Laparoscopic Splenectomy for the Treatment of Refractory Immune Thrombocytopenia in Pregnancy

CASE REPORT

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Laparoscopic Splenectomy for the Treatment of Refractory Immune Thrombocytopenia in Pregnancy Jill Griffiths, MD,l Winnie Sia, MD, FRCPC,1,2 A.M. James Shapiro, MD, PhD, FRCS(Eng), FRCSC,3 Ivanna Tataryn, MD, FRCSC, DABOG,l A.Robert Turner, MD, FRCPC2 1 Department

of Obstetrics and Gynecology, University of Alberta, Edmonton AB

2Department of Medicine, University of Alberta, Edmonton AB 3Department of Surgery, University of Alberta, Edmonton AB

Abstract

hebdomadaires en alternance avec des immunoglobulines anti-D; toutefois la splenectomie laparoscopique s'est averee indiquee a 20 semaines de gestation en raison d'une thrombocytopenie. A la suite de la chirurgie, on a continue a lui administrer de la prednisone et un traitement IglV intermittent jusqu'a I'accouchement spontane a 34 semaines de gestation. A la suite de I'accouchement, on a detecte une petite rate accessoire par imagerie medicale nucleaire. Une numeration des plaquettes suffisante a ete maintenue au cours de la periode post-partum au moyen du danazol et de la prednisone.

Background: Immune thrombocytopenic purpura (ITP) is a condition with potential hazard during pregnancy for both mother and fetus if platelet concentrations fall below a critical level. This report describes the use of laparoscopic splenectomy following unsuccessful medical management. Case: A 35-year-old primigravid woman with systemic lupus erythematosis (SLE) developed ITP several years before becoming pregnant. She was treated early in pregnancy with high-dose oral prednisone and weekly intravenous immunoglobulin (IVIG) alternating with anti-D immune globulin, but laparoscopic splenectomy was indicated at 20 weeks' gestation because of thrombocytopenia. Following surgery, she continued prednisone and intermittent IVIG therapy until spontaneous delivery at 34 weeks' gestation. A small accessory spleen was identified postpartum by nuclear medicine scan. Satisfactory platelet concentrations were maintained postpartum using danazol and predisone. Conclusion: Laparoscopic splenectomy is a therapeutic option for women with ITP during pregnancy that fails to respond to medical management.

Resume Contexte: Le purpura thrombocytopenique idiopathique (PTI) est une pathologie comportant des dangers possibles au cours de la grossesse tant pour la mere que pour Ie foetus si la numeration des plaquettes chute en de<;:a d'un seuil critique. Ce rapport decrit Ie recours a une splenectomie laparoscopique a la suite de I'echec de la prise en charge medicale. Cas: Une femme primigeste de 35 ans atteinte de lupus erythemateux dissemine (LED) a developpe un PTI plusieurs annees avant de devenir enceinte. Elle a ete traitee, aux debuts de la grossesse, au moyen de fortes doses de prednisone orale, ainsi qu'au moyen d'immunoglobulines intraveineuses (lglV) Key Words: Idiopathic thrombocytopenic purpura, splenectomy, pregnancy, systemic lupus erythematosis, laparoscopy Competing interests: None declared. Received on February 4, 2005 Accepted on March 21, 2005

Conclusion: La splenectomie laparoscopique est un traitement potentiel pour les femmes presentant, au cours de la grossesse, un PTI sur lequella prise en charge medicale n'a pas d'effets.

J Obstet Gynaecol Can 2005;27(8):771-774

INTRODUCTION

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mmune thrombocytopenic purpura (ITP) affects between 1 and 3 women per 1000 pregnancies 1 and may lead to hemorrhagic complications in the mother and fetus. 2 ITP during pregnancy can usually be controlled with use of corticosteroids, intravenous immunoglobulin (IVIG) , or anti-D immunoglobulin. Occasionally, however, splenectomy is required when thrombocytopenia is severe and refractory to medical therapy. We present a case of surgical management of ITP by laparoscopic splenectomy in the second trimester. CASE

Jessica (pseudonym), a 35-year-old primigravida, presented to her obstetrician at 8 weeks' gestation with a 13-year history of systemic lupus erythematosis (SLE) and a 6-year history of ITP. The diagnosis of SLE was made in 1991 after she developed severe renal dysfunction and arthralgias. A renal biopsy confirmed lupus nephritis, and she was treated with corticosteroids and cyclophosphamide. She responded well and remained in remission until a second episode of

