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PLATELET DYSFUNCTION
502
Rapid remission was induced by cortisone therapy. A trial of desensitisation to tree and grass pollens has been undertaken. We are particularly indebted to Prof. R. M. Kark, who called our attention to the eosinophilic infiltration in this case, and Brewer for help with the histology.
to
Dr. D. B.
REFERENCES
Fanconi, G., Kowmine, C., Frischknecht, W. (1951) Helv. Pœdiat.
acta.
6, 199. Kark, R. M., Muehrcke, R. C. (1954) Lancet, i, 1047. Pirani, C. L., Pollak, V. E., Muehrcke, R. C., Blainey, J. D. (1958) Ann. intern. Med. 49, 751. McCall, M. F. (1952) Arch. Dis. Childh. 27, 309. Metcoff, J. (1956) Proceedings of the 8th Annual Conference on Nephrotic Syndrome; p. 158. Rytand, D. A. (1948) Amer. J. Med. 5, 548. (1955) Stanf. med. Bull. 13, 224. Squire, J. R., Blainey, J. D., Hardwicke, J. (1957) Brit. med. Bull. 13, 43. -
sumption test, which was equivocal, was 20 seconds:aonestage teclinique was used (Quick 1951). This test was repeated several times with the same result. Clot-retraction (Ackroyd 1949) was 56.5%; there was no lysis of the clot at 37°C within 24 hours. The plasma-fibrinogen level was 183 mg. per 100 ml. The bone-marrow showed a simple myeloerythroid hyperplasia. The megakaryocytes were not increased in number, and had no abnormal features. The thromboplastin-generation test (Biggs and Douglas 1953), using a suspension of 1,000,000 platelets per c. mm., showed that the patient’s platelets were defective in the production of thromboplastin. This abnormality was demonstrated on three separate occasions:
-
PLATELET DYSFUNCTION M.A. LATE
REGISTRAR,
A. K. FRAZER Cantab., M.B. Lpool
DEPARTMENT OF PATHOLOGY, LIVERPOOL
WOMEN’S HOSPITAL,
thrombocytopenic purpura is not a rare cause of dysfunctional uterine haemorrhage (Buxton 1941, Dameshek and Rheingold 1949), thromboasthenia, in which there is a disturbance not of platelet numbers but of platelet function, is extremely uncommon (Biggs and Macfarlane 1957). In thrombocytopenic purpura the defect is in the formation of the platelet-thromboplastic factor (de Nicola 1954, Bonnin 1956); therefore the cause of the symptoms may be a dysfunction rather than a shortage of platelets. In thromboasthenia, although the platelet-count remains within the normal range, the ability to produce platelet-thromboplastic factor is grossly deficient (Braunsteiner 1955); therefore purpuric bleeding WHILST
occurs.
The following case of dysfunctional uterine hxmorrhage may be classified in the group of hasmorrhagic diatheses due to platelet dysfunction.
Case-report A woman, aged 40, had been married 5 years and had had two children, the last 3 years previously. Menarche was at 14 and the menstrual cycle was usually 7/28 but since her last confinement had been 14/21. 3 months before admission to hospital on Feb. 23, 1957, she had had uterine bleeding almost continuously for 7 weeks followed by irregular losses. She gave a history of bruising easily, often without obvious trauma. There was no family history of excessive bleeding; but her mother had had a hysterectomy for uterine haemorrhage at the age of 30. On examination all systems appeared normal; there was no gross gynaecological lesion. A symptomatic diagnosis of epimenorrhagia was made.
Laboratory findings Haemoglobin 9-5 g. per 100 ml. (65%); packed-cell volume 30%. A blood-film showed that the red cells were hypochromic, but the white cells appeared normal; the platelets were plentiful but there were some abnormally large forms. The platelet-count varied between 180,000 per c.mm. and 240,000. The tourniquet test was positive. The bleeding-time (Ivy et al. 1940) was within normal limits on the first occasion (41/2 minutes) and increased on two other occasions (8 minutes and 13 minutes). The whole-blood coagulation-time was 26 minutes, using the Lee and White (1913) method with silicone-treated test-tubes (normal range in this laboratory 18-30 minutes). The prothrombin-time (Quick 1935) was 12 seconds-i.e., 100% prothrombin activity. The result of the prothrombin-con-
The patient’s plasma and serum formed normal amounts of thromboplastin with control platelets. A diagnosis of non-thrombocytopenic purpura or thromboasthenia
was
therefore made.
