490
Evidence from research and mortality and morbidity rates suggests clearly that community-based care and non-intervention management of childbirth in low-risk women is the safest form of care. Moreover, women regard these as the most acceptable forms of care, according to the select committee report. Developing community-based care would "... help engender the belief that pregnancy for most women is a normal event... provide the ability for obstetricians to concentrate on abnormal pregnancies and give continuity of care, which may improve pregnancy outcomes". (Rider ACE, during a lecture at Surrey University, May, 1992). Professionals involved in childbirth should start thinking of what is best for women and their babies, and stop trying to retain control over a process which, after all, belongs only to those affected by
it-pregnant women. Obstetric
Hospital, University College Hospital,
MARIA-JOSE CONTI
London WC1 E 2AU, UK
IM, Parsons RJ, Lawrence GF, Arora SS. An assessment of continuous fetal heart rate monitoring in labour. Am J Obstet Gynecol 1978; 131: 526-32. 2. Wood C, Rain P, Oats J, Farrel E, Beischer N, Anderson I. A controlled trial of fetal heart rate monitoring in a low risk obstetric population. Am J Obstet Gynecol 1981; 141: 527-34. 3. MacDonald D, Grant A, Sheridan-Pereira M, Boylan P, Chalmers I. The Dublin randomized controlled trial of intrapartum fetal heart rate monitoring. Am J Obstet Gynecol 1985; 152: 524-39. 4. MacArthur C, Lewis M, Knox EG. Health after childbirth. London: HM Stationery 1. Kelso
Office, 1991. 5. Van Allen D, Eskes M, Treffers PE.
Midwifery in the Netherlands: the Wormerveer study; selection, mode of delivery, perinatal mortality and infant morbidity. Br J Obstet Gynaecol 1989; 96: 656-62. 6. European Community. Midwives Directive 80/155/EEC article 4.
Vincristine for thrombotic
thrombocytopenic
purpura
SIR,- Thrombotic thrombocytopenic purpura (TTP) is and characterised by consumption thrombocytopenia, fragmentation haemolytic anaemia, renal impairment, neurological deficit, and pyrexia, although not every patient has all these features. Treatment with fresh frozen plasma (FFP) has reduced the mortality from 80% to less than 20%,1-3 but such therapy is not always successful, may be difficult to administer in patients with renal failure, and carries the risk of transmitting viral infections. We report a 52-year-old man with TTP refractory to intensive FFP therapy (at least 4daily for 18 days). After 18 days vincristine was administered: 5 days later the platelet count improved, but fell after a further 6 days. A further bolus of vincristine led to a second response, again at 5 days and followed by clinical improvement. The patient received weekly maintenance vincristine for 3 weeks and rare
remains well 2 years later.4 This reproducible result encouraged us to introduce vincristine for other patients with TTP, and we have now treated 5 patients aged 20-72. All had severe TTP with platelets under 50 x 109/1 (range 4-46), haemoglobin under 12 g/dl (5-5-11-7), and
neurological dysfunction (3 encephalopathy, 1 hemiplegia, 1 seizure); 3 patients required renal dialysis for at least 10 days and 3 had fever. Vincristineinduced disease remission in every patient, all of whom
are
well
at
least 6 months later with
no
residual
neurological or renal impairment. Each patient responded with a rise in platelet count at around 5 days after treatment (figure). Vincristine has been little used for the treatment of TTP; indeed in two reports, only 2 out of 210 patients received this drug.2,3 Anecdotal reports of vincristine’s efficacy’-6 have been treated sceptically because the drug has usually been used with FFP or other therapies. 1-3 Although FFP had been given to 3 of our 5 patients, such treatment had failed in the index case and only small quantities were given to the other 2 cases. Steroids had been given to our index patient and 1 other, but in both for less than 5 days. Therefore neither FFP nor steroids had an important role in achieving remission of TTP in at least 3 of our patients. In contrast, the consistent time from the start of vincristine to the rise in platelet count is compelling evidence that this drug was effective. Furthermore, the fact that improvement in the platelet count predicted clinical improvement in every case confirms the belief that abnormal platelet aggregation is central to the pathophysiology of TTP.
Vincristine therapy for TTP (six treatments in 5 patients):
Drug administered
on
day 0.
