Thrombocytopenia in pregnancy: is this immunethrombocytopenia or?

Terry B. Gernsheimer1,2

1Puget Sound Blood Center, Seattle, WA, and 2University of Washington, Seattle, WA

Thrombocytopenia is a common finding in pregnancy. Establishing the diagnosis of immune thrombocytopenia (ITP) ina pregnant patient is similar to doing so in a nonpregnant patient, except that the evaluation must specifically rule outother disorders of pregnancy associated with low platelet counts that present different risks to the mother and fetusand may require alternate distinct therapy. Many of the same treatment modalities are used to manage the pregnantpatient with ITP, but others have not been determined to be safe for the fetus, are limited to a particular gestationalperiod, or side effects may be more problematic during pregnancy. The therapeutic objective differs from that inchronic ITP in the adult becausemany pregnant patients recover or improve spontaneously after delivery and thereforemaintenance of a safe platelet count, rather than prolonged remission, is the goal. Thrombocytopenia may the limitchoices of anesthesia, but does not guide mode of delivery, and the fetus is rarely severely affected at birth. Patientsshould be advised that a history of ITP or ITP in a previous pregnancy is not a contraindication to future pregnanciesand that, with proper management and monitoring, positive outcomes can be expected in the majority of patients.

Scope of the problemThrombocytopenia is a very common finding in pregnancy, occur-ring in approximately 10% of women.1,2 Although most womenmaintain a normal platelet count throughout gestation, the normalrange of platelet counts decreases, and it is not uncommon for theplatelet count to decrease as pregnancy progresses. Most lowplatelet counts observed in the pregnant patient are due to normalphysiologic changes,3 whereas some disorders associated withthrombocytopenia occur with higher frequency and some causes areexclusive to pregnancy.4 When considering the diagnosis of im-mune thrombocytopenia (ITP) in pregnancy, all potential causes ofthrombocytopenia must be considered and ruled out in turn.

Differential diagnosis of thrombocytopenia duringpregnancy

Gestational thrombocytopeniaIncidental or gestational thrombocytopenia is the most commoncause of pregnancy-associated thrombocytopenia, accounting for65%-80% of cases.1,4 Increased blood volume, an increase inplatelet activation, and increased platelet clearance contribute to aphysiologic decrease in the platelet count.3 Platelet counts areslightly lower in women with twin compared with singletonpregnancies, possibly due to increased coagulation system activa-tion in the placenta. These changes generally bring about only amild decrease in the platelet count, typically approximately 10%.5The mean platelet count in pregnant women at term was found to be213 000/L compared with 248 000/L in age-matched controls.1,6Gestational thrombocytopenia tends to occur late, usually during thethird trimester,7 but it should be noted that thrombocytopenia thatappears during the last weeks of pregnancy can be the harbinger ofHELLP syndrome (hemolysis, elevated liver function tests, lowplatelets) or acute fatty liver.8 Platelet counts 70 000-80 000/Lor occurring during the first or early in the second trimester suggestan etiology other than gestational thrombocytopenia and requirefurther evaluation.9

Gestational thrombocytopenia is not associated with adverse out-comes to the mother or fetus, and if the infant is thrombocytopenic,other etiologies such as infection and neonatal alloimmune thrombo-cytopenia should be investigated.4 Thrombocytopenia in the mothergenerally resolves quickly after delivery, usually within days andalways within weeks.

Disorders associated with thrombocytopenia inpregnancyMany disorders are exacerbated by pregnancy or may be quiescentuntil the immunologic stimulation that occurs with pregnancyprovokes their recrudescence (Table 1). Autoimmune disorderssuch as systemic lupus erythematosus may first appear or increase inseverity during pregnancy, and hypothyroidism may first manifestduring gestation. The antiphospholipid Ab syndrome, which isaccompanied by thrombocytopenia in approximately 10%-30% ofcases,10 must be considered because of its association with fetal lossand the need for anticoagulation.11

Thrombocytopenia first noted in the second or third trimesterrequires evaluation. Disorders that may first manifest at that time

