704
Letters
the yearly number of new cases of cervical cancer in Israel (approximately 80 new cases per year) did not change during the years referred to in this article.' Today, when the cost of medical care is an important national problem and there are second thoughts about the benefit of routine screening programs for cervical cancer/ it seems to us that the authors' recommendation for changing national policy for cervical cancer screening in a low-risk group such as the Israeli Jewish women is not based on sound epidemiologic data and statistical analysis. G. Ben Baruch, MD, and J. Mencz.er, MD Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Tel Hashomer 52621 , Israel
REFERENCES I. Katz L, IscovitchJ, Steinitz R. Israel Cancer Registry: can-
cer in Israel, incidence and mortality, 1980-1986. Jerusalem : Ministry of Health, 1990:8. 2. McCormick JS. Cervical smears: a questionable practice? Lancet 1989;2:207-9.
Reply
To the Editors: One of the aims of our article was to point to a rising trend of incidence rates for cervical cancer in Jewish women in South Israel. This trend was expected on the basis of an earlier report that was cited in our article and demonstrated high incidence rates of preinvasive lesions of the uterine cervix among young Jewish women in Israel.' We stated that this trend had not reached statistical significance when compared with the population increase. Today, we have 140 Jewish women with invasive cervical cancer in our tumor registry, which covers complete data for the South of Israel. These patients were entered during a period of 30 years. Of these, 30.7% of cases were diagnosed during the past 5 years. In our Gynecological Tumor Registry, the percentage of living patients with invasive cervical cancer today equals those living with ovarian cancer (28% for each malignancy) . We have been alerted by these facts. As for other comments made by Drs. Ben Baruch and Menczer, they may want to again read our article. In the Material and methods section we have presented data concerning our population base and in Table II we have presented data on the ethnic distribution of our population. Moreover, we have elaborated on the unique position of our hospital being the only major health care center for South Israel. Virtually all patients from this defined geographic area are treated at our hospital, a well-known fact within the Israeli medical community. It is true therefore that prevalence trends and incidence rates at our hospital indeed reflect the population base that we serve. Drs. Ben Baruch and Menczer base their comments on one personal communication and on one article questioning the benefit of routine screening for cervical cancer. We feel that their conclusion is u~ustified. The value of screening procedures for cervical cancer is well established, and Drs. Ben Baruch and Menczer may want to consult the literature in this regard. In the population of the South of Israel, which is served by our hospital, only one out
August 1990 Am J Obstel Gynecol
of every five cases of cervical cancer is diagnosed in a preinvasive state. Given this situation, we feel that screening procedures are urgently needed at least with regard to the South of Israel. M. Glez.erman, MD, B. Piura, MD, and V. Insler, MD Obstetrics and Gynecology, Soroka Medical Center and Faculty of Health Sciences, Ben Gurion Univel'Sity, B eer Sheba, Israel
REFERENCE I . Schachter A, Avraham E. Changing trends of cervical neoplasia in Israeli Jews. Lancet 1984;2:1150.
