Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Immune Thrombocytopenia and Pregnancy Medication

  • Author: Muhammad A Mir, MD, FACP; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
 
Updated: Oct 09, 2015
 

Medication Summary

Immune thrombocytopenia

Treatment for ITP in pregnancy is well established and effective.[32, 33, 34] Medical therapy is initiated if the maternal platelet count decreases to less than 20,000/µL, if spontaneous bleeding occurs and the platelet count is less than 50,000/µL, or if surgery or delivery is anticipated and the platelet count is less than 50,000/µL. Patients with ITP and platelet counts greater than 50,000/µL with active bleeding need to be evaluated for other causes of hemorrhage. If no other etiology of bleeding can be identified, then the patient with ITP and active bleeding should be treated medically for ITP until her platelet count increases to greater than 100,000/µL.

Prednisone (1-2 mg/kg/d) usually is first-line therapy in stable patients. An increase in platelet count usually is observed within 3-5 days, and maximal effect occurs in 2-3 weeks. The optimal duration of prednisone therapy is unknown. Steroids are not entirely benign during pregnancy and orofacial fetal abnormalities such as cleft palate occur 3-fold more commonly in infants exposed in the first trimester.[35] Maternal hyperglycemia and hypertension may also result.

Opinions vary concerning the minimal platelet count required for epidural anesthesia; however, many anesthesiologists are hesitant to utilize epidural anesthesia for labor with a patient whose platelet count is less than 100,000/µL. Thus, patients with platelet counts below this level often are treated with prednisone at 36-37 weeks' gestation.

Intravenous immunoglobulin (IVIG) can be used in women who do not respond to prednisone. Because patients respond more quickly to IVIG than prednisone (a response can be observed as quickly as 6 h), IVIG is a good choice for first-line therapy in women with platelet counts less than 10,000/µL or in association with perioperative or postpartum bleeding. IVIG (usual prescription 0.4 mg/kg/d for 3-5 d) is costly and of limited availability, thus it should be used judiciously.[36] A retrospective study of 67 neonates with thrombocytopenia born to mothers with ITP suggested benefit of starting IVIG when the platelet count is below 50 x 109/L, after the first platelet transfusion to avoid multiple transfusions.[37]

Intravenous anti-D (WinRho, WinRho SD) has been utilized in both children and adults to treat ITP. Children have a better response than adults; overall, approximately 70% of treated individuals respond to intravenous anti-D with increasing platelet counts.[38] Doses utilized have ranged from 25-200 mcg/kg/d. Some studies administered intravenous anti-D daily for 5 days, others administered a single dose. Toxicity was minimal, and infusions were completed in less than 5 minutes.[38, 39] Anti-D is effective in Rh-positive individuals only and may be associated with immune hemolysis.[40]

Experience with intravenous anti-D in pregnancy to treat ITP has been limited. This is likely because of concerns of possible fetal hemolysis from transplacental passage of the IgG molecules. Significant fetal hemolysis from maternal antepartum prophylaxis has not been reported[41] ; however, doses of intravenous anti-D used for prophylaxis to prevent Rh disease are much lower than those used to treat ITP. Thus, IVIG tends to be used more commonly in pregnancy.

Platelet transfusions should be used sparingly because maternal antiplatelet antibodies result in rapid destruction of transfused platelets.[42] Administer platelet transfusions to women with hemorrhage or platelet counts less than 10,000/µL. Generally, at time of delivery or just prior to cesarean delivery, 6-10 units of platelets are administered if the maternal platelet count is less than 50,000/µL to prevent intrapartum or postpartum bleeding.

The safety and efficacy of thrombopoietin mimetics is not established in pregnant women with ITP. In one case report, in which romiplostim was used during pregnancy in addition to steroids and IVIG, the newborns still manifested intraventricular hemorrhage, although there was no developmental delay at 10 months.[43]

Rituximab crosses the placenta, and data are insufficient to recommend use in ITP during pregnancy.[44]

Cyclophosphamide, mycophenolate, vincristine, and danazol are contraindicated during pregnancy.

Neonatal alloimmune thrombocytopenia

The goal of treatment in NAIT is to prevent intracranial or visceral bleeds in the fetus and newborn. Prenatal diagnosis and treatment is important because 25-50% of fetal intracranial hemorrhages occur while the fetus is in utero.[12] The only reliable method of determining the fetal platelet count is to perform cordocentesis and check the fetal blood directly because fetal platelet counts do not correlate with maternal antibody levels. Cordocentesis is associated with a 1-2% chance of emergent cesarean delivery for fetal indications.[10] Thus, a risk for fetal loss exists with each cordocentesis procedure performed.