Table 1. Causes of thrombocytopenia in pregnancy

Gestational (incidental) thrombocytopeniaPreeclampsiaHELLP syndromeAcute fatty liver of pregnancyThrombotic thrombocytopenic purpuraHemolytic uremic syndromeSystemic lupus erythematosusAntiphospholipid Ab syndromeDisseminated intravascular coagulationViral infectionNutritional deficiencyDrug usePrimary BM disorder

HEMATOLOGIC DISEASES IN PREGNANCY

198 American Society of Hematology

include preeclampsia, HELLP syndrome, acute fatty liver, dissemi-nated intravascular coagulation, thrombotic thrombocytopenic pur-pura, and hemolytic uremic syndrome. The abnormal clinical andlaboratory findings that accompany these nutritional and BMdisorders are the basis for distinguishing them from ITP. Carefulreview of the blood smear will help to exclude the thromboticmicroangiopathies associated with pregnancy (ie, HELLP syn-drome, thrombotic thrombocytopenic purpura, and hemolytic ure-mic syndrome) by the absence of schistocytes. Normal coagulationstudies will be helpful in excluding acute fatty liver and dissemi-nated intravascular coagulation.

Thrombocytopenia may be the primary manifestation of viralinfections such as HIV, viral hepatitis, EBV, and CMV. Thrombocy-topenia is also a common adverse reaction from many drugs andsupplements. Women who receive low-molecular-weight or unfrac-tionated heparin are at risk of heparin-induced thrombocytopeniaand should undergo testing, particularly in the presence of new orworsening thrombosis.

Evaluation of the pregnant patient with thrombocytopeniaThe history and physical examination are important in providingclues to the diagnosis of thrombocytopenia in pregnancy, either bydisclosure of preexisting thrombocytopenia or bleeding symptomsor by clinical findings of hypertension, edema, neurologic abnormali-ties, or signs of autoimmune disease. ITP diagnosed during preg-nancy is usually relatively asymptomatic, and manifests in onlymild symptoms and physical signs.12,13 Changes associated with aprocoagulant state in pregnancyincreased levels of fibrinogen,factor VIII, and VWF; suppressed fibrinolysis; and decreasedprotein S activitymay explain in part why severe bleeding is onlyrarely seen in the pregnant patient with ITP.14 Although fatigue is acommon symptom during pregnancy, other constitutional symp-toms such a weight loss or drenching night sweats may signaletiologies of greater concern.

Medical history may be helpful in elucidating associated disorderssuch as thyroid disease or other autoimmune disorders. Frequentchildhood infections may suggest an immune deficiency syndromethat can be associated with ITP.15 It is important to ascertain all drugand toxin exposures, including over-the-counter remedies andsupplements. The nutritional history or a history suggestive ofmalabsorption may be helpful in the discovery of deficiencies thatcan manifest with thrombocytopenia. A family history of thrombo-cytopenia must also be investigated so that congenital thrombocyto-penia is not mistaken for an acquired disorder.

Laboratory investigation of thrombocytopenia inpregnancyA complete blood count and review of the peripheral blood smearis mandatory in the evaluation of the thrombocytopenic patient(Table 2). Occasional large platelets may be seen in ITP, but theyshould otherwise appear normal. The presence of large and/orhypogranular platelets may suggest a congenital thrombocytopenia.Morphologic RBC abnormalities such as schistocytes, target cells,macrocytosis, or spherocytes may be clues to thrombotic micro-angiopathy, liver disease, nutritional deficiency, or autoimmunehemolysis. By definition, thrombocytopenia is an isolated hemato-logic abnormality in ITP, but anemia of pregnancy or anemiaassociated with chronic bleeding and iron deficiency may also bepresent. A direct antiglobulin test or Coombs test is necessary to ruleout complicating autoimmune hemolysis (Evans syndrome). Screen-

ing for coagulation abnormalities (ie, with prothrombin time,activated partial thromboplastin time, and fibrinogen time), liverfunction (ie, tests for bilirubin, albumin, total protein, transferases,and alkaline phosphatase), antiphospholipid Abs, and lupus anti-coagulant and serology may all be helpful in differentiating ITPfrom other disorders with associated low platelet counts. Viralscreening (ie, for HIV, hepatitis C virus, and hepatitis B virus), as inthe evaluation of nonpregnant patients with ITP,16 is recommended.A careful assessment of thyroid function is indicated becauseabnormalities are common in both ITP and pregnancy. Thyroiddisorders are associated with significant pregnancy-related compli-cations and with significant fetal risk, and the associated thrombo-cytopenia frequently responds to therapy. If the medical historysuggests frequent infections, quantitative Ig testing may be appro-priate. A review of preexisting laboratory data may reveal abnor-malities that preceded the pregnancy or were present only during aprior pregnancy.

