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The effect of maternal steroid administration on fetal platelet count in immunologic thrombocytopenic purpura
The effect of maternal steroid administration on fetal platelet count in immunologic thrombocytopenic purpura Management of pregnancy and mode of delivery T. E. LOGARIDIS, M.D. T. A. DORAN, M.D.
J.
G. SCOTT, M.D.
D. G. GARE, M.D. C. COMTESSE Toronto, Ontario, Canada Eight pregnancies complicated by immunologic thrombocytopenic purpura are described and the literature is reviewed. We conclude that, while steroid treatment favorably influenced fetal platelet counts in our cases, overall experience with this disease indicates that such protection is incomplete in some cases and unnecessary in others. Antiplatelet antibody levels show promise as excellent indicators of fetal thrombocytopenia, and elevated levels may be an indication for steroid therapy for the improvement of fetal well-being in some cases. (AM. J. OeSTET. GYNECOL. 145:147, 1983.)
IMMt:NOLOGIC thrombocytopenic purpura is a hematologic disorder in which there is production of antibodies against platelets. 1 The antibody has been shown to be a 7S immunoglobulin of the lgG fraction. Immunologic thrombocytopenic purpura complicating pregnancy is not a common occurrence, but in this situation there is a threat to both the mother and the fetus. Earlier reports noted a significant number of maternal deaths, but no maternal deaths have been reported since 1951. 2 This improvement is probably due to a number of factors, i.e., availability of blood and platelet transfusions but most likely the efficacy of steroids in causing a remission in this disease. Immunologic thrombocytopenic purpura also poses a threat to the fetus in that it has been demonstrated
From the Departments of Obstetrics and Gynaecology and Ml'diciw, Toronto Gml'ral Hospital, University of Toronto. Pre:semed at the Thirty-eighth Annual Meeting of The Society of Obstetricians and Gynaecologists of Canada, Toronto, Ontario, Canada, June 15-19, 1982. Reprim requests: T. A. Doran, M.D., Department of Obstf!trics ami GJ1U1Rcology, Toronto General Hospital NUW6-135, Toronto, Ontario, Canada M5G 1L7. 0002-9378/83/020147+05$00.50/0
©
1983 The C. V. Mosby Co.
that the antibody is actively transported across the placenta,3· 4 both when the disease is active and when it is in remission, 5• 6 which results in a variable incidence of fetal thrombocytopenia (34% to 67%). 1 The major threat to the fetus is that of intracranial hemorrhage during labor and delivery, although this can occur in the absence of labor. It is not surprising that there has been a high perinatal mortality rate reported in association with this disease (18/133 or 13%}. 1 Stillbirths and neonatal deaths have been most commonly associated with prematurity, intracranial hemorrhage, and shock. Significant neonatal morbidity with lifelong sequelae (cerebral palsy) has been reported as the result of intracranial hemorrhage, secondary to thrombocytopenia and birth injuryJ· 8 The management of pregnancy and delivery, and particularly the mode of delivery, remains controversial. Territo and associates' found neonatal thrombocytopenia in 79% of patients with maternal platelets < IOO,OOO/mm3 and in 27% of patients where maternal platelets were greater than this level. They advocated cesarean section or vaginal delivery according to maternal platelet levels. Others found this thesis unacceptable or unproved and advocated routine cesarean section for any patient with immunologic thrombocy147
148 Logaridis et al.
January 15, 1983 Am. J. Obstet. Gynecol.
Table I. Mothers in untreated group
Patient No.
Parity and Age (yr) gravidity 30
P2Gs
IIA
26
P1G2
liB
28
P2Ga
lllB
25
PIG2
Previous diagnosis of ITP
Maternal platelet count at delivery Antiplatelet (No. lmm 3) antibodies Steroids
Onset of menorrhagia at age 24; currently asymptomatic Symptomatic at age 18; splenectomy at age 19 Same patient as IIA, currently asymptomatic Same patient as lilA in Table II
135,000
Slightly pos- None itive Not done None
285,000
Not done
142,000
Slightly ele- None vated at
123,000
None
Mode
if delivery
Vaginal, 39 wk Cesarean section, 38 wk Cesarean section (repeat), 39 wk Cesarean section (repeat), 42 wk
Postpartum course if mother
Asymptomatic; no steroids Asymptomatic; no steroids Asymptomatic; no steroids Asymptomatic; no steroids
28 wk
ITP = Idiopathic thrombocytopenic purpura.
