Immune Thrombocytopenia and Pregnancy Medication

Updated: Aug 19, 2019
  • Author: Muhammad A Mir, MD, FACP; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Medication

Medication Summary

Immune thrombocytopenic purpura (ITP)

Treatment for ITP in pregnancy is well established and effective. [39, 40, 41, 1] 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. [42] 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. [43] 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. [44]

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. [45] 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. [45, 46] Anti-D is effective in Rh-positive individuals only and may be associated with immune hemolysis. [47]

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 [48] ; 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. [49] 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 experienced intraventricular hemorrhage, although there was no developmental delay at 10 months. [50]

Rituximab crosses the placenta, and data are insufficient to recommend use in ITP during pregnancy. [51]

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. [13] 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 human platelet antigen–1b (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 that this therapy is effective in increasing the fetal platelet count. [52, 53, 54] Brussel et al have advocated a less invasive management and treatment plan, reporting on a total of 73 patients with NAIT. [55, 56] 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. [56] 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. [57] Fetuses that fail to respond to IVIG receive weekly platelet transfusions for the duration of the pregnancy. [22]

Results of a meta-analysis of 26 studies found comparable outcomes regarding the occurrence of intracranial hemorrhage, regardless of the antenatal management strategy: serial fetal blood sampling (FBS), intrauterine platelet transfusions (IUPT), or weekly IVIG, with or without corticosteroids. There was no consistent evidence for benefit for the addition of steroids to IVIG. [58]

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. [9]

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. [9] 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 HPA-matched donor platelets. [59] 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.

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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.

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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.

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