Route of delivery for patients with immune

thrombocytopenic purpura

Russell K. Laros, Jr., M.D., and Risa Kagan, M.D.

San Francisco, California

Over the past 15 years, we managed 19 pregnancies in 18 women afflicted with immune thrombocytopenic

purpura. Our policy has been to treat the mother with corticosteroids if her platelet count was below

100 x 109/L and to use cesarean section only for obstetric indications; 14 patients received corticosteroids. The perinatal outcomes were intrauterine fetal death (two), neonatal death (0), and live birth (17). The methods of delivery for the 17 live-born infants were spontaneous vaginal (seven), low forceps or

midforceps (five), cesarean section (five). Although seven of the live-born infants (41%) were

thrombocytopenic «100 x 109/L), only two received therapy, and none suffered significant hemorrhagic morbidity. Maternal treatment with corticosteroids did not affect the neonatal platelet count, nor was there a

correlation between maternal and neonatal platelet counts. On the basis of our experience, we think that cesarean section is not routinely indicated as the method of delivery for parturient patients with immune thrombocytopenic purpura. (AM. J. OBSTET. GVNECOL. 148:901, 1984.)

In the early 1970s, several investigators recom­mended cesarean section as the delivery method of choice for mothers with immune thrombocytopenic purpura. I, 2 This recommendation was predicated on the supposition that trauma to the fetal head during vaginal delivery was responsible for intracranial bleed­ing and subsequent neonatal morbidity and mortality. The recommendation for cesarean section delivery quickly spread into the hematologic literature despite a lack of validation of the hypothesis that cesarean sec­tion delivery yielded less neonatal morbidity and mor­tality than did vaginal delivery.3-6

Because we are not convinced that cesarean section, other than for obstetric indications, is beneficial to the neonate, we have continued to allow mothers with im­mune thrombocytopenic purpura to undergo labor and vaginal delivery. In this report, we detail our ex­perience with 19 parturient patients and review the recent literature that pertains to the issue of route of delivery.

Material and methods

During the years 1969-1983, we personally cared for

or consulted in the management of 18 women with immune thrombocytopenic purpura during 19 preg­nancies. Our criteria for diagnosis included throm­bocytopenia of 50 x 109/L or less without leukopenia

From the Department of Obstetrics, Gynecology and Reproductive Sciences, University of California (San Francisco).

Presented by invitation at the Second Annual Meeting of the Ameri­can Gynecological and Obstetrical Society, Phoenix, Arizona, Sep­tember 7-10, 1983.

Reprint requests: Dr. Russell K. Laros, Jr., M 1480, University of California (San Francisco), San Francisco, California 94143.

or splenomegaly and with adequate numbers of mega­karyocytes in the bone marrow. Fifteen of our patients had idiopathic immune thrombocytopenic purpura and, three had lupus erythematosus. Initial treatment consisted of steroids alone in 11 cases, steroids and splenectomy in five, steroids, splenectomy, and chemo­therapy in one, and no treatment in one. Antiplatelet antibody assays and fetal platelet counts were not per­formed on a regular basis. The route of delivery was determined solely by obstetric events. Data were ana­lyzed by standard statistical techniques, including the Student's t test and X2 test.

Results

Maternal treatment and outcome. The mean age of our parturient patients was 26.5 years (18 to 33 years). Six patients were nulliparous. In seven cases, the diag­nosis of immune thrombocytopenic purpura was made during pregnancy; in the remainder, the diagnosis had been made from 1 to 12 years before the current preg­nancy. Eigh t patients had episodes of bleeding related to their immune thrombocytopenic purpura during pregnancy, but only two of these instances were seri­

ous. The clinical events of these two cases are sum­marized.

Case 5-JD. J. D. had three episodes of severe epi­staxis beginning at 12 weeks' gestation. An episode at 14 weeks was not controlled with nasal packing and resulted in a four point drop in hematocrit. She was hospitalized and given four units of platelet concen­trates, with prompt cessation of bleeding. The remain­der of her pregnancy was uneventful.

Case ll-MN. M. N. was first diagnosed as having immune thrombocytopenic purpura during the second trimester of pregnancy. Treatment with corticosteroids

901

902 Laros and Kagan April I, 1984 Am. J. Obstet. Gynecol.

Table I. Maternal and fetal data in cases of immune thrombocytopenic purpura

Platelet count at delivery Steroids

Case Patient Year (x 109fL) Method of delivery at delivery

1 D. H.* 1969 5 Cesarean section-2t Yes 2 C. H.* 1970 250 Cesarean section-3 Yes 3 D. H.* 1971 16 Cesarean section-2 Yes 4 ]. C.* 1972 132 Spontaneous vaginal delivery Yes 5 ]. D.* 1972 60 Spontaneous vaginal delivery No 6 C.]. 1974 320 Spontaneous vaginal delivery Yes 7 J. K.:j: 1975 283 Low-forceps or vacuum delivery Yes 8 M. K. 1976 280 Low-forceps or vacuum delivery Yes 9 M.T. 1976 64 Low-forceps or vacuum delivery Yes

