Immune Thrombocytopenia and Pregnancy Guidelines

Updated: Sep 21, 2020
  • Author: Shamudheen Rafiyath, MD; Chief Editor: Srikanth Nagalla, MD, MS, FACP  more...
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Guidelines

Guidelines Summary

The following organizations have issued guidelines for the management of immune thrombocytopenia (ITP) during pregnancy:

  • International Consensus Report
  • American College of Obstetricians and Gynecologists (ACOG)
  • American Society of Hematology (ASH)

Diagnosis

In 2019, an international group of experts published an International Consensus Report update to their previous consensus report, including up-to-date evidence, expert opinion from around the world, and the incorporation of a new focus on the patient's perspective. [52] Recommendations (except where noted, all of them grade C—ie, absence of directly applicable clinical studies of good quality) include the following:

  • Patients with a history suggestive of ITP or those with a platelet count < 80 × 10 9/L should be investigated for possible ITP.
  • As in nonpregnant patients, the diagnosis of ITP is one of exclusion, using the patient’s history, physical examination, blood counts, and blood smear examination.
  • Laboratory evaluation is similar to the nonpregnant patient, but special consideration should be given to rule out hypertensive, microangiopathic, coagulopathic, and hepatic disorders associated with pregnancy.

Tests recommended for all patients include the following: 

  • Complete blood cell count (CBC) and peripheral blood smear review - May reveal macrothrombocytopenia or signs of other inherited thrombocytopenias; depending on family history and smear, consider genetic testing, platelet function testing, and testing for type 2b von Willebrand disease and platelet-type von Willebrand disease. Schistocytes may suggest microangiopathy in hemolysis and hypertensive disorders
  • Reticulocyte count - Elevated in hemolysis and hypertensive disorders
  • Coagulation screening (prothrombin time [PT], partial thromboplastin time (PTT) fibrinogen) - PTT may be prolonged in patients with a history of thrombosis or pregnancy loss. Consider testing for antiphospholipid antibodies, anti-cardiolipin antibodies, and lupus anticoagulant.
  • Liver function studies - If levels are elevated, consider viral infection or HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets  
  • Thyroid function studies
  • Viral serologies (HIV, hepatitis C virus)
  • Kidney function studies - Hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) may manifest for the first time in pregnancy. Consider testing for  ADAMTS-13, alternative complement pathway. Consider atypical HUS due to autoantibodies against complement components

Other recommended tests should be based on the clinical features. The following may be considered:

  • Antinuclear antibody (ANA)
  • Helicobacter pylori testing -  H pylori stool or antigen test should be performed in patients with history of thrombocytopenia prior to pregnancy
  • Immunoglobulin levels - Quantitative immunoglobulin testing should be performed in patients with a history of thrombosis or pregnancy loss

The following tests are not recommended:

  • Bone marrow examination - Not recommended unless there are atypical features
  • Anti-platelet antibody testing  - Does not predict the course of maternal or neonatal thrombocytopenia or distinguish ITP from gestational thrombocytopenia
  • Fetal blood sampling
  • Thrombopoietin (TPO) levels - Not recommended, although it may be of value in the future

American Society of Hematology

ASH recommends the following tests for diagnosis of thrombocytopenia in pregnant patients [64] :

  • CBC
  • Reticulocyte count
  • Peripheral blood smear
  • Liver function tests
  • Viral screening (HIV, HCV, HBV)

Tests to consider if clinically indicated include the following [64] :

  • Antiphospholipid antibodies
  • ANA
  • Thyroid function tests
  • H pylori testing
  • Disseminated intravascular coagulation testing—PT, PTT, fibrinogen, fibrin split products
  • Von Willebrand disease type IIB testing
  • Direct antiglobulin (Coombs) test
  • Quantitative immunoglobulin levels

The following studies are not recommended [64] :

  • Antiplatelet antibody testing
  • Bone marrow biopsy
  • TPO levels

Treatment

International Consensus Report recommendations for the treatment of maternal ITP are as follows [52] :

