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The obstetrical management of patients with immunologic thrombocytopenic purpura
Int. J. Gynaecol. Obstet., 1982, 20: 23-28 International Federation of Gynaecology & Obstetrics
THE OBSTETRICAL MANAGEMENT OF PATIENTS WITH IMMUNOLOGIC THROMBOCYTOPENIC PURPURA I. KESSLER, M. LANCET, R. BORENSTEIN, A. BERREBI and B.M. MOGILNER Departments of Obstetrics and Gynecology, Hematology and Neonatology, Hebrew University Medical School, Jerusalem, Israel
Kaplan Hospital, Rehovot, Affiliated
to the Hadassah-
(Received April 20th, 1981) (Accepted July lOth, 1981)
Abstract Kessler I, Lancet M, Borenstein R, Berrebi A, Mogilner BM (Depts of Obstetrics and Gynecology, Hema tology and Neonatology, Kaplan Hospital, Rehovot, Affiliated to the Hadassah-Hebrew University Medical School, Jerusalem, Israel). The obstetrical management of patients with immunologic thrombocy topenic purpura. Int J Gynaecol Obstet 20: 23-28, I982 Pregnant women with immunologic thrombocytopenic purpura (ITPI run the risk of complications during pregnancy and labor, mainly due to the possibility of hemorrhage. Antibodies pass through the placenta, causing a transient, but dangerous thrombocytopenia in the fetus and infant. Four women with ITP, having five deliveries, are presented, showing that the modern treatment of these patients includes corticosteroids during pregnancy, thrombocyte transfusion during labor, and splenectomy before or after the pregnancy in selected cases. Cesarean section is not indicated for the disease per se, and fetal scalp blood sampling for thrombocyte count during labor is not necessary. The newborn needs immediate, careful control and, if necessary, thrombocyte transfusion and even steroids. Prolonged follow-up of the infants is n ecessary . Key words: Immunologic OOZ-7292/82/0000-0000/$02.75 0 1982 International Federation
thrombocytopenic
purpura; Hemorrhage; Corticosteroids during pregnancy; Thrombocyte transfusion; Splenectomy Introduction Immunologic thrombocytopenic purpura (ITP), known in earlier years under the name of idiopathic thrombocytopenic purpura, is an auto-immune disease of unknown etiology. Auto-antibodies against the thrombocytes are produced in the body, and they are of the IgG type, sub-group 3 [ 5,11,123 . They are incomplete blocking antibodies and bind to the surface of the thrombocytes [ 101. The antibodies have been demonstrated in 85% of the patients with the clinical disease [ 111, and they cause an early and large-scale destruction of the thrombocytes in the reticula-endothelial system, leading to thrombocytopenia, which may be quite severe. In pregnancy, the disease has to be differentiated from leukemia, lupus erythematosus, thrombocytopenia in severe toxemia of pregnancy, thrombotic thrombocytopenia, megaloblastic anemia, etc. As the antibodies can pass the placental barrier, a temporary, passive thrombocytopenia is seen in the fetus and the newborn, which may cause brain hemorrhage with neurologic symptoms, bleeding in the gut and the lungs, with a relatively high incidence of perinatal morbidity, and also an increased rate of perinatal mortality. Most authorities agree on the management In t J Gynaecol Obstet 20
of Gynaecology & Obstetrics
24
Kessler et al.