Table II. Mothers in treated group Parity Patient Age and (yr) gravidity No.
Previous diagnosis of ITP
Maternal platelets at delivery Antiplatelet (No.lmrn 3) antibodies
IliA
24
PoG4
Symptomatic at 33 wk on steroids; same patient as IIIB in Table I
158,000
Not done
IV
23
PzGa
Diabetes, class A; symptomatic at 28 wk on steroids
83,000
Not done
v
35
P2Ga
Symptomatic at 37 wk on steroids
35,000
Not done
VI
32
PoG 1
Symptomatic at age 22; splenectomy at age 26; steroids since
109,000
Negative
Steroids
Mode if delivery
Postpartum course of mother
Prednisone, Cesarean sec- Asymptomatic; steroids not continued 60-5 tion secondary to CPD mg/day and ITP, 40 wk Prednisone, Vaginal, 35 Asymptomatic; penis· 60-140 wk tent thrombocytopenia (80,000/ mg/day mm 3 ); steroids continued Asymptomatic (platePrednisone, Vaginal, 39 80-120 wk let count, 80,000/ rnm3 ); splenectomy mg/day 10 days post partum; steroids con· tinued Prednisone, Cesarean sec- Asymptomatic; ste30-60 tion, 39 wk roids continued mg/day
CPD ""' Cephalopelvic disproportion. topenic purpura in pregnancy. 1• 8 Karpatkin and associates9 found that steroid treatment of the mother favorably influenced platelet counts in the neonate. They advocated steroid treatment so that vaginal delivery could be allowed and cesarean section avoided. Cines and associates 6 and Scharfman and associates, 10 however, described three cases where treatment with steroids did not prevent neonatal thrombocytopenia. Others 11 • 12 have based the mode of delivery on results of fetal scalp sampling; however, this is not always possible; there remains some risk to the thrombocytopenic fetus and labor must progress to a certain point before it is technically feasible. In an effort to review our experience with immu-
nologic thrombocytopenic purpura in pregnancy, and particularly the relationship between maternal and neonatal platelet counts and treatment, all cases at our hospital where immunologic thrombocytopenic purpura preceded or complicated pregnancy from 1975 to 1981 were reviewed.
Results A summary of the clinical and laboratory data regarding untreated and treated mothers is given in Tables I and II; data pertaining to their infants are shown in Tables Ill and IV, respectively. One patient with immunologic thrombocytopenic purpura in pregnancy had a therapeutic abortion and one had an early
Volume H5 Number 2
Maternal steroids and immunologic thrombocytopenic purpura
149
Table III. Infants of untreated mothers
5 min
Neonat-al platelet count at !Jirth (No. /rnm 3)
2
9 6
130,000 10,000
2,720
6
9
20,000
3,480
8
9
251,000
Apgar scores
Patient No.
Sex of infant
Weight of infant (grn)
I IIA
Male Male
3,570 2,860
7
liB
Male
IIIB
Male
I
1 rnin
Treatment of infant
Follow-up
None Platelet transfusions, x20 days Platelet transfusions, x 14 days None
Well, 11;2 yr Well, 6 yr Well, 8 yr Well, 6 wk
Table IV. Infants of treated mothers Apgar scores
Patient No.