Only rarely is BM examination necessary for the finding ofthrombocytopenia in a pregnant patient, and it is not required tomake the diagnosis of ITP. As in the nonpregnant patient, themeasurement of antiplatelet Abs has no value in the routinediagnosis of ITP in pregnancy, is not predictive of neonatalthrombocytopenia, nor is it specific.17 Women with gestationalthrombocytopenia cannot be distinguished from women with ITPbased on detection of antiplatelet Abs, suggesting either that somecases thought to be physiologic gestational thrombocytopenia areactually due to immune destruction playing a role or may be anunmasking of previously compensated ITP.

Presentation of ITP during pregnancyITP occurs in approximately 2 of 1000 pregnant women.18 ITP maydevelop at any time during pregnancy, but is often initiallyrecognized in the first trimester and is the most common cause ofisolated thrombocytopenia in this time period. In some cases, ITPpresents for the first time during pregnancy, whereas preexistingcases of ITP may either worsen or remain quiescent.19,20 A review ofthe clinical courses of 92 women with ITP during 119 pregnanciesover an 11-year period found that women with previously diagnosedITP were less likely to require therapy for ITP than those with newlydiagnosed ITP,11 but the course varies widely.

Table 2. Recommended testing in the differential diagnosis ofthrombocytopenia in pregnancy

Peripheral blood smear reviewReticulocyte countDirect antiglobulin testCoagulation screeningLiver function testsLupus anticoagulant, cardiolipin, and -2-glycoprotein IgG and

IgM AbsSystemic lupus erythematosus serologyThyroid function testsViral screening (HIV, HBV, HCV, and CMV)

Consider testingQuantitative Igs

Not routinely recommended:Antiplatelet Ab testingBM examination

HBV indicates hepatitis B virus; and HCV, hepatitis C virus.

Hematology 2012 199

Okay, I think its ITP: now what?

Management of ITP during gestationITP in the first and second trimesters is generally treated when thepatient is symptomatic with bleeding, platelet counts are in the20-30 000/L range, or a planned procedure requires a higherplatelet count. In a retrospective analysis of 119 pregnancies in ITPpatients, Webert et al found that only 89% of patients had plateletcounts 150 000/L.11 Most patients had only mild to moderatethrombocytopenia and the pregnancies were uneventful, but 31%required intervention to increase the platelet count. Despite remain-ing relatively stable through most of the pregnancy, platelet countsmay decrease during the third trimester and monitoring should bemore frequent.15 Therapy late in gestation is generally based on therisk of maternal hemorrhage at delivery.

First-line therapy for ITP in pregnancy is similar to the managementof acute ITP: corticosteroids21 and IV Igs.22 A combination of the216 may be effective when a patient does not respond to a singleagent alone. There are no comparative trials of the 2 agents, butresponses appear to be similar to that in nonpregnant patients. Oralprednisone or prednisolone may be started at a low dose (10-20 mg/d)and adjusted to maintain a safe platelet count. Prednisone isgenerally safe in pregnancy, but it can increase weight gain andexacerbate hypertension and hyperglycemia, resulting in adverseeffects on pregnancy outcome.23 Very high doses of corticosteroidsare not harmful to the fetus and may have an effect of acceleratinglung maturation, but antenatal corticosteroids have not been foundto have an effect on the neonatal platelet count24 and should not beadministered to the near-term mother with this objective. Theemotional effect of corticosteroids or their rapid withdrawal in thepostpartum period should be carefully monitored and dosage shouldbe tapered to avoid a rapid decrease in the platelet count afterdelivery. IV Igs can be used for a rapid increase in platelet count orto maintain safe platelet counts when patients are not responsive tosteroids or there are poorly tolerated side effects. Anti-RhD Ig isgenerally not used as a first-line agent because of concerns for acutehemolysis and anemia, but has been used in refractory casesthroughout pregnancy with successful outcomes.25 If anti-RhD(50-75 g/kg) is administered, the neonate should be carefullymonitored for a positive direct antiglobulin test, anemia, andjaundice because the Ab may cross the placenta.

