.4 You also describe how the clue to microtubule involvement in Kartagener’s syndrome came from the examination of microtubules in immotile spermatozoa; it would certainly be worthwhile to examine platelet function in this condition also. Platelet aggregation is measured by the light-transmission method of Bornafunction that implies anatomical and biochemical integrity. Vinca alkaloids cause depolymerisation of platelet microtubules in vitro.’ I have exposed platelets to vinca alkaloids and noted the disappearance of microtubules by electronmicroscopy. These platelets also show inhibition of function as measured by Born’s method, and loss of microtubules on electronmicroscopy can be related to loss of function. Microtubules play a functional role in many inaccessible tissues. The examination of platelets may prove to be a good indicator of their function.
It would, however, be prudent to remain alert to the dangers of post-heparin thromboembolism and to adopt the anticoagulant regimen you propose and to ensure that heparin administration is never stormed abruntlv.
I
am
supported by
an
M.R.C.
fellowship.
Academic Division of Medicine, University of Sheffield, Royal Hospital,
J. F.
Sheffield S1 3SR
MARTIN
thrombosis did
not occur
until
a
few hours after the end of the
heparin treatment. The mechanism described in your editorial provides a satisfactory explanation for these observations and confirms the hypothetical mechanism suggested in my previous letter. 12
79 North End
House,
Fitzjames Avenue, London W14
AMIRAM UR
SERUM-FERRITIN IN HIEMOCHROMATOSIS
SiR,—Dr Valberg and his colleagues (Feb. 4, p. 279) reported a progressive decline in serum-ferritin concentrations in patients with idiopathic heemochromatosis with little weekto-week variation, which accords with the work of Prieto et al.’ but contrasts with our experience.2 We measured serum-ferritin by immunoradiometric assay,3 with human spleen ferritin antibodies and human spleen ferritin for the standard curve. All sera were measured at two dilutions in duplicate against the same standard which was prepared from stock at each assay. Two control sera were
ANTITHROMBIN III AND HEPARIN
SIR, The observations discussed in your editorial (March 11, p. 538) suggest that the enhanced turnover of antithrom-
(A.T. III) may lead to a state of hypercoagulability when heparin administration is stopped. You suggest, however, that bin
III
this may prove to be more of a theoretical hazard than an important clinical problem. Several reports indicate that the risk of thromboembolism is real. Some described heparin-induced thrombosis as "paradoxical", and several possible explanations have been suggested. Roberts et a1.8 reported "11 patients suffering unexplained arterial embolism for the first time while being treated with heparin for some condition that could not of itself reasonably be expected to cause arterial emboli". Barker et al.,’who studied 110 cases of arterial embolism, were impressed that 12% of these were induced by heparin therapy. Spracklen et al."’demonstrated that such a thrombus could not have started before heparin was given. No doubt many more cases are not reported because the thromboembolism is attributed to the underlying disease. My search for these clinical reports was instigated by my own findings in animals. Application of an impedance technique for whole-blood clotting-time determination," showed that after heparin administration, with the clotting-time returning to normal, there followed a period during which the Schneider, W., Morgenstern, E. 4th meeting of the International Society of Hæmatology (Istanbul, September, 1977); abstr. 200. 3. Costa, J. L., Fauci, A. S., Sheldon, M. W. Blood, 1976, 48, 517. 4. Bell, T. G., Meyers, K. M., Prieur, D. J., Fauci, A. S., Sheldon, M. W., Padgett, G. A. ibid. p. 175. 5. Banks, P., Till, R. J. Physiol. 1975, 252, 283. 6. Born, G. V. R. ibid. 1962, 162, 67p. 7. White, J. G. Am. J. Path. 1968, 53, 447. 8. Roberts, B., Rosato, F. E., Rosato, E. F. Surgery, 1964, 55, 803. 9. Barker, C. F., Rosato, F. E., Roberts, B. Surgery Gynec. Obstet. 1966, 123, 2.
22. 10. 11.
Spracklen, F. H., Model, D. G., Besterman, 42, 724. Ur, A. Am. J. clin. Path. 1977, 67, 72.