Laboratory identification of the lupus anticoagulant in normal pregnancy and pregnancy-Induced hypertension
To the Editors: It was interesting to read the article written by Lockwood et al. (Lockwood CJ , Romero R, Feinberg RF, Clyne LP, Coster B, Hobbins JC. The prevalence and biologic significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population. AM J OBSTET GVNECOL 1989; 161:369-73) because the results could be useful to clarify the complex relationship between lupus anticoagulant and adverse pregnancy outcomes.' However, we are in disagreement concerning the detection of lupus anticoagulant in this article because it was assessed exclusively by activated partial thromboplastin time (aPTT) and mixing studies. Lupus anticoagulant exhibits considerable laboratory heterogeneity and discordance exists to define the most sensitive and specific test for its identification.'" The aPTT is the most common assay used to screen for lupus anticoagulant, but its sensitivity varies depending on the test system used.' In addition, the aPTT could be normal in pregnant women with lupus anticoagulant because of the elevated factor VIII levels seen in pregnancy.' For this reason other screening tests are particulary useful in pregnant women . In January 1989 we initiated in our laboratory a 2year prospective study to establish the prevalence of lupus anticoagulant in women with hypertensive disorders of pregnancy or idiopathic intrauterine growth retardation. Over the first-year period, we studied 20 patients and lupus anticoagulant was detected in five (preliminary results). Two of the five patients with lupus anticoagulant-positive results had normal aPTTs but abnormal kaolin clotting times,' abnormal dilute Russell viper venom time corrected by addition of freezethawed platelets," 6 and the apparent increase of factor VIII and IX activities as the patients' plasma was assayed at progressively greater dilutions. 7 On the other hand, Lockwood et al. found a discrepancy between the presence of anticardiolipin antibodies detected by an enzyme-linked immunosorbent assay and the presence of lupus anticoagulant detected by aPTT (2.2% vs 0.27%, respectively). In contrast, in a retrospective study of obstetric history in 21 women with systemic lupus erythematosus we found an equal
Letters 705
Volume 163 Number 2
relative frequency (47%) of anticardiolipin antibodies and lupus anticoagulant, with an enzyme-linked immunosorbent assay method and a complete panel for lupus anticoagulant (unpublished data). For these reasons we believe that, to establish the prevalence and biologic significance of lupus anticoagulant in pregnant women, it is mandatory to perform the lupus anticoagulant detection with tests other than the aPTT, such as kaolin clotting time and dilute Russell viper venom time. Dardo A. Riveros, MD, Beatriz E. Grand, MD, Alicia N. Blanco, PhD, Graciela Pieroni, PhD, and Maria Lazzari, MD Department of Hemostasis and Thrombosis, Academia Nacional de Medicina,JA Pacheco de Melo 3081,1425 Buenos Aires, Argentina
Liliana S. Voto, MD Department of Obstetrics and Gynecology, Hospital "JUilnA. Fernandez," Ceroiiio 3356,1425 Buenos Aires, Argentina
REFERENCES I. Lubbe WF, Liggins GC. Role of lupus anticoagulant and
2. 3.
4. 5. 6.
7.
aUlOimmunity in recurrent pregnancy loss. Semin Reprod Endocrinol 1988;6: 181-90. Triplett DA, Brandt JT, Maas RL. The laboratory heterogeneity of lupus anticoagulants. Arch Pathol Lab Med 1985; 109: 946-51. Triplett DA, Brandt J. Laboratory identification of the lupus anticoagulant [Annotation). Br J HaemalOl 1989; 73 :139-42. BrandtJT, Triplett DA, Musgrave K, Orr C. The sensitivity of different coagulation reagents lo the presence of lupus anticoagulants. Arch Pathol Lab Med 1987;111:120-4. Exner T, Rickard KA, Kronenberg H . Asensitive test demonstrating lupus anticoagulant and its behavioural patterns. Br J Haematol 1978;40: 143-51. Thiagarajan P, Pengo V, Shapiro SS. The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants. Blood 1986;68:869-74. Green D, Hougie C, Kazmier FJ, et at. Report of the Working Party on Acquired Inhibitors of Coagulation: studies of the "lupus" anticoagulant. Thromb Haemost 1983; 49:144-6.