When a patient is only partially responsive or refractory to first-linetherapy, azathioprine may be effective and has been safely adminis-tered during pregnancy.26,27 High-dose methylprednisolone mayalso be used in combination with IV Igs or azathioprine for thepatient who is refractory to oral corticosteroids or IV Igs alone orhas a less than adequate response.

Many agents that are frequently used in nonpregnant ITP patients,such as vinca alkaloids and cyclophosphamide, cannot be used inpregnant patients because of known or concern for teratogenicity.Cyclosporine A has not been associated with significant toxicity tothe mother or fetus during pregnancy when used for inflammatorybowel disease,28 but there is no published experience on its use inITP in pregnancy.

Although there are case reports of treatment of lymphoproliferativedisorders with rituximab early in pregnancy,29,30 experience islimited and its use for pregnancy-associated ITP cannot be recom-mended because of its potential for crossing the placenta. Short-term therapy with danazol in combination with high-dose IV Igs and

corticosteroids has been used for refractory thrombocytopenia in thethird trimester,31 but longer-term use is likely to be teratogenic andshould be avoided. There are no data on the use of thrombopoietinreceptor agonists in pregnancy, and their effects on the fetus areunknown.

Splenectomy can be safely performed during the second trimes-ter,32,33 when risks of anesthesia to the fetus are minimal and uterinesize will not complicate the procedure. This approach may be usefulfor patients who remain refractory to therapy or who incursignificant toxicity, and may even induce a remission.

Management of deliveryITP in the mother is not an indication for Caesarean section,34 andthe mode of delivery in a pregnant patient with ITP is based onobstetric indications. Most neonatal hemorrhage occurs at24-48 hours35,36 and is not related to trauma at the time of delivery.Determination of the fetal platelet count by periumbilical bloodsampling37 or fetal scalp vein blood draws present a potentialhemorrhagic risk to the fetus and may inaccurately predict a lowplatelet count.16 For this reason, fetal platelet count measurement isnot recommended. The best predictor of thrombocytopenia at birthis its occurrence in an older sibling. In this case, Caesarean sectionmay be more prudent than vaginal delivery.

Maternal anesthesia must be based on safety of the mother. The riskof spinal hematoma at lower platelet counts is unknown, but recentrecommendations are to withhold spinal anesthesia for women withplatelet counts below 75 000/L.38-40 Thromboelastograms havebeen suggested to evaluate the entire hemostatic state of themother,41 but their usefulness is unclear. The bleeding time has alsobeen suggested as a mode of establishing the safety of the plateletcount,42 but most centers no longer offer this test and the experiencein using it to predict bleeding at delivery is limited. For patients whohave not required therapy during gestation but have platelet countsbelow the threshold required for epidural anesthesia, short-termcorticosteroids (1-2 weeks) or IV Igs may help in preparing for theprocedure. Platelet transfusion is not appropriate to prepare themother for spinal anesthesia because posttransfusion incrementsmay be inadequate or short-lived and should be reserved to treatbleeding only.

Monitoring and management of the neonateNeonatal ITP accounts for only 3% of all cases of thrombocytopeniaat delivery.43 There are no accurate predictors of fetal platelet countand the correlation between maternal and fetal platelet counts ispoor.1,44,45 A recent retrospective study of 127 pregnancies in88 women with ITP in Japan showed a trend toward lower plateletcounts in the offspring of mothers with less than 100 000 platelets,but this was not statistically significant.46 Splenectomized motherswere also found to have a greater risk. Platelet count at birth appearsto be related to the presence of alloantibody (in neonatal alloim-mune thrombocytopenia), but not autoantibody, so platelet Abtesting is not recommended. A history of thrombocytopenia in aprevious affected sibling appears to be the best predictor ofthrombocytopenia in the neonate.45,47 Severe thrombocytopenia inthe neonate delivered to a mother with ITP is relatively uncommon,with platelet counts 50 000/L occurring in 4.9%-25%.34,35,48,49Mortality is rare ( 1%) and estimates of the incidence of intracra-nial hemorrhage in the neonate range from 0%-1.5%. At delivery, acord blood platelet count should be obtained to determine the needfor immediate therapy. Intramuscular injections such as vitamin K