Treatment
The’patient had a cervical dilatation and a uterine curettage; radium 50 mg. was inserted into the uterine cavity for 40 hours. The curettings were of normal secretory endometrium. (Dr. H. R. Harris.) Discussion
Stefanini and Dameshek (1955) suggest that platelet dysfunction is probably more common than appears from the published accounts. Biggs and Macfarlane (1957) state that thromboasthenia may be hereditary or acquired; the latter can sometimes be explained on the basis of a coexistent blood dyscrasia-e.g., leukaemia or polycythxmia-or it can be secondary to toxic damage ". In the case described above, the uterine hxmorrhage appears to be due to defective platelet function, but no initiating factor could be found. In the light of recent observations on the changes in the blood during the normal menstrual cycle (Salvidio 1954, de Nicola et al. 1954, de Nicola 1954), one might postulate that the change in function of the platelets was initiated by an endocrine imbalance. A more detailed and thorough hasmatological investigation of the patients presenting with a dysfunctional uterine haemorrhage will be required if any advance is to be made in understanding the pathogenesis of menorrhagia. "
My thanks are due to Mr. Percy Malpas of the Women’s Hospital, Liverpool, for permission to publish this case, and to Dr. W. R. Pitney, haematologist to the Royal Perth Hospital, Western Australia, for his help and criticism. REFERENCES
Ackroyd, J. F. (1949) Clin. Sci. 7, 231. Biggs, R., Douglas, A. S. (1953) J. clin. Path. 6, 23. Macfarlane, R. G. (1957) Human Blood Coagulation and its -
Disorders. Oxford.
Bonnin, J. A. (1956) Brit. J. Hœmat. 2, 160. Braunsteiner, H. (1955) Wien. Z. inn. Med. 36, 421. Buxton, C. L. (1941) Amer. J. Obstet. Gynec. 42, 502. Dameshek, W., Rheingold, J. J. (1949) J. Amer. med. Ass. 139, 993. de Nicola, P. (1954) Rev. Hémat. 9, 536. Rosti, P., Carcupino, C. (1954) Schweiz. med. Wschr. 39, 1130. Ivy, A. C., Nelson, D., Bucher, G. (1940) J. Lab. clin. Med. 26, 1812. Lee, R. I., White, P. D. (1913) Amer. J. med. Sci. 145, 495. Quick, A. J. (1935) J. biol. Chem. 109, 73. (1951) The Physiology and Pathology of Hæmostasis. London, Salvidio, E. (1954) Acta Hœmat. 11, 301. Stefanini, M., Dameshek W. (1955) The Hæmorrhagic Disorders. New —
—
York.
Rapid remission was induced by cortisone therapy. A trial of desensitisation to tree and grass pollens has been undertaken. We are particularly indebted to Prof. R. M. Kark, who called our attention to the eosinophilic infiltration in this case, and Brewer for help with the histology.
to
Dr. D. B.
REFERENCES
Fanconi, G., Kowmine, C., Frischknecht, W. (1951) Helv. Pœdiat.
acta.
6, 199. Kark, R. M., Muehrcke, R. C. (1954) Lancet, i, 1047. Pirani, C. L., Pollak, V. E., Muehrcke, R. C., Blainey, J. D. (1958) Ann. intern. Med. 49, 751. McCall, M. F. (1952) Arch. Dis. Childh. 27, 309. Metcoff, J. (1956) Proceedings of the 8th Annual Conference on Nephrotic Syndrome; p. 158. Rytand, D. A. (1948) Amer. J. Med. 5, 548. (1955) Stanf. med. Bull. 13, 224. Squire, J. R., Blainey, J. D., Hardwicke, J. (1957) Brit. med. Bull. 13, 43. -
sumption test, which was equivocal, was 20 seconds:aonestage teclinique was used (Quick 1951). This test was repeated several times with the same result. Clot-retraction (Ackroyd 1949) was 56.5%; there was no lysis of the clot at 37°C within 24 hours. The plasma-fibrinogen level was 183 mg. per 100 ml. The bone-marrow showed a simple myeloerythroid hyperplasia. The megakaryocytes were not increased in number, and had no abnormal features. The thromboplastin-generation test (Biggs and Douglas 1953), using a suspension of 1,000,000 platelets per c. mm., showed that the patient’s platelets were defective in the production of thromboplastin. This abnormality was demonstrated on three separate occasions:
-
PLATELET DYSFUNCTION M.A. LATE
REGISTRAR,
A. K. FRAZER Cantab., M.B. Lpool
DEPARTMENT OF PATHOLOGY, LIVERPOOL
WOMEN’S HOSPITAL,
thrombocytopenic purpura is not a rare cause of dysfunctional uterine haemorrhage (Buxton 1941, Dameshek and Rheingold 1949), thromboasthenia, in which there is a disturbance not of platelet numbers but of platelet function, is extremely uncommon (Biggs and Macfarlane 1957). In thrombocytopenic purpura the defect is in the formation of the platelet-thromboplastic factor (de Nicola 1954, Bonnin 1956); therefore the cause of the symptoms may be a dysfunction rather than a shortage of platelets. In thromboasthenia, although the platelet-count remains within the normal range, the ability to produce platelet-thromboplastic factor is grossly deficient (Braunsteiner 1955); therefore purpuric bleeding WHILST
occurs.
