Thrombocytopenia is defined as a platelet count below 150 000/ml. Thrombocytopenia occurs approximately in 10% of pregnant women. Immune thrombocytopenic purpura (ITP) occurs in one or two of every 1000 pregnancies, and accounts approximately for 5% of pregnancy-associated thrombocytopenia cases; it is an autoimmune disorder characterized by platelet destruction in the reticuloendothelial system, particularly the spleen, due to platelet autoantibodies against several platelet membrane glycoproteins. Despite its rarity compared with gestational thrombocytopenia, ITP is the most common cause of isolated thrombocytopenia in the first and early second trimesters. ITP is characterized by a moderate to severe decrease in the platelet count 1,2. ITP can present at any age; however, it commonly affects women of childbearing age and does not interfere with pregnancy 3. The use of automated blood testing in routine prenatal screening resulted in an increased diagnosis of thrombocytopenia 4.
Although pregnancy is not discouraged in women with ITP, maternal and fetal complications can occur, and so pregnant patients with ITP require close monitoring during pregnancy and after delivery, due to the potential risk of maternal hemorrhage when the platelet count is low 5. Also, neonatal monitoring is needed as antibodies cross the placenta in the pregnant patient, with a minor risk of thrombocytopenia in the newborn 3.
Patients and methods
This is a retrospective prospective study conducted over the period from April 2009 to May 2013 that included 25 pregnant women with ITP admitted in the High-Risk Pregnancy Unit, Department of Obstetrics and Gynecology, Kasr Al Aini Hospital. Some of the patients were diagnosed before pregnancy by the hematologists as ITP and were under treatment, whereas the others were diagnosed during pregnancy after consultation of the hematologist and exclusion of other causes of low platelet count, especially gestational thrombocytopenia. On the basis of its severity, thrombocytopenia is classified as mild at a platelet count of 100 000–150 000/ml, moderate at 50 000–100 000/ml, and severe at counts less than 50 000/ml 6.
During the hospitalization period, patients were strictly followed by an obstetric and a hematology team; neonates were also followed up after delivery. All data, including the age of the patients, date of diagnosis of ITP, clinical manifestations, laboratory investigations, treatments given to increase the platelet count during pregnancy, response to therapy and platelet counts at delivery were obtained from patients’ files and recorded. Also, any complications during the antenatal period such as bleeding symptoms, gestational diabetes, pre-eclampsia, intrauterine growth restriction or intrauterine fetal death (IUFD), and preterm labor were obtained. The mode of delivery, whether vaginal or cesarean, blood products transfused, and if any complications at delivery or in the postpartum period were reviewed. The neonatal platelet count at birth and treatments received, if any, were also recorded.
The exclusion criteria were other causes of low platelet count such as gestational thrombocytopenia, systemic lupus erythematosis, lymphomas, leukemias and hypertensive disorders of pregnancy such as hemolysis elevated liver enzymes low platelet count syndrome.
Data were statistically described in terms of range, mean, SD, frequencies and percentages.
Twenty-five patients diagnosed as ITP with pregnancy were followed up till delivery in the High-Risk Pregnancy Unit, Department of Obstetrics and Gynecology, Kasr Al Aini Hospital, during the study interval from April 2009 to May 2013. ITP pregnant patients included in the study were managed according to a specific protocol by both a hematology and an obstetric team. After delivery, platelet levels of the newborns were monitored by the neonatologist. Out of the 25 patients, 11 patients (44%) were previously diagnosed as ITP and were already on treatment with prednisolone before pregnancy, whereas 14 patients (56%) were diagnosed during pregnancy, two patients (8%) were diagnosed in the first trimester, and seven (28%) and five patients (20%) were diagnosed in the second and the third trimesters, respectively. The mean age (±SD) of the patients was 29.84±6.03 years (range 18–41 years). The mean (±SD) parity of patients was 1.52±1.41 (range 0–5) and the mean gestation was 2.68±1.43.
During the antenatal period, the decisions of treatment given to increase the platelet count were made by the hematologist depending on many factors such as the level of platelets, if there is any bleeding symptoms, and the gestational age of pregnancy. The duration and the dose of therapy depended on the response of the patient. In this study, there were 22 patients (88%) on oral predinsolone, 17 (68%) patients received treatment with pulse methylprednisolone during the hospitalization period, three patients (12%) were given intravenous immunoglobulin (Ig) in addition to the methylprednisolone, and there was history of splenectomy in two (8%) patients before pregnancy.