Sex of infant
Weight of infant (grn)
1 min
IliA IV
Male Male Male Male
3,180 3,390 3,660 2,692
5 9 8 8
v
VI
I
5 min
spontaneous abortion: these two patients are not included in this review. There were eight pregnancies which progressed to fetal viability in our retrospective review over the past 7 years. Four patients were observed through one pregnancy and two patients were observed through two pregnancies. In three patients, immunologic thrombocytopenic purpura antedated pregnancy, and in three, immunologic thrombocytopenic purpura was first manifest during pregnancy (at 28, 37, and 37 weeks). The most common complaints were menorrhagia and purpuric skin lesions. There were no maternal deaths, although one patient had persistent thrombocytopenia and bruising after delivery and required splenectomy 10 days post partum. There were no neonatal deaths, although two infants were severely thrombocytopenic at birth (both were delivered by cesarean section) and both required multiple platelet transfusions. There was no early or long-term significant neonatal morbidity, and follow-up of the infants ranged from 2 months to 7 months. The two neonates who were severely thrombocytopenic at birth were delivered of the same patient by cesarean section in two different pregnancies. She was in clinical remission 22 years after splenectomy (IIA and liB). The other patient in the series was observed through two pregnancies. She was symptomatic at 17 weeks (IliA): she was on a regimen of steroids and was delivered by cesarean section of an infant who was not thrombocytopenic ( l88,000/mm 3 ). In her second pregnancy, she was symptomatic, not on a regimen of steroids, and had a slightly elevated antiplatelet antibody level. 6 She was delivered by repeat cesarean section of
8 9 9
9
N e~JMtal platelet count at birth (No.lmm 3)
Treatment of infant
188,000 200,000 380,000 224,000
None None None None
Follow-up Well, Well, Well. Well,
l yr
2V2 yr 4 mo 8 mo
an infant with a normal platelet count (251.000/mma). In four pregnancies, steroids were not used, and in four other pregnancies, steroids were used in varying dosages and duration of therapy (3 to 40 weeks). In the group not treated with steroids, maternal platelet counts were I23,000/mm 3 , 135,000/mm3 , 285,000/ mm 3 , and 142,000/mm3 (mean, 171,250 ± 76,238/ mm 3). Neonatal platelet counts in the same group at birth were 130,000/mm3 , 20,000/mm 3 , 20,000/mm 3 , and 251,000/mm 3 (mean, 105,250 ± ll0.137/mm 3). In the four pregnancies in which steroids were used, maternal platelet counts were 158,000/mm3 , 83,000/ mm 3 , 35,000/mm3 , and l09,000/mm 3 (mean, 96,250 ± 51,324/mm 3 ). The neonatal platelet counts at birth in the same group were l88,000/mm 3 , 100.000/mma, 380,000/mm3 , and 224,000/mm 3 (mean, 223,000 ± 116,910/mm 3). Five of the eight pregnancies were delivered by cesarean section (two repeat), and the two infants who were severely thrombocytopenic at. birth were both delivered by cesarean section (one repeat). Antiplatelet antibody levels were obtained in three patients (two slightly elevated and one negative).
Comment We did not find any relationship between maternal and fetal platelet counts in this series, and this parallels the findings of others. 6• 9 Maternal platelet counts > 100,000/mm3 may be associated with a lower incidence of fetal thrombocytopenia in a large series.:; However, in this small group of patients two of six neonates in pregnancies where maternal platelet counts were > l00,000/mm 3 had neonatal thrombocytopenia, and neither of two neonates had thrombocytopenia when
150 Logaridis et al.
maternal platelets were < 100,000/ mm3 • Thus, in our opinion, maternal platelet counts cannot be used as a guide to the presence of fetal thrombocytopenia. We found, as did Karpatkin and assodates, 9 that the mean neonatal platelet counts in the steroid treatment group (223,000 ± ll6,910/mm 3 ) were higher than the mean value in the untreated group (105,250 ± ll0,137/mm 3). One possible mechanism for the effects of steroids in the fetus is related to the transplacental passage of the steroid into the fetal circulation. Prednisone, the commonly used steroid in this disease, is biologically inactive but is reduced by the maternal liver and other organs by 11-reductase to the active form prednisolone, which then crosses the placenta and affects the fetal platelets directly. 9 • 13• 14 A second mechanism is the effect of steroids in suppressing maternal antiplatelet antibody production, thus reducing the amount of antibody that crosses the placenta. 