Gestational Thrombocytopenia: What is the Threshold for Further Follow-Up?

BACKGROUND AND PURPOSE:

• Gestational thrombocytopenia is defined as platelet count < 150,000 per cubic millimeter (see ‘Related ObG Topics’, below)
• However, data on platelet counts throughout pregnancy is limited
• Reese et al. (NEJM, 2018) sought to determine the platelet counts in complicated and uncomplicated pregnancies to assess the occurrence and severity of thrombocytopenia throughout pregnancy

METHODS:

• Cohort Study (2011-2014)
• Participants
  • Women 15 to 44 years of age
• Platelet counts were compared with those of non-pregnant women
• Data on complications were also recorded, including those known to be associated with low platelet counts (e.g., HELLP and ITP)
• Twins were analyzed separately
  • Preterm defined as <37 weeks in singletons and <34 weeks in twins
• National Health and Nutrition Examination Survey (NHANES) data (nonpregnant women 15 to 44 years of age) were used for comparisons
• Primary objectives
  • Determine change in platelet counts during pregnancy
  • Determine whether rate of decrease differed during pregnancy between women with uncomplicated pregnancies compared to pregnancy-related complications/preexisting disorders
  • Recurrence risk

RESULTS:

• 7,351 provided sufficient data for the analyses
  • 4,568 had uncomplicated pregnancies
  • 2,586 had pregnancy-related complications
  • 197 had preexisting disorders associated with thrombocytopenia
• Mean platelet counts in uncomplicated pregnancies were as follows
  • First trimester (mean gestation, 8.7 weeks): 251,000 per cubic millimeter
  • Second trimester (mean gestation, 22.0 weeks): 230,000 per cubic millimeter
  • Third trimester (mean gestation, 32.1 weeks): 225,000 per cubic millimeter
  • Delivery (mean gestation, 39.0 weeks): 217,000 per cubic millimeter
  • Postpartum period (mean time after delivery, 7.1 weeks): 264,000 per cubic millimeter
• Uncomplicated pregnancies had lower platelet counts throughout pregnancy during each trimester and at delivery compared to nonpregnant women (P<0.001)
  • There was no difference in the postpartum period (P=0.10)
• At delivery
  • 9.9% of uncomplicated pregnancies had a platelet count <150,000 per cubic millimeter
  • Platelet counts <150,000 per cubic millimeter were more common among women who had pregnancy-related complications (11.9%) than among women who had uncomplicated pregnancies (9.9%); P=0.01
• In uncomplicated pregnancies
  • only 1% had a platelet count <100,000 per cubic millimeter
  • Only 0.1% of women with platelet counts <80,000 per cubic millimeter (median 65,000) had no explanation for their thrombocytopenia
• In women with pregnancy-related complications
  • 2.3% of women had a platelet count <100,000 per cubic millimeter throughout pregnancy and/or delivery
  • 1.2% had a platelet count <80,000 per cubic millimeter throughout pregnancy and/or delivery
  • HELLP: 28.0% had a platelet count <80,000 per cubic millimeter (median, 61,000; range, 32,000 to 78,000)
• Risk of recurrence was 14.2 (95% CI, 8.9 to 22.6) times as high among women who had previously had a platelet count <150,000 per cubic millimeter

CONCLUSION:

• Mean platelet counts are lower in pregnancy throughout gestation starting in the first trimester
• Platelet counts of less <100,000 per cubic millimeter warrants further investigation

Learn More – Primary Sources:

Platelet Counts during Pregnancy

Gestational Thrombocytopenia – a Diagnosis of Exclusion

Thrombocytopenia is a common finding which occurs in 7-12% of pregnant women. The cause of isolated thrombocytopenia may be differentiated by history, physical examination, laboratory investigation, and medical imaging.