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lupus nephritis in 2000. This was confirmed again by renal biopsy and treated with mycophenolate mofetil, hydroxychloroquine sulphate, and corticosteroids, with good response. When she began attempts to conceive, azathioprine was substituted for mycophenolate mofetil and hydroxychloroquine sulphate, but she became severely thrombocytopenic, and treatment with azathioprine was withdrawn. After she had conceived, the corticosteroid treatment continued; despite this, she remained significantly thrombocytopenic, and at a platelet concentration of 20 X 109 /L, she began to experience extensive bruising of her extremities. Her renal function, liver function, and blood pressure remained normal. Her levels of complement and double-strand anti-DNA were normal, but she was anti-SSA positive. Antiphospholipid antibodies were not identified. Jessica's care between 8 and 16 weeks' gestation was provided by a multidisciplinary team that included an internist, a haematologist, a nephrologist, an obstetrician, and a perinatologist. Her oral prednisone therapy was increased to 50 mg daily, and she received weekly IVIG (50 g) to stabilize her platelet concentration. She experienced significant headaches with the weekly administration ofIVIG, and as a result, her weekly treatment was changed to alternating IVIG and intravenous anti-D immunoglobulin (50 g/kg). Despite this treatment, her platelet concentration remained low, eventually falling to 8 X 109 /L. At 16 weeks' gestation, Jessica was admitted to hospital with vaginal bleeding. Although her platelet concentration again responded to treatment with IVIG, her condition led to concern that she would be unable to continue her pregnancy to term and deliver safely. In anticipation of the possibility of her undergoing splenectomy and because of the potential risk of postsplenectomy sepsis, she was immunized against Haemophilus influenza b, Meningococcus, and Streptococcus pneumoniae. Jessica Was referred to a general surgeon experienced in laparoscopic splenectomy for consideration of possible surgery. She underwent a laparoscopic splenectomy at 20 weeks' gestation. Insertion of a Verres needle approach was not used for inducing pneumoperitoneum, to avoid potential injury to the uterus. Instead, a peritoneal cutdown was made under direct visualization to the left of the midline below the costal margin, and a 10 mm port was secured. Three 5 mm ports were placed radially in an arc around the spleen in the left upper quadrant, which is standard in laparoscopic splenectomy. The placement did not require modification because of the enlarged uterus. A small spleen was visualized, and no accessory splenic tissue was seen. Although space for intra-abdominal manipulation was initially restricted by the enlarged uterus (which reached the level of

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the umbilicus), it was no longer restricted when peritoneal C02 insufflation was complete (15 mm Hg intraperitoneal pressure). The spleen was freed from its ligamentous attachments, and an endoscopic vascular stapler was used to divide the splenic vessels. The spleen was easily transferred into a 15 mm Endocatch II bag and removed. During the case, standard maternal physiologic monitoring (electrocardiogram, pulse oximetry, arterial line, and end-tidal C02 monitoring) was provided, without intraoperative fetal monitoring. Five units of platelets were transfused during surgery. Estimated blood loss was 150 to 200 cc, and the patient tolerated the surgery well. She was discharged home 5 days after the surgery in stable condition. Following the splenectomy, Jessica's platelet concentration increased for 2 weeks. However, when an attempt was made to discontinue the use of prednisone, she became acutely thrombocytopenic and required IVIG therapy (see Figure). Throughout the remainder of her pregnancy, she required IVIG therapy, less often than preoperatively, and was maintained on a lower dosage of prednisone (25 mg daily). Her gestational diabetic screen was positive, but subsequent oral glucose tolerance testing was normal. Her blood pressure remained normal, and renal function was stable. She had no recurrence of vaginal bleeding and did not require readmission to hospital. Fetal surveillance, with serial biophysical proftles and nons tress tests, remained reassuring; fetal growth was satisfactory,· and fetal echocardiography showed no abnormality. At 34 weeks' gestation, Jessica had spontaneous rupture of membranes and was admitted to hospital. She had received IVIG several days before admission, and her platelet concentration on admission was 81 X 109 /L. Epidural analgesia was administered and induction of labour with oxytocin was begun. At a cervical dilatation of 4 em, fetal heart rate monitoring showed repetitive variable decelerations and sustained bradycardia. Emergency Caesarean section was performed without complication, with delivery of a live male infant weighing 2220 g. Estimated blood loss was average « 1000 mL), and the baby's Apgar scores were 8 and 9, at 1 and 5 minutes, respectively. The baby was admitted to the level II nursery and underwent phototherapy on day 3 for mild jaundice. No arrhythmia was evident, and his platelet concentration was 149 x 109/L. Jessica's platelet concentration fell to 39 X 109 /L at 6 hours after delivery. She again responded well to IVIG therapy and required IVIG several times over the subsequent 2 months. Eventually, her platelet concentration stabilized, and the prednisone dosage was successfully tapered to 10 mg every 2 days. She began treatment with danazol and hydroxychloroquine sulphate and no longer required IVIG.