First-line treatment for TTP is FFP, preferably by plasmapheresis,2 but we propose that vincristine should also be given at the time of diagnosis. We start with a 2 mg bolus followed by two further injections on alternate days, with assessment of any benefit after 5 days. If the platelet count responds, we continue
vincristine 1 mg every week for
at
least 3 weeks and monitor the
platelet count for evidence of relapse. Vincristine therapy for TTP should be assessed against historical controls, rather than denying patients entered into prospective studies the benefit of this treatment.
Departments of Haematology and Medicine, Royal Shrewsbury Hospital, Shrewsbury SY3 8QR, UK
N. T. J. O’CONNOR M. J. O’SHEA L. F. HILL
Kennedy SS, Zacharski LR, Beck JR. Thrombotic thrombocytopenic purpura. analysis of 48 unselected cases. Semin Thromb Hemost 1980; 6: 341-49. 2. Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura N Engl J Med 1991; 325: 393-97. 3. Bell WR, Brame HG, Ness PM, Kiekler TS. Improved survival in thrombotic thrombocytopenic purpura: hemolytic uraemic syndrome. N Engl J Med 1991; 1
325: 398-403.
4. O’Connor NTJ, Bruce-Jones P, Hill LF. Vincristine therapy for thrombotic thrombocytopenic purpura. Am J Hematol 1992; 39: 234-36. 5. Gutterman LA, Stevenson TD. Treatment of thrombotic thrombocytopenic purpura with vincristine. JAMA 1982; 247: 1433-36. 6. Welborn JL, Emrick P, Acevedo M. Rapid improvement of thrombotic thrombocytopenic purpura with vincristine and plasmapheresis. Am J Hematol
1990; 35: 18-21.
Screening
for
cystic fibrosis carriers
SIR,-A July 25 editorial on carrier screening for cystic fibrosis (CF) compares two strategies-one preconceptional and based in primary care and one aimed at women attending the antenatal clinic. The difficulties that studies of both these strategies have revealed cause you to caution against nationwide adoption of such screening. We agree: neither approach has the merit of cascade screening, starting off with individuals with CF. Carrier screening for any recessive genetic disease requires an adequate level of background knowledge in the population who are offered screening and of self-motivation in wishing to be screened. Cascade testing, starting with individuals with a family history and their spouses, then offering to test the relatives of all those who are positive, allows one to reach a knowledgeable group at increased risk and who are interested in being tested. We have found cascade testing very popular and successful
Evidence from research and mortality and morbidity rates suggests clearly that community-based care and non-intervention management of childbirth in low-risk women is the safest form of care. Moreover, women regard these as the most acceptable forms of care, according to the select committee report. Developing community-based care would "... help engender the belief that pregnancy for most women is a normal event... provide the ability for obstetricians to concentrate on abnormal pregnancies and give continuity of care, which may improve pregnancy outcomes". (Rider ACE, during a lecture at Surrey University, May, 1992). Professionals involved in childbirth should start thinking of what is best for women and their babies, and stop trying to retain control over a process which, after all, belongs only to those affected by
it-pregnant women. Obstetric
Hospital, University College Hospital,
MARIA-JOSE CONTI
London WC1 E 2AU, UK
IM, Parsons RJ, Lawrence GF, Arora SS. An assessment of continuous fetal heart rate monitoring in labour. Am J Obstet Gynecol 1978; 131: 526-32. 2. Wood C, Rain P, Oats J, Farrel E, Beischer N, Anderson I. A controlled trial of fetal heart rate monitoring in a low risk obstetric population. Am J Obstet Gynecol 1981; 141: 527-34. 3. MacDonald D, Grant A, Sheridan-Pereira M, Boylan P, Chalmers I. The Dublin randomized controlled trial of intrapartum fetal heart rate monitoring. Am J Obstet Gynecol 1985; 152: 524-39. 4. MacArthur C, Lewis M, Knox EG. Health after childbirth. London: HM Stationery 1. Kelso
Office, 1991. 5. Van Allen D, Eskes M, Treffers PE.
Midwifery in the Netherlands: the Wormerveer study; selection, mode of delivery, perinatal mortality and infant morbidity. Br J Obstet Gynaecol 1989; 96: 656-62. 6. European Community. Midwives Directive 80/155/EEC article 4.
