Thrombocytopenia, defined as a platelet count of under 150 x 10^9/L, is the second most common hematological abnormality in pregnancy. The International working group (IWG) adopted a lower threshold of platelets, 100 x 10^9/L, to define immune thrombocytopenia, which is observed in less than 1% of all pregnancies. Thrombocytopenia in pregnancy occurs either due to obstetric conditions (like gestational thrombocytopenia, pre-eclampsia/eclampsia) or secondary to systemic disorders (like thrombocytopenic thrombotic purpura, immune thrombocytopenia). For the present discussion, the approach to thrombocytopenia has its basis on the trimester in which the thrombocytopenia develops and the etiology of the thrombocytopenia. This division will help in understanding the workup and guiding management. Even though thrombocytopenia is a common abnormality in pregnancy, it seldom leads to life-threatening complications by itself. The management of thrombocytopenia focuses on the underlying cause. Platelet transfusion is usually not required to achieve a particular goal and is only for bleeding patients. Local hospital policies govern the goal of platelet counts and are quite variable between institutions. Nevertheless, a hematologist must be involved in the management of thrombocytopenia in pregnancy, especially if the platelet count drops below 70 x 10^9/L, or if a coexistent bleeding disorder is either encountered or suspected.
Thrombocytopenia in pregnancy happens secondary to many etiologies, differing in their pathophysiology and presentation. A summary of possible etiologies is listed here:
It is also worthwhile to distribute the etiology of thrombocytopenia according to the trimester and the platelet count.
Thrombocytopenia affects 7 to 11% of all pregnancies. However, less than 1% of pregnancies experience a drop in platelet count below 100 x 10^9/L. It is the second most common hematologic abnormality in pregnancy after anemia. Overall, gestational thrombocytopenia is the most common cause of low platelets in pregnancy, followed by pre-eclampsia (20% patients) and ITP (1 to 4%). The rest of the etiologies mentioned in the previous section (TMA, HT, DIC, HT, and other causes) rarely cause thrombocytopenia in pregnancy (less than 1%). Although the rare causes of thrombocytopenias do not constitute more than 1% of pregnant patients with low platelet counts, they often designate severe conditions that contribute significantly to maternal morbidity and mortality.
The pathophysiology of thrombocytopenia is dependent on the etiology. This section will discuss the pathophysiology of the major causes of thrombocytopenia in pregnancy.
In any patient with thrombocytopenia, a thorough history and physical exam help in establishing the etiology behind the low platelet count. Usually, the signs and symptoms of thrombocytopenia do not occur unless the platelet count drops to a very low level or the patient presents with symptoms of the underlying disorder. A temporal profile of thrombocytopenia or its bleeding manifestations (acute, chronic, or relapsing-remitting) does not help in determining the etiology of thrombocytopenia but helps in determining the clinical phenotype. The past medical history of other diseases such as existing autoimmune disorders (systemic lupus erythematosus, rheumatoid arthritis, etc.), infections (rickettsiosis, malaria, etc.), malignancies and transplant recipients is essential to establish the diagnosis. Likewise, a history of medications (quinine, antibiotics, heparin, etc.), recent vaccinations, travel history, dietary practices, high-risk behaviors (sexual practices, illicit drug use, smoking, alcohol consumption) also helps in guiding the evaluation of thrombocytopenia. Thorough family history is vital in delineating congenital thrombocytopenia, which can present for the first time well into adulthood.
A physical exam provides clues towards determining the etiology of thrombocytopenia. Patients with gestational thrombocytopenia are often healthy, asymptomatic women who are found to have low platelets on lab investigations. On the contrary, a pregnant woman with TMA is usually a gravely-ill patient often presenting to the emergency room or admitted to high-risk obstetric units. Patients with low platelet count usually present with mucocutaneous bleeding. However, joint bleed or severe bleeding should prompt a workup towards severe coagulopathies like DIC. Physical exam should also evaluate for hepatomegaly and/or splenomegaly (cirrhosis, lymphoproliferative disorders, etc.), skeletal deformities (like absent radius, humeral abnormality and sometimes phocomelia seen in thrombocytopenia absent radii syndrome) and skin exam (like petechiae or purpura seen commonly with ITP, or, eczema seen in Wiskott-Aldrich Syndrome).
Specific clues in the history and physical exam can point a clinician towards an underlying etiology.
Laboratory evaluation of thrombocytopenia starts with a review of peripheral smear. Pseudothrombocytopenia, defined as clumping of platelets on peripheral smear, can happen in up to 1% of all pregnancies. This 'fictitious' thrombocytopenia occurs due to the collection of blood in ethylenediaminetetraacetic acid (EDTA) anticoagulated tubes. The EDTA-dependent platelet auto-antibodies lead to artifactual clumping on the peripheral smear. It can be corrected by collecting the blood in a heparin tube and then performing a manual count on the peripheral smear. A review of a peripheral blood smear helps to determine the morphology of all three cell lines and the detection of red cell fragments (schistocytes) and atypical white cells like myeloblasts; this is particularly important in a critically-ill pregnant patient with thrombocytopenia, where a review of peripheral smear must be done to look for schistocytes and rule out TMA.