Reply To the Editors: We would like to thank Dr. Riveros and associates for their interest in our study. They assert that the activated partial thromboplastin time (aPTT) "is the most common assay used to screen for lupus anticoagulant, but its sensitivity varies depending on the test system used." Indeed we chose the aPTT with the use of platelet-poor plasma precisely because it is the most commonly used "screening" test for lupus anticoagulant. Prior work has attested to its reliability in this capacity. J The use of more sensitive but elaborate functional coagulation assays such as the dilute Russell viper venom time and the kaolin clotting time was deemed inappropriate for a screening study. Riveros and associates report a 25% prevalence of lupus anticoagulant, presumably utilizing the dilute Russell viper venom time and/or kaolin clotting time, in 20 patients with hypertensive disorders of pregnancy
or idiopathic intrauterine growth retardation. This figure appears extraordinarily high, thus suggesting a significant number of false-positive results. In addition, their observation that patients (n = 21) with systemic lupus erythematosus had an equal prevalence of lupus anticoagulant and anticardiolipin antibodies (47%) is inconsistent with previous reports. Petri et al. 2 evaluated 60 patients with systemic lupus erythematosus and described a 6.7% prevalence of lupus anticoagulant as ascertained by a Russell viper venom time but a 25% prevalence of anticardiolipin antibodies. Harris et aP evaluated 65 patients with systemic lupus erythematosus and related autoimmune disorders and detected a 49% prevalence of lupus anticoagulant and a 61 % prevalence of anticardiolipin antibodies. 3 Thus, while Riveros and colleagues may increase sensitivity with the use of the dilute Russell viper venom time and/or kaolin clotting time, they may also increase the rate of false-positive results. In short, Riveros and associates are quite correct to assert that the dilute Russell viper venom time and kaolin clotting time are more sensitive indices of the presence of circulating lupus anticoagulant. However, the application of these tests for large-scale screening, while useful, may be impractical. Charles J. Lockwood, MD Department of Obstetrics, Gynecology and Reproductive Sciences, The Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1170, New York, NY 10029-6574
REFERENCES I. Green D, Hougie C, Kazmier F, et al. Report of the Working Party on Acquired Inhibitors of Coagulation: studies of the "lupus" anticoagulant. Thromb Haemost 1983;49:144-6. 2. Petri M, Rheinschmidt M, Whiting-O'Keefe Q, Hellmann D, Corash L. The frequency of lupus anticoagulant in systemic lupus erythematosus. Ann Intern Med 1987;106: 524-31. 3. Harris EN, Boey ML, Mackworth-Young CG, et al. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983;2:12))-4.
Role of hormones in cervical ripening To the Editors: I would like to refer to a very interest-
ing letter in the Correspondence section (Thiery M, DeBoever J, Merchiers E, Martens G. Hormones and cervical ripening [Letter]. AM J OBSTET GVNECOL 1989; 160: 1251-3). I had previously read with great interest the article
Table I. Characteristics of the patients Number Maternal age (yr) Gestational age (wk) Gravidity Parity Birth weight (gm) Time between first and second blood samples (hr)
53 22.2 ± 3.1 39.1 ± 1.7 I
o
3187.7 ± 450.6
10 ± 2
Letters
the yearly number of new cases of cervical cancer in Israel (approximately 80 new cases per year) did not change during the years referred to in this article.' Today, when the cost of medical care is an important national problem and there are second thoughts about the benefit of routine screening programs for cervical cancer/ it seems to us that the authors' recommendation for changing national policy for cervical cancer screening in a low-risk group such as the Israeli Jewish women is not based on sound epidemiologic data and statistical analysis. G. Ben Baruch, MD, and J. Mencz.er, MD Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Tel Hashomer 52621 , Israel
REFERENCES I. Katz L, IscovitchJ, Steinitz R. Israel Cancer Registry: can-
cer in Israel, incidence and mortality, 1980-1986. Jerusalem : Ministry of Health, 1990:8. 2. McCormick JS. Cervical smears: a questionable practice? Lancet 1989;2:207-9.
Reply
To the Editors: One of the aims of our article was to point to a rising trend of incidence rates for cervical cancer in Jewish women in South Israel. This trend was expected on the basis of an earlier report that was cited in our article and demonstrated high incidence rates of preinvasive lesions of the uterine cervix among young Jewish women in Israel.' We stated that this trend had not reached statistical significance when compared with the population increase. Today, we have 140 Jewish women with invasive cervical cancer in our tumor registry, which covers complete data for the South of Israel. These patients were entered during a period of 30 years. Of these, 30.7% of cases were diagnosed during the past 5 years. In our Gynecological Tumor Registry, the percentage of living patients with invasive cervical cancer today equals those living with ovarian cancer (28% for each malignancy) . We have been alerted by these facts. As for other comments made by Drs. Ben Baruch and Menczer, they may want to again read our article. In the Material and methods section we have presented data concerning our population base and in Table II we have presented data on the ethnic distribution of our population. Moreover, we have elaborated on the unique position of our hospital being the only major health care center for South Israel. Virtually all patients from this defined geographic area are treated at our hospital, a well-known fact within the Israeli medical community. It is true therefore that prevalence trends and incidence rates at our hospital indeed reflect the population base that we serve. Drs. Ben Baruch and Menczer base their comments on one personal communication and on one article questioning the benefit of routine screening for cervical cancer. We feel that their conclusion is u~ustified. The value of screening procedures for cervical cancer is well established, and Drs. Ben Baruch and Menczer may want to consult the literature in this regard. In the population of the South of Israel, which is served by our hospital, only one out
August 1990 Am J Obstel Gynecol
of every five cases of cervical cancer is diagnosed in a preinvasive state. Given this situation, we feel that screening procedures are urgently needed at least with regard to the South of Israel. M. Glez.erman, MD, B. Piura, MD, and V. Insler, MD Obstetrics and Gynecology, Soroka Medical Center and Faculty of Health Sciences, Ben Gurion Univel'Sity, B eer Sheba, Israel
REFERENCE I . Schachter A, Avraham E. Changing trends of cervical neoplasia in Israeli Jews. Lancet 1984;2:1150.