of the disease during pregnancy but there are controversies about the best mode of delivery, so that the effect of the thrombocytopenia on the newborn would be minimal. Because of the rarity of the disease in pregnant women and the controversies just mentioned, four cases with five deliveries are presented, with a review of the relevant literature. Methods and results All patients complied with the criteria of ITP: (1) the number of thrombocytes equal or less than 50,000/mm3, without any other systemic disease or toxic effects of drugs; (2) the existence of purpura; (3) no enlargement of the spleen or the liver; (4) no change in the bone marrow picture, and especially a normal or somewhat increased count of megakaryocytes in it; (5) normal clotting function tests; and (6) the existence of antithrombocytic antibodies in the serum. (Thus they could be sharply differentiated from isoimmune thrombocytopenia of the newborn i131.1 Table I shows the details of the four patients, and the method of treatment before
Table I. Patient
and during the pregnancy. The pregnancies were normal, and in the antecedent pregnancies there were no abortions or premature deliveries. In the present pregnancies there was no ante-par-turn bleeding or premature rupture of the membranes. In all cases, the fetus was monitored during the pregnancy by gray-scale ultrasound, non-stress tests and the measurement of estriol in the maternal urine. All these parameters were normal throughout the pregnancies. All deliveries were vaginal, both in the three primiparae, and the two multiparae (Table II). Episiotomies were done in all patients, and there was no excessive bleeding either during, or immediately after the deliveries. In one patient there was an infiltrate around the suture of the episiotomy, and the same woman had a severe hemorrhage 6 weeks after delivery, necessitating a curettage. All the women received corticosteroid treatment during the pregnancy (Table I); one had a splenectomy at the age of 5 years, and another 4 months after her second delivery (Table II). Only two of the patients needed the transfusion of thrombocytes in large doses during and after delivery. Two women received immune-suppressive therapy: one twice (at
Patients and treatment of thrombocytopenia prior and during the pregnancy. Age of patient at delivery (years)
Age when ITP was $a+gn;sed
24
Treatment prior to pregnancy
Parity
Thrombocytes count during pregnancy (per mm”)
Treatment during pregnancy
Prednisone 30 mg
1
56,000-118,000
Prednisone 30 mg
Prednisone 30 mg
2
60,000-140,000
Prednisone 60 mg Prednisone 30-60 mg
10
K.N. 21 Ch.E.
19
17
Prednisone 60 mg
1
20,000-
T.A.
30
18
Prednisone 60 mg
3
10,200-118,000
Prednisone 30 mg
J.Sh.
21
4
Splenectomy ACTH 6 Mercaptopurine Azathioprine Prednisone 30 mg D&C
1
s,ooo-100,000
Prednisone 60 mg
ZntJ Gynaecol Obstet 20
80,000
Immunologic thrombocytopenia in pregnancy Table II.
Mode of delivery, the treatment during labor and after delivery. Mode of delivery
Treatment during labor
Thrombocytes count at delivery (per mm3)
Treatment after delivery
Spontaneous Vaginal
None
50,000
Prednisone 30 mg
Spontaneous Vaginal
None
46,000
Prednisone 30-60 mg Splenectomy 4 months after delivery
Ch.E.
Spontaneous Vaginal
Thrombocytes transfusion
12,000
Prednisone 60 mg Immuran
T.A.
Spontaneous Vaginal
None
10,000
Prednisone 30 mg
JSh.
Spontaneous Vaginal
Dextran Hydrocortisone Thrombocytes transfusion
Patient
25
K.N.
5,000
Thrombocytes D&Ca
transfusion
aSee text
the age of 6 and 12), and the other soon after her delivery (Table II). The newborns were in good condition and all had an Apgar score of 9-10 at 1 mm. Only one was in need of a thrombocyte transfusion and steroids (Table III). The cephalhaematomata were not large enough to necessitate transfusions and they underwent a rapid healing, leading to calcification and new bone formation. No signs of central nervous system damage were detected and the babies Table III.
behaved normally during the neonatal period. Follow-up for prolonged periods showed no physical or developmental abnormality in any infant. Discussion The frequency of ITP in pregnancy is similar to its frequency in the general population, viz: l-2 in 10,000 [22,28]. The influence of the pregnancy on the
The newborn at delivery and later development.
Patient
Sex
Weight (8)
Thrombocytes count at delivery (per mm”)
Chnical picture
Treatment
Later development
K.N.
F
2800
50,000
Normal
-
Nornal
K.N.
M
3400
110,000
Polycythemia Hypoglycemia
Dilutional exchange
Normal
Ch.E.
M
3100
12,000
Cephalhematoma
-
Normal
T.A.
M
4300
120,000
Cephalhematoma
-
Normal
J.Sh.
M
3360
2,000
Purpura G.I. bleeding Hematuria
Thrombocytes and blood transfusion Steroids
Normal
In t J Gynaecol Obstet 20
26
Kessler et al.