CLINICAL ACTIONS:

When evaluating a patient for gestational thrombocytopenia (GT), consider the following

• ≥Use platelet count <150 x 10⁹/L to define thrombocytopenia in pregnancy
  • Normal platelet range in nonpregnant women is 165-415 x 10⁹/L
  • Expect lower platelet counts in pregnant women, especially 3^rd trimester
• Order the following tests to assist with diagnosis/underlying cause
  • complete blood count and peripheral smear
  • liver enzymes
  • thyroid function tests
  • vitamin B12 and folate
  • HCV,HIV,HBV
  • PT/PTT
  • antinuclear antibody, anticardiolipin antibodies, lupus inhibitor
  • Based on clinical context, may require medical imaging to evaluate splenic size
• Diagnose GT in the absence of historical, clinical, hematological and biochemical findings that would suggest another underlying condition
• Transfuse platelets to achieve minimum platelet counts if
  • <10 x 10⁹/L even without surgery and/or procedures
  • <50 x 10⁹/L if active bleeding present unless undergoing cesarean in which case prophylactic platelet transfusion is recommended  (or other major surgery as per AABB guidance)
• Epidural and spinal “are considered acceptable” if ≥70 x 10⁹/L prior to epidural and
  • Platelet level stable | No coagulopathy | Platelet function normal | No antiplatelet or anticoagulant therapy
  • Limited evidence regarding low-dose aspirin combined with thrombocytopenia and neuraxial blockade

SYNOPSIS:

GT is the most common cause of thrombocytopenia in pregnancy and accounts for 80% of such cases.  GT may be a result of hemodilution and enhanced platelet clearance. The low platelet counts associated with GT are seen during the second and third trimesters with the nadir rarely lower than 70 x 10⁹/L. The diagnosis of GT is made by the presence of a decreased platelet count during pregnancy and should be considered a diagnosis of exclusion. GT usually resolves within days to two months postpartum.

KEY POINTS:

Primary immune thrombocytopenia (ITP) may be difficult to distinguish from GT

• ITP induces development of platelet autoantibodies that may cross the placenta
• Features that may help distinguish GT from ITP
  • GT usually mid-late 2^nd & 3^rd trimester / ITP all trimesters
  • GT only in pregnancy / ITP may occur outside pregnancy
  • GT will resolve postpartum / ITP may not resolve
  • GT does not affect fetus or neonate / ITP may cause neonatal thrombocytopenia
• If the diagnosis thrombocytopenia is unclear at the time of delivery, assume ITP and manage accordingly due to fetal/newborn risk for thrombocytopenia
  • Mode of delivery in ITP should be based on obstetric indications alone
• ITP treatment options comparable to non-pregnant management – corticosteroids and intravenous immune globulin (IVIG)
  • In pregnancy, may start at lower end of prednisone dose (10-20 mg daily) and titrate up
• Both GT and ITP may recur

Other disorders resulting in non-isolated thrombocytopenia that will present with other related findings include

• Primary thrombotic microangiopathies (TMA)
  • ADAMTS13-deficient TMA – Thrombotic thrombocytopenic purpura (TTP)
  • Complement-mediated TMA – Atypical hemolytic uremic syndrome
• Preeclampsia
  • 50% of women with preeclampsia will have <150 x 10⁹/L
  • HELLP syndrome
• Disseminated intravascular coagulation (DIC)
  • Severe preeclampsia
  • Intrauterine fetal demise (IUFD)
  • HELLP syndrome
  • Acute fatty liver of pregnancy
• Infection (e.g., HIV, hepatitis C, CMV, Helicobacter pylori)
• Drug induced (e.g. heparin, antimicrobials, anticonvulsants)

Learn More – Primary Sources:

Thrombocytopenic syndromes in pregnancy

ACOG Practice Bulletin 207: Thrombocytopenia in Pregnancy

Platelet Transfusion: A Clinical Practice Guideline From the AABB

Locate a Maternal Fetal Medicine Specialist:

Maternal Fetal Medicine Specialist Locator-SMFM