10 D. S. 1978 29 Spontaneous vaginal delivery Yes II M.N. 1978 I Cesarean section-4 Yes 12 E. H. 1979 234 Cesarean section-2 No 13 M. W. 1980 262 Cesarean section-2 No 14 M.L. 1981 250 Low-forceps or vacuum delivery No 15 P. F. 1981 83 Low-forceps or vacuum delivery No 16 L. F. 1982 80 Spontaneous vaginal delivery Yes 17 G. B. 1982 50 Spontaneous vaginal delivery Yes 18 L. B. 1983 115 Spontaneous vaginal delivery Yes 19 D. H. 1983 130 Spontaneous vaginal delivery Yes

*Reported previously.8 tlndications for cesarean section: 2-repeat; 3-breech; 4-failed induction. :j:Twins.

was initiated, without any substantial improvement in the platelet count. Because she was a Jehovah's Wit­ness, splenectomy had not been performed prior to her transfer to our institution. At the time of her transfer, the hemoglobin was 12.9 gm/dl and the platelet count 10 x 109 /L. Treatment with intravenous vincristine, 0.025 mg/kg at weekly intervals, was begun. During the second week of hospitalization, mild uterine contrac­tions were noted, and oral isoxsuprine was begun in hopes of forestalling delivery until there was an im­provement in the platelet count. The following day, spontaneous rupture of the membranes occurred and the amniotic fluid was noted to be meconium stained. The isoxsuprine was discontinued, and mild uterine contractions ensued and were associated with an omi­nous fetal heart rate pattern. Because of the mother's hematologic status and her continued refusal to accept transfusion of blood products, a cesarean section was not performed. Approximately 2 hours later, fetal death occurred. Because uterine contractions con­tinued to be infrequent and of low intensity, oxytocin augmentation was begun. After 12 hours of stimula­tion, the cervix remained undilated and the patient's temperature increased to 38° C. Antibiotic therapy with penicillin, gentamicin, and c1indamycin was initiated. Continued vigorous attempts at oxytocin induction of labor were continued for the next 2 days, without suc­cess. During this time, the patient's hemoglobin had fallen to 8.2 gm/dl, and the uterus had grown in size. These findings were interpreted as indicating either a subtle abruptio placentae or the accumulation of pus within the uterus. The decision was made to proceed

with a splenectomy and hysterectomy (placenta and fetus left within the uterus). The operative procedure was carried out under general anesthesia and with aor­tic compression. The estimated loss of blood was 300 ml. Pathologic examination of the uterine contents re­vealed a stillborn fetus who weighed 3,800 gm and a uterus full of pus but without evidence of abruptio pla­centae. Autopsy of the fetus revealed pneumonia and chorioamnionitis, but no hemorrhage was noted.

Fetal outcome. Table I summarizes maternal and neonatal platelet studies, treatment, and method of de­livery. Two of 19 infants were stillborn; all live-born infants were discharged in good health. This yielded a perinatal mortality rate of 105 per 1,000 live births. One of the stillbirths was described above; the other is reported as follows.

Case 4-JC. J. C. had had immune thrombocytopenic purpura diagnosed when she was 9 years old and she had been treated unsuccessfully with steroids and splenectomy. She was first seen during the twenty­ninth week of the current gestation complaining of epistaxis and gingival bleeding. Her prior two preg­nancies had been uneventful. Because of her symptoms and a platelet count of 15 X 109/L, she was started on prednisone, which was continued at a dose of 50 mg/day in order to maintain the platelet count above 50 X 109/L. She was discharged and did not reappear until the thirty-fifth week of gestation, at which time she confessed to having stopped corticosteroids im­mediately on being discharged from the hospital. Be­cause her platelet count had dropped to 2 X 109/L, she

Volume 148 Number 7

Cord

II 174 115

170 178 275 180

7 280

278 274 300 172 196 68 83 25

I Days 1-2

108 250 102

150 90

343 255

26

273 273 255

144 35 81 14

N eonatat platelet counts

I Days 3-4

35

80

200 60

298

8 208

310 240 195

8 42 11

I Days 5-6 (X 1091L)

81

116

209 58

10

8 140

12

I

was rehospitalized, and prednisone was restarted in a dose of 60 mg/day. The platelet count rose to 58 X

109/L over a 5-day period. On the tenth hospital day at 37Y2 weeks' gestation, the patient described lack of fetal movement; the maternal platelet count on that day was 132 x 109/L. Fetal death was confirmed, and labor was induced with oxytocin. Vaginal delivery occurred and yielded a macerated, 3,000 gm infant. Autopsy re­vealed subgaleal hemorrhage, subarachnoid hemor­rhage, and bilateral pleural hemorrhages.