course of the disease is generally deleterious, with an exacerbation in 30-50% of the cases [9,14,26]. As for the impact of ITP on the pregnancy, it is quite evident that there is an increase in maternal and fetal complications. An increase in the rate of abortions has been reported, reaching up to 33% of the pregnancies [ 2,261, possibly because of an increase in the rate of the circulating serotonin, due to the destruction of thrombocytes [26]. Hemorrhage in pregnancy has been noted in 7-22% of the patients [6,7], excessive bleeding in the third stage of labor in up to 7% [4,6,7,23,30] and bleeding from the episiotomy in 1 l-l 2% [ 4,23,25,30]. A few decades ago there was a high rate of maternal mortality in cases of ITP, reaching 11% [ 18,24,29] but since the introduction of steroid treatment in 195 1, this rate has diminished considerably, and now equals the incidence of maternal mortality in the general population [ 10,18,20] . Territo [ 301 claims that no cases of mortality occurred when the delivery was by cesarean section. In about 50-70% of the newborns antithrombocyte antibodies have been demonstrated [ 21 and purpura in 50-73% [ 2,25,291. Thrombocytopenia was seen in a large percentage of the babies [8,15,18,25,30]. Even after maternal splenectomy, about 40% of the newborn showed purpura [ 251. The thromboand the purpura disappear cytopenia gradually 2-12 weeks after birth [4,6,301. Intracranial hemorrhage was found in 1O-30% of the newborn, leading to neurologic and mental deficiencies [28], as well as bleeding in the intestines and lungs [ 23,261. Most authors report an increase in perinatal mortality to 6-3 1% due to intracranial hemorrhage [8,15,17,21]. The mainstay of treatment during pregnancy is corticosteroids, reaching a daily dose of 40-80 mg of prednisone [ 16,191. A definite remission in the disease is seen in up to 80% of the cases [ 15,201. This treatment reduces the rate of destruction of the platelets in the reticulo-endothelial system, improves the capillary integrity and influences the ZntJ Gynaecol Obstet 20
immunologic state. Although it has been claimed that steroid therapy may be teratogenie [6,29] and may cause adrenal insufficiency in the fetus [6], no such signs were observed, and the normal estriol excretion proved that fetal adrenal function was unimpaired [3]. Due to steroid therapy, the maternal mortality has dropped to nil, and women suffering from the disease were given the possibility to bear children. This type of treatment cannot lower the titer of the antibodies in the fetus, as they are found in its serum as a result of passive transfer from the mother. Splenectomy is indicated only in the cases in which steroid therapy has not been successful, and the rate of remission after this operation is about 60-90% [ 15,191. It is preferable to perform splenectomy prior to the pregnancy [4,6,10,291. Fetal thrombocytopenia in post-splenectomy patients may also be seen. The transfusion of large amounts of thrombocytes during labor will prevent bleeding in most cases [10,15,19], but it cannot influence the number of thrombocytes in the newborn and there is the danger of viral hepatitis. Immunosuppressive therapy has been advocatedin cases resistant to other forms of treatment. Azathioprine and cyclophosphamide, as well as the vinca alkaloids have been given to such patients [20], but cytotoxic agents may be dangerous to the fetus. Since the thrombocytopenia in the newborn is a self-limited condition, the treatment should be related to the number of thrombocytes and bleeding symptoms. The therapeutic procedures are: transfusion of thrombocyte concentrate, and blood exchange transfusion, if the former step does not keep the thrombocyte count over 25,000 mm3. Steroids should be the last step if bleeding tendency continues. Mode of delivery
Controversies among obstetricians as to the best and safest mode of delivery in patients
Immunologic thrombocytopenia in pregnancy
with ITP have been, and still are, rampant. Some advocate elective cesarean section in all cases, to prevent compression of the head by the birth canal [8,14,17,181, even proposing the classical incision of the uterus [ 17 I , or cesarean and splenectomy in the same session [8,16,18]. Another method is to do a cesarean according to rate of thrombocytopenia in the mother, 100,000 platelets/mm3 being the limit below which the delivery should be abdominal [ 16,28,30 1. Some definitely forbid the use of forceps [22,30], while others allow either forceps or the vacuum extractor in some cases [7,19,21,261. Lately, some have thought that the decision whether delivery should be by cesarean depends on the count of the thrombocytes from a scalp blood sample of the fetus, taken during