Thrombocytopenia in pregnancy is most frequently a benign process that does not require intervention. However, 35% of cases of thrombocytopenia in pregnancy are related to disease processes that may have serious bleeding consequences at delivery or for which thrombocytopenia may be an indicator of a more severe systemic disorder requiring emergent maternal and fetal care. Thus, all pregnant women with platelet counts less than 100,000/μL require careful hematological and obstetric consultation to exclude more serious disorders.
Thrombocytopenia affects up to 10% of all pregnancies. Thrombocytopenia in pregnancy may be related to preexisting conditions commonly seen in women of childbearing age, such as systemic lupus erythematosus (SLE) and immune thrombocytopenia (ITP), or it may be attributable to disorders intrinsic to pregnancy, such as gestational thrombocytopenia or HELLP syndrome. Occasionally, a previously undiagnosed congenital platelet disorder may be recognized for the first time during evaluation of the thrombocytopenic obstetric patient. Fortunately, most thrombocytopenia in pregnancy is physiologic. Although women with severe thrombocytopenia or platelet functional defects are generally able to maintain a normal pregnancy, it is at delivery that the hemostatic consequences of more significant thrombocytopenia in pregnancy become life-threateningly apparent. At delivery, placental separation occurs at a time when the normal maternal blood flow is approximately 700 mL/minute through the placental vessels. This flow is dampened by uterine contraction leading to placental/myometrial extravascular compression and simultaneous occlusion by physiologic thrombosis of the open maternal vessels. Defects in either mechanism to arrest uterine bleeding can lead to significant and potentially lethal hemorrhage. Careful analysis of the time of onset of thrombocytopenia, associated clinical manifestations, and specific laboratory testing is critical to provide timely diagnosis and appropriate maternal and fetal care in preparation for this hemostatic challenge.
The platelet count decreases by approximately 10% during normal pregnancy, most apparent in the third trimester. In addition, platelet counts may be slightly lower in women with twin or multiple fetus pregnancies. There is no clear numerical definition of thrombocytopenia in pregnancy. A count below 115,000 to 120,000/μL in pregnancy is a suggested threshold and it is recommended that all pregnant women with a platelet count below 100,000/μL undergo evaluation. Of women presenting with mild thrombocytopenia during pregnancy, defined as platelet count greater than 70,000/μL, 65% will not be associated with any definable pathology. Statistically, the most common causes of thrombocytopenia are gestational thrombocytopenia (70%), preeclampsia (21%), immune thrombocytopenia (3%), and other causes (6%).
Gestational thrombocytopenia
Gestational thrombocytopenia is a benign disorder that occurs in about 5% of pregnancies. Platelet counts are typically greater than 70,000/μL with about 70% of platelet counts being between 130,000 and 150,000/μL. The etiology of gestational thrombocytopenia may be related to increased activation and peripheral consumption of platelets, but an immune clearance mechanism may also be present during pregnancy. Evidence for an immune-based destruction is the transient, reversible nature of the thrombocytopenia following pregnancy and the presence of platelet-associated antibody levels indistinguishable from levels found in women with ITP. Thus, gestational thrombocytopenia is not easily differentiated from mild immune thrombocytopenia.
Diagnosis
Diagnostic features of gestational thrombocytopenia include a mild, asymptomatic thrombocytopenia with platelet count of greater than 70,000/μL, typically occurring in the third trimester of pregnancy. There is no prior history of thrombocytopenia in the nongravid state and resolution of the thrombocytopenia follows delivery by 7 days. Recurrent thrombocytopenia in subsequent pregnancies is observed in 20% of women with gestational thrombocytopenia. The peripheral blood smear shows no red blood cell morphologic changes other than those associated with a possible coincidental microcytic, hypochromic anemia of iron deficiency commonly seen in young women and during pregnancy.
Management
There is no indication for therapy in the patient with gestational thrombocytopenia. Epidural anesthesia is safe at platelet counts above 100,000/μL and some studies indicate that epidural can be performed even at counts of 50,000 to 80,000/μL. However, individual anesthesiology practice policies will necessarily dictate the absolute platelet count required. Some physicians recommend preterm anesthesia consultation about the risks and benefits of intravenous analgesics versus a brief course of corticosteroids (<1–2 weeks) to increase the platelet count above the required threshold for epidural anesthesia. Vaginal delivery is the preferred method of delivery unless other obstetric concerns arise.
The risk of neonatal thrombocytopenia in infants born to mothers with gestational thrombocytopenia is considered to be negligible. Nevertheless, all infants born to mothers with thrombocytopenia should be evaluated by a neonatologist.
Immune thrombocytopenia
Chronic immune thrombocytopenia (ITP) is a disorder of both increased platelet destruction and insufficient compensatory bone marrow production of new platelets. In chronic ITP, most autoantibodies are directed against platelet glycoprotein receptors GPIIb–IIIa or GPIb-IX-V and are formed in the white pulp of the spleen. The stimulus for autoantibody production in ITP is probably attributable to abnormal T-cell activity. Antibody-coated platelets are then susceptible to opsonization and Fc receptor-mediated phagocytosis by mononuclear macrophages, primarily but not exclusively in the spleen. The IgG autoantibodies are also thought to damage megakaryocytes. ITP may be idiopathic or secondary to medications, lymphoid malignancies, viral processes, such as HIV and hepatitis C, or autoimmune diseases such as SLE or autoimmune thyroiditis. ITP occurs in 1 to 2 of every 1000 pregnancies and accounts for 5% of cases of pregnancy-associated thrombocytopenia. Distinction between ITP and gestational thrombocytopenia, the most frequent cause of maternal thrombocytopenia, is important because pregnancies in women with ITP are complicated by severe neonatal thrombocytopenia in 9% to 15% of all cases with a risk of neonatal intracranial hemorrhage of 1% to 2%.
Diagnosis
ITP is a diagnosis of exclusion. Women with ITP complicating pregnancy generally report a history of thrombocytopenia in the nonpregnant state. Evidence for preexisting thrombocytopenia includes a history of easy bruisability, epistaxis, petechiae, and menorrhagia before pregnancy, generally when platelet count is less than 50,000/μL. Splenomegaly is absent in ITP. The peripheral blood smear shows thrombocytopenia with an increased mean platelet volume and normal red blood cell morphology. Laboratory testing for liver enzymes, prothrombin time (PT), activated partial thromboplastin time (aPTT), and urinalysis are normal. Testing for HIV or hepatitis C should also be considered. Bone marrow aspirate and biopsy are generally performed only if there are abnormalities in other blood cell lines or if splenectomy is entertained. Platelet antibody testing is not recommended as a routine procedure in clinical decision making because of the poor sensitivity and specificity, and low positive predictive value of results. Women with a history of previous miscarriage and thrombocytopenia should be carefully evaluated for other clinical features of antiphospholipid syndrome or SLE because additional management considerations are necessary in those disorders. Inquiry should be made as to whether prior pregnancies were complicated by thrombocytopenia and whether the newborn had thrombocytopenia or bleeding complications. When ITP is diagnosed for the first time during pregnancy, the platelet count is typically abnormal early in pregnancy with mean platelet count below 70,000/μL. This contrasts with gestational thrombocytopenia where the thrombocytopenia is noted for the first time late in pregnancy and platelet counts are above 70,000/μL. In one study of 92 women during 119 pregnancies over 11 years, women with a diagnosis of ITP before pregnancy were less likely to require therapy of ITP than those pregnant patients with newly diagnosed ITP. There are variable reports of exacerbation of ITP during pregnancy or in the postpartum period, however. Approximately half of patients with a prior diagnosis of ITP experience a mild decline in platelet count progressively during pregnancy.
Management
The clinical management of the pregnant patient with ITP requires close consultation between the obstetrician and the hematologist. Pregnant women with ITP should be evaluated once a month in the first and second trimesters, once every 2 weeks after the seventh month, and once a week after 36 weeks with routine obstetric care and assessment of blood pressure, urinalysis for protein, and serial platelet count. Fetal assessment with ultrasounds can be performed as indicated and if there is concern for fetal hemorrhage, Doppler assessment of peak systolic velocity in the fetal middle cerebral artery can be performed.
Decisions to treat thrombocytopenia are determined by the patient’s bleeding symptoms. As term approaches, more aggressive therapy may be required to improve platelet count as the potential need for surgery or epidural anesthesia is considered. The American Society of Hematology (ASH) and the British Committee for Standards in Hematology General Hematology Task Force Guidelines consider treatment to be appropriate for severe thrombocytopenia or thrombocytopenia with bleeding. Treatment is recommended for women with a platelet count below 10,000/μL at any time during pregnancy. Because of the increasing potential for imminent delivery, treatment is also recommended for platelet counts of less than 30,000/μL in the second and third trimesters. There is no consensus in treatment of the asymptomatic patient in the first trimester with platelet counts between 10,000 and 30,000/μL. Therapies for ITP in pregnancy are similar to initial therapy for ITP in the nonpregnant state. Platelet transfusion is generally not indicated except in cases of severe hemorrhage or immediately before surgery or delivery owing to the very short period of response in platelet count.
Glucocorticoids, such as prednisone, are generally the first line of treatment. The mechanism of action of glucocorticoid is to block antibody production and to reduce phagocytosis of antibody-coated platelets by the reticuloendothelial system in the spleen. A typical starting dose is 1 mg/kg of prednisone based on the prepregnancy weight with taper once a response has been achieved. Unfortunately, the adverse effects of steroids are increased in pregnancy and include gestational diabetes, weight gain, bone loss, hypertension, placental abruption, and premature labor.
Intravenous immunoglobulin (IVIg) may also be used in steroid-resistant patients or as a first-line agent, sparing the adverse side effects of prednisone. IVIg can be administered for platelets less than 10,000/μL during the third trimester or less than 30,000/μL in presence of acute hemorrhage, or for improvement of platelet count several days before delivery. The therapeutic response to IVIg is attributable to several different immunologic mechanisms including blockade of splenic macrophages. High-dose IVIg of 2 g/kg over 2 to 5 days is effective in raising the platelet count rapidly over several days but the effects are transient, generally lasting 1 to 4 weeks. The disadvantages of IVIg are that it is more costly than prednisone and IVIg is a blood product with a theoretic risk of blood-borne infections. IVIg is also helpful in patients with secondary immune thrombocytopenia as seen in SLE and HIV.
In pregnant patients with ITP beyond the optimal second trimester for splenectomy, who fail steroids, and for whom IVIg has been ineffective or is not an option, intravenous anti-RhD may be considered. Anti-RhD is a pooled IgG product taken from the plasma of RhD-negative donors who have been immunized to the D antigen. Experience with its use in pregnancy is limited, however. Use of anti-RhD in the second and third trimesters in 6 of 8 patients resulted in a partial response with no major maternal or fetal complications noted. Anti-RhD immunoglobulin binds to maternal red blood cells. Presentation of antibody-bound red cells to Fc receptors in the spleen results in preferential splenic phagocytosis of the red cells rather than platelets. Response occurs in 75% of patients within 1 to 2 days with peak effect in 7 to 14 days and duration up to 4 weeks. Use of anti-RhD results in mild anemia. In a series reported by Michel and colleagues, there was only one instance in which the hemoglobin fell greater than 2 gm/dL. The direct antiglobulin test was positive in 3 of the 7 newborns but none were anemic or jaundiced. In a series of 120 patients treated with anti-RhD during pregnancy in 2009, only one infant had jaundice, which resolved on phototherapy. Anti-RhD therapy in ITP has been associated with acute hemoglobinemia or hemoglobinuria and subsequent acute renal insufficiency with 5 deaths reported of 121,389 nonpregnant patients treated.
Rituxan is classified as a category C drug in pregnancy and its use has been limited to pregnant patients with lymphoma. No fetal malformations have been reported, nor any immune deficits described, but information is limited.
Other agents used in the treatment of the nonpregnant patient with ITP, such as cytotoxic and immunsuppressive agents with potential teratogenic effects, are discouraged in pregnancy. Interpretation of the hazards in using these agents in pregnancy is complicated by the fact that they have been generally used in situations unrelated to ITP and in which multiple agents including radiation were also used. Use of cyclophosphamide (Category D), an alkylating agent, during pregnancy has resulted in birth defects. In humans, exposure during the first trimester is associated with multiple defects of the calvaria and craniofacial and eye malformations. Use after the first trimester is associated with less risk of congenital malformations but growth retardation, impaired hematopoiesis, and developmental delay are reported. Low-dose cyclosporin A has been used in pregnant patients with no documented defects in the infant immune system and with nonsignificant increases reported in congenital malformations, rate of prematurity, and low birth weight. Azathioprine (category D) has been used safely in female renal transplant patients who are pregnant. The human fetal liver lacks the enzyme inosinate pyrophosphorylase, which converts azathioprine to its active form and it is therefore protected from the drug even though it crosses the placenta. Neonatal hematologic and immune impairment have been reported in some exposed infants, however.
Splenectomy during pregnancy is reserved for severe refractory ITP and is generally performed in the second trimester owing to risks of inducing premature labor in the first trimester and obstruction of the surgical field by the gravid uterus in the third trimester. Remission is achieved in 75% of women initially. Splenectomy does not affect the incidence of neonatal thrombocytopenia or the transplacental passage of circulating maternal antiplatelet antibodies.
There is little information on the effects of the thrombopoietin mimetics, romiplostim and eltrombopag, in pregnancy or the developing fetal bone marrow. A pregnancy registry has been developed for patients who become pregnant while on either of these agents.
Delivery
Vaginal delivery is the preferred method of delivery. Epidural anesthesia during labor in thrombocytopenic patients is controversial because of concern for epidural hematoma. There are several reports of successful use of regional anesthesia in patients with ITP who have platelet counts of less than 100,000/μL without bleeding complications. Current guidelines state that there is no contraindication to regional anesthesia in patients with platelet counts of greater than 100,000/μL. Individuals with platelet counts between 50,000 and 100,000/μL require careful individual assessment. Regional anesthesia is contraindicated in those pregnant patients with platelet counts below 50,000/μL.
Fetal platelet counts do not correlate with maternal platelet counts. Fortunately, 90% of fetuses of mothers with ITP do not have thrombocytopenia. Determination of fetal platelet count requires an invasive procedure such as fetal scalp vein sampling or cordocentesis. The safety of these procedures needs to be weighed against the likelihoods of significant thrombocytopenia and subsequent birth process–related intracranial hemorrhage. Fetal scalp vein monitoring is technically difficult and requires ruptured membranes and cervical dilatation to at least 3 cm. Contamination of the fetal blood sample with amniotic fluid frequently results in fetal platelet clumping and spurious lab results. Cordocentesis has a 1% to 2% complication rate with risk of cord hematoma and pregnancy loss. Several studies comparing vaginal delivery to cesarean section found no increased risk in intracranial hemorrhage after vaginal delivery even in infants with severe thrombocytopenia. Monitoring for neonatal thrombocytopenia is required for several days following delivery, as fetal platelet counts continue to drop after delivery with nadir 1 to 2 days after delivery in pregnancies complicated by ITP.
Immune thrombocytopenia
Chronic immune thrombocytopenia (ITP) is a disorder of both increased platelet destruction and insufficient compensatory bone marrow production of new platelets. In chronic ITP, most autoantibodies are directed against platelet glycoprotein receptors GPIIb–IIIa or GPIb-IX-V and are formed in the white pulp of the spleen. The stimulus for autoantibody production in ITP is probably attributable to abnormal T-cell activity. Antibody-coated platelets are then susceptible to opsonization and Fc receptor-mediated phagocytosis by mononuclear macrophages, primarily but not exclusively in the spleen. The IgG autoantibodies are also thought to damage megakaryocytes. ITP may be idiopathic or secondary to medications, lymphoid malignancies, viral processes, such as HIV and hepatitis C, or autoimmune diseases such as SLE or autoimmune thyroiditis. ITP occurs in 1 to 2 of every 1000 pregnancies and accounts for 5% of cases of pregnancy-associated thrombocytopenia. Distinction between ITP and gestational thrombocytopenia, the most frequent cause of maternal thrombocytopenia, is important because pregnancies in women with ITP are complicated by severe neonatal thrombocytopenia in 9% to 15% of all cases with a risk of neonatal intracranial hemorrhage of 1% to 2%.
Diagnosis
ITP is a diagnosis of exclusion. Women with ITP complicating pregnancy generally report a history of thrombocytopenia in the nonpregnant state. Evidence for preexisting thrombocytopenia includes a history of easy bruisability, epistaxis, petechiae, and menorrhagia before pregnancy, generally when platelet count is less than 50,000/μL. Splenomegaly is absent in ITP. The peripheral blood smear shows thrombocytopenia with an increased mean platelet volume and normal red blood cell morphology. Laboratory testing for liver enzymes, prothrombin time (PT), activated partial thromboplastin time (aPTT), and urinalysis are normal. Testing for HIV or hepatitis C should also be considered. Bone marrow aspirate and biopsy are generally performed only if there are abnormalities in other blood cell lines or if splenectomy is entertained. Platelet antibody testing is not recommended as a routine procedure in clinical decision making because of the poor sensitivity and specificity, and low positive predictive value of results. Women with a history of previous miscarriage and thrombocytopenia should be carefully evaluated for other clinical features of antiphospholipid syndrome or SLE because additional management considerations are necessary in those disorders. Inquiry should be made as to whether prior pregnancies were complicated by thrombocytopenia and whether the newborn had thrombocytopenia or bleeding complications. When ITP is diagnosed for the first time during pregnancy, the platelet count is typically abnormal early in pregnancy with mean platelet count below 70,000/μL. This contrasts with gestational thrombocytopenia where the thrombocytopenia is noted for the first time late in pregnancy and platelet counts are above 70,000/μL. In one study of 92 women during 119 pregnancies over 11 years, women with a diagnosis of ITP before pregnancy were less likely to require therapy of ITP than those pregnant patients with newly diagnosed ITP. There are variable reports of exacerbation of ITP during pregnancy or in the postpartum period, however. Approximately half of patients with a prior diagnosis of ITP experience a mild decline in platelet count progressively during pregnancy.
Management
The clinical management of the pregnant patient with ITP requires close consultation between the obstetrician and the hematologist. Pregnant women with ITP should be evaluated once a month in the first and second trimesters, once every 2 weeks after the seventh month, and once a week after 36 weeks with routine obstetric care and assessment of blood pressure, urinalysis for protein, and serial platelet count. Fetal assessment with ultrasounds can be performed as indicated and if there is concern for fetal hemorrhage, Doppler assessment of peak systolic velocity in the fetal middle cerebral artery can be performed.
Decisions to treat thrombocytopenia are determined by the patient’s bleeding symptoms. As term approaches, more aggressive therapy may be required to improve platelet count as the