Introduction:
Thrombocytopenia is characterized by a platelet count of less than 150 × 10^9/Liter. It ranks second only to anemia among the common hematologic abnormalities during pregnancy. Three extensive studies involving over 26,000 women collectively suggest that its prevalence at the end of pregnancy ranges between 6.6 and 11.6 percent. However, severe thrombocytopenia is defined as platelet counts below 100 × 10^9/Liter. According to an International Working Group, it is observed in only one percent of pregnant women.
The clinician's challenge is determining the underlying cause of thrombocytopenia and assessing its risks to the mother and the fetus. Treatment strategies need to be adaptable, particularly during labor and delivery, when surgical risks and the newborn's passage through the birth canal must be considered.
In this article, the approach and challenges are discussed. The focus will be on understanding the clinical characteristics and management of primary immune thrombocytopenia (ITP), differentiating it from gestational thrombocytopenia, and addressing thrombotic microangiopathies during pregnancy.
What Is Thrombocytopenia?
Thrombocytopenia, characterized by a platelet count below 150,000 mm3, is common during pregnancy, affecting approximately seven to 12 percent of pregnancies. Mild thrombocytopenia refers to a platelet count greater than 100,000 mm3, moderate falls between 50,000 and 100,000 mm3, and severe thrombocytopenia is defined as platelet counts below 50,000 mm3. This condition can arise due to physiological changes or pathological factors, some of which are specific to pregnancy and can pose significant risks to both the mother and the fetus.
Thrombocytopenia typically manifests as mucosal bleeding due to a defect in primary hemostasis. Common symptoms include nosebleeds, gum bleeding, abnormal uterine bleeding, petechiae, and ecchymosis. While life-threatening bleeding is rare and usually occurs in patients with extremely low platelet levels, it may present as hematuria, gastrointestinal bleeding, and, in rare cases, intracranial hemorrhage.
However, platelet counts above 50,000 mm3 are often asymptomatic, provided their function is normal. During pregnancy, most instances of thrombocytopenia are attributed to hemodilution and increased platelet destruction. Reduced production is less common, and when present, it is typically linked to nutritional deficiencies. A thorough medical history includes medication use, medical conditions, and a physical examination. Laboratory tests should encompass a complete blood count, peripheral blood smear, liver and renal function tests, coagulation studies, assessment of antiphospholipid antibodies, antinuclear antibodies, human immunodeficiency virus (HIV) serology, as well as testing for hepatitis C antibodies and hepatitis B surface antigen.
What Are Physiological Changes of Thrombocytopenia in Pregnancy?
In pregnant women, it is common to observe a decrease in platelet count, starting in the initial trimester and progressively declining throughout gestation, reaching its lowest point at delivery. This phenomenon is attributed to physiological factors such as hemodilution, increased activation and clearance of platelets, and temporary sequestration in the placental circulation. A recent retrospective cohort study involving 4,568 women investigated the trajectory of platelet counts during uncomplicated pregnancies.
Compared to the average platelet count in non-pregnant women (273,000 mm3), pregnant women showed a lower platelet count starting in the first trimester, with further decline during gestation. Additionally, twin pregnancies exhibited lower platelet counts throughout pregnancy and delivery than singleton pregnancies, possibly due to increased plasma volume or larger placental size.
What Are the Causes of Thrombocytopenia in Pregnancy?
The following are the causes of thrombocytopenia in pregnancy:
Pregnancy-Specific Thrombocytopenia:
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Isolated thrombocytopenia.
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Gestational thrombocytopenia (70 to 80 percent).
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Thrombocytopenia associated with systemic disorders.
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Preeclampsia (15 to 20 percent).
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HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome (< 1 percent).
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Acute fatty liver of pregnancy (< 1 percent).
Not pregnancy-specific thrombocytopenia:
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Isolated thrombocytopenia.
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Primary immune thrombocytopenia–ITP (1 to 4 percent).
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Secondary ITP (< 1 percent).
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Drug-induced thrombocytopenia (< 1 percent).
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Congenital (< 1 percent).
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Thrombocytopenia associated with systemic disorders.
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SLE (< 1 percent).
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Antiphospholipid antibody syndrome (< 1 percent).
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Viral infections (< 1 percent).
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Bone marrow disorders (< 1 percent).
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Nutritional deficiency (< 1 percent).
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Splenic sequestration (liver diseases, portal vein thrombosis, and storage disease. < 1 percent).
What Are the Treatments for Thrombocytopenia in Pregnancy?
Administration of antenatal corticosteroids does not impact neonatal platelet counts and should not be given to near-term mothers to affect platelet levels. However, discontinuing corticosteroids after childbirth should be closely monitored, and dosages should be gradually reduced to prevent a sudden decrease in platelet count.
In cases where the response to prednisone is inadequate, or the drug's side effects are intolerable, intravenous immunoglobulin (IVIg) can be utilized (at a dosage of 1 g/kg in a single dose or divided into two doses), either alone or in conjunction with low doses of prednisone, to maintain safe platelet counts.
Although anti-RhD immunoglobulin is not recommended as a first-line treatment due to concerns about acute hemolysis and anemia, it has been employed in refractory cases during pregnancy with successful outcomes. If administered to a pregnant patient, anti-RhD (at doses of 50 to 75 μg/kg) necessitates monitoring of the neonate for a positive direct antiglobulin test, anemia, and jaundice, as the antibody can cross the placenta.
If the patient's response to initial treatments is inadequate, second-line therapy may be necessary, albeit with adjustments for safety considerations in pregnant patients. Azathioprine has been safely used during pregnancy, and although immune impairment has been reported in some exposed infants, it remains a reasonably safe option.
High-dose methylprednisolone may also be employed in combination with IVIg or azathioprine for patients who do not respond adequately to oral corticosteroids or IVIg or those with a suboptimal response. While cyclosporine A has not been linked to significant toxicity in either the mother or fetus when utilized for inflammatory bowel disease during pregnancy, there is a lack of published data on its use in ITP during pregnancy, and it should only be considered when other safe second-line agents have proven ineffective.
Conclusion:
Gestational thrombocytopenia is the most prevalent cause of low platelet levels during pregnancy, posing no significant risks to either the fetus or the mother. The diagnosis of immune thrombocytopenia (ITP), an autoimmune disorder, relies on the exclusion of other conditions; however, in nearly two-thirds of cases, it is diagnosed before pregnancy. In the majority of instances, treatment is unnecessary.
Thrombocytopenia associated with conditions like pre-eclampsia and HELLP syndrome may necessitate early delivery. Thrombotic microangiopathy, such as thrombotic thrombocytopenic purpura (TTP) and complement-mediated hemolytic uremic syndrome (CM-HUS), rarely occurs during pregnancy. Distinguishing between these conditions and pre-eclampsia/HELLP syndrome can be challenging, often requiring a multidisciplinary approach. Vigilant intensive care and close monitoring can enhance pregnancy outcomes, while discussions regarding the prognosis for future pregnancies are vital for these individuals. The limited research on the use of novel effective treatments for ITP and HUS (such as thrombopoietin-receptor agonists or eculizumab) presents challenges in decision-making regarding the risks to fetal and maternal health associated with disease progression versus the safety concerns of using these agents during pregnancy.