The methods of delivery for the 17 live-born infants were cesarean section (five), mid forceps or midvacuum (five), and spontaneous vaginal (seven). The indications for the five cesarean sections are detailed in Table I. The mean birth weight and gestational age at delivery for these infants were 3,045 gm (1,475 to 4,550 gm) and 37 weeks (29 to 40 weeks), respectively. All live­born infants had 1- and 5-minute Apgar scores of 8 or more.

Seven of the live-born infants had or developed platelet counts of less than 100 x 109/L (41%); five counts were below 50 x 109/L (29%), and four were below 30 X 109/L (24%). Newborn Infant 9-MT was noted to have a few petechiae on the first day of life, and Infant 18-LB had }:>etechiae at birth. Neither of these infants required treatment. Newborn Infant 19-DH had a mild shoulder dystocia at birth, with bruising of the shoulder. He was treated with predni­sone and two units of platelet concentrate. Newborn Infant 17-GB was treated with prednisone but never had clinical manifestations of thrombocytopenia.

All 17 live-born infants were discharged without any evidence of morbidity related to their mother's im-

Delivery in patients with immune thrombocytopenic purpura 903

Days 7-8

250

126

236 56

23

44 178 II

Treatment

None None None

None None None None None None

None None None None None Pred None

Prednisone plus platelet transfusion

Outcome

Well Well Well

Stillborn Well Well Well Well Well Well

Stillborn Well Well Well Well Well Well Well Well

mune thrombocytopenic purpura. No infant had clini­cal evidence of intracranial hemorrhage; computerized tomography scans and/or brain sonograms were ob­tained on only three newborn infants (l5-PF, 18-LB, and 19-DH). The latter two infants were studied be­cause of their thrombocytopenia, and the former in­fant because gestational age at delivery was 29 weeks and birth weight was 2,900 gm.

We found no significant relationship between the maternal platelet count and either the fetal platelet count at delivery or the development of neonatal thrombocytopenia. Additionally, the incidence of neo­natal thrombocytopenia was not related to whether the mother was receiving corticosteroids at the time of de­livery.

Comment

Most obstetricians and hematologists would agree that the overall management of pregnant women with immune thrombocytopenic purpura should be similar to that of nonpregnant individuals. The major con­troversial issue has been the mode of delivery. Prior to the mid-1970s, little thought was given to the route of delivery as a possible cause of morbidity and mortality in infants of mothers with immune thrombocytopenic purpura. In 1973, Territo and associates l suggested that the maternal platelet count correlated with the neonatal count and advocated cesarean section for all women whose platelet count was less than 100 x 109/L at the onset of labor. In 1976, Murray and Harris2 re­ported two cases and extended Territo and associates' recommendation by stating that, "we conclude and recommend that infants born to mothers with immune

904 Laros and Kagan April I, 1984 Am. J. Obstet. Gynecol.

Table II. Cases of immune thrombocytopenic purpura in patients delivered vaginally (stillbirths excluded)

Neonates with lowest platelet count

(XI09/L) Any neonatal

No. of <100 I <50 I 1 Serious 1 Author Year cases <30 Hemorrhage hemorrhage Treatment

Territo et al. I 1973 1 1 0 0 0 0 0 Jones et al. 12 1977 42 10 7 6 4 1 3 O'Reilly and Taber8 1978 8* 6 5 5 3 0 3 Noriega et al." 1979 18 9 7 4 8 0 8 Scott et al.I> 1980 8 3 0 0 0 0 0 Karpatkin et al. 14 1981 18 12 II 7 1 0 Kelton et al. IS 1982 27 4 4 3 3 0 3 Laros 1983 12 5 4 3 2 0 1

Total 134 50 38 28 21

*One set of triplets.

Table III. Cases of immune thrombocytopenic purpura in patients delivered by cesarean section (stillbirths excluded)

Neonates with lowest platelet count

(X 109/L) Any neonatal

No. of <100 I Author Year cases

Territo et al.I 1973 5 3 Jones et al. 12 1974 2 2 Murray and Harris2 1975 2 2 Scott et al." 1980 4 3 Karpatkin et al. 14 1981 1 1 Kelton et al. IS 1982 12 4 Laros 1983 5 2

Total 31 17

thrombocytopenic purpura, whether symptomatic or in remission at the time of delivery, should not be sub­jected to the trauma of vaginal delivery but rather should be delivered by cesarean section." This recom­mendation quickly spread into both the general medi­cal and hematologic literature despite the lack of sub­stantive data to support it. More recently, Carloss and associates3 and McMillan7 have supported this ap­proach, although other reports question the validity of the recommendations.8 - 11