Laboratory identification of the lupus anticoagulant in normal pregnancy and pregnancy-Induced hypertension
To the Editors: It was interesting to read the article written by Lockwood et al. (Lockwood CJ , Romero R, Feinberg RF, Clyne LP, Coster B, Hobbins JC. The prevalence and biologic significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population. AM J OBSTET GVNECOL 1989; 161:369-73) because the results could be useful to clarify the complex relationship between lupus anticoagulant and adverse pregnancy outcomes.' However, we are in disagreement concerning the detection of lupus anticoagulant in this article because it was assessed exclusively by activated partial thromboplastin time (aPTT) and mixing studies. Lupus anticoagulant exhibits considerable laboratory heterogeneity and discordance exists to define the most sensitive and specific test for its identification.'" The aPTT is the most common assay used to screen for lupus anticoagulant, but its sensitivity varies depending on the test system used.' In addition, the aPTT could be normal in pregnant women with lupus anticoagulant because of the elevated factor VIII levels seen in pregnancy.' For this reason other screening tests are particulary useful in pregnant women . In January 1989 we initiated in our laboratory a 2year prospective study to establish the prevalence of lupus anticoagulant in women with hypertensive disorders of pregnancy or idiopathic intrauterine growth retardation. Over the first-year period, we studied 20 patients and lupus anticoagulant was detected in five (preliminary results). Two of the five patients with lupus anticoagulant-positive results had normal aPTTs but abnormal kaolin clotting times,' abnormal dilute Russell viper venom time corrected by addition of freezethawed platelets," 6 and the apparent increase of factor VIII and IX activities as the patients' plasma was assayed at progressively greater dilutions. 7 On the other hand, Lockwood et al. found a discrepancy between the presence of anticardiolipin antibodies detected by an enzyme-linked immunosorbent assay and the presence of lupus anticoagulant detected by aPTT (2.2% vs 0.27%, respectively). In contrast, in a retrospective study of obstetric history in 21 women with systemic lupus erythematosus we found an equal
Letters 705
Volume 163 Number 2
relative frequency (47%) of anticardiolipin antibodies and lupus anticoagulant, with an enzyme-linked immunosorbent assay method and a complete panel for lupus anticoagulant (unpublished data). For these reasons we believe that, to establish the prevalence and biologic significance of lupus anticoagulant in pregnant women, it is mandatory to perform the lupus anticoagulant detection with tests other than the aPTT, such as kaolin clotting time and dilute Russell viper venom time. Dardo A. Riveros, MD, Beatriz E. Grand, MD, Alicia N. Blanco, PhD, Graciela Pieroni, PhD, and Maria Lazzari, MD Department of Hemostasis and Thrombosis, Academia Nacional de Medicina,JA Pacheco de Melo 3081,1425 Buenos Aires, Argentina
Liliana S. Voto, MD Department of Obstetrics and Gynecology, Hospital "JUilnA. Fernandez," Ceroiiio 3356,1425 Buenos Aires, Argentina
REFERENCES I. Lubbe WF, Liggins GC. Role of lupus anticoagulant and
2. 3.
4. 5. 6.