Laparoscopic Splenectomy for the Treatment of Refractory Immune Thrombocytopenia in Pregnancy

Patient's platelet counts from splenectomy to delivery subsequent requirement for intravenous immunoglobulin (IVIG)

300

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'"Q 200 ...-!

X 150

II III

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100

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20 weeks' gestation Splenectomy

'l

, IVIG administered

34 weeks' gestation Delivery

A scan using isotope-labelled erythrocytes demonstrated a 2.1 cm accessory spleen lateral to the upper pole of the left kidney. Removal was not indicated in view of Jessica's stable condition with medical management. DISCUSSION

Although pregnancy does not affect the incidence and severity ofITP, severe thrombocytopenia during pregnancy can occur and carries a significant risk of hemorrhage, particularly during labour and delivery. The American Society of Hematology and the British Committee for Standards in Haematology have published guidelines3,4 recommending treatment of ITP when the platelet concentration falls below lOx 109 /L at any time during pregnancy or below 30 x 109 /L in the presence of bleeding or after the second trimester. Corticosteroid or IVIG therapy is usually effective and is recommended as first-line treatment during pregnancy. Administration of anti-D immune globulin is also an option for Rh-positive women and is less timeconsuming, less expensive, and generally better tolerated than IVIG,3,4 Immunosuppressants commonly used in the nonpregnant population are usually avoided during pregnancy because of their potential teratogenic effect. Systemic lupus erythematosis is associated with maternal and fetal morbidity and mortality, particularly if antiphospholid antibodies, reduced levels of complement, or hypertension are present. s Patients whose ITP is part of SLE seem to respond less well to standard therapies, although it is difficult to separate the effects of nonhematological organ failure from ITP disease activity.6

Jessica had quiescent SLE during her pregnancy, which may account for her benign course. Splenectomy is a second-line treatment for ITP that is refractory to the above medical therapies. Remission is achieved in up to 90% of patients following splenectomy,7,8 and the side effects of systemic medications can often be avoided. Laparoscopic splenectomy has become the preferred surgical method for splenectomy since its introduction in 1991. 9 It carries multiple advantages over laparotomy, including smaller incisions, faster recovery and discharge from hospital, less postoperative pain, and lower analgesic requirements. Possible concerns with the laparoscopic approach during pregnancy include the effect of the pneumoperitoneum on the fetus and the altered cardiovascular status of the mother. Several studies in pregnant ewes have suggested that a carbon dioxide pneumoperitoneum can produce maternal and fetal acidosis even when the mothers are actively ventilated; however, it is not possible to ascertain whether this results in clinically significant or deleterious effects. 1O- 12 The risk of fetal loss following laparoscopy appears to be related to the underlying disease and to be independent of the operative intervention, but it approximates 5% in the second trimester, compared with 12% in the first trimester. 13 Adequate accessibility is also of concern and is generally minimized by performing surgery in the second trimester, before the uterus has become very enlarged. Although there have been reports of injury to the uterus caused by insertion of the Verres needle or

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CASE REPORT

trocar,14,15 this risk is minimal if an open or left-subcostal entry technique is used. The third concern is the limitation of the surgeon's ability to explore the abdomen for accessory splenic tissue, since 15% to 30% of the population have an accessory spleen. 16 It is possible that the restriction of the peritoneal cavity by the pregnancy could have contributed to the nonvisualization of the accessory spleen in this case. To date, there have been only 4 published reports oflaparoscopic splenectomy during pregnancy,17-20 and only 2 of these were for ITP.18,19 One case was performed at 23 weeks' gestation, when a pregnant woman with ITP failed to respond to medical treatment. 18 She continued to require prednisone following splenectomy but went on to deliver vaginally at term following premature rupture of the membranes. Her prednisone therapy was discontinued at 2 weeks postpartum, and her platelet concentrations thereafter remained stable. The second report described laparoscopic splenectomy at 23 weeks' gestation, also for refractory ITP.19 After surgery, the woman's platelet concentration remained normal without medical treatment, and she delivered uneventfully at term. The third report described surgery performed at 18 weeks for thrombocytopenia secondary to antiphospholipid syndrome,17 and the fourth report described surgery at 24 weeks for hereditary spherocytosis. 2o The women in both these cases responded well to splenectomy and delivered vaginally at term with no perinatal complications.