delivery: less than 50,000/mm3 points towards operation, while a higher count allows the obstetrician to permit vaginal delivery [ 1,22,27]. The most modern approach to the problem is to permit vaginal delivery, unless other obstetric indications for a cesarean exist [2,6,9,15,19,23,26] Pearson [21] adds as an indication for operation the fact that there are already some children with neurologic or intellectual dysfunction in the family. The decision to allow for a vaginal delivery has been based on several facts: no concordance between the number of thrombocytes in the mother and the infant [ 191: the number of thrombocytes in the infant is not a good prognostic sign for the occurrence of intracranial hemorrhage even after cesarean section [ 15,161 ; the high morbidity of the mothers during and after the operation and the lack of evidence that section improves the state of the infant. Conclusions
In the cases presented in this paper, it has been shown that through good cooperation between the hematologist and the obstetrician, efficient steroid treatment, and the
27
transfusion of thrombocytes when needed, safe vaginal delivery in cases of ITP can be achieved. There is no need for a thrombocyte count from the scalp during delivery, but the neonatologist must be present at the delivery, so that immediate blood sampling can be done and appropriate treatment instituted to the newborn, if and when it becomes necessary. The follow-up of the infant must be prolonged, and of course, the mother’s state must not be lost from the eyes of the doctors treating the case. References 1 Ayromlooi J: A new approach to the management of immunologic thrombocytopenic purpura in pregnancy. Am J Obstet GynecolI30: 235,1978. 2 Bell WR: Hematologic abnormalities in pregnancy. Med Clin North Am 61: 183, 1977. Saunders (Philadelphia). 3 Dickey PR, Thompson PJ: Effect of ACTH and Metyrapone on estriol, 17-hydroxycorticosteroid, 17ketosteroid, pregnandiol and pregnanetriol excretion late in pregnancy. J Clin Endocrlnol Metab 29: 701, 1969. 4 Goodhue PA, Evans TS: Idiopathic thrombocytopenic purpura in pregnancy. Obstet Gynecol Surv 18: 671, 1963. 5 Harrington WJ, Minnich V, Hollingsworth JW et al.: Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura. J Lab Clin Med 38: 1,195l. 6 Heys RF. Steroid therapy for idiopathic thrombocytopenic purpura during pregnancy. Obstet Gynecol 28: 532,1966. -I Heys RF. Child bearing and idiopathic thrombocytopenic purpura. J Obstet Gynecol Br Commonw 73: 205,1966. 8 Jones WR, Storey B, Norton G et al.: Pregnancy complicated by acute idiopathic thrombocytopenic purpura a report of two patients treated by simultaneous caesarean section and splenectomy. J Obstet Gynaecol Br Commonw 81: 330,1974. 9 Jones WR, Asher MI, Ruthenford CJ et al.: Autoimmune (idiopathic) thrombocytopenic purpura in pregnancy and newborn. Br J Obstet Gynecol 84: 679, 1977. 10 Jones WR: Tissue-specific autoimmune disease in pregnancy. Clinics in Obstet Gynecol: Immunological aspect of reproduction. 6: 3, p. 473, 1979. Saunders (Philadelphia-London-Toronto). 11 Karpatkin S, Siskind GW: In vitro detection of platelet antibody in patients with idiopathic thrombocytopenic purpura and systemic lupus erythematous. Blood 33: 795,1969. Int J Gynaecol Obstet 20
28
Kessler
et al.
12 Karpatkin S, Achur PH, Strick N et al.: Heavy chain subclass of human antiplatelet antibodies. Clin Immunol Immunopathol2: 1,1973. 13 Kelton GJ, Blanchette SV, Wilson EW et al.: Neonatal thrombocytopenia due to passive immunization: prenatal diagnosis and distinction between maternal platelet alloantibodies and autoantibodies. N Eng J Med 302: 1401,198O. 14 KitzmiIler JL: Autoimmune disorders: maternal, fetal and neonatal risks. Clin Obstet Gynecol21: 385, 1978. Harper & Row. 15 Laros RK, Sweet RL: Management of idiopathic thrombocytopenic purpura during pregnancy. Am J Obstet Gynecol122: 182,197s. 16 Levine, PR, Adams RR, Silver A et al.: Idiopathic thrombocytopenic purpura, diabetes meBitus and pregnancy. Obstet Gynecol (Suppl) 48: 31S, 1976. 17 Memmti M, Schwarz RH, Gill F: Obstetric management of isoimmune thrombocytopenia. Am J Obstet Gynecol 118: 565,1974. 18 Murray JM, Harris RE: The management of the pregnant patient with idiopathic thrombocytopenic purpura. Am J Obstet Gynecol126: 449,1976. 19 NoriegaGuerra L, Aviles-Miranda A, Alvarez de la Cadena 0 et al.: Pregnancy in patients with autoimmune thrombocytopenic purpura. Am J Obstet Gynecol 133: 439, 1979. 20 O’Reilly RA, Taber B. Immunologic thrombocytopenic purpura and pregnancy. Obstet GynecolSI: 590, 1978. 21 Pearson HA, Shuhnan NR, Marder VJ et al.: Isoimmune neonatal thrombocytopenic purpura; clinical and therapeutic considerations. Blood 23: 154.1964.