Vincristine for thrombotic
thrombocytopenic
purpura
SIR,- Thrombotic thrombocytopenic purpura (TTP) is and characterised by consumption thrombocytopenia, fragmentation haemolytic anaemia, renal impairment, neurological deficit, and pyrexia, although not every patient has all these features. Treatment with fresh frozen plasma (FFP) has reduced the mortality from 80% to less than 20%,1-3 but such therapy is not always successful, may be difficult to administer in patients with renal failure, and carries the risk of transmitting viral infections. We report a 52-year-old man with TTP refractory to intensive FFP therapy (at least 4daily for 18 days). After 18 days vincristine was administered: 5 days later the platelet count improved, but fell after a further 6 days. A further bolus of vincristine led to a second response, again at 5 days and followed by clinical improvement. The patient received weekly maintenance vincristine for 3 weeks and rare
remains well 2 years later.4 This reproducible result encouraged us to introduce vincristine for other patients with TTP, and we have now treated 5 patients aged 20-72. All had severe TTP with platelets under 50 x 109/1 (range 4-46), haemoglobin under 12 g/dl (5-5-11-7), and
neurological dysfunction (3 encephalopathy, 1 hemiplegia, 1 seizure); 3 patients required renal dialysis for at least 10 days and 3 had fever. Vincristineinduced disease remission in every patient, all of whom
are
well
at
least 6 months later with
no
residual
neurological or renal impairment. Each patient responded with a rise in platelet count at around 5 days after treatment (figure). Vincristine has been little used for the treatment of TTP; indeed in two reports, only 2 out of 210 patients received this drug.2,3 Anecdotal reports of vincristine’s efficacy’-6 have been treated sceptically because the drug has usually been used with FFP or other therapies. 1-3 Although FFP had been given to 3 of our 5 patients, such treatment had failed in the index case and only small quantities were given to the other 2 cases. Steroids had been given to our index patient and 1 other, but in both for less than 5 days. Therefore neither FFP nor steroids had an important role in achieving remission of TTP in at least 3 of our patients. In contrast, the consistent time from the start of vincristine to the rise in platelet count is compelling evidence that this drug was effective. Furthermore, the fact that improvement in the platelet count predicted clinical improvement in every case confirms the belief that abnormal platelet aggregation is central to the pathophysiology of TTP.
Vincristine therapy for TTP (six treatments in 5 patients):
Drug administered
on
day 0.
First-line treatment for TTP is FFP, preferably by plasmapheresis,2 but we propose that vincristine should also be given at the time of diagnosis. We start with a 2 mg bolus followed by two further injections on alternate days, with assessment of any benefit after 5 days. If the platelet count responds, we continue
vincristine 1 mg every week for
at
least 3 weeks and monitor the
platelet count for evidence of relapse. Vincristine therapy for TTP should be assessed against historical controls, rather than denying patients entered into prospective studies the benefit of this treatment.
Departments of Haematology and Medicine, Royal Shrewsbury Hospital, Shrewsbury SY3 8QR, UK
N. T. J. O’CONNOR M. J. O’SHEA L. F. HILL
Kennedy SS, Zacharski LR, Beck JR. Thrombotic thrombocytopenic purpura. analysis of 48 unselected cases. Semin Thromb Hemost 1980; 6: 341-49. 2. Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura N Engl J Med 1991; 325: 393-97. 3. Bell WR, Brame HG, Ness PM, Kiekler TS. Improved survival in thrombotic thrombocytopenic purpura: hemolytic uraemic syndrome. N Engl J Med 1991; 1
325: 398-403.
4. O’Connor NTJ, Bruce-Jones P, Hill LF. Vincristine therapy for thrombotic thrombocytopenic purpura. Am J Hematol 1992; 39: 234-36. 5. Gutterman LA, Stevenson TD. Treatment of thrombotic thrombocytopenic purpura with vincristine. JAMA 1982; 247: 1433-36. 6. Welborn JL, Emrick P, Acevedo M. Rapid improvement of thrombotic thrombocytopenic purpura with vincristine and plasmapheresis. Am J Hematol
1990; 35: 18-21.
Screening
for
cystic fibrosis carriers
SIR,-A July 25 editorial on carrier screening for cystic fibrosis (CF) compares two strategies-one preconceptional and based in primary care and one aimed at women attending the antenatal clinic. The difficulties that studies of both these strategies have revealed cause you to caution against nationwide adoption of such screening. We agree: neither approach has the merit of cascade screening, starting off with individuals with CF. Carrier screening for any recessive genetic disease requires an adequate level of background knowledge in the population who are offered screening and of self-motivation in wishing to be screened. Cascade testing, starting with individuals with a family history and their spouses, then offering to test the relatives of all those who are positive, allows one to reach a knowledgeable group at increased risk and who are interested in being tested. We have found cascade testing very popular and successful