CONCLUSION Having to perform laparoscopic splenectomy during pregnancy for the management ofITP that is refractory to medical treatment is uncommon. For the woman described here, laparoscopic splenectomy in the second trimester resulted in an improvement in her clinical condition, with less medical therapy required postoperatively, even though an accessory spleen was later identified. Neither the maternal nor the fetal outcome was compromised, and the patient's thrombocytopenia currently remains stable with minimal medical intervention.

ACKNOWLEDGEMENTS The woman whose story is told in this case report has provided signed permission for its publication.

REFERENCES 1. Gabbe SG, Niebyl JR, Simpson JL, editors. Obstetrics: normal and problem pregnancies. 4th ed. London: Churchill Livingstone Inc; 2002. p.1170-2.

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2. Webert KE, Mittal R, Sigouin C, HeddJe NM, KeltonJG. A retrospective II-year analysis of obstetric patients with ITP. Blood 2003;102:4306--11. 3. George IN, WoolfSH, Raskob GE, WasserJS, Aledort LM, Ballem PJ, et aI. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996;88:3-40. 4. Provan D, Newland A. ITP in adults. J Pediatr Hematol Oncol 2003;25(Suppl 1):34-8. 5. Cortes-Hernandez J, Ordi-Ros J, Paredes F, Casellas M, Castillo F, Vilardell-Tarres M. Clinical predictors of fetal and maternal outcome in SLE: a prospective study of 103 patients. Rheumatology 2002;41:643-50. 6. You YN. Outcome of splenectomy for thrombocytopenia associated with SLE. Ann Surg 2004;240:286--92. 7. Winde G, Schmid KW, Lugering N, Fischer R, Brandt B, Berns T, et al. Results and prognostic factors of splenectomy in idiopathic thrombocytopenic purpura. J Am Coli Surg 1996;183:565-74. 8. Gadenstatter M, Lamprecht B, Klingler A, Wetscher G], Greil R, Schmid T. Splenectomy versus medical treattnent for idiopathic thrombocytopenic purpura. Am J Surg 2002;184(6):606--9. 9. Delaitre B, Maignein B, Icard P. Laparoscopic splenectomy. Br J Surg 1992;79:1334. 10. Cruz AM, Southerland LC, Duke T, Townsend HG, Ferguson JG, Crone LL. Intra-abdominal carbon dioxide insufflation in the pregnant ewe. Anesthesiology 1996;85: 1395-1402. 11. Curet MJ, Voget DA, Schob 0, Qualls C, Izquierdo LA, Zucker KA. Effects of C02 pneumoperitoneum in pregnant ewes. J Surg Res 1996;64:339-44. 12. Hunter JG, Swanstrom L, Thornburg K. Carbon dioxide pneumoperitoneum induces fetal acidosis in a pregnant ewe model. Surg Endosc 1995:9:272-9. 13. Al-Fozan H, Tulandi T. Safety and risks oflaparoscopy in pregnancy. Curr Opin Obstet GynecoI2002;14:375-9. 14. FriedmanJD, Ramsey PS, Ramin KD, Berry C. Pneumoamnion and pregnancy loss after second trimester laparoscopic surgery. Obstet Gynecol 2002;99:512-3. 15. Barnett MB, Liu DT. Comoplication of laparoscopy during early pregnancy Detter]. BMJ 1974;1:328. 16. Rudowski WJ. Accessory spleens clinical significance with particular reference to the recurrence of idiopathic thrombocytopenic purpura. World J Surg 1985;9:422-30. 17. Hardwick RH, Slade RR, Smith PA, Thompson MH. Laparoscopic splenectomy in pregnancy.] Laparoendosc Adv Surg Tech A 1999;9(5):439-40. 18. Iwase K, HigakiJ, Yoon HE, Mikata S, Tanaka Y, Takahashi T, et aI. Hand-assisted laparoscopic splenectomy for idiopathic thrombocytopenic purpura during pregnancy. Surg Laparosc Endosc Percutan Tech 2001;11(1):53-6. 19. Anglin BV, Rutherford C, Ramus R, Lieser M, Jones D. Immune thrombocytopenic purpura during pregnancy: laparoscopic treatment. JSLS 2001 ;5:63-7. 20. Allran CF, Weiss CA, Park AE. Urgent laparoscopic splenectomy in a morbidly obese pregnant woman: case report and literature review. J Laparoendosc Adv Surg Tech A 2002:12(6):445-7.