Tables II and III summarize data on 165 cases re­ported over the past 10 years. Series were included if the data were sufficient to allow evaluation of the method of delivery, neonatal platelet count, and neonatal outcome. Stillborn infants were excluded from analysis because the method of delivery no longer influenced their outcomes. Of the 134 infants delivered vaginally, 50 (37%) either had or developed platelet counts below 100 x 109 /L, and 28 (21 %) had counts below 30 X 109/L. Only one infant was described as having intracerebral bleeding; this was nonfatal. By

<50 I I Serious

I <30 Hemorrhage hemorrhage Treatment

3 2 2 3 0 3 2

15

3 3 3 2 2 1 0 I 0 0 0 0 3 3 0 ? 0 0 0 ? 1 0 0 1 0 0 0 0

9 6 3

contrast, of the 31 infants delivered by cesarean sec­tion, 17 (55%) had platelet counts below 100 x 109/L and nine (29%) had counts below 30 x 109/L. There were three serious hemorrhages, one of which was an intracranial hemorrhage at 3 days of age. These data do not support the premise that delivery by cesarean section prevents intracerebral bleeding in a thrombocy­topenic infant of women with immune thrombocyto­penic purpura.

If cesarean section delivery is ever demonstrated to be beneficial for fetuses, it will be so only for those who have or develop thrombocytopenia. Territo and asso­ciates' suggestion that the fetal platelet count correlates with the maternal platelet count has not been sup­ported by other investigators.9• 13. 16 We also found no relationship between the maternal and neonatal plate­let counts. Ayromlooi17 and, more recently, Scott and associates13 have documented the correlation between fetal scalp platelet counts obtained during labor and the platelet count of newborn infants immediately after delivery. They suggest that the use of fetal scalp plate-

Volume 148 Number 7

let counts will allow cesarean section delivery for only those fetuses who are actually thrombocytopenic. Al­

though we agree with this conclusion, it begs the issue of whether the occurrence of intracranial hemorrhage is, in fact, lowered by cesarean section delivery.

The most recent prospect for identifying fetuses at risk for thrombocytopenia involved the actual mea­surement of anti platelet antibodies in parturient pa­tients with immune thrombocytopenic purpura. Cines and associates 16 studied 23 pregnant women with either

a history of immune thrombocytopenic purpura or clinically active disease. No relationship was noted be­tween maternal and neonatal platelet counts, and the level of platelet-associated IgG (direct assay) in the

mother did not correlate with the risk of throm­

bocytopenia in the neonate. However, the level of cir­culating antibodies, determined by indirect assay, did

correlate with the presence and severity of neonatal thrombocytopenia. In a more recent study, Kelton and associates15 prospectively measured anti platelet anti­bodies (direct assay) in 41 pregnancies. The levels of maternal platelet-associated IgG were highly predictive of neonatal thrombocytopenia. However, it should be

noted that the level of platelet-associated IgG did not predict the severity of the neonatal thrombocytopenia. Again, the ability prospectively to detect the infant who

is truly at risk does not shed any light on whether ce­

sarean section delivery is protective for that infant. Until more convincing data become available, we are not willing to base our decision on the route of delivery on either the presence of antiplatelet antibodies in the maternal circulation or the fetal scalp platelet count.

We wish to thank Drs. Charles Kalstone, Daniel E. McGunegle, Robert E. Roe, and Charles M. Scott for consulting with us and allowing us to include their pa­tients in this report.

REFERENCES

1. Territo, M., Finklestein, ]., Oh, W., Hobel, C., and Kottlove, H.: Management of autoimmune thrombocyto­penia in pregnancy and in the neonate, Obstet. Gyneco!. 41:579, 1973.

2. Murray,]. M., and Harris, R. E.: The management of the pregnant patient with idiopathic thrombocytopenia pur­pura, AM.]. OBSTET. GYNECOL. 126:449, 1976.

3. in: Wintrobe, M. M., editor: Clinical Hematology, Phila­delphia, 1981, Lea & Febiger, p. 1107.

4. Nathan, D. G., editor: Hematology of Infancy and Child­hood, Philadelphia, 1981, W. B. Saunders Co., p. 126.

5. Coleman, R. W., editor: Hemostasis and Thrombosis, Philadelphia, 1982,]. B. Lippincott Co., p. 327.

6. Carloss, H. W., McMillan, R., and Crosby, W. H.: Man­agement of pregnancy in women with immune throm­bocytopenic purpura, JAMA 244:2756, 1980.

7. McMillan, R.: Chronic idiopathic thrombocytopenic pur­pura, N. Eng!.]. Med. 304:1135,1981.

8. O'Reilly, R. A., and Taber, B. Z.: Immunologic throm­bocytopenic purpura and pregnancy: Six new cases, Obstet. Gyneco!. 51:590, 1978.