15 It is not clear which of these two mechanisms predominates. Two of the four mothers in our untreated group were delivered of infants without thrombocytopenia; therefore, steroid treatment would not have been necessary in half of the pregnancies in this group. Similarly, in a review of recent literature, three of seven neonates whose mothers had immunologic thrombocytopenic purpura and did not receive steroids did not have thrombocytopenia (<50,000/mm3 ). 2 • 8· 16 Conversely, in the cases described by Cines and associates 6 and Scharfman and associates 10 and in three of eight other cases described, steroids did not prevent neonatal thrombocytopenia.~· 8 • 16 It would appear that, while steroid treatment generally has a favorable effect on the fetal platelet count, it is unnecessary in some cases and ineffective in others. This latter problem may well relate to the level of anti platelet antibody. If the level is high, then steroid treatment may not protect the fetus. Since this report was prepared, Cines and associates,6 in an excellent paper, have reported a direct relationship between the level of circulating antiplatelet anti-
January 15, 1983 Am. J. Obstet. GynecoL
body and the presence and extent of neonatal thrombocytopenia. This work indicates that antiplatelet antibody levels may well be an accurate tool in assessing the risk of fetal thrombocytopenia in an individual situation. ln our series it is of interest that in three pregnancies where antiplatelet antibodies were measured, levels were mildly elevated in two and negative in the third. None of the three neonates had thrombocytopenia. There are, however, many variables involved in interpreting antiplatelet antibody levels, including the dosage and duration of steroid therapy and both the values and trends of antiplatelet antibody levels, as well as the efficiency of transfer of antibodies across the placenta. In summary, we feel that pregnancy management and mode of delivery must be individualized in this disease. While steroid therapy may provide some protection to the fetus, it is not absolute and may not be needed in some cases. Many patients will require steroid therapy for maternal indications (active immunologic thrombocytopenic purpura); however, there may be a place for steroid therapy for fetal indications in some patients, particularly if the antiplatelet antibody level is high. Where all factors point to a benign fetal course (low antiplatelet antibody !eve!, previous nonthrombocytopenic neonate), vaginal delivery can be contemplated, but fetal scalp sampling should be considered for confirmation early in labor in such cases. In patients where neonatal thrombocytopenia seems likely, cesarean section is advisable in view of the potential risks to the fetus. The management of these patients remains difficult and controversial. However, recent advances in knowledge, particularly the work of Cines and associates/ have provided us with much more accurate prognostic indicators of fetal platelet status than were previously available. The use of such knowledge in the management of pregnancy and delivery in these patients will undoubtedly result in improved results both for the fetus and for the mother.
REFERENCES 1. Horger, E. 0., and Keone, M. W. D.: Platelet disorders in pregnancy, Clin. Obstet. Gynecol. 22:843, 1979. 2. O'Reilly, R. A., and Taber, B. Z.: Immunologic thrombocytopenic purpura and pregnancy: Six new cases, Obstet. Gynecol. 51:590, 1978. 3. Cines, D. B., and Schreiber, A. D.: Immune thrombocytopenia: Use of a Coombs antiglobulin test to detect IgG and C 3 on platelets, N. Engl. J. Med. 300: l06, 1979. 4. Veenhoven, W. A., Van Des Schans, G. S., and Nieweg, H. 0.: Platelet antibodies in idiopathic thrombocytopenic purpura, Clin. Exp. Immunol. 39:645, 1980. 5. Territo, M., Finklestein, J., Oh, W., Hobel, C., and Kattlove, H.: Management of autoimmune thrombocyto-
6. 7. 8. 9.
penia in pregnanq· and in the neonate, Obstet. Gynecol. 41:579, 1973. Cines, D. B., Dusak, B., Tomaski, B.S., Mennuti, M., and Schreiber, A. D.: Immune thrombocytopenic purpura and pregnancy, N. Engl.]. Med. 300:826, 1982. Starz, A. L., Driscoll,]. A., and Wolff,J. A.: Management of isoimmune neonatal thrombocytopenia, AM. J. OBSTET. GYNECOL. J%4:39, 1976. Murray,]. M., and Harris, R. E.: The management of the pregnant patient with idiopathic thrombocytopenic purpura, AM. J. OBSTET. GYNECOL. l%6:449, 1976. Karpatkin, M., Porges, R. F., and Karpatkin, S.: Platelet counts in infants of women with autoimmune thrombocy-
Volume l·t5 Number 2
10. 11.
12.