The following case of dysfunctional uterine hxmorrhage may be classified in the group of hasmorrhagic diatheses due to platelet dysfunction.
Case-report A woman, aged 40, had been married 5 years and had had two children, the last 3 years previously. Menarche was at 14 and the menstrual cycle was usually 7/28 but since her last confinement had been 14/21. 3 months before admission to hospital on Feb. 23, 1957, she had had uterine bleeding almost continuously for 7 weeks followed by irregular losses. She gave a history of bruising easily, often without obvious trauma. There was no family history of excessive bleeding; but her mother had had a hysterectomy for uterine haemorrhage at the age of 30. On examination all systems appeared normal; there was no gross gynaecological lesion. A symptomatic diagnosis of epimenorrhagia was made.
Laboratory findings Haemoglobin 9-5 g. per 100 ml. (65%); packed-cell volume 30%. A blood-film showed that the red cells were hypochromic, but the white cells appeared normal; the platelets were plentiful but there were some abnormally large forms. The platelet-count varied between 180,000 per c.mm. and 240,000. The tourniquet test was positive. The bleeding-time (Ivy et al. 1940) was within normal limits on the first occasion (41/2 minutes) and increased on two other occasions (8 minutes and 13 minutes). The whole-blood coagulation-time was 26 minutes, using the Lee and White (1913) method with silicone-treated test-tubes (normal range in this laboratory 18-30 minutes). The prothrombin-time (Quick 1935) was 12 seconds-i.e., 100% prothrombin activity. The result of the prothrombin-con-
The patient’s plasma and serum formed normal amounts of thromboplastin with control platelets. A diagnosis of non-thrombocytopenic purpura or thromboasthenia
was
therefore made.
Treatment
The’patient had a cervical dilatation and a uterine curettage; radium 50 mg. was inserted into the uterine cavity for 40 hours. The curettings were of normal secretory endometrium. (Dr. H. R. Harris.) Discussion
Stefanini and Dameshek (1955) suggest that platelet dysfunction is probably more common than appears from the published accounts. Biggs and Macfarlane (1957) state that thromboasthenia may be hereditary or acquired; the latter can sometimes be explained on the basis of a coexistent blood dyscrasia-e.g., leukaemia or polycythxmia-or it can be secondary to toxic damage ". In the case described above, the uterine hxmorrhage appears to be due to defective platelet function, but no initiating factor could be found. In the light of recent observations on the changes in the blood during the normal menstrual cycle (Salvidio 1954, de Nicola et al. 1954, de Nicola 1954), one might postulate that the change in function of the platelets was initiated by an endocrine imbalance. A more detailed and thorough hasmatological investigation of the patients presenting with a dysfunctional uterine haemorrhage will be required if any advance is to be made in understanding the pathogenesis of menorrhagia. "
My thanks are due to Mr. Percy Malpas of the Women’s Hospital, Liverpool, for permission to publish this case, and to Dr. W. R. Pitney, haematologist to the Royal Perth Hospital, Western Australia, for his help and criticism. REFERENCES
Ackroyd, J. F. (1949) Clin. Sci. 7, 231. Biggs, R., Douglas, A. S. (1953) J. clin. Path. 6, 23. Macfarlane, R. G. (1957) Human Blood Coagulation and its -
Disorders. Oxford.
Bonnin, J. A. (1956) Brit. J. Hœmat. 2, 160. Braunsteiner, H. (1955) Wien. Z. inn. Med. 36, 421. Buxton, C. L. (1941) Amer. J. Obstet. Gynec. 42, 502. Dameshek, W., Rheingold, J. J. (1949) J. Amer. med. Ass. 139, 993. de Nicola, P. (1954) Rev. Hémat. 9, 536. Rosti, P., Carcupino, C. (1954) Schweiz. med. Wschr. 39, 1130. Ivy, A. C., Nelson, D., Bucher, G. (1940) J. Lab. clin. Med. 26, 1812. Lee, R. I., White, P. D. (1913) Amer. J. med. Sci. 145, 495. Quick, A. J. (1935) J. biol. Chem. 109, 73. (1951) The Physiology and Pathology of Hæmostasis. London, Salvidio, E. (1954) Acta Hœmat. 11, 301. Stefanini, M., Dameshek W. (1955) The Hæmorrhagic Disorders. New —
—
York.