Delivery in patients with immune thrombocytopenic purpura 905

9. Noriega-Guerra, L., Aviles-Miranda, A., de la Cadena, O. A., Espinosa, L. M., Chavez, F., and Pizzuto,].: Preg­nancy in patients with autoimmune thrombocytopenic purpura, AM.]. OBSTET. GYNECOL. 133:439, 1979.

10. Goodhue, P. A., and Evans, T. S.: Idiopathic throm­bocytopenic purpura in pregnancy, Obstet. Gynecol. Surv. 18:671, 1963.

II. Laros, R. K., and Sweet, R. L.: Management of idiopathic thrombocytopenic purpura during pregnancy, AM. ]. OBSTET. GYNECOL. 122: 182, 1975.

12. Jones, R. W., Asher, M. 1., Rutherford, C.]., and Monro, H. M.: Autoimmune (idiopathic) thrombocytopenic pur­pura in pregnancy and the newborn, Br. ]. Obstet. Gynaeco!. 84:679, 1977.

13. Scott,]. R., Cruikshank, D. P., Kochenour, N. K., Pitkin, R., and Warenski, ]. C.: Fetal platelet counts in the obstetric management of immunologic thrombocytopenic purpura, AM.]. OBSTET. GYNECOL. 136:495, 1980.

14. Karpatkin, M., Porges, R., and Karpatkin, S.: Platelet counts in infants of women with autoimmune throm­bocytopenia, N. Eng!. ]. Med. 305:936, 1981.

15. Kelton,]. C., Inwood, M. ]., Barr, R. M., Effer, S. B., Hunter, D., Wilson, W. E., Ginsburg, D. A., and Powers, P. ].: The prenatal prediction of thrombocytopenia in infants of mothers with clinically diagnosed immune thrombocytopenia, AM. ]. OBSTET. GYNECOL. 144:449, 1982.

16. Cines, D., Dussk, B., Tomaski, A., Mennuti, M., and Schreiber, A.: Immune thrombocytopenic purpura and pregnancy, N. Eng!.]. Med. 306:826, 1982.

17. Ayromlooi,].: A new approach to the management of immunologic thrombocytopenia purpura in pregnancy, AM.]. OBSTET. GYNECOL. 130:235, 1978.

Discussion

DR. ALAN E. BEER, Ann Arbor, Michigan. Chronic idiopathic or autoimmune thrombocytopenic purpura, a syndrome characterized by persistent thrombocyto­penia in the mother, is caused by circulating antiplate­let autoantibodies that result in the destruction of plate­lets by her own reticuloendothelial system. During pregnancy, the free unabsorbed antiplatelet IgG is transferred across the syncytiotrophoblast to the infant via Fc receptors on the placenta and results in the de­struction of platelets in the infant. Clinicians ac­quainted with immune disorders that result in hemo­lytic disease in newborn infants have assumed that this immune process in the mother directed toward platelet antigens would follow dynamic processes similar to those that operate in mothers with IgG antibodies to erythrocyte antigens. This has not been the case be­cause, unlike the erythrocyte antigens, platelet-associ­ated antigens are very heterogeneous and include a multiplicity of autoantigens as well as isoantigens. These include antigens of the ABO blood group sys­tem, all of the class I major histocompatibility antigens, HLA-A, B, and C, as well as platelet-specific antigens KOa&b, Pia 1&2, Pis 1&2, KO, Duzo, BAKa , ZWa&b, and glycoproteins lB, 2B, and 3A. Assaying for free anti­body in the mother to any of these antigens on platelets mayor may not predict fetal thrombocytopenia, for some may be lacking from platelets of the infant who has inherited a different set from the father. In addi­tion, assays for antiplatelet antibodies have proved to be very difficult for three reasons. (1) Normal platelets

906 Laros and Kagan

have a very large amount of background cell-associated IgG, cytophilic antibody that has no specificity for platelet antigens. (2) The antibody in autoimmune thrombocytopenic purpura does not readily activate complement. (3) Current assays with the use of mono­clonal antibodies are available that distinguish between free anti platelet IgG and antiplatelet IgG associated with free circulating platelet antigens. In this latter case the antigen-antibody complex, although present in the mother, poses no risk to the fetus in that it will not cross the placenta.

Dr. Scott and his associates in a report presented to this Society last year described a sensitive antiplatelet antibody enzyme-linked immunosorbent assay to mea­sure anti platelet antibody concentrations in the mater­nal blood, amniotic fluid, and the umbilical cord blood. This is a highly sensitive assay that will detect very small quantities of antiplatelet antibodies in the serum that absorb onto the surface of fresh platelets. The assay is limited only by the fact that donor type 0 Rh-positive platelets are used as targets, and the platelet-specific antigens on these test platelets may in no way relate to the specific platelet isoantigens of the infant. Nonethe­less, with this assay, the concentration of anti platelet antibody in maternal serum frequently, but not always, reflected the severity of neonatal thrombocytopenia. However, direct sampling of fetal scalp blood early in labor or at term after rupture of the membranes gave a reliable indication of the fetal platelet count.

