Click here to view next page of this article Hematologic Complications of PregnancyAnemia Anemia is a common complication of pregnancy. Although the red cell mass increases 20-30%, it is less than the plasma volume increase (40-50%), resulting in a net reduction in HGB and HCT. The total iron requirement of a 40-week pregnancy is 680 to 1000 mg. As noted in Table I, almost half of this increase is in response to the expanding red cell mass. Before regular iron supplementation was utilized for normal pregnancy, women were commonly iron-deficient. Because B-12 deficiency is rare in pregnant women, folic acid has been added to regular prenatal vitamins, because folate requirements increase 5-10 fold by the third trimester. As is the case with other nutrients, the fetus can accumulate adequate folate even when the mother is deficient. Women carrying multiple fetuses, or those recovering from infection or hemolysis have further increased folate requirements. Pregnant women suffering from sickle cell anemia suffer increased rates of painful crises, stillbirths, and spontaneous abortions. Infants of sickle cell mothers are often small for gestational age and suffer more frequently from premature delivery. Both maternal and fetal morbidity has improved in recent years, because of improved prenatal care and aggressive treatment of complications. Transfusions or exchange transfusions are no longer used routinely, (at least until the final weeks of pregnancy), although either is appropriate in patients having recurrent crises or other sickle cell-related problems. Thrombocytopenia The most common cause of a low platelet count in pregnant women is gestational thrombocytopenia. The etiology is primarily dilutional, resulting from an excessively expanded plasma volume. In most patients with gestational thrombocytopenia, the platelet count remains between 100-150,000/dL, and these mothers can be delivered normally. Immune thrombocytopenic purpura occurs in approximately 3% of pregnant women with thrombocytopenia. It remains predominantly a diagnosis of exclusion with platelet counts dropping to 20,000/dL or lower. Unfortunately, platelet-associated Ig measurements remain poorly reproducible. The diagnosis is suggested when thrombocytopenia develops in a woman with pre-existing ITP, or when the platelet count falls before 50,000/dL. It can be distinguished from gestational thrombocytopenia because platelet counts are typically lower. The concern in maternal ITP, of course, is that not only will the mother demonstrate progressively lower platelet counts, but that the fetus may be affected as well. Fortunately, symptomatic fetal thrombocytopenia is uncommon. Babies born with ITP must be monitored closely since neonatal thrombocytopenia over the first several days of life can worsen before improving. Standard therapy for pregnant women with ITP includes Prednisone and Mg. Unfortunately, scalp vein sampling is rarely successfu. The overall management of pregnant women with ITP is similar to the treatment of non-pregnant patients. Therapy is typically reserved for evidence of bleeding or platelet count below 20-30,000/dl.. Pregnant patients typically improve their platelet count after delivery. Splenectomy can be performed during pregnancy as a last resort, preferably during the second trimester. The treatment of fetal thrombocytopenia is more complicated. Immune thrombocytopenia may occur in 20-50% of patients with anti-phospholipid antibody syndrome. These antibodies are associated with early, spontaneous abortion. Women who have recurrent fetal loss should be screened for lupus anticoagulant and anticardiolipin antibodies. Those that have positive studies combined with thrombocytopenia, thrombosis, and fetal loss, likely suffer from the disease. The treatment of the anti-phospholipid antibody syndrome is not clearly defined. Patients are often given aspirin, steroids, heparin, and occasionally IVIg. Aspirin is the most commonly used treatment. Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic Uremic Syndrome (HUS) are occasionally seen in association with pregnancy. TTP is defined by the pentad of clinical features, including thrombocytopenia, microangiopathic hemolytic anemia, impaired renal function, fever, and neurologic abnormalities. The underlying Pathophysiology remains unclear but is thought to involve large VWF multimers and widespread endothelial damage, impaired fibrinolytic function, circulating platelet aggregation factors and antibodies against endothelial cells. Once a diagnosis of TTP or HUS is made, therapy should consist of daily plasmapheresis. HUS is similar to TTP except that major manifestations. Preeclampsia is a common disorder and effects 5-13% of all pregnancies. Women who are prima-gravidas are at increased risk. The diagnosis of pre-eclampsia is based on: blood pressure 140/90 or higher, proteinuria (greater than 0.3g/24hr or 10mg/dl in two random samples collected six hours apart). Thrombocytopenia is seen in 15-50% of all women with pre-eclampsia, usually in the later stages of their disease. The pathophysiology of pre-eclampsia is unclear, although the thrombocytopenia appears to be a consequence. The HELLP syndrome is defined as Hemolysis, Elevated Liver enzymes, and Low Platelets. It includes microangiopathic hemolytic anemia, bilirubin greater than 1.2mg/dL. LDH greater than 600u/L, SGOT greater than 70u/L and thrombocytopenia less than 100,000. Up to 12% of pre-eclamptic patients also meet diagnostic criteria for HELLP. Patients with HELLP syndrome often suffer from nausea, malaise, right upper quadrant/upper gastric pain. Affected patients should be delivered as soon as possible. Patients with HELLP may continue to have profound thrombocytopenia for several days after delivery, but then a rapid return to normal platelet count is the rule. If the platelet count does not rebound, then a trial of plasmapheresis. The inheritance by the fetus of platelet isoantigens lacking in the mother. Fetal thrombocytopenia occurs when these isoantigens cross the placenta and attack fetal platelets. Immunization to multiple isoantigens has been documented. The most common are HPA-la and HPA-5b. The true incidence of NAIT is unknown but estimates place it between 1 in 1,000 and 1 in 5,000 live births. Women who are at high risk for delivering an infant with NAIT are: related by blood to a woman who has previously given birth to an infant with NAIT. The diagnosis of NAIT is made on clinical grounds after the infant is delivered and other causes of thrombocytopenia have been ruled out. NAIT typically is diagnosed in a well, term infant with isolated thrombocytopenia whose mother has no history of ITP. Definitive diagnosis is based on demonstrating incompatibility of platelet antigens either by determining the maternal and fetal phenotype or determining the genotype of the father 0aetero or homozygous) for the platelet antigen in question. This assessment should be performed by a laboratory skilled in performing these evaluations. Also important but not essential to the diagnosis is the demonstration of specific antibodies to the specific platelet antigens in the maternal circulation. The most severe complication of NAIT is intracranial hemorrhage. The most common time for intracranial bleeding to occur is during or immediately post delivery; however, an increasing body of evidence suggests that 10% to 50% of intracranial bleeding may occur in utero. The treatment of NAIT in the neonatal period relies on an accurate and prompt diagnosis. The treatment of choice is the infusion of washed maternal or other antigen negative platelets until the infant is able to maintain adequate platelet counts without transfusion. The best antenatal treatment of patients with NAIT is still under study. |