As shown in Table 1, four (16%) patients developed gestational diabetes during pregnancy, and all of them were on treatment with corticosteroids. There was one case (4%) complicated by pre-eclampsia. Bleeding symptoms in the form of ecchymotic patches, bleeding gums, and epistaxis were observed in three pregnancies, and all three patients had platelets counts below 20 000/ml and treatment was given to correct the thrombocytopenia; one of these patients had a platelet count of 5000/ml; after increasing the platelet count to 70 000/ml, suddenly at 36 weeks, the platelet count decreased to 18 000/ml, and the patient developed placental abruption. There was one (4%) unexplained IUFD at 37 weeks of gestation. The fetus had no signs of hemorrhage or congenital anomalies; however, postmortem examination was not conducted. There were no cases of abortions or intrauterine growth restriction in the study. Three patients (12%) had preterm deliveries (<37 weeks of gestation).
At the time of delivery, four (16%) patients had mild thrombocytopenia with a platelet count between 110 000 and 120 000/ml, 13 (52%) had moderate thrombocytopenia (>50 000/ml) and eight patients (44%) had severe thrombocytopenia with a platelet count <50 000/ml; three (12%) of them had very low platelet counts below 20 000/ml as shown in Table 2. All 25 women were delivered at the High-Risk Unit; there were nine vaginal deliveries (36%) and 16 cesarean sections (64%), as shown in Table 3. All of the cesareans were performed for obstetric indications only.
Overall, six (24%) patients received platelet transfusion, four (16%) had intrapartum platelet transfusion and two (8%) women had mild postpartum bleeding, but no serious complications. None of the patients received blood transfusion. Although there were three cases with platelet count less than 20 000/ml, only one patient required platelet transfusion during vaginal delivery (platelet count 18 000/ml). The other two patients delivered vaginally without episiotomy or any bleeding complications at counts of 18 000 and 19 000/ml. Two patients with platelet counts of 35 000 000 and 48 000/ml encountered excessive bleeding during the cesarean section, and they needed intraoperative platelet transfusion. The first patient was a primigravida referred from the hematology unit at 35 weeks of gestation and a platelet count of 9 000/ml, after pulse steroids were given; she developed contractions and delivered preterm by cesarean section at 36 weeks at a count of 35 000/ml with platelets given intraoperatively. The fourth patient was a second gravida presented at 36 weeks in the first stage of labor with a platelet count of 25 000/ml and on no treatment; she delivered vaginally, but two units of platelets were needed intrapartum.
Neonatal platelets were measured in all 24 neonates (one patient had unexplained IUFD): four neonates (16.6%) developed mild thrombocytopenia, platelet count less than 150 000/ml, and 20 newborns (83.3%) had a normal platelet count (Table 4). None of the infants showed signs of hemorrhage, especially intracranial hemorrhage, or received any treatment (intravenous Ig or platelet transfusion); they were just followed up by the neonatology team, and the platelet count increased to normal within 7 days after delivery. None of the fetuses underwent cordocentesis for fetal blood sampling before delivery in our study.
Many studies reported that pregnancy in patients with ITP can be safe 7,8; other studies did not conclude that pregnancy can aggravate ITP; however, the nadir of maternal platelets was found in the third trimester of pregnancy with the risk of both maternal and fetal hemorrhage during delivery 9,10. In this study, we had a satisfactory maternal and neonatal outcome with no maternal and neonatal morbidity or mortality.