Unlike Scott and his associates, who followed a novel approach to determine whether vaginal or abdominal delivery of infants is indicated in mothers with au­toimmune thrombocytopenic purpura based on the level of the fetal platelet count obtained from a scalp sample, Drs. Laros and Kagan used corticosteroid therapy for the mother if the platelet count was below 100 x 109/L, and used cesarean section only for ob­stetric indications. The rationale for corticosteroid ther­apy is as follows. (1) Corticosteroids induce responses that are accompanied by an increase in the platelet­associated IgG, thus decreasing the free IgG in the ma­ternal serum. (2) The platelet count often increases and the steroids slow down the reticuloendothelial clearing in the mother. (3) Corticosteroids transferred to the infant may result in an increase in the serum anti plate­let antibody levels, thus suggesting that these drugs interfere with antibody binding. (4) Corticosteroids do not alter platelet production. (5) Corticosteroids may reduce the transfer of antibody across the placenta.

The study of Laros and Kagan spans a IS-year pe­riod in which corticosteroid therapy coupled with splenectomy was the only therapy available for patients with autoimmune thrombocytopenic purpura. In ad­dition, since assays for unbound anti platelet antibodies in the mother during their study period were in no way predictive of the degree of fetal thrombocytopenic purpura, their approach of using cesarean section for obstetric indications was essentially the only option available to them, and their results and the results of

April 1, 1984 Am. J. Obstet. Gynecol.

others reveal essentially two things that are already firmly established in the literature. (1) Ten percent to 20% of infants of mothers with autoimmune throm­bocytopenic purpura die in utero or in the neonatal period. (2) A significant proportion of the others are born with platelet counts known to be associated with significant neonatal hemorrhage and morbidity.

On the basis of the experience of these authors gleaned from managing only 19 patients, they force­fully state that cesarean section is not routinely indi­cated as a method of delivery for parturient patients with autoimmune thrombocytopenic purpura.

This report, essentially a compilation of case reports by senior and respected academic obstetricians and gynecologists, is a dangerous one because the casual protocol of the authors will be followed by countless numbers of obstetricians and gynecologists who are even less aware of the major immunologic strides that have surfaced over the past 3 years that are giving strong scientific underpinning for safe and sure man­agement of infants born of mothers with immune thrombocytopenic purpura. Modern management must include the following. (1) Analysis of the target of the platelet autoantigen or isoantigen in the mother by means of ELIZA or monoclonal antibody techniques that focus attention on free circulating antibody in the mother. (2) Testing to determine whether the focus of the immune attack is greater for paternal platelets than third-party platelets. (3) Ultrasonographic examina­tions with the same periodicity as in the management of the severely Rh-sensitized patient to look for the ap­pearance of any collections of fluid in the infant that may represent hemorrhage. (4) Assessment of the fetal platelet count from a sample of fetal scalp blood once parameters indicate that the infant is mature. (5) Avoidance of neonatal hypoxia.

In my opinion, modern obstetrics should not tolerate a perinatal mortality of 10511,000 live births, the inci­dence associated with this disorder. If the modern management that I have just described cannot be fol­lowed, then the recommendation for management of the patient is the same as with the primigravid breech, i.e., cesarean section should be performed in all cases of maternal autoimmune thrombocytopenic purpura whether in remission or not.

I ask the authors whether they are satisfied with their 20% neonatal mortality figure. Will the management that you strongly advocate in this report reduce this further? Have recent dramatic advances in immunol­ogy already altered your approach to and manage­ment of pregnant patients with autoimmune throm­bocytopenic purpura? If not, why not? Working in a progressive and elite institution, such as the University of California (San Francisco), why did your group not associate with competent immunologists who could have helped refine your approach to patients and in­fants with this serious life-threatening disorder? Sensi­tive assays for free anti platelet antibody described by Dixon have been available since 1975. In Table II, you

Volume 148 Number 7

summarize cases of immune thrombocytopenic pur­pura, and all stillborn infants were excluded from this analysis. Can you give us information on the number of stillborn infants in this group and whether the platelet counts or antibody profiles in their mothers were pre­dictive of the infants' serious thrombocytopenia?