E. M.
Postgrad. med. J. 1966,
Differing affinities for spleen, liver,
and heart ferritins.
included in each assay, the deviation about the means of which is
clotting-time was shortened, sometimes to two-thirds of its original value. Some of the collected reports, together with my observation, were reported in a previous letter !2 In all the clinical cases reported the doses of heparin were substantial and
sociated with defective microtubules, but you omit to say that defective platelet function is part of the disease both in man and cattle. 3.4 You also describe how the clue to microtubule involvement in Kartagener’s syndrome came from the examination of microtubules in immotile spermatozoa; it would certainly be worthwhile to examine platelet function in this condition also. Platelet aggregation is measured by the light-transmission method of Bornafunction that implies anatomical and biochemical integrity. Vinca alkaloids cause depolymerisation of platelet microtubules in vitro.’ I have exposed platelets to vinca alkaloids and noted the disappearance of microtubules by electronmicroscopy. These platelets also show inhibition of function as measured by Born’s method, and loss of microtubules on electronmicroscopy can be related to loss of function. Microtubules play a functional role in many inaccessible tissues. The examination of platelets may prove to be a good indicator of their function.
It would, however, be prudent to remain alert to the dangers of post-heparin thromboembolism and to adopt the anticoagulant regimen you propose and to ensure that heparin administration is never stormed abruntlv.
I
am
supported by
an
M.R.C.
fellowship.
Academic Division of Medicine, University of Sheffield, Royal Hospital,
J. F.
Sheffield S1 3SR
MARTIN
thrombosis did
not occur
until
a
few hours after the end of the
heparin treatment. The mechanism described in your editorial provides a satisfactory explanation for these observations and confirms the hypothetical mechanism suggested in my previous letter. 12
79 North End
House,
Fitzjames Avenue, London W14
AMIRAM UR
SERUM-FERRITIN IN HIEMOCHROMATOSIS
SiR,—Dr Valberg and his colleagues (Feb. 4, p. 279) reported a progressive decline in serum-ferritin concentrations in patients with idiopathic heemochromatosis with little weekto-week variation, which accords with the work of Prieto et al.’ but contrasts with our experience.2 We measured serum-ferritin by immunoradiometric assay,3 with human spleen ferritin antibodies and human spleen ferritin for the standard curve. All sera were measured at two dilutions in duplicate against the same standard which was prepared from stock at each assay. Two control sera were
ANTITHROMBIN III AND HEPARIN
SIR, The observations discussed in your editorial (March 11, p. 538) suggest that the enhanced turnover of antithrom-
(A.T. III) may lead to a state of hypercoagulability when heparin administration is stopped. You suggest, however, that bin
III
this may prove to be more of a theoretical hazard than an important clinical problem. Several reports indicate that the risk of thromboembolism is real. Some described heparin-induced thrombosis as "paradoxical", and several possible explanations have been suggested. Roberts et a1.8 reported "11 patients suffering unexplained arterial embolism for the first time while being treated with heparin for some condition that could not of itself reasonably be expected to cause arterial emboli". Barker et al.,’who studied 110 cases of arterial embolism, were impressed that 12% of these were induced by heparin therapy. Spracklen et al."’demonstrated that such a thrombus could not have started before heparin was given. No doubt many more cases are not reported because the thromboembolism is attributed to the underlying disease. My search for these clinical reports was instigated by my own findings in animals. Application of an impedance technique for whole-blood clotting-time determination," showed that after heparin administration, with the clotting-time returning to normal, there followed a period during which the Schneider, W., Morgenstern, E. 4th meeting of the International Society of Hæmatology (Istanbul, September, 1977); abstr. 200. 3. Costa, J. L., Fauci, A. S., Sheldon, M. W. Blood, 1976, 48, 517. 4. Bell, T. G., Meyers, K. M., Prieur, D. J., Fauci, A. S., Sheldon, M. W., Padgett, G. A. ibid. p. 175. 5. Banks, P., Till, R. J. Physiol. 1975, 252, 283. 6. Born, G. V. R. ibid. 1962, 162, 67p. 7. White, J. G. Am. J. Path. 1968, 53, 447. 8. Roberts, B., Rosato, F. E., Rosato, E. F. Surgery, 1964, 55, 803. 9. Barker, C. F., Rosato, F. E., Roberts, B. Surgery Gynec. Obstet. 1966, 123, 2.
22. 10. 11.
Spracklen, F. H., Model, D. G., Besterman, 42, 724. Ur, A. Am. J. clin. Path. 1977, 67, 72.
E. M.
Postgrad. med. J. 1966,
Differing affinities for spleen, liver,
and heart ferritins.
included in each assay, the deviation about the means of which is