Platelet membrane specific antigens are present in the fetus at 18 weeks' gestation; therefore, cordocentesis commonly is initiated in HPA-1b mothers with platelet alloantibodies at 20 weeks' gestation. Continued monitoring and treatment for NAIT is quite controversial. Controversy exists because NAIT is rare and only small numbers of successfully treated patients are reported in the literature.

European authors have advocated weekly platelet transfusions and have demonstrated this therapy is effective in increasing the fetal platelet count.[45, 46, 47] Brussel et al have advocated a less invasive management and treatment plan, reporting on a total of 73 patients with NAIT.[48, 49] Mothers of fetuses determined to be thrombocytopenic at initial cordocentesis were treated with IVIG 1 g/kg/wk. A repeat cordocentesis was performed after 4-6 weeks to assess efficacy of treatment.

In their randomized controlled trial, some mothers were treated with IVIG, others with IVIG and dexamethasone.[49] The addition of dexamethasone did not enhance the effect of IVIG. At least 62% of patients responded to IVIG alone. Patients failing to respond either were delivered early or were continued on IVIG plus prednisone (60 mg/d). This salvage therapy was effective in 50% of cases that failed to respond to IVIG alone. None of the mothers treated according to this management plan had a fetus with an intracranial hemorrhage. These authors advocate administering platelet transfusions if the fetal platelet count is less than 20,000/µL at the time of cordocentesis because they noted an increased rate of fetal exsanguination secondary to cordocentesis when the platelet count was in this range.

Other authors have advocated using IVIG as a primary treatment, particularly in patients who are at risk for NAIT and have no history of a previous child affected with intracranial hemorrhage.[50] Fetuses that fail to respond to IVIG receive weekly platelet transfusions for the duration of the pregnancy.[18]

The fetus should be delivered as soon as fetal lung maturity is documented to minimize the risk of hemorrhage in utero. Usually, if the fetal platelet count is less than 50,000/µL, a cesarean delivery is performed, although no clear evidence in the literature supports this.

Management of the newborn with NAIT is fairly straightforward. Because of the significant risk of intracranial hemorrhage, an immediate cranial ultrasound should be performed. Severely thrombocytopenic newborns (< 10,000/µL) or newborns with intracranial or visceral hemorrhages should receive a matched platelet transfusion (maternal or homozygous HPA-1b donor) as soon as possible. If maternal platelets are utilized, they must be processed to remove platelet alloantibodies. Reserve random platelets for life-threatening hemorrhage when matched platelets are not immediately available because reports exist of worsening thrombocytopenia and disseminated intravascular coagulation (DIC) following random platelet transfusion in cases of NAIT.[6]

IVIG (1 g/kg/d) has been demonstrated to increase newborn platelet counts in most cases of NAIT. A substantial increase is observed in 24-72 hours, which is adequate for newborns who are stable and without evidence of bleeding.

Exchange transfusions can be performed to remove antiplatelet antibody and shorten the course of neonatal disease.[6] Approximately 30% of available immunoglobulin G antiplatelet antibodies are estimated to be removed per double volume procedure.

In a retrospective study, Giers et al concluded that in the treatment of fetal alloimmune thrombocytopenia, there was equal clinical effectiveness in the intrauterine transfusion of either maternal platelets or human platelet antigen (HPA)–matched donor platelets.[51] No procedure-related fetal or neonatal loss resulted from the use of either maternal (15 fetuses) or donor (42 fetuses) platelets, and both types of treatment reliably increased fetal platelet counts.

Next

Glucocorticoids

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Prednisone (Sterapred)

 

Inhibits phagocytosis of antibody-covered platelets. Used to increase platelet count.

Previous
Next

Blood products

Class Summary

Used to increase platelet count.

Intravenous immune globulin (Gammagard S/D, Gammar-P, Gamunex, Carimune, Polygam S/D)

 

Has rapid onset of action and is DOC (used in conjunction with platelet transfusion) when severe thrombocytopenia or life-threatening hemorrhage occurs.

Previous
 
 
Contributor Information and Disclosures
Author

Muhammad A Mir, MD, FACP Assistant Professor of Medicine (Hematology, Blood/Marrow Transplant) Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

Muhammad A Mir, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Hematology, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.