Treatment is generally recommended when the platelet count is unacceptably low or when the patient has bleeding symptoms, such as petechiae or mucosal bleeding. The first line of treatment in ITP is corticosteroid therapy 11–14, an initial dose of prednisolone 1 mg/kg is recommended and sequentially tapering to a minimal haemostatic effective dose 3. Intravenous Ig is given as the initial treatment for patients with platelet counts below 10 000/ml in the third trimester or a platelet count of 10 000–30 000/ml who have bleeding manifestations 15. Splenectomy is recommended when the platelet count is unacceptably low or when the patient has bleeding symptoms and does not respond to glucocorticoid and intravenous Ig therapy; however, it should be avoided during pregnancy because of the risk of hemorrhage and the difficult technique. Splenectomy, if performed, should be performed in the second trimester 15. In this study, 22 patients (88%) were on oral predinsolone, 17 (68%) patients received treatment with pulse methylprednisolone, three patients (12%) were given intravenous Ig in addition to the methylprednisolone and there was history of splenectomy in two (8%) patients before pregnancy (splenectomy was not attempted during pregnancy in our study). However, patients taking steroids have an increased risk of developing gestational diabetes 14; in this study, four patients (16%) developed gestational diabetes mellitus, and all received treatment with steroids.
The route of delivery in women with ITP was debated for a long time, as to whether vaginal delivery or cesarean section will be less risky with regard to both maternal and fetal hemorrhage. Previously, cesarean section was suggested to prevent fetal intracranial hemorrhage 5; however, there are no data to support the fact that cesarean section was superior to vaginal delivery in lowering the risks for the thrombocytopenic fetus 3,5,7,11–13,16. In this study, nine (36%) of the 25 patients delivered by the vaginal route and 16 patients (64%) delivered by cesarean sections; all cesarean sections were performed for obstetric indications, and none because of thrombocytopenia, as is the case in many previous studies 7,11,13,17. There were no clinically significant maternal or neonatal bleeding complications in patients delivered by vaginal route or cesarean deliveries 10.
At the time of delivery, four (16%) patients after treatment in the antenatal period delivered with mild thrombocytopenia (platelet count between 110 000 and 120 000/ml). Among the rest of the patients, 13 (52%) had moderate thrombocytopenia (50 000–100 000/ml), eight patients (44%) had severe thrombocytopenia with platelet count less than 50 000/ml and three (12%) of them had very low platelet counts below 20 000/ml. Platelet transfusion was received by six patients (24%): four cases intrapartum and two cases postpartum. There was no serious bleeding complication. None of the patients received blood transfusion. Although there were three cases of vaginal delivery with severe thrombocytopenia, platelet count less than 20 000/ml, only one patient required platelet transfusion during the vaginal delivery (platelet count 18 000/ml). The other two patients delivered vaginally without episiotomy or any bleeding complications at counts of 18 000 and 19 000/ml.
During the antenatal period, one patient developed preeclampsia. This complication was reported by previous studies 8,14. IUFD had been also reported (we had one unexplained IUFD despite good Doppler studies and cardiotocography) 8,11. Abruptio placenta occurred in one of our patients, which is also a reported complication 8. Preterm deliveries have been reported by several studies 18; there were three patients who delivered preterm in our study.
Maternal platelet antibodies can cross the placenta causing neonatal thrombocytopenia; however, many studies reported that there was no serious hemorrhagic complication such as intracranial hemorrhage in the neonates 7,8,17,19. In this study, 20 newborns (83.3%) had a normal platelet count, four neonates (16.6%) developed mild thrombocytopenia (platelet count<150 000/ml), but none of them suffered from intracranial hemorrhage or required treatment. The maternal platelet count cannot predict the neonatal platelet count, which can be detected during labor by fetal scalp sampling or by percutaneous umbilical blood sampling before delivery; however, these two procedures are invasive and can carry complications such as fetal scalp hematoma or fetal bradycardia 20,21. These invasive procedures were not performed on any of the patients in this study, as it was recommended to follow-up neonates after delivery, and if neonatal thrombocytopenia occurs, it was to be managed postpartum.
The maternal and fetal outcome in this study was similar to previous studies 3,8 in which there was a low risk of serious hemorrhagic complications in infants and mothers. None of the patients had serious bleeding complication during antepartum (except for abruptio placenta), intrapartum and postpartum periods. The good pregnancy outcomes in our patients were likely to be the result of the cooperation between obstetricians, hematologists and neonatologists. Therefore, it is concluded that a safe pregnancy outcome in women with ITP requires close monitoring of mothers and neonates by the teamwork of hematology, obstetric and neonatology teams.
Conflicts of interest
There are no conflicts of interest.