In t J Gynaecol
Obstet
20
22 Perkins RP: Thrombocytopenia in obstetric syndromes. A review. Obstet Gynecol Surv 34: 101,1979. 23 Peterson OH, Larson P: Thrombocytopenic purpura in pregnancy. Obstet Gynecol4: 454,1954. 24 Robson HN, Davidson LSP. Purpura in pregnancy, with specialreference to idiopathic thrombocytopenic purpura. Lancet 2: 164,195O. 25 Rogers TE Jr, Macon AG: Thrombocytopenia in pregnancy following splenectomy. Am J Obstet Gynecol 78: 806,1959. 26 Schenker JG, Polishuk WZ: Idiopathic thrombocytopenia in pregnancy. Gynaecologia (Basel) 165: 271, 1968. 27 Scott JR, Cruikshank DP, Kochenour NR et al.: Fetal platelet count in the obstetric management of immunologic thrombocytopenic purpura. Am J Obstet Gynecol 136: 495,198O. 28 Sitarz AL, DriscoIl JM, Wolff JA: Management of isoimmune neonatal thrombocytopenia. Am J Obstet Gynecol124: 39,1976. 29 Tamer ML: Idiopathic thrombocytopenic purpura and pregnancy. Am J Obstet Gynecol 79: 148, 1960. 30 Territo M, Fhrklestein J, Oh W et al.: Management of autoimmune thrombocytopenia in pregnancy and in neonate. Obstet Gynecol41: 579, 1973.
Address for reprints: Professor M. Lancet Kaplan Hospital 76400 Rehovot Israel
THE OBSTETRICAL MANAGEMENT OF PATIENTS WITH IMMUNOLOGIC THROMBOCYTOPENIC PURPURA I. KESSLER, M. LANCET, R. BORENSTEIN, A. BERREBI and B.M. MOGILNER Departments of Obstetrics and Gynecology, Hematology and Neonatology, Hebrew University Medical School, Jerusalem, Israel
Kaplan Hospital, Rehovot, Affiliated
to the Hadassah-
(Received April 20th, 1981) (Accepted July lOth, 1981)
Abstract Kessler I, Lancet M, Borenstein R, Berrebi A, Mogilner BM (Depts of Obstetrics and Gynecology, Hema tology and Neonatology, Kaplan Hospital, Rehovot, Affiliated to the Hadassah-Hebrew University Medical School, Jerusalem, Israel). The obstetrical management of patients with immunologic thrombocy topenic purpura. Int J Gynaecol Obstet 20: 23-28, I982 Pregnant women with immunologic thrombocytopenic purpura (ITPI run the risk of complications during pregnancy and labor, mainly due to the possibility of hemorrhage. Antibodies pass through the placenta, causing a transient, but dangerous thrombocytopenia in the fetus and infant. Four women with ITP, having five deliveries, are presented, showing that the modern treatment of these patients includes corticosteroids during pregnancy, thrombocyte transfusion during labor, and splenectomy before or after the pregnancy in selected cases. Cesarean section is not indicated for the disease per se, and fetal scalp blood sampling for thrombocyte count during labor is not necessary. The newborn needs immediate, careful control and, if necessary, thrombocyte transfusion and even steroids. Prolonged follow-up of the infants is n ecessary . Key words: Immunologic OOZ-7292/82/0000-0000/$02.75 0 1982 International Federation
thrombocytopenic
purpura; Hemorrhage; Corticosteroids during pregnancy; Thrombocyte transfusion; Splenectomy Introduction Immunologic thrombocytopenic purpura (ITP), known in earlier years under the name of idiopathic thrombocytopenic purpura, is an auto-immune disease of unknown etiology. Auto-antibodies against the thrombocytes are produced in the body, and they are of the IgG type, sub-group 3 [ 5,11,123 . They are incomplete blocking antibodies and bind to the surface of the thrombocytes [ 101. The antibodies have been demonstrated in 85% of the patients with the clinical disease [ 111, and they cause an early and large-scale destruction of the thrombocytes in the reticula-endothelial system, leading to thrombocytopenia, which may be quite severe. In pregnancy, the disease has to be differentiated from leukemia, lupus erythematosus, thrombocytopenia in severe toxemia of pregnancy, thrombotic thrombocytopenia, megaloblastic anemia, etc. As the antibodies can pass the placental barrier, a temporary, passive thrombocytopenia is seen in the fetus and the newborn, which may cause brain hemorrhage with neurologic symptoms, bleeding in the gut and the lungs, with a relatively high incidence of perinatal morbidity, and also an increased rate of perinatal mortality. Most authorities agree on the management In t J Gynaecol Obstet 20
of Gynaecology & Obstetrics
24
Kessler et al.
