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DEFIBRINATION WITH HEAD INJURY
1206 from such cells can infect chick-embryo cells, transform them, and allow release of progeny virus.22 Moreover, the D.N.A. extracted from mouse and hamster cells transformed with murine-sarcoma virus, which do not produce progeny virus, transformed mouse cells after a long time in culture.This happened even under conditions where the sarcomavirus genome could not be rescued by superinfection with Rauscher leukaemogenic virus. Thus cellular transformation can take place in the absence of a complete viral genome, as is known also from transformation by defective viruses. It is conceivable that some human cancers are due to transformation by incomplete virus genomes. Karpas and Tuckerman now report 4 that D.N.A. extracted from cultured human-rhabdomyosarcoma cells, when added to cultures of skin fibroblasts from normal human embryos, resulted in delayed transformation of the latter. Control fibroblasts died out after 8 months in culture, whereas cells treated with tumour-cell D.N.A. continued to grow and formed dense layers in culture as described for transformed cells. They suggest that the malignant cells may have provided virus-coded D.N.A. to the normal cells. If reproducible, this could be an interesting approach to the recovery of provirus genetic material in human tumours. The experiments will have to be controlled carefully to make sure that the observed effects are found only with D.N.A. from tumours. The D.N.A.treated cells showed many chromosomal abnormalities, the significance of which is not yet clear. It is especially important to exclude the possibility that the transformed cells are not laboratory contaminants that have a habit of getting into long-term cultures. Moreover, independent evidence of a relationship to primate C-type viruses,55 by nucleic-acid hybridisation or other methods, would support the view that a provirus is involved.
DEFIBRINATION WITH HEAD INJURY DEFIBRINATION is a common cause of excessive
bleeding in certain obstetric emergencies, especially abruptio placentae, and obstetric departments today always have materials on hand for a rapid test of plasma-fibrinogen and a store of human fibrinogen for administration if needed. It occurred to Goodnight and his colleagues, at the University of Southern California, that defibrination might be responsible for the serious bleeding that sometimes complicates head injury; they had found evidence of the syndrome in two cases of gunshot wounds to the head and two others had been reported elsewhere. They therefore set out to investigate the changes in the fibrinolytic and blood-clotting systems after head injury. Since exposure to damaged tissue is known to activate fibrinolysis, they divided their cases into two groups: group I consisted of 13 patients with brain-tissue destruction seen in the wound or at operation, and Hill, M., Hillova, J. Nature new Biol. 1972, 237, 35. Karpas, A., Milstein, C. Eur. J. Cancer, 1973, 9, 295. Karpas, A., Tuckerman, E. Lancet, June 8, 1974, p. 1138. Todaro, G. J., Scherr, C. J., Benveniste, R. E., Lieber, M. M. Cell, 1974, 2, 55. 6. Goodnight, S. H., Kenoyer, G., Rapaport, S. I., Patch, M. J., Lee, J. A., Kurze, T. New Engl. J. Med. 1974, 290. 1043. 2. 3. 4. 5.
group II comprised 13 patients who were unconscious but without clinical evidence of brain-tissue damage.
An extensive battery of tests was performed; the most important ones for diagnosis turned out to be estimation of plasma-fibrinogen and the protamine-sulphate test which detects fibrin-degradation products (F.D.P.S). Clotting-factors v and vm were sometimes decreased, as was the platelet-count. These other changes were not surprising since the defibrination syndrome is one aspect of disseminated intravascular coagulation, which involves clotting-factors, platelets, and sometimes red cells in addition to the fibrinogen/fibrin
system. None of the 13 group-II patients showed excessive bleeding or evidence of defibrination. In group I, however, 4 patients had very low fibrinogen concentrations, between 0 and 40 mg. per 100 ml. (normal over 150 mg. per 100 ml.) and strongly positive protamine tests for F.D.P.S; they also had low factor-v concentrations and 3 had low factor vm; platelets were not seriously affected. In 5 other patients there was a lesser degree of hypofibrinogenaemia (103-124 mg. per 100 ml.), positive protamine tests and increased fibrinogen-related-antigen levels showed the presence of F.D.P.s, and occasional abnormalities were found in other indices; these effects in combination could have influenced the extent of the bleeding. The remaining 4 patients had normal fibrinogen concentrations. Occasional fragmented red blood-cells were seen in blood smears from 2 of the severe group. Goodnight et al. believe that the injury to brain tissue is the operative factor. Many of their group-II patients had extensive trauma to other areas of the body, and they cite the data of Simmons et al.’ who found only minor abnormalities of blood coagulation in 240 soldiers with extensive wounds but without head injury. The active phase of defibrination did not last long; 4 of the California patients were not treated and fibrinogen concentration became normal in 5-18 hours. But, in the first hours after brain injury, treatment to correct the haemostatic defect may make all the difference between saving or losing a patient. They recommend that blood should be taken for tests, and then treatment given immediately afterwards. They give 12 bags of cryoprecipitate and 2-4 units of fresh-frozen plasma; this combination provides fibrinogen, factor vmx in the cryoprecipitate, and factor v in the frozen plasma. If the plateletcount is below 75,000 per .1., platelet concentrate is given if available. Such treatment should not delay essential neurological investigation or operationindeed, the treatment will prevent undue bleeding during the operation. They report 2 cases in which they think treatment ensured survival with minimum permanent damage. None of the blood products used in the recommended treatment is plentiful or even available on a large scale. Therefore it is essential to select patients with clear evidence of brain-tissue damage, in whom clinical assessment indicates a fair chance of recovery without too much disability. A further trial of this type of management would be worth while at headiniurv centres. 7. Simmons, R. L., Collins, J. A., 1969, 169, 455.