A complete blood count with differential helps in realizing the degree of thrombocytopenia and provides a clue about the etiology. Evaluation of thrombocytopenia in pregnancy starts by differentiating between isolated thrombocytopenia and thrombocytopenia, which occurs along with changes in red cell and white cell lines.
Gestational thrombocytopenia is a diagnosis of exclusion which is based on a thorough history and physical exam and ruling out of conflicting diagnosis with lab support. With sufficient exclusion of other etiologies, then no further laboratory evaluation is needed to confirm a diagnosis of gestational thrombocytopenia. Rarely, the platelet count drops below 70 x 10^9/L in patients with gestational thrombocytopenia. If the platelet count goes below 70 x 10^9/L, then the patient should be evaluated for a secondary cause like ITP. 
In pregnancy, thrombocytopenia usually does not lead to an increased risk of bleeding. Even in patients with ITP, where thrombocytopenia is often quite severe, the risk of bleeding remains low. The obstetric indication decides the mode of delivery. Vaginal delivery is preferable from a hematologic standpoint due to the lower risk of bleeding; however, this is not a deciding factor. Administration of neuraxial anesthesia (epidural anesthesia) is a challenge. The American College of Obstetrics and Gynecology recommend a platelet count of 80 x 10^9/L (level C recommendation) as the goal of administering epidural anesthesia. The platelet goal for delivery is more than 50 x 10^9/L, especially if planning a cesarean section. Here we will briefly discuss the management of pregnant patients with thrombocytopenia according to the etiology of the disease.
The workup of thrombocytopenia in pregnancy focuses on establishing the etiology of low platelets. A list of potential diagnoses is listed above.
The prognosis depends on the underlying etiology for thrombocytopenia. While thrombocytopenia does not lead to complications in pregnancy, the etiology behind the thrombocytopenia can pose significant challenges. The mode of delivery is chosen based on the obstetric indication.
Neonatal outcome in women with thrombocytopenia:
Thrombocytopenia in pregnancy seldom leads to bleeding in pregnancy, even with very low platelet counts seen in ITP The complications are secondary to the underlying etiology and get discussed in the Management section.
Aa high-risk obstetric clinic should follow any patient with thrombocytopenia in pregnancy. A hematology consult is needed if the platelet count drops below 70 x 10^9/L or if a pregnant woman with thrombocytopenia develops bleeding. It is critical to involve a hematologist in the management of TMA not specific to pregnancy (TTP and atypical HUS) and other rare causes of thrombocytopenia.
Though thrombocytopenia in pregnancy is benign in the majority of patients, it should be investigated thoroughly, especially if the platelet count drops below 70 x 10^9/L. In the case of gestational thrombocytopenia, patients require reassurance about the benign nature of the diagnosis. Appropriate treatment directed towards the underlying etiology should start as soon as possible, and the patients and family members should receive appropriately targeted education. Patients should be followed for platelet counts every 2 to 4 weeks to observe a trend in their platelet counts and every two weeks near term. Patients and family members should understand that the mode of delivery (vaginal or cesarean section) will be decided based on obstetric indication and not the platelet count. In addition to this, patients should also know that platelet transfusions are not routine therapy for thrombocytopenia in pregnancy. The delivery is usually uncomplicated if their platelet count is more than 50 x 10^9/L. However, a goal of more than 80 x 10^9/L is considered appropriate for administering epidural anesthesia. An expert hematologist should be involved in the care of the pregnant women with thrombocytopenia, if the platelet count drops below 70 x 10^9/L or if bleeding develops.
Thrombocytopenia in pregnancy is a benign condition in the majority of patients. However, it may be associated with more severe etiologies in a few patients. A few noteworthy points are listed here.
Important points to remember for both physicians and patients:
Thrombocytopenia in pregnancy is the second most prevalent hematological abnormality in pregnancy. Less than 1% of pregnant women with thrombocytopenia during pregnancy would have a platelet count of less than 100 x 10^9/L. Gestational thrombocytopenia is the most frequent cause of thrombocytopenia in pregnancy and requires vigilant monitoring in the clinic and reassurance to the patient. There is a need for communication between the obstetrics team, hematologists, pediatricians, and nurses involved in the management of pregnant women with thrombocytopenia. Most evidence in the management of patients with gestational thrombocytopenia and ITP comes from retrospective observational studies or Cohort-Control studies (Level III). The rarer causes of thrombocytopenia in pregnancy are investigated based on the presenting sign and symptoms.
Pregnancy-related thrombocytopenia requires an interprofessional approach to care. Clinician involvement was discussed above, but they do not operate alone. Specialty-trained nursing staff (maternal-newborn and neonatal) will be on hand to assist with delivery, medication administration, and monitoring of the mother and baby before and throughout the delivery process. The various medications used in thrombocytopenia require input from the pharmacists, who will verify dosing, check for interactions, and suggest therapeutic alternatives when necessary. The clinicians may be running the show, but they need their supporting actors on the interprofessional healthcare team to effectively bring both the mother and newborn to a successful outcome. [Level V]
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