200 American Society of Hematology

should be avoided unless it has been determined that the neonate hasa safe platelet count. The nadir platelet count frequently occurs 2-5days after birth, so the mother needs to be made aware of signs ofbleeding and the baby should be checked early on by a pediatricianif he/she has been discharged to home. The thrombocytopenia canlast weeks to months.50 A platelet count 50 000/L may betreated with IV Ig (1 g/kg), which can be repeated every few weeksas necessary to maintain a safe platelet count until the countspontaneously recovers.

ConclusionITP occurs fairly commonly in otherwise uncomplicated, normalpregnancies, but must be distinguished from more commonlyoccurring incidental gestational thrombocytopenia. Other disordersthat may be associated with thrombocytopenia must be consideredand ruled out so that appropriate therapy can be instituted. Thediagnosis and management of ITP in pregnancy is similar to that inthe nonpregnant adult patient, but the risks to the developing fetusmust be taken into account when choosing treatment and themaintenance of a safe platelet count, rather than prolonged remis-sion, is the goal. Mode of delivery must be guided by obstetricalindications. A history of ITP or ITP in a previous pregnancy is not acontraindication to pregnancy, and the majority of patients delivernonthrombocytopenic or only mildly thrombocytopenic infants.

DisclosuresConflict-of-interest disclosure: The author has received researchfunding from Shionogi; has consulted for Glaxo-SmithKline, Clini-cal Options, Symphogen, Amgen, and Cangene; and has receivedhonoraria from Hemedicus, Laboratorios Raffo, and Amgen. Off-label drug use: rituximab and azathioprine for ITP in pregnancy.

CorrespondenceTerry B. Gernsheimer, MD, Box 357710, University of Washing-ton, Seattle, WA 98195; Phone: 206-292-6521; Fax: 206-233-3331;e-mail: bldbuddy@u.washington.edu.

References1. Sainio S, Kekomaki R, Riikonen S, Teramo K. Maternal

thrombocytopenia at term: a population-based study. ActaObstet Gynecol Scand. 2000;79(9):744-749.

2. Burrows RF, Kelton JG. Incidentally detected thrombocytope-nia in healthy mothers and their infants. N Engl J Med.1988;319(3):142-145.

3. Matthews JH, Benjamin S, Gill DS, Smith NA. Pregnancy-associated thrombocytopenia: definition, incidence and naturalhistory. Acta Haematol. 1990;84(1):24-29.

4. Burrows RF, Kelton JG. Thrombocytopenia at delivery: aprospective survey of 6715 deliveries. Am J Obstet Gynecol.1990;162(3):73134.

5. Verdy E, Bessous V, Dreyfus M, et al. Longitudinal analysis ofplatelet count and volume in normal pregnancy. ThrombHaemost. 1997;77(4):806-807.

6. Boehlen F, Hohlfeld P, Extermann P, et al. Platelet count atterm pregnancy: A reappraisal of the threshold. Obstet Gynecol.2000;95(1):29-33

7. Gernsheimer T, McCrae KR. Immune thrombocytopenic pur-pura in pregnancy. Curr Opin Hematol. 2007;14(5):574-580.

8. Minakami H, Yamada H, Suzuki S. Gestational thrombocytope-nia and pregnancy-induced antithrombin deficiency: progeni-

tors to the development of the HELLP syndrome and acute fattyliver of pregnancy. Semin Thromb Hemost. 2002;28(6):515-518.

9. British Committee for Standards in Haematology GeneralHaematology Task Force. Guidelines for the investigation andmanagement of idiopathic thrombocytopenic purpura in adults,children and in pregnancy. Br J Haematol. 2003;120(4):574-596.