Heisterkamp, C. A., et al. Ann. Surg.
DEFIBRINATION WITH HEAD INJURY DEFIBRINATION is a common cause of excessive
bleeding in certain obstetric emergencies, especially abruptio placentae, and obstetric departments today always have materials on hand for a rapid test of plasma-fibrinogen and a store of human fibrinogen for administration if needed. It occurred to Goodnight and his colleagues, at the University of Southern California, that defibrination might be responsible for the serious bleeding that sometimes complicates head injury; they had found evidence of the syndrome in two cases of gunshot wounds to the head and two others had been reported elsewhere. They therefore set out to investigate the changes in the fibrinolytic and blood-clotting systems after head injury. Since exposure to damaged tissue is known to activate fibrinolysis, they divided their cases into two groups: group I consisted of 13 patients with brain-tissue destruction seen in the wound or at operation, and Hill, M., Hillova, J. Nature new Biol. 1972, 237, 35. Karpas, A., Milstein, C. Eur. J. Cancer, 1973, 9, 295. Karpas, A., Tuckerman, E. Lancet, June 8, 1974, p. 1138. Todaro, G. J., Scherr, C. J., Benveniste, R. E., Lieber, M. M. Cell, 1974, 2, 55. 6. Goodnight, S. H., Kenoyer, G., Rapaport, S. I., Patch, M. J., Lee, J. A., Kurze, T. New Engl. J. Med. 1974, 290. 1043. 2. 3. 4. 5.
group II comprised 13 patients who were unconscious but without clinical evidence of brain-tissue damage.
An extensive battery of tests was performed; the most important ones for diagnosis turned out to be estimation of plasma-fibrinogen and the protamine-sulphate test which detects fibrin-degradation products (F.D.P.S). Clotting-factors v and vm were sometimes decreased, as was the platelet-count. These other changes were not surprising since the defibrination syndrome is one aspect of disseminated intravascular coagulation, which involves clotting-factors, platelets, and sometimes red cells in addition to the fibrinogen/fibrin
system. None of the 13 group-II patients showed excessive bleeding or evidence of defibrination. In group I, however, 4 patients had very low fibrinogen concentrations, between 0 and 40 mg. per 100 ml. (normal over 150 mg. per 100 ml.) and strongly positive protamine tests for F.D.P.S; they also had low factor-v concentrations and 3 had low factor vm; platelets were not seriously affected. In 5 other patients there was a lesser degree of hypofibrinogenaemia (103-124 mg. per 100 ml.), positive protamine tests and increased fibrinogen-related-antigen levels showed the presence of F.D.P.s, and occasional abnormalities were found in other indices; these effects in combination could have influenced the extent of the bleeding. The remaining 4 patients had normal fibrinogen concentrations. Occasional fragmented red blood-cells were seen in blood smears from 2 of the severe group. Goodnight et al. believe that the injury to brain tissue is the operative factor. Many of their group-II patients had extensive trauma to other areas of the body, and they cite the data of Simmons et al.’ who found only minor abnormalities of blood coagulation in 240 soldiers with extensive wounds but without head injury. The active phase of defibrination did not last long; 4 of the California patients were not treated and fibrinogen concentration became normal in 5-18 hours. But, in the first hours after brain injury, treatment to correct the haemostatic defect may make all the difference between saving or losing a patient. They recommend that blood should be taken for tests, and then treatment given immediately afterwards. They give 12 bags of cryoprecipitate and 2-4 units of fresh-frozen plasma; this combination provides fibrinogen, factor vmx in the cryoprecipitate, and factor v in the frozen plasma. If the plateletcount is below 75,000 per .1., platelet concentrate is given if available. Such treatment should not delay essential neurological investigation or operationindeed, the treatment will prevent undue bleeding during the operation. They report 2 cases in which they think treatment ensured survival with minimum permanent damage. None of the blood products used in the recommended treatment is plentiful or even available on a large scale. Therefore it is essential to select patients with clear evidence of brain-tissue damage, in whom clinical assessment indicates a fair chance of recovery without too much disability. A further trial of this type of management would be worth while at headiniurv centres. 7. Simmons, R. L., Collins, J. A., 1969, 169, 455.
Heisterkamp, C. A., et al. Ann. Surg.