Chief Editor

Srikanth Nagalla, MBBS, MS, FACP Director, Clinical Hematology, Cardeza Foundation for Hematologic Research; Assistant Professor of Medicine, Division of Hematology, Associate Program Director, Hematology/Medical Oncology Fellowship, Assistant Program Director, Internal Medicine Residency, Jefferson Medical College of Thomas Jefferson University

Srikanth Nagalla, MBBS, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Nothing to disclose.

Acknowledgements

Wadie F Bahou, MD Chief, Division of Hematology, Hematology/Oncology Fellowship Director, Professor, Department of Internal Medicine, State University of New York at Stony Brook

Wadie F Bahou, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Lynnae Millar, MD Professor, Chair, Department of Obstetrics and Gynecology, University of Hawaii, John A Burns School of Medicine

Lynnae Millar, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Obstetricians and Gynecologists, American Medical Association, and Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

References
  1. Burrows RF, Kelton JG. Thrombocytopenia at delivery: a prospective survey of 6715 deliveries. Am J Obstet Gynecol. 1990 Mar. 162(3):731-4. [Medline].

  2. Sainio S, Jarvenpaa AL, Renlund M. Thrombocytopenia in term infants: a population-based study. Obstet Gynecol. 2000 Mar. 95(3):441-6. [Medline].

  3. Blanchette VS, Chen L, de Friedberg ZS. Alloimmunization to the PlA1 platelet antigen: results of a prospective study. Br J Haematol. 1990 Feb. 74(2):209-15. [Medline].

  4. Dreyfus M, Kaplan C, Verdy E. Frequency of immune thrombocytopenia in newborns: a prospective study. Immune Thrombocytopenia Working Group. Blood. 1997 Jun 15. 89(12):4402-6. [Medline].

  5. Davis GL. Platelet specific alloantigens. Clin Lab Sci. 1998 Nov-Dec. 11(6):356-61. [Medline].

  6. Bussel JB. Immune thrombocytopenia in pregnancy: autoimmune and alloimmune. J Reprod Immunol. 1997 Dec 15. 37(1):35-61. [Medline].

  7. Yamada H, Kato EH, Kobashi G. Passive immune thrombocytopenia in neonates of mothers with idiopathic thrombocytopenic purpura: incidence and risk factors. Semin Thromb Hemost. 1999. 25(5):491-6. [Medline].

  8. Biswas A, Arulkumaran S, Ratnam SS. Disorders of platelets in pregnancy. Obstet Gynecol Surv. 1994 Aug. 49(8):585-94. [Medline].

  9. Durand-Zaleski I, Schlegel N, Blum-Boisgard C. Screening primiparous women and newborns for fetal/neonatal alloimmune thrombocytopenia: a prospective comparison of effectiveness and costs. Immune Thrombocytopenia Working Group. Am J Perinatol. 1996 Oct. 13(7):423-31. [Medline].

  10. ACOG practice bulletin, American College of Obstetricians and Gynecologists. Thrombocytopenia in pregnancy. Number 6, September 1999. Clinical management guidelines for obstetrician- gynecologists. Int J Gynaecol Obstet. 1999 Nov. 67(2):117-28. [Medline].

  11. George JN, el-Harake MA, Raskob GE. Chronic idiopathic thrombocytopenic purpura. N Engl J Med. 1994 Nov 3. 331(18):1207-11. [Medline].

  12. Herman JH, Jumbelic MI, Ancona RJ. In utero cerebral hemorrhage in alloimmune thrombocytopenia. Am J Pediatr Hematol Oncol. 1986 Winter. 8(4):312-7. [Medline].

  13. Kadir RA, McLintock C. Thrombocytopenia and disorders of platelet function in pregnancy. Semin Thromb Hemost. 2011 Sep. 37(6):640-52. [Medline].

  14. Koyama S, Tomimatsu T, Kanagawa T, Kumasawa K, Tsutsui T, Kimura T. Reliable predictors of neonatal immune thrombocytopenia in pregnant women with idiopathic thrombocytopenic purpura. Am J Hematol. 2012 Jan. 87(1):15-21. [Medline].

  15. Gernsheimer T, James AH, Stasi R. How I treat thrombocytopenia in pregnancy. Blood. 2013 Jan 3. 121(1):38-47. [Medline].

  16. Christiaens GC, Nieuwenhuis HK, von dem Borne AE. Idiopathic thrombocytopenic purpura in pregnancy: a randomized trial on the effect of antenatal low dose corticosteroids on neonatal platelet count. Br J Obstet Gynaecol. 1990 Oct. 97(10):893-8. [Medline].