  • Counseling for women with ITP wishing to become pregnant is recommended.
  • A platelet count between 20 and 30 × 10 9/L in a nonbleeding patient is safe for most of pregnancy. A platelet count ≥50 × 10 9/L (see separate anesthesia recommendation below) is preferred for delivery.
  • Initial treatment is with oral steroids or IVIg.
  • IV anti-D in Rh(D)-positive nonsplenectomized women appears to be well tolerated and effective based on results from a small pilot study (grade B recommendation); however, this may potentially cause maternal or fetal hemolysis.
  • IVIg can provide a rapid, but often very transient, increase in platelet count and can be used to urgently increase platelet counts during bleeding or for delivery (grade B recommendation).
  • Combining therapies (prednisone with IVIg and/or IV anti-D) may elicit a response in patients refractory to single agents alone. High-dose methylprednisolone, in combination with IVIg and/or azathioprine, is suggested for patients refractory to oral corticosteroids or IVIg alone.
  • Rituximab can be considered in pregnancy for very severe cases, but perinatal and neonatal immunosuppression and subsequent infection are potential complications and require monitoring.
  • Thrombopoietin receptor antagonists (TPO-RAs) may be considered in late pregnancy when other treatments have failed, but published information is limited.
  • In the rare instances when splenectomy is required, it should be performed in the second trimester. Women who had a splenectomy may have a thrombocytopenic newborn, even if their platelet count is normal.
  • Vinca alkaloids, danazol, and immunosuppressive drugs not listed in these recommendations should be avoided in pregnancy.

Recommendations for obstetric analgesia and anesthesia are as follows [52] :

  • At a platelet count ≥ 70 × 10 9/L, in the absence of other hemostatic abnormalities, regional axial anesthesia can be safely performed.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided for postpartum or postoperative analgesia in women with platelet counts < 70 × 10 9/L because of increased hemorrhagic risk.
  • A platelet count ≥50 × 10 9/L should be obtained for delivery.
  • All women, despite having ITP, who are at an increased risk for thromboembolism should receive appropriate prophylaxis for venous thromboembolism.
  • The mother with a rapidly falling platelet count should be observed more closely than those with low, but stable, levels (grade B recommendation).

Recommendations for management of delivery and newborn infants are as follows [52] :

  • Cordocentesis and fetal scalp blood sampling should be avoided in the management of the fetus/neonate of a mother with ITP in pregnancy.
  • Neonatal alloimmune thrombocytopenia should be excluded by parental testing if the neonate presents with severe thrombocytopenia.
  • The mode of delivery should be determined by obstetric indications, not by anticipation of the neonatal platelet count (grade B recommendation).
  • Procedures during labor that may be associated with increased hemorrhagic risk to the fetus should be avoided, specifically the use of fetal scalp electrodes, fetal blood sampling, ventouse delivery, and rotational forceps.
  • Previous splenectomy has been associated with worsening of maternal ITP in pregnancy and a higher risk for neonatal thrombocytopenia (grade B recommendation).
  • A mother with a previous newborn, thrombocytopenic or not, is likely to have a second baby with a similar platelet count.

American College of Obstetricians and Gynecologists

In 2016, the American College of Obstetricians and Gynecologists (ACOG) published a practice bulletin on thrombocytopenia in pregnant women, which included the following key recommendations. [12] :

  • Given the very low risk of serious neonatal hemorrhage, the mode of delivery in pregnancies complicated with ITP should be determined based upon obstetric considerations alone.
  • In pregnancies with high risk of intracranial hemorrhage (fetal platelet counts by umbilical cord blood sampling at 20 weeks of gestation of    < 20 x 10 9/L or a sibling with a perinatal intracranial hemorrhage), maternal intravenous immunoglobulin (IVIG) combined with prednisone is more effective than IVIG alone in eliciting a satisfactory fetal platelet response.
  • In pregnancies at standard risk (no history of intracranial hemorrhage in a previously affected sibling and initial fetal platelet counts > 20 × 10 9/L at 20 weeks of gestation), IVIG or prednisone therapy is beneficial, with no significant advantage of one therapy over another.
  • Epidural or spinal anesthesia is considered acceptable in patients with platelet counts ≥ 80 × 10 9/L, provided that the platelet level is stable, the patient has no other acquired or congenital coagulopathy, her platelet function is normal, and she is not on any antiplatelet or anticoagulant therapy.
  • Fetal–neonatal alloimmune thrombocytopenia should be suspected in cases of otherwise unexplained fetal or neonatal thrombocytopenia, hemorrhage, or ultrasonographic findings consistent with intracranial bleeding.