13.
topenia. Effect of steroid administration to the mother, N. Engl. .J. Med. 305:936. 1981. Scharfman, W. B., Babcock, R. B., and Rauch, A. E.: Correspondence, N. Engl. J. Med. 306:745, 1982. Ayromlooi, J.: A new approach to the management of immunologic thrombocytopenic purpura in pregnancy, AM. J. 0BSTET. GYNECOL. 130:235, 1978. Scott, J. R., Cruikshank, D.P., Kochenour, N. K., Pitkin, R. M., and Warenski, J. C.: Fetal platelet counts in the obstetric management of immunologic thrombocytopenic purpura, AM. J. 0BSTET. GYNECOL. 136:495, 1980. Smith, B. T., and Torday,J. S.: Steroid administration in pregnant women with autoimmune thrombocytopenia, N. Engl. J. Med. 306:744, 1982.
Maternal steroids and immunologic thrombocytopenic purpura
151
14. Levitz, M., Jansen, V., and Dancis, J.: The transfer and metabolism of corticosteroids in the perfused human placenta, AM. J. OssTET. GvNECOL. 132:363. 1978. 15. Dixon, R., Rosse, W., and Ebbert, L.: Quantitative determination of antibody in idiopathic thrombocytopenic purpura: Correlation of serum and platelet bound antibody with clinical response, N. Engl. .J. !lvfed. 292:230, 1975. 16. Laros, R. K., and Sweet, R. L.: Management of idiopathic thrombocytopenic purpura during pregnane\', AM . .J. 0BSTET. GYNECOL. 122: 182, 197 5.
J.
G. SCOTT, M.D.
D. G. GARE, M.D. C. COMTESSE Toronto, Ontario, Canada Eight pregnancies complicated by immunologic thrombocytopenic purpura are described and the literature is reviewed. We conclude that, while steroid treatment favorably influenced fetal platelet counts in our cases, overall experience with this disease indicates that such protection is incomplete in some cases and unnecessary in others. Antiplatelet antibody levels show promise as excellent indicators of fetal thrombocytopenia, and elevated levels may be an indication for steroid therapy for the improvement of fetal well-being in some cases. (AM. J. OeSTET. GYNECOL. 145:147, 1983.)
IMMt:NOLOGIC thrombocytopenic purpura is a hematologic disorder in which there is production of antibodies against platelets. 1 The antibody has been shown to be a 7S immunoglobulin of the lgG fraction. Immunologic thrombocytopenic purpura complicating pregnancy is not a common occurrence, but in this situation there is a threat to both the mother and the fetus. Earlier reports noted a significant number of maternal deaths, but no maternal deaths have been reported since 1951. 2 This improvement is probably due to a number of factors, i.e., availability of blood and platelet transfusions but most likely the efficacy of steroids in causing a remission in this disease. Immunologic thrombocytopenic purpura also poses a threat to the fetus in that it has been demonstrated
From the Departments of Obstetrics and Gynaecology and Ml'diciw, Toronto Gml'ral Hospital, University of Toronto. Pre:semed at the Thirty-eighth Annual Meeting of The Society of Obstetricians and Gynaecologists of Canada, Toronto, Ontario, Canada, June 15-19, 1982. Reprim requests: T. A. Doran, M.D., Department of Obstf!trics ami GJ1U1Rcology, Toronto General Hospital NUW6-135, Toronto, Ontario, Canada M5G 1L7. 0002-9378/83/020147+05$00.50/0
©
1983 The C. V. Mosby Co.
that the antibody is actively transported across the placenta,3· 4 both when the disease is active and when it is in remission, 5• 6 which results in a variable incidence of fetal thrombocytopenia (34% to 67%). 1 The major threat to the fetus is that of intracranial hemorrhage during labor and delivery, although this can occur in the absence of labor. It is not surprising that there has been a high perinatal mortality rate reported in association with this disease (18/133 or 13%}. 1 Stillbirths and neonatal deaths have been most commonly associated with prematurity, intracranial hemorrhage, and shock. Significant neonatal morbidity with lifelong sequelae (cerebral palsy) has been reported as the result of intracranial hemorrhage, secondary to thrombocytopenia and birth injuryJ· 8 The management of pregnancy and delivery, and particularly the mode of delivery, remains controversial. Territo and associates' found neonatal thrombocytopenia in 79% of patients with maternal platelets < IOO,OOO/mm3 and in 27% of patients where maternal platelets were greater than this level. They advocated cesarean section or vaginal delivery according to maternal platelet levels. Others found this thesis unacceptable or unproved and advocated routine cesarean section for any patient with immunologic thrombocy147
148 Logaridis et al.
January 15, 1983 Am. J. Obstet. Gynecol.