10. Godeau B, Piette JC, Fromont P, et al. Specific antiplateletglycoprotein autoantibodies are associated with the thrombocy-topenia of primary antiphospholipid syndrome. Br J Haematol.1997;98(4):873-879.

11. Oshiro BT, Silver RM, Scott JR, et al. Antiphospholipid antibodiesand fetal death. Obstet Gynecol. 1996;87(4):489-493.

12. Webert KE, Mittal R, Sigouin C, et al. A retrospective 11-yearanalysis of obstetric patients with idiopathic thrombocytopenicpurpura. Blood. 2003;102(13):4306-4311.

13. Fujimura K, Harada Y, Fujimoto T, et al. Nationwide study ofidiopathic thrombocytopenic purpura in pregnant women andthe clinical influence on neonates. Int J Hematol. 2002;75(4):426-433.

14. Calderwood CJ. Thromboembolism and thrombophilia in preg-nancy. Curr Obstet Gynaecol. 2006;16:321-326.

15. Cines DB, Liebman HA. The immune thrombocytopenia syn-drome: a disorder of diverse pathogenesis and clinical presenta-tion. Hematol Oncol Clin North Am. 2009;23(6):1155-1161.

16. Provan D, Stasi R, Newland AC, et al. International consensusreport on the investigation and management of primary immunethrombocytopenia. Blood. 2010;115(2):168-186.

17. Boehlen F, Hohlfeld P, Extermann P, de Moerloose P. Maternalantiplatelet antibodies in predicting risk of neonatal thrombocy-topenia. Obstet Gynecol. 1999;93(2):169-173.

18. Gill KK, Kelton JG. Management of idiopathic thrombocytope-nic purpura in pregnancy. Semin Hematol. 2000;37(3):275-289.

19. Won YW, Moon W, Yun YS, et al. Clinical aspects ofpregnancy and delivery in patients with chronic idiopathicthrombocytopenic purpura (ITP). Korean J Intern Med. 2005;20(2):129-134.

20. Fujimura K, Harada Y, Fujimoto T, et al. Nationwide study ofidiopathic thrombocytopenic purpura in pregnant women andthe clinical influence on neonates. Int J Hematol. 2002;75(4):426-433.

21. Karpatkin S. Autoimmune thrombocytopenic purpura. SeminHematol. 1985;22(4):260-288.

22. Besa EC, MacNab MW, Solan AJ, et al. High-dose intravenousIgG in the management of pregnancy in women with idiopathicthrombocytopenic purpura. Am J Hematol. 1985;18(4):373-379.

23. Metzger BE, Lowe LP, Dyer AR, et al; HAPO Study Coopera-tive Research Group. Hyperglycemia and adverse pregnancyoutcomes. N Engl J Med. 2008;358(19):1991-2002.

24. Christiaens GCML, Nieuwenhuis HK, von dem Borne AEGKr,et al. Idiopathic thrombocytopenic purpura in pregnancy: Arandomized trial on the effect of antenatal low dose corticoste-roids on neonatal platelet count. Br J Obstet Gynaecol.1990;97(10):893-898.

25. Michel M, Novoa MV, Bussel JB. Intravenous anti-D as atreatment for immune thrombocytopenic purpura (ITP) duringpregnancy. Br J Haematol. 2003;123(1):142-146.

26. Alstead EM, Ritchie JK, Lennard-Jones JE, et al. Safety ofazathioprine in pregnancy in inflammatory bowel disease.Gastroenterology. 1990;99(2):443-446.

Hematology 2012 201

27. Price HV, Salaman JR, Laurence KM, Langmaid H. Immuno-suppressive drugs and the foetus. Transplantation. 1976;21(4):294-298.

28. Reddy D, Murphy SJ, Kane SV, Present DH, Kornbluth AA.Relapses of inflammatory bowel disease during pregnancy:in-hospital management and birth outcomes. Am J Gastroen-terol. 2008;103(5):1203-1209.

29. Kimby E, Sverrisdottir A, Elinder G. Safety of rituximabtherapy during the first trimester of pregnancy: a case history.Eur J Haematol. 2004;72(4):292-295.