of the disease during pregnancy but there are controversies about the best mode of delivery, so that the effect of the thrombocytopenia on the newborn would be minimal. Because of the rarity of the disease in pregnant women and the controversies just mentioned, four cases with five deliveries are presented, with a review of the relevant literature. Methods and results All patients complied with the criteria of ITP: (1) the number of thrombocytes equal or less than 50,000/mm3, without any other systemic disease or toxic effects of drugs; (2) the existence of purpura; (3) no enlargement of the spleen or the liver; (4) no change in the bone marrow picture, and especially a normal or somewhat increased count of megakaryocytes in it; (5) normal clotting function tests; and (6) the existence of antithrombocytic antibodies in the serum. (Thus they could be sharply differentiated from isoimmune thrombocytopenia of the newborn i131.1 Table I shows the details of the four patients, and the method of treatment before
Table I. Patient
and during the pregnancy. The pregnancies were normal, and in the antecedent pregnancies there were no abortions or premature deliveries. In the present pregnancies there was no ante-par-turn bleeding or premature rupture of the membranes. In all cases, the fetus was monitored during the pregnancy by gray-scale ultrasound, non-stress tests and the measurement of estriol in the maternal urine. All these parameters were normal throughout the pregnancies. All deliveries were vaginal, both in the three primiparae, and the two multiparae (Table II). Episiotomies were done in all patients, and there was no excessive bleeding either during, or immediately after the deliveries. In one patient there was an infiltrate around the suture of the episiotomy, and the same woman had a severe hemorrhage 6 weeks after delivery, necessitating a curettage. All the women received corticosteroid treatment during the pregnancy (Table I); one had a splenectomy at the age of 5 years, and another 4 months after her second delivery (Table II). Only two of the patients needed the transfusion of thrombocytes in large doses during and after delivery. Two women received immune-suppressive therapy: one twice (at
Patients and treatment of thrombocytopenia prior and during the pregnancy. Age of patient at delivery (years)
Age when ITP was $a+gn;sed
24
Treatment prior to pregnancy
Parity
Thrombocytes count during pregnancy (per mm”)
Treatment during pregnancy
Prednisone 30 mg
1
56,000-118,000
Prednisone 30 mg
Prednisone 30 mg
2
60,000-140,000
Prednisone 60 mg Prednisone 30-60 mg
10
K.N. 21 Ch.E.
19
17
Prednisone 60 mg
1
20,000-
T.A.
30
18
Prednisone 60 mg
3
10,200-118,000
Prednisone 30 mg
J.Sh.
21
4
Splenectomy ACTH 6 Mercaptopurine Azathioprine Prednisone 30 mg D&C
1
s,ooo-100,000
Prednisone 60 mg
ZntJ Gynaecol Obstet 20
80,000
Immunologic thrombocytopenia in pregnancy Table II.
Mode of delivery, the treatment during labor and after delivery. Mode of delivery
Treatment during labor
Thrombocytes count at delivery (per mm3)
Treatment after delivery
Spontaneous Vaginal
None
50,000
Prednisone 30 mg
Spontaneous Vaginal
None
46,000
Prednisone 30-60 mg Splenectomy 4 months after delivery
Ch.E.
Spontaneous Vaginal
Thrombocytes transfusion
12,000
Prednisone 60 mg Immuran
T.A.
Spontaneous Vaginal
None
10,000
Prednisone 30 mg
JSh.
Spontaneous Vaginal
Dextran Hydrocortisone Thrombocytes transfusion
Patient
25
K.N.
5,000
Thrombocytes D&Ca
transfusion
aSee text
the age of 6 and 12), and the other soon after her delivery (Table II). The newborns were in good condition and all had an Apgar score of 9-10 at 1 mm. Only one was in need of a thrombocyte transfusion and steroids (Table III). The cephalhaematomata were not large enough to necessitate transfusions and they underwent a rapid healing, leading to calcification and new bone formation. No signs of central nervous system damage were detected and the babies Table III.
behaved normally during the neonatal period. Follow-up for prolonged periods showed no physical or developmental abnormality in any infant. Discussion The frequency of ITP in pregnancy is similar to its frequency in the general population, viz: l-2 in 10,000 [22,28]. The influence of the pregnancy on the
The newborn at delivery and later development.