From immunologic and obstetric points of view, it is my opinion that this report adds nothing to our un­derstanding of the management of patients with im­mune thrombocytopenic purpura and could poten­tially serve to retard research and study urgently needed in pregnant patients with this disorder. We must be as immunologically attentive to this disease as we have been to other hemolytic diseases of the neo­nate, and, as obstetricians, we must commit ourselves to

working with cutting-edge immunologists who will help us more precisely define infants at risk. In addition, we must broaden our horizons and focus attention on pa­tients with severe toxemia who often develop anti plate­let antibodies that render the infant thrombocytopenic, and study more thoroughly patients who develop anti­lymphocyte antibodies to Class I histocompatibility antigens present on platelets that may result in throm­bocytopenia of the fetus. We are only beginning our scientific homework in regard to the relevance, spec­ificity, and danger to the infant of anti platelet an­tibodies. I would urge the authors, who are privileged to work in a health care facility to which patients with this disorder are referred, to direct their efforts toward assays and procedures that will unequivocally identify the infant at risk. The authors conclude, "Until more convincing data become available, we are not willing to base our decision on the route of delivery on either the presence of anti platelet antibodies in the maternal cir­culation or the fetal scalp platelet count." As an obstetrician-immunologist, I challenge you in working with others to generate data that are convincing, so that a subsequent report on this topic can be less of an editorial on the subject and one more filled with con­clusions that are buttressed by strong scientific under­pinning. Until data are available that adequately and readily predict the affected fetuses of mothers with autoimmune thrombocytopenic purpura, cesarean sec­tion should be performed in all cases of maternal au­toimmune thrombocytopenic purpura, whether in re­mission or not. The only exception to this indication, in my estimation, may be basing obstetric management on the platelet concentration in blood obtained from fetal scalp sampling.

DR.JAMFS R. SCOTI, Salt Lake City, Utah. Drs. Laros and Kagan should be congratulated on critically eval­uating the role of cesarean section in the obstetric man­agement of isoimmune thrombocytopenic purpura, and pointing out the difficulties in determining whether vaginal delivery is associated with intracranial hemor­rhage in these infants. However, the definition of thrombocytopenia is important, since we have shown that severe neontal bleeding occurs only when the platelet count at birth is <50,000/mm3

, and, even then,

Delivery in patients with immune thrombocytopenic purpura 907

the risk is only 28%.1 Dr. Laros, do you believe that your series, in which only four infants were delivered vaginally and had platelet counts <50,000/mm3

, proves that the vaginal route is safe in all instances (and am I quoting your numbers correctly)? It should be noted that at least three intrapartum or neonatal deaths of thrombocytopenic infants without any precipitating cause other than vaginal delivery have been reported,2 and another infant who survived an intracranial hem­orrhage now has psychomotor retardationY In addi­tion, permanent neurological sequelae and death have occurred in infants with isoimmune thrombocyto­penia4

• 5 and other coagulation defects6 who were de­livered vaginally. Consequently, we still believe that it is prudent to avoid vaginal delivery in any instance in which the fetus is known to have a platelet count <50,000/mm3

, in order to minimize the possibility of cerebral trauma. However, when intrapartum fetal scalp blood platelet counts are used as we described to this society last year, only 20% of the patients will re­quire cesarean section for fetal thrombocytopenia.7

REFERENCES

1. Scott, j. R., Cruikshank, D. P., Kochenour, N., Pitkin, R., and Warenski, j. C.: Fetal platelet counts in the obstetric management of immunologic thrombocytopenic purpura, AM. j. OBSTET. GYNECOL. 136:495, 1980.

2. Heys, R. F.: Steroid therapy for idiopathic thrombocyto­penic purpura during pregnancy, Obstet. Gynecol. 28: 532, 1966.

3. Jones, R. W., Asher, M. I., Rutherford, C. j., and Monro, H. M.: Autoimmune (idiopathic) thrombocytopenic pur­pura in pregnancy and the newborn, Br. j. Obstet. Gynaecol. 84:679, 1977.

4. Pearson, H., Shulman, N. R., Marder, V. j., et al.: Isoim­mune neonatal thrombocytopenia purpura-Clinical and therapeutic considerations, Blood 23: 154, 1967.

5. Galea, P., Patrick, M. j., and Goel, K. M.: Isoimmune neonatal thrombocytopenia, Arch. Dis. Child. 56: 112, 1981.

6. Matthay, K. K., Koerper, M. A., and Ahlin, A. R.: In­tracranial hemorrhage in congenital factor VII deficiency, J. Pediatr. 94:413, 1979.

7. Scott,j. R., Rote, N. S., and Cruikshank, D. P.: Antiplatelet antibodies and platelet counts in pregnancies complicated by autoimmune thrombocytopenia purpura, AM. j. OB­STET. GYNECOL. 145:932, 1983.

DR. FRITZ K. BELLER, Muenster, West Germany. Drs. Laros and Kagan focused their discussions on the danger for the fetus. However, the mother is at risk, too. In the literature, the point is made frequently that, if the maternal platelet count drops below 60,000 or 80,000 mm3

, then the mother will be in jeopardy from failure of hemostasis.