1. Cunningham FG, Gant NF, Leveno KJ, Gilstrap LC III, Hauth JC, Wenstrom KDWilliams WO.Williams obstetrics [Chapter 49].Hematological disorders2001:21st ed..USA:McGraw-Hill;1307–1338.
2. Cines DB, Blanchette VS.Immune thrombocytopenic purpura.N Engl J Med2002;346:995–1008.
3. Kelton JG.Idiopathic thrombocytopenic purpura complicating pregnancy.Blood Rev2002;16:43–46.
4. Sullivan CA, Martin JN Jr.Management of the obstetric patient with thrombocytopenia.Clin Obstet Gynecol1995;38:521–534.
5. Gill KK, Kelton JG.Management of idiopathic thrombocytopenic purpura in pregnancy.Semin Hematol2000;37:275–289.
6. Kam PCA, Thompson SA, Liew ACS.Thrombocytopenia in the parturient.Anaesthesia2004;59:255–264.
7. Wang Q, Nie LL.Clinical analysis of 92 cases of pregnancy with idiopathic thrombocytopenic purpura.Zhonghua Fu Chan Ke Za Zhi2004;39:729–732.
8. Ali R, Özkalemkaş F, Özçelik T, Özkocaman V, Ozan Ü, Kimya Y, et al..Idiopathic thrombocytopenic purpura in pregnancy: a single institutional experience with maternal and neonatal outcomes.Ann Hematol2003;82:348–352.
9. Burrows RF, Kelton JGGreer IA, Turpie AGG, Forbes CD.Thrombocytopenia during pregnancy.Haemostasis and thrombosis in obstetrics and gynaecology1992.London:Chapman & Hall Medical;414–423.
10. Sainio S, Joutsi L, Järvenpää A-L, Kekomäki R, Koistinen E, Riikonen S, Teramo K.Idiopathic thrombocytopenic purpura in pregnancy.Acta Obstet Gynecol Scand1998;77:272–277.
11. Al-Jama FE, Rahman J, Al-Suleiman SA, Rahman MS.Outcome
of pregnancy in women with idiopathic thrombocytopenic purpura.Aust N Z J Obstet Gynaecol1998;38:410–413.
12. Peleg D, Hunter SK.Perinatal management of women with immune thrombocytopenic purpura: survey of United States perinatologists.Am J Obstet Gynecol1999;1803 I645–649.
13. Sukenik-Halevy R, Ellis MH, Fejgin MD.Management of immune thrombocytopenic purpura in pregnancy.Obstet Gynecol Surv2008;63:182–188.
14. Suri V, Aggarwal N, Saxena S, Malhotra P, Varma S.Maternal and perinatal outcome
in idiopathic thrombocytopenic purpura (ITP) with pregnancy.Acta Obstet Gynecol Scand2006;85:1430–1435.
15. [No authors listed].Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy.Br J Haematol2003;120:574–596.
16. Nisaratanaporn S, Sukcharoen N.Outcome
of idiopathic thrombocytopenic purpura in pregnancy in King Chulalongkorn Memorial Hospital.J Med Assoc Thai2006;89Suppl 4S70–S75.
17. Özkan H, Çetinkaya M, Köksal N, Ali R, Güne AM, Baytan B, et al..Neonatal outcomes of pregnancy complicated by idiopathic thrombocytopenic purpura.J Perinatol2010;30:38–44.
18. Belkin A, Levy A, Sheiner E.Perinatal outcomes and complications of pregnancy in women with immune thrombocytopenic purpura.J Matern Fetal Neonatal Med2009;22:1081–1085.
19. Won Y-W, Moon W, Yun Y-S, Oh H-S, Choi J-H, Lee Y-Y, et al..Clinical aspects of pregnancy and delivery in patients with chronic idiopathic thrombocytopenic purpura (ITP).Korean J Intern Med2005;20:129–134.
20. Hwa HL, Chen RJ, Chen YC, Wang TR, Huang SC, Chow SN.Maternal and fetal outcome
of pregnant women with idiopathic thrombocytopenic purpura: retrospective analysis of 25 pregnancies.J Formos Med Assoc1993;92:957–961.
21. Sainio S, Kekomäki R, Riikonen S, Teramo K.Maternal thrombocytopenai at term: a population-based study.Acta Obstet Gynecol Scand2000;79:744–749.