30. Herold M, Schnohr S, Bittrich H. Efficacy and safety of acombined rituximab chemotherapy during pregnancy. J ClinOncol. 2001;19(14):3439.

31. Orisaka M, Shukunami K, Orisaka S, et al. Combinationtherapy for a pregnant woman with severe refractory ITP. Eur JObstet Gynecol Reprod Biol. 2005;121(1):119-120.

32. Anglin BV, Rutherford C, Ramus R, et al. Immune thrombocy-topenic purpura during pregnancy: laparoscopic treatment.JSLS. 2001;5(1):63-67.

33. Griffiths J, Sia W, Shapiro AM, et al. Laparoscopic splenec-tomy for the treatment of refractory immune thrombocytopeniain pregnancy. J Obstet Gynaecol Can. 2005;27(8):771-774.

34. Laros RK, Kagan R. Route of delivery for patients withimmune thrombocytopenic purpura. Am J Obstet Gynecol.1984;148(7):901.

35. Kaplan C, Daffos F, Forestier F, et al. Fetal platelet counts inthrombocytopenic pregnancy. Lancet. 1990;336(8727):979-982.

36. Bussel JB, Druzin ML, Cines DB, Samuels P. Thrombocytope-nia in pregnancy. Lancet. 1991;337(8735):251.

37. Scioscia AL, Grannum PA, Copel JA, Hobbins JC. The use ofpercutaneous umbilical blood sampling in immune thrombocy-topenic purpura. Am J Obstet Gynecol. 1988;159(5):1066-1068.

38. Beilin Y, Zahn J, Comerford M. Safe epidural analgesia inthirty parturients with platelet counts between 69,000 and98,000 mm3. Anesth Analg. 1997;85(2):385-388.

39. Choi S, Brull R. Neuraxial techniques in obstetric and non-

obstetric patients with common bleeding diatheses. AnesthAnalg. 2009;109(2):648-660.

40. van Veen JJ, Nokes TJ, Makris M. The risk of spinalhaematoma following neuraxial anaesthesia or lumbar puncturein thrombocytopenic individuals. Br J Haematol. 2010;148(1):15-25.

41. Hunt BJ, Lyons G. Thromboelastography should be available inevery labour ward. Int J Obstet Anesth. 2005;14(4):324-325.

42. Ballem PJ, Buskard N, Wittmann BK, et al. ITP in pregnancy:Use of the bleeding time as an indicator for treatment. Blut.1989;59(1):132-135.

43. Gill KK, Kelton JG. Management of idiopathic thrombocytope-nic purpura in pregnancy. Semin Hematol. 2000;37(3):275-289.

44. Kelton JG. Management of the pregnant patient with idiopathicthrombocytopenic purpura. Ann Intern Med. 1983;99(6):796-800.

45. Burrows RF, Kelton JG. Fetal thrombocytopenia and itsrelation to maternal thrombocytopenia. N Engl J Med. 1993;329(20):1463-1466.

46. Koyama S, Tomimatusu T, Kanagawa T, et al. Reliablepredictors of neonatal immune thrombocytopenia in pregnantwomen with idiopathic thrombocytopenic purpura. Am J Hema-tol. 2012;87(1):15-21.

47. Christiaens GC, Nieuwenhuis HK, Bussel JB. Comparison ofplatelet counts in first and second newborns of mothers withimmune thrombocytopenic purpura. Obstet Gynecol. 1997;90(4 Pt 1):546-552.

48. Samuels P, Bussel JB, Braitman LE, et al. Estimation of the riskof thrombocytopenia in the offspring of pregnant women withpresumed immune thrombocytopenic purpura. N Engl J Med.1990;323(4):229-235.

49. Kadir RA, McLintock C. Thrombocytopenia and disorders ofplatelet function in pregnancy. Semin Thromb Hemost. 2011;37(6):640-652.

50. Burrows RF, Kelton JG. Low fetal risks in pregnanciesassociated with idiopathic thrombocytopenic purpura. Am JObstet Gynecol. 1990;163(4 Pt 1):1147-1150.

202 American Society of Hematology