  17. Gresikova M. Learning from errors: when a low platelet count in neonate excludes immune thrombocytopenic purpura in mother. Bratisl Lek Listy. 2013. 114(4):232-6. [Medline].

  18. Cohen DL, Baglin TP. Assessment and management of immune thrombocytopenia in pregnancy and in neonates. Arch Dis Child Fetal Neonatal Ed. 1995 Jan. 72(1):F71-6. [Medline].

  19. Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002 Mar 28. 346(13):995-1008. [Medline].

  20. Nicolescu A, Vladareanu AM, Voican I, Onisai M, Vladareanu R. Therapeutic Options for Immune Thrombocytopenia (ITP) During Pregnancy. Maedica (Buchar). 2013 Jun. 8(2):182-188. [Medline]. [Full Text].

  21. Gernsheimer TB. Thrombocytopenia in pregnancy: is this immune thrombocytopenia or...?. Hematology Am Soc Hematol Educ Program. 2012. 2012:198-202. [Medline].

  22. Kawaguchi K, Matsubara K, Takafuta T, Shinzato I, Tanaka Y, Iwata A, et al. Factors predictive of neonatal thrombocytopenia in pregnant women with immune thrombocytopenia. Int J Hematol. 2014 May. 99(5):570-6. [Medline].

  23. Yamada H, Kato EH, Kishida T. Risk factors for neonatal thrombocytopenia in pregnancy complicated by idiopathic thrombocytopenic purpura. Ann Hematol. 1998 May. 76(5):211-4. [Medline].

  24. Mahey R, Kaur SD, Chumber S, Kriplani A, Bhatla N. Splenectomy during pregnancy: treatment of refractory immune thrombocytopenic purpura. BMJ Case Rep. 2013 Dec 20. 2013:[Medline].

  25. Moise KJ Jr, Patton DE, Cano LE. Misdiagnosis of a normal fetal platelet count after coagulation of intrapartum scalp samples in autoimmune thrombocytopenic purpura. Am J Perinatol. 1991 Sep. 8(5):295-6. [Medline].

  26. Burrows RF, Kelton JG. Pregnancy in patients with idiopathic thrombocytopenic purpura: assessing the risks for the infant at delivery. Obstet Gynecol Surv. 1993 Dec. 48(12):781-8. [Medline].

  27. Berry SM, Leonardi MR, Wolfe HM. Maternal thrombocytopenia. Predicting neonatal thrombocytopenia with cordocentesis. J Reprod Med. 1997 May. 42(5):276-80. [Medline].

  28. Cook RL, Miller RC, Katz VL. Immune thrombocytopenic purpura in pregnancy: a reappraisal of management. Obstet Gynecol. 1991 Oct. 78(4):578-83. [Medline].

  29. Bussel J, Kaplan C. The fetal and neonatal consequences of maternal alloimmune thrombocytopenia. Baillieres Clin Haematol. 1998 Jun. 11(2):391-408. [Medline].

  30. Kawaguchi K, Matsubara K, Takafuta T, Shinzato I, Tanaka Y, Iwata A, et al. Factors predictive of neonatal thrombocytopenia in pregnant women with immune thrombocytopenia. Int J Hematol. 2014 Mar 13. [Medline].

  31. Mahey R, Kaur SD, Chumber S, Kriplani A, Bhatla N. Splenectomy during pregnancy: treatment of refractory immune thrombocytopenic purpura. BMJ Case Rep. 2013 Dec 20. 2013:[Medline].

  32. Martí-Carvajal AJ, Peña-Martí GE, Comunián-Carrasco G. Medical treatments for idiopathic thrombocytopenic purpura during pregnancy. Cochrane Database Syst Rev. 2009 Oct 7. CD007722. [Medline].

  33. Sukenik-Halevy R, Ellis MH, Fejgin MD. Management of immune thrombocytopenic purpura in pregnancy. Obstet Gynecol Surv. 2008 Mar. 63(3):182-8. [Medline].

  34. Gasim T. Immune thrombocytopenic purpura in pregnancy: a reappraisal of obstetric management and outcome. J Reprod Med. 2011 Mar-Apr. 56(3-4):163-8. [Medline].

  35. Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L, Hunnisett L. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology. 2000 Dec. 62(6):385-92. [Medline].

  36. Howman RA, Barr AL, Shand AW, Dickinson JE. Antenatal intravenous immunoglobulin in chronic immune thrombocytopenic purpura: case report and literature review. Fetal Diagn Ther. 2009. 25(1):93-7. [Medline].