Table I. Mothers in untreated group
Patient No.
Parity and Age (yr) gravidity 30
P2Gs
IIA
26
P1G2
liB
28
P2Ga
lllB
25
PIG2
Previous diagnosis of ITP
Maternal platelet count at delivery Antiplatelet (No. lmm 3) antibodies Steroids
Onset of menorrhagia at age 24; currently asymptomatic Symptomatic at age 18; splenectomy at age 19 Same patient as IIA, currently asymptomatic Same patient as lilA in Table II
135,000
Slightly pos- None itive Not done None
285,000
Not done
142,000
Slightly ele- None vated at
123,000
None
Mode
if delivery
Vaginal, 39 wk Cesarean section, 38 wk Cesarean section (repeat), 39 wk Cesarean section (repeat), 42 wk
Postpartum course if mother
Asymptomatic; no steroids Asymptomatic; no steroids Asymptomatic; no steroids Asymptomatic; no steroids
28 wk
ITP = Idiopathic thrombocytopenic purpura.
Table II. Mothers in treated group Parity Patient Age and (yr) gravidity No.
Previous diagnosis of ITP
Maternal platelets at delivery Antiplatelet (No.lmrn 3) antibodies
IliA
24
PoG4
Symptomatic at 33 wk on steroids; same patient as IIIB in Table I
158,000
Not done
IV
23
PzGa
Diabetes, class A; symptomatic at 28 wk on steroids
83,000
Not done
v
35
P2Ga
Symptomatic at 37 wk on steroids
35,000
Not done
VI
32
PoG 1
Symptomatic at age 22; splenectomy at age 26; steroids since
109,000
Negative
Steroids
Mode if delivery
Postpartum course of mother
Prednisone, Cesarean sec- Asymptomatic; steroids not continued 60-5 tion secondary to CPD mg/day and ITP, 40 wk Prednisone, Vaginal, 35 Asymptomatic; penis· 60-140 wk tent thrombocytopenia (80,000/ mg/day mm 3 ); steroids continued Asymptomatic (platePrednisone, Vaginal, 39 80-120 wk let count, 80,000/ rnm3 ); splenectomy mg/day 10 days post partum; steroids con· tinued Prednisone, Cesarean sec- Asymptomatic; ste30-60 tion, 39 wk roids continued mg/day
CPD ""' Cephalopelvic disproportion. topenic purpura in pregnancy. 1• 8 Karpatkin and associates9 found that steroid treatment of the mother favorably influenced platelet counts in the neonate. They advocated steroid treatment so that vaginal delivery could be allowed and cesarean section avoided. Cines and associates 6 and Scharfman and associates, 10 however, described three cases where treatment with steroids did not prevent neonatal thrombocytopenia. Others 11 • 12 have based the mode of delivery on results of fetal scalp sampling; however, this is not always possible; there remains some risk to the thrombocytopenic fetus and labor must progress to a certain point before it is technically feasible. In an effort to review our experience with immu-
nologic thrombocytopenic purpura in pregnancy, and particularly the relationship between maternal and neonatal platelet counts and treatment, all cases at our hospital where immunologic thrombocytopenic purpura preceded or complicated pregnancy from 1975 to 1981 were reviewed.
Results A summary of the clinical and laboratory data regarding untreated and treated mothers is given in Tables I and II; data pertaining to their infants are shown in Tables Ill and IV, respectively. One patient with immunologic thrombocytopenic purpura in pregnancy had a therapeutic abortion and one had an early
Volume H5 Number 2
Maternal steroids and immunologic thrombocytopenic purpura
149
Table III. Infants of untreated mothers
5 min
Neonat-al platelet count at !Jirth (No. /rnm 3)
2
9 6
130,000 10,000
2,720
6
9
20,000
3,480
8
9
251,000
Apgar scores
Patient No.