We have observed that the patient with long­standing chronic thrombocytopenia-whether from destruction, reduced production, an antigen, or even platelet dysfunction-can have a reduced threshold, which means that the patient with 20,000 platelets mm3

can still produce hemostasis. The only way to clarify whether hemostasis is functioning properly is by the

908 Laros and Kagaf'l

bleeding time. The patient with low platelet count and/or platelet dysfunction but with a normal bleeding time can produce hemostasis.

In regard to Dr. Laros and Kagan's report that five patients had infants who were delivered by forceps and/or by vacuum extraction, I want to ask how many of those newborn infants had low platelet counts.

I believe that we can discuss either cesarean section or vaginal delivery, but the one thing that is contraindi­cated is forceps delivery of infants whose mothers have immune thrombocytopenic purpura.

DR. DWIGHT P. CRUIKSHANK, Richmond, Virginia. First, I have a question about neonatal outcome and platelet counts in the offspring of Drs. Laros and Ka­gan's six patients who had splenectomy, since there are reports that these fetuses, these newborn infants, are at increased risk for thrombocytopenia.

Second, would the authors review the indications for cesarean section. Their cesarean rate was 33%, and I wonder whether there was some selection process which might be skewing the results.

DR. JACK A. PRITCHARD, Dallas, Texas. The argu­ments presented concerned with the route of delivery seem to involve vaginal delivery to minimize risk to the mother and cesarean section delivery to avoid risk to the fetus-infant. However, cesarean section delivery does not always protect the fetus-infant from serious hemorrhage. We have observed severe cephalohema­tomas in a newborn infant delivered by cesarean sec­tion in the absence of any labor.! At birth, he had se­vere thrombocytopenia, even though his mother, who was on steroids, did not. After a very stormy course, the infant survived. Interestingly, his older brother, also thrombocytopenic, was delivered vaginally without such problems, until he was immunized, and then he bled severely.

REFERENCE

1. Pritchard, J. A., and MacDonald, P. C. P.: Williams' Obstetrics, New York, 1980, Appleton-Century-Croft, Figure 28-4, p. 729.

DR. NORBERT GLEICHER, Chicago, Illinois. Throm­bocytopenia is not only a problem in conjunction with immune thrombocytopenia. In fact, most cases occur in conjunction with other medical conditions associated with pregnancy, such as severe eclampsia, as it was formerly called, systemic lupus erythematosus, and HELLP, as it is frequently called nowadays.

My question is whether we consider and manage se-

April 1, 1984 Am. J. Obstet. Gynecol.

vere thrombocytopenia in those conditions similarly, or whether the confusion is similarly profound.

DR. LAROS (Closing). It is clear that we engendered controversy, which was a major purpose of our report.

Dr. Beer gave us an excellent discussion and review of the immunology of immune thrombocytopenic purpura.

The difficulty with all of the modern technology, I think, is brought to focus by Dr. Pritchard's comments. It is very useful to determine the platelet count in the infant, and there is no doubt that this can be done accurately. The issue is whether cesarean section pro­tects those infants who are thrombocytopenic. Obvi­ously, it did not in the case that Dr. Pritchard showed us, and it has not in other cases.

I do not think that we are trying to be nonscientific by performing cesarean section only for obstetric rea­sons, and certainly a very reasonable middle-of-the­road course would be to assure oneself by using fetal platelet counts that one is only performing cesarean sections in instances in which they are really needed. However, this approach is only appropriate if one be­lieves that cesarean section will protect the infants. Our experience, as well as that in the literature, does not convince me that this is true, and I am concerned by the fact that we again seem to be moving into a stan­dard of care without any data to show that the action taken is beneficial.

Dr. Scott's comments were most appropriate. We ourselves had only a few infants with platelet counts less than 50 x 109/L-only two who were delivered by cesarean section, and four delivered vaginally with counts less than 50 x 109/L, and three with counts less than 30 x 109/L.

Dr. Beller's comment was most appropriate. In chronic immune thrombocytopenic purpura, the bleed­ing time is critically important because it reflects the patient'S chances of spontaneous bleeding. I would ad­vise you all to encourage your laboratories to evaluate bleeding time in such cases. Many laboratories will not evaluate bleeding time in patients with a platelet count under 50 x 109/L, because they claim that it is always 20 minutes or more. This is not necessarily true.

Dr. Beller, you may be right that the use of forceps is contraindicated, but our most profound neonatal thrombocytopenia was 6 X 109 /L in an infant delivered by midforceps, and that infant had absolutely no prob­lem. A single case does not prove that midforceps is safe, but it does, I hope, show you that we lack knowledge.