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Thrombocytopenia in pregnancy
Causes of thrombocytopenia during pregnancy can be directly related to pregnancy, or be unrelated. Average platelet counts are decreased during pregnancy, especially during the third trimester, and when this decrease is mild and otherwise unexplained it is termed gestational thrombocytopenia, the most common cause of thrombocytopenia during pregnancy. Gestational thrombocytopenia develops due to the combination of hemodilution and platelet consumption. Increased levels of thromboxane A2 can contribute to increased platelet aggregation. Gestational thrombocytopenia usually develops during the late second or third trimester and disappears within months after delivery; there is no risk of fetal/neonatal thrombocytopenia in this condition. Therapy is virtually never given for this condition unless the platelet count is <80−100 × 109/L, the threshold needed for epidural anesthesia. Other causes of thrombocytopenia during pregnancy should be differentiated from gestational thrombocytopenia because the approach to these conditions is different. For pregnant women, it is reasonable to define thrombocytopenia as a platelet count below the 2.5th percentile: 116 × 109/L (2.5th percentile in non-pregnant women is 150 × 109/L). The reasonable trigger for further investigation, unless certain findings suggest otherwise, is a platelet count lower than 80 × 109/L [35]. Diagnosis is largely dependent on the time of the onset of thrombocytopenia, its severity and association with other abnormal findings, and whether hemolysis or organ dysfunction are involved. Mild to moderate thrombocytopenia developing in the second or third trimester can be associated with pre-eclampsia. To diagnose pre-eclampsia, new onset hypertension and proteinuria are required, sometimes associated with liver enzyme elevation and mild LDH elevation. More prominent liver enzyme elevation and LDH elevation, associated with microangiopathic hemolytic anemia, suggest HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome. Moderate to severe thrombocytopenia is typical for HELLP syndrome. Pre-eclampsia, associated with HELLP syndrome, is treated symptomatically, but the most effective treatment is the delivery of the fetus, although seizures after delivery have occurred. Sometimes plasmapheresis is needed for HELLP. Another cause of thrombocytopenia during pregnancy (and the second most common cause after gestational thrombocytopenia) is ITP. It is impossible to distinguish this kind of thrombocytopenia from gestational thrombocytopenia, as a diagnostic test for both conditions does not exist. It is reasonable to use a cut-off of 50−70 × 109/L platelets as a lower limit for gestational thrombocytopenia. If ITP is suspected, frequent follow up (every 1-3 weeks) is required, depending upon the count and the time to expected delivery. During the first and second trimester, treatment for ITP is necessary only if a patient is symptomatic, if a procedure is required, for example, an amniocentesis, or the platelet count drops below 20 × 109/L. If the patient is asymptomatic and the platelet count is >20 × 109/L, treatment may be required only during the last part of the third trimester to elevate the platelet count prior to epidural anesthesia or Caesarian section. Low dose (10-20 mg/day) prednisone or intravenous immunoglobulin or both are reasonable options in these situations. Other treatment modalities can be used in symptomatic pregnant ITP patients (e.g. if there is bleeding) or if a platelet count is less than 20 × 109/L. A high dose of steroids can be used, especially in combination with intravenous immunoglobulin and/or intravenous anti-D (if Rhesus positive, direct antiglobulin test-negative and not splenectomized). In a very refractory patient other medications can be used, including azathioprin and/or cyclosporin (if needed). Splenectomy can be performed during the second trimester for severe ITP cases but this option is very rarely pursued. Limited data are available to describe rituximab use during pregnancy but, as an IgG1 monoclonal, it is expected to cross the placenta and thus cannot be recommended for fear of depleting fetal B cells, although a series of lymphoma cases treated during pregnancy have been accumulated demonstrating an apparent absence of serious fetal/neonatal effects. Many other agents, typically used for ITP treatment, cannot be used during pregnancy due to their potential for crossing the placenta and being teratogenic. The effect on the fetus of thrombopoietin-agonists is unknown, and these medications cannot be recommended due to the lack of data and the anticipation that they will cross the placenta and stimulate the fetal marrow in utero. Other types of thrombocytopenia should be taken into account in pregnant patients. Inherited thrombocytopenia, for example, can be diagnosed occasionally during pregnancy.