Sex of infant
Weight of infant (grn)
I IIA
Male Male
3,570 2,860
7
liB
Male
IIIB
Male
I
1 rnin
Treatment of infant
Follow-up
None Platelet transfusions, x20 days Platelet transfusions, x 14 days None
Well, 11;2 yr Well, 6 yr Well, 8 yr Well, 6 wk
Table IV. Infants of treated mothers Apgar scores
Patient No.
Sex of infant
Weight of infant (grn)
1 min
IliA IV
Male Male Male Male
3,180 3,390 3,660 2,692
5 9 8 8
v
VI
I
5 min
spontaneous abortion: these two patients are not included in this review. There were eight pregnancies which progressed to fetal viability in our retrospective review over the past 7 years. Four patients were observed through one pregnancy and two patients were observed through two pregnancies. In three patients, immunologic thrombocytopenic purpura antedated pregnancy, and in three, immunologic thrombocytopenic purpura was first manifest during pregnancy (at 28, 37, and 37 weeks). The most common complaints were menorrhagia and purpuric skin lesions. There were no maternal deaths, although one patient had persistent thrombocytopenia and bruising after delivery and required splenectomy 10 days post partum. There were no neonatal deaths, although two infants were severely thrombocytopenic at birth (both were delivered by cesarean section) and both required multiple platelet transfusions. There was no early or long-term significant neonatal morbidity, and follow-up of the infants ranged from 2 months to 7 months. The two neonates who were severely thrombocytopenic at birth were delivered of the same patient by cesarean section in two different pregnancies. She was in clinical remission 22 years after splenectomy (IIA and liB). The other patient in the series was observed through two pregnancies. She was symptomatic at 17 weeks (IliA): she was on a regimen of steroids and was delivered by cesarean section of an infant who was not thrombocytopenic ( l88,000/mm 3 ). In her second pregnancy, she was symptomatic, not on a regimen of steroids, and had a slightly elevated antiplatelet antibody level. 6 She was delivered by repeat cesarean section of
8 9 9
9
N e~JMtal platelet count at birth (No.lmm 3)
Treatment of infant
188,000 200,000 380,000 224,000
None None None None
Follow-up Well, Well, Well. Well,
l yr
2V2 yr 4 mo 8 mo
an infant with a normal platelet count (251.000/mma). In four pregnancies, steroids were not used, and in four other pregnancies, steroids were used in varying dosages and duration of therapy (3 to 40 weeks). In the group not treated with steroids, maternal platelet counts were I23,000/mm 3 , 135,000/mm3 , 285,000/ mm 3 , and 142,000/mm3 (mean, 171,250 ± 76,238/ mm 3). Neonatal platelet counts in the same group at birth were 130,000/mm3 , 20,000/mm 3 , 20,000/mm 3 , and 251,000/mm 3 (mean, 105,250 ± ll0.137/mm 3). In the four pregnancies in which steroids were used, maternal platelet counts were 158,000/mm3 , 83,000/ mm 3 , 35,000/mm3 , and l09,000/mm 3 (mean, 96,250 ± 51,324/mm 3 ). The neonatal platelet counts at birth in the same group were l88,000/mm 3 , 100.000/mma, 380,000/mm3 , and 224,000/mm 3 (mean, 223,000 ± 116,910/mm 3). Five of the eight pregnancies were delivered by cesarean section (two repeat), and the two infants who were severely thrombocytopenic at. birth were both delivered by cesarean section (one repeat). Antiplatelet antibody levels were obtained in three patients (two slightly elevated and one negative).
Comment We did not find any relationship between maternal and fetal platelet counts in this series, and this parallels the findings of others. 6• 9 Maternal platelet counts > 100,000/mm3 may be associated with a lower incidence of fetal thrombocytopenia in a large series.:; However, in this small group of patients two of six neonates in pregnancies where maternal platelet counts were > l00,000/mm 3 had neonatal thrombocytopenia, and neither of two neonates had thrombocytopenia when
150 Logaridis et al.
maternal platelets were < 100,000/ mm3 • Thus, in our opinion, maternal platelet counts cannot be used as a guide to the presence of fetal thrombocytopenia. We found, as did Karpatkin and assodates, 9 that the mean neonatal platelet counts in the steroid treatment group (223,000 ± ll6,910/mm 3 ) were higher than the mean value in the untreated group (105,250 ± ll0,137/mm 3). One possible mechanism for the effects of steroids in the fetus is related to the transplacental passage of the steroid into the fetal circulation. Prednisone, the commonly used steroid in this disease, is biologically inactive but is reduced by the maternal liver and other organs by 11-reductase to the active form prednisolone, which then crosses the placenta and affects the fetal platelets directly. 9 • 13• 14 A second mechanism is the effect of steroids in suppressing maternal antiplatelet antibody production, thus reducing the amount of antibody that crosses the placenta. 15 It is not clear which of these two mechanisms predominates. Two of the four mothers in our untreated group were delivered of infants without thrombocytopenia; therefore, steroid treatment would not have been necessary in half of the pregnancies in this group. Similarly, in a review of recent literature, three of seven neonates whose mothers had immunologic thrombocytopenic purpura and did not receive steroids did not have thrombocytopenia (<50,000/mm3 ). 2 • 8· 16 Conversely, in the cases described by Cines and associates 6 and Scharfman and associates 10 and in three of eight other cases described, steroids did not prevent neonatal thrombocytopenia.~· 8 • 16 It would appear that, while steroid treatment generally has a favorable effect on the fetal platelet count, it is unnecessary in some cases and ineffective in others. This latter problem may well relate to the level of anti platelet antibody. If the level is high, then steroid treatment may not protect the fetus. Since this report was prepared, Cines and associates,6 in an excellent paper, have reported a direct relationship between the level of circulating antiplatelet anti-
January 15, 1983 Am. J. Obstet. GynecoL
body and the presence and extent of neonatal thrombocytopenia. This work indicates that antiplatelet antibody levels may well be an accurate tool in assessing the risk of fetal thrombocytopenia in an individual situation. ln our series it is of interest that in three pregnancies where antiplatelet antibodies were measured, levels were mildly elevated in two and negative in the third. None of the three neonates had thrombocytopenia. There are, however, many variables involved in interpreting antiplatelet antibody levels, including the dosage and duration of steroid therapy and both the values and trends of antiplatelet antibody levels, as well as the efficiency of transfer of antibodies across the placenta. In summary, we feel that pregnancy management and mode of delivery must be individualized in this disease. While steroid therapy may provide some protection to the fetus, it is not absolute and may not be needed in some cases. Many patients will require steroid therapy for maternal indications (active immunologic thrombocytopenic purpura); however, there may be a place for steroid therapy for fetal indications in some patients, particularly if the antiplatelet antibody level is high. Where all factors point to a benign fetal course (low antiplatelet antibody !eve!, previous nonthrombocytopenic neonate), vaginal delivery can be contemplated, but fetal scalp sampling should be considered for confirmation early in labor in such cases. In patients where neonatal thrombocytopenia seems likely, cesarean section is advisable in view of the potential risks to the fetus. The management of these patients remains difficult and controversial. However, recent advances in knowledge, particularly the work of Cines and associates/ have provided us with much more accurate prognostic indicators of fetal platelet status than were previously available. The use of such knowledge in the management of pregnancy and delivery in these patients will undoubtedly result in improved results both for the fetus and for the mother.
REFERENCES 1. Horger, E. 0., and Keone, M. W. D.: Platelet disorders in pregnancy, Clin. Obstet. Gynecol. 22:843, 1979. 2. O'Reilly, R. A., and Taber, B. Z.: Immunologic thrombocytopenic purpura and pregnancy: Six new cases, Obstet. Gynecol. 51:590, 1978. 3. Cines, D. B., and Schreiber, A. D.: Immune thrombocytopenia: Use of a Coombs antiglobulin test to detect IgG and C 3 on platelets, N. Engl. J. Med. 300: l06, 1979. 4. Veenhoven, W. A., Van Des Schans, G. S., and Nieweg, H. 0.: Platelet antibodies in idiopathic thrombocytopenic purpura, Clin. Exp. Immunol. 39:645, 1980. 5. Territo, M., Finklestein, J., Oh, W., Hobel, C., and Kattlove, H.: Management of autoimmune thrombocyto-
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