7.
aUlOimmunity in recurrent pregnancy loss. Semin Reprod Endocrinol 1988;6: 181-90. Triplett DA, Brandt JT, Maas RL. The laboratory heterogeneity of lupus anticoagulants. Arch Pathol Lab Med 1985; 109: 946-51. Triplett DA, Brandt J. Laboratory identification of the lupus anticoagulant [Annotation). Br J HaemalOl 1989; 73 :139-42. BrandtJT, Triplett DA, Musgrave K, Orr C. The sensitivity of different coagulation reagents lo the presence of lupus anticoagulants. Arch Pathol Lab Med 1987;111:120-4. Exner T, Rickard KA, Kronenberg H . Asensitive test demonstrating lupus anticoagulant and its behavioural patterns. Br J Haematol 1978;40: 143-51. Thiagarajan P, Pengo V, Shapiro SS. The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants. Blood 1986;68:869-74. Green D, Hougie C, Kazmier FJ, et at. Report of the Working Party on Acquired Inhibitors of Coagulation: studies of the "lupus" anticoagulant. Thromb Haemost 1983; 49:144-6.
Reply To the Editors: We would like to thank Dr. Riveros and associates for their interest in our study. They assert that the activated partial thromboplastin time (aPTT) "is the most common assay used to screen for lupus anticoagulant, but its sensitivity varies depending on the test system used." Indeed we chose the aPTT with the use of platelet-poor plasma precisely because it is the most commonly used "screening" test for lupus anticoagulant. Prior work has attested to its reliability in this capacity. J The use of more sensitive but elaborate functional coagulation assays such as the dilute Russell viper venom time and the kaolin clotting time was deemed inappropriate for a screening study. Riveros and associates report a 25% prevalence of lupus anticoagulant, presumably utilizing the dilute Russell viper venom time and/or kaolin clotting time, in 20 patients with hypertensive disorders of pregnancy
or idiopathic intrauterine growth retardation. This figure appears extraordinarily high, thus suggesting a significant number of false-positive results. In addition, their observation that patients (n = 21) with systemic lupus erythematosus had an equal prevalence of lupus anticoagulant and anticardiolipin antibodies (47%) is inconsistent with previous reports. Petri et al. 2 evaluated 60 patients with systemic lupus erythematosus and described a 6.7% prevalence of lupus anticoagulant as ascertained by a Russell viper venom time but a 25% prevalence of anticardiolipin antibodies. Harris et aP evaluated 65 patients with systemic lupus erythematosus and related autoimmune disorders and detected a 49% prevalence of lupus anticoagulant and a 61 % prevalence of anticardiolipin antibodies. 3 Thus, while Riveros and colleagues may increase sensitivity with the use of the dilute Russell viper venom time and/or kaolin clotting time, they may also increase the rate of false-positive results. In short, Riveros and associates are quite correct to assert that the dilute Russell viper venom time and kaolin clotting time are more sensitive indices of the presence of circulating lupus anticoagulant. However, the application of these tests for large-scale screening, while useful, may be impractical. Charles J. Lockwood, MD Department of Obstetrics, Gynecology and Reproductive Sciences, The Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1170, New York, NY 10029-6574
REFERENCES I. Green D, Hougie C, Kazmier F, et al. Report of the Working Party on Acquired Inhibitors of Coagulation: studies of the "lupus" anticoagulant. Thromb Haemost 1983;49:144-6. 2. Petri M, Rheinschmidt M, Whiting-O'Keefe Q, Hellmann D, Corash L. The frequency of lupus anticoagulant in systemic lupus erythematosus. Ann Intern Med 1987;106: 524-31. 3. Harris EN, Boey ML, Mackworth-Young CG, et al. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983;2:12))-4.
Role of hormones in cervical ripening To the Editors: I would like to refer to a very interest-
ing letter in the Correspondence section (Thiery M, DeBoever J, Merchiers E, Martens G. Hormones and cervical ripening [Letter]. AM J OBSTET GVNECOL 1989; 160: 1251-3). I had previously read with great interest the article
Table I. Characteristics of the patients Number Maternal age (yr) Gestational age (wk) Gravidity Parity Birth weight (gm) Time between first and second blood samples (hr)
53 22.2 ± 3.1 39.1 ± 1.7 I
o
3187.7 ± 450.6
10 ± 2