Patient
Sex
Weight (8)
Thrombocytes count at delivery (per mm”)
Chnical picture
Treatment
Later development
K.N.
F
2800
50,000
Normal
-
Nornal
K.N.
M
3400
110,000
Polycythemia Hypoglycemia
Dilutional exchange
Normal
Ch.E.
M
3100
12,000
Cephalhematoma
-
Normal
T.A.
M
4300
120,000
Cephalhematoma
-
Normal
J.Sh.
M
3360
2,000
Purpura G.I. bleeding Hematuria
Thrombocytes and blood transfusion Steroids
Normal
In t J Gynaecol Obstet 20
26
Kessler et al.
course of the disease is generally deleterious, with an exacerbation in 30-50% of the cases [9,14,26]. As for the impact of ITP on the pregnancy, it is quite evident that there is an increase in maternal and fetal complications. An increase in the rate of abortions has been reported, reaching up to 33% of the pregnancies [ 2,261, possibly because of an increase in the rate of the circulating serotonin, due to the destruction of thrombocytes [26]. Hemorrhage in pregnancy has been noted in 7-22% of the patients [6,7], excessive bleeding in the third stage of labor in up to 7% [4,6,7,23,30] and bleeding from the episiotomy in 1 l-l 2% [ 4,23,25,30]. A few decades ago there was a high rate of maternal mortality in cases of ITP, reaching 11% [ 18,24,29] but since the introduction of steroid treatment in 195 1, this rate has diminished considerably, and now equals the incidence of maternal mortality in the general population [ 10,18,20] . Territo [ 301 claims that no cases of mortality occurred when the delivery was by cesarean section. In about 50-70% of the newborns antithrombocyte antibodies have been demonstrated [ 21 and purpura in 50-73% [ 2,25,291. Thrombocytopenia was seen in a large percentage of the babies [8,15,18,25,30]. Even after maternal splenectomy, about 40% of the newborn showed purpura [ 251. The thromboand the purpura disappear cytopenia gradually 2-12 weeks after birth [4,6,301. Intracranial hemorrhage was found in 1O-30% of the newborn, leading to neurologic and mental deficiencies [28], as well as bleeding in the intestines and lungs [ 23,261. Most authors report an increase in perinatal mortality to 6-3 1% due to intracranial hemorrhage [8,15,17,21]. The mainstay of treatment during pregnancy is corticosteroids, reaching a daily dose of 40-80 mg of prednisone [ 16,191. A definite remission in the disease is seen in up to 80% of the cases [ 15,201. This treatment reduces the rate of destruction of the platelets in the reticulo-endothelial system, improves the capillary integrity and influences the ZntJ Gynaecol Obstet 20
immunologic state. Although it has been claimed that steroid therapy may be teratogenie [6,29] and may cause adrenal insufficiency in the fetus [6], no such signs were observed, and the normal estriol excretion proved that fetal adrenal function was unimpaired [3]. Due to steroid therapy, the maternal mortality has dropped to nil, and women suffering from the disease were given the possibility to bear children. This type of treatment cannot lower the titer of the antibodies in the fetus, as they are found in its serum as a result of passive transfer from the mother. Splenectomy is indicated only in the cases in which steroid therapy has not been successful, and the rate of remission after this operation is about 60-90% [ 15,191. It is preferable to perform splenectomy prior to the pregnancy [4,6,10,291. Fetal thrombocytopenia in post-splenectomy patients may also be seen. The transfusion of large amounts of thrombocytes during labor will prevent bleeding in most cases [10,15,19], but it cannot influence the number of thrombocytes in the newborn and there is the danger of viral hepatitis. Immunosuppressive therapy has been advocatedin cases resistant to other forms of treatment. Azathioprine and cyclophosphamide, as well as the vinca alkaloids have been given to such patients [20], but cytotoxic agents may be dangerous to the fetus. Since the thrombocytopenia in the newborn is a self-limited condition, the treatment should be related to the number of thrombocytes and bleeding symptoms. The therapeutic procedures are: transfusion of thrombocyte concentrate, and blood exchange transfusion, if the former step does not keep the thrombocyte count over 25,000 mm3. Steroids should be the last step if bleeding tendency continues. Mode of delivery
Controversies among obstetricians as to the best and safest mode of delivery in patients