  37. van der Lugt NM, van Kampen A, Walther FJ, Brand A, Lopriore E. Outcome and management in neonatal thrombocytopenia due to maternal idiopathic thrombocytopenic purpura. Vox Sang. 2013 Oct. 105(3):236-43. [Medline].

  38. Bussel JB, Graziano JN, Kimberly RP. Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect. Blood. 1991 May 1. 77(9):1884-93. [Medline].

  39. Scaradavou A, Woo B, Woloski BM. Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients. Blood. 1997 Apr 15. 89(8):2689-700. [Medline].

  40. Nicolescu A, Vladareanu AM, Voican I, Onisai M, Vladareanu R. Therapeutic Options for Immune Thrombocytopenia (ITP) During Pregnancy. Maedica (Buchar). 2013 Jun. 8(2):182-188. [Medline].

  41. Copel JA, Gollin YG, Grannum PA. Alloimmune disorders and pregnancy. Semin Perinatol. 1991 Jun. 15(3):251-6. [Medline].

  42. Bussel JB, Zabusky MR, Berkowitz RL. Fetal alloimmune thrombocytopenia. N Engl J Med. 1997 Jul 3. 337(1):22-6. [Medline].

  43. Patil AS, Dotters-Katz SK, Metjian AD, James AH, Swamy GK. Use of a thrombopoietin mimetic for chronic immune thrombocytopenic purpura in pregnancy. Obstet Gynecol. 2013 Aug. 122(2 Pt 2):483-5. [Medline]. [Full Text].

  44. Chakravarty EF, Murray ER, Kelman A, Farmer P. Pregnancy outcomes after maternal exposure to rituximab. Blood. 2011 Feb 3. 117(5):1499-506. [Medline].

  45. Kaplan C, Daffos F, Forestier F. Management of alloimmune thrombocytopenia: antenatal diagnosis and in utero transfusion of maternal platelets. Blood. 1988 Jul. 72(1):340-3. [Medline].

  46. Nicolini U, Tannirandorn Y, Gonzalez P. Continuing controversy in alloimmune thrombocytopenia: fetal hyperimmunoglobulinemia fails to prevent thrombocytopenia. Am J Obstet Gynecol. 1990 Oct. 163(4 Pt 1):1144-6. [Medline].

  47. Murphy MF, Pullon HW, Metcalfe P. Management of fetal alloimmune thrombocytopenia by weekly in utero platelet transfusions. Vox Sang. 1990. 58(1):45-9. [Medline].

  48. Lynch L, Bussel JB, McFarland JG. Antenatal treatment of alloimmune thrombocytopenia. Obstet Gynecol. 1992 Jul. 80(1):67-71. [Medline].

  49. Bussel JB, Berkowitz RL, Lynch L. Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin. Am J Obstet Gynecol. 1996 May. 174(5):1414-23. [Medline].

  50. Radder CM, Brand A, Kanhai HH. A less invasive treatment strategy to prevent intracranial hemorrhage in fetal and neonatal alloimmune thrombocytopenia. Am J Obstet Gynecol. 2001. 185(3):683-8.

  51. Giers G, Wenzel F, Fischer J, et al. Retrospective comparison of maternal vs. HPA-matched donor platelets for treatment of fetal alloimmune thrombocytopenia. Vox Sang. 2009 Oct 27. [Medline].

  52. Monteith C, Ní Áinle F, Cooley S, Lambert JS, Kelleher B, Jackson V, et al. Hepatitis C virus-associated thrombocytopenia in pregnancy: impact upon multidisciplinary care provision. J Perinat Med. 2014 Jan. 42(1):135-8. [Medline].

 
Previous
Next
 
Immune thrombocytopenia. Nonstress test 1 week before delivery showing a normal reactive fetal heart rate pattern.
Immune thrombocytopenia. Nonstress test 4 days before delivery showing a reactive fetal heart rate with an unusual pseudosinusoidal pattern that lasted 9 minutes.
Immune thrombocytopenia. Neonatal brain at autopsy showing extensive subdural hemorrhage.
Immune thrombocytopenia. Neonatal spine at autopsy showing extensive hemorrhage at base of spine.
Immune thrombocytopenia. An infant born with neonatal lupus syndrome and severe thrombocytopenia. Note extensive bruising and petechiae.
Immune thrombocytopenia. An infant born with a cephalohematoma.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.