American Society of Hematology

ASH treatment considerations include the following [64] :

  • Women with no bleeding manifestations and platelet counts ≥30 x 10 9/L do not require any treatment until 36 weeks’ gestation (sooner if delivery is imminent)
  • If platelet counts are < 30 × 10 9/L or clinically relevant bleeding is present, first-line therapy is oral corticosteroids or intravenous immunoglobulin (IVIg)
  • The recommended starting dose of IVIg is 1 g/kg
  • Prednisone and prednisolone are preferred to dexamethasone, which crosses the placenta more readily.
  • Recommended starting doses of prednisone by different experts vary from 0.25 to 0.5 to 1 mg/kg daily; no evidence exists that a higher starting dose is better.
  • Medications are adjusted to maintain a safe platelet count

Expected responses to first-line therapy are as follows [64] :

  • Oral corticosteroids—initial response 2-14 days, peak response 4-28 days
  • IVIg—initial response 1-3 days, peak response 2-7 days

Second-line therapy for refractory ITP is with combined corticosteroids and IVIg or, in the second trimester, splenectomy.  For third-line therapy, anti-D immunoglobulin and azathioprine are relatively contraindicated. Agents that are not recommended, but whose use in pregnancy has been described, include the following [64] :

  • Cyclosporine
  • Dapsone
  • Thrombopoietin receptor agonists
  • Alemtuzumab
  • Rituximab

Contraindicated agents include the following [64] :

  • Mycophenolate mofetil
  • Cyclophosphamide
  • Vinca alkaloids
  • Danazol

ASH recommendations for management at the time of delivery are as follows [64] :

  • Because of the possible need for cesarean delivery, the recommended target platelet count prior to labor and delivery is ≥50 x 10 9/L
  • A woman whose platelet count is < 80 × 10 9/L but who has not required therapy during pregnancy can be started on oral prednisone (or prednisolone) 10 days prior to anticipated delivery at a dose of 10-20 mg daily and titrated as necessary
  • The mode of delivery should be determined by obstetric indications
  • Although the minimum platelet count for the placement of regional anesthesia is unknown and local practices may differ, many anesthesiologists will place a regional anesthetic if the platelet count is ≥80 × 10 9/L
  • While platelet transfusion alone is generally not effective in ITP, its use in conjunction with IVIg can be considered if an adequate platelet count has not been achieved and delivery is emergent
  • Percutaneous umbilical blood sampling (PUBS) or fetal scalp blood sampling is not recommended, as it is not helpful in predicting neonatal thrombocytopenia and is potentially harmful
  • In the newborn, the platelet count reaches its nadir 2-5 days after delivery and rises spontaneously by day 7
  • Postpartum thromboprophylaxis should be considered, as women with ITP are at increased risk of venous thromboembolism

Neonatal care

International Consensus Report recommendations for management of neonates born to women with ITP are as follows [52] :

  • Umbilical cord platelet count should be obtained at the time of delivery or as soon as possible.
  • Repeat the platelet count as needed depending on platelet levels, trends in the count, and response to treatment (if any). If cord platelet count is < 100 × 10 9/L, repeat the platelet count daily until stable. The incidence of pseudothrombocytopenia is high in neonates because of the difficulties encountered in obtaining unclotted blood with blood draws.
  • If the platelet count is < 50 × 10 9/L at birth, perform a cranial ultrasound. A magnetic resonance imaging for confirmation or clarification can be performed without anesthesia using the sleep and swaddle approach 30 to 60 minutes prior.
  • In the case of intracranial hemorrhage, give IVIg and limited steroids to maintain platelet count > 100 × 10 9/L for 1 week if possible and > 50 × 10 9/L for another week. Platelet transfusions may increase neonatal risk.
  • If there is symptomatic bleeding or if platelet count is < 30 × 10 9/L, with or without platelet transfusion, give IVIg.
  • If severe thrombocytopenia continues for > 1 week in a breast-fed infant, consider pausing breastfeeding for a few days to see whether the platelet count increases.