Immunologic thrombocytopenia in pregnancy
with ITP have been, and still are, rampant. Some advocate elective cesarean section in all cases, to prevent compression of the head by the birth canal [8,14,17,181, even proposing the classical incision of the uterus [ 17 I , or cesarean and splenectomy in the same session [8,16,18]. Another method is to do a cesarean according to rate of thrombocytopenia in the mother, 100,000 platelets/mm3 being the limit below which the delivery should be abdominal [ 16,28,30 1. Some definitely forbid the use of forceps [22,30], while others allow either forceps or the vacuum extractor in some cases [7,19,21,261. Lately, some have thought that the decision whether delivery should be by cesarean depends on the count of the thrombocytes from a scalp blood sample of the fetus, taken during delivery: less than 50,000/mm3 points towards operation, while a higher count allows the obstetrician to permit vaginal delivery [ 1,22,27]. The most modern approach to the problem is to permit vaginal delivery, unless other obstetric indications for a cesarean exist [2,6,9,15,19,23,26] Pearson [21] adds as an indication for operation the fact that there are already some children with neurologic or intellectual dysfunction in the family. The decision to allow for a vaginal delivery has been based on several facts: no concordance between the number of thrombocytes in the mother and the infant [ 191: the number of thrombocytes in the infant is not a good prognostic sign for the occurrence of intracranial hemorrhage even after cesarean section [ 15,161 ; the high morbidity of the mothers during and after the operation and the lack of evidence that section improves the state of the infant. Conclusions
In the cases presented in this paper, it has been shown that through good cooperation between the hematologist and the obstetrician, efficient steroid treatment, and the
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transfusion of thrombocytes when needed, safe vaginal delivery in cases of ITP can be achieved. There is no need for a thrombocyte count from the scalp during delivery, but the neonatologist must be present at the delivery, so that immediate blood sampling can be done and appropriate treatment instituted to the newborn, if and when it becomes necessary. The follow-up of the infant must be prolonged, and of course, the mother’s state must not be lost from the eyes of the doctors treating the case. References 1 Ayromlooi J: A new approach to the management of immunologic thrombocytopenic purpura in pregnancy. Am J Obstet GynecolI30: 235,1978. 2 Bell WR: Hematologic abnormalities in pregnancy. Med Clin North Am 61: 183, 1977. Saunders (Philadelphia). 3 Dickey PR, Thompson PJ: Effect of ACTH and Metyrapone on estriol, 17-hydroxycorticosteroid, 17ketosteroid, pregnandiol and pregnanetriol excretion late in pregnancy. J Clin Endocrlnol Metab 29: 701, 1969. 4 Goodhue PA, Evans TS: Idiopathic thrombocytopenic purpura in pregnancy. Obstet Gynecol Surv 18: 671, 1963. 5 Harrington WJ, Minnich V, Hollingsworth JW et al.: Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura. J Lab Clin Med 38: 1,195l. 6 Heys RF. Steroid therapy for idiopathic thrombocytopenic purpura during pregnancy. Obstet Gynecol 28: 532,1966. -I Heys RF. Child bearing and idiopathic thrombocytopenic purpura. J Obstet Gynecol Br Commonw 73: 205,1966. 8 Jones WR, Storey B, Norton G et al.: Pregnancy complicated by acute idiopathic thrombocytopenic purpura a report of two patients treated by simultaneous caesarean section and splenectomy. J Obstet Gynaecol Br Commonw 81: 330,1974. 9 Jones WR, Asher MI, Ruthenford CJ et al.: Autoimmune (idiopathic) thrombocytopenic purpura in pregnancy and newborn. Br J Obstet Gynecol 84: 679, 1977. 10 Jones WR: Tissue-specific autoimmune disease in pregnancy. Clinics in Obstet Gynecol: Immunological aspect of reproduction. 6: 3, p. 473, 1979. Saunders (Philadelphia-London-Toronto). 11 Karpatkin S, Siskind GW: In vitro detection of platelet antibody in patients with idiopathic thrombocytopenic purpura and systemic lupus erythematous. Blood 33: 795,1969. Int J Gynaecol Obstet 20
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Address for reprints: Professor M. Lancet Kaplan Hospital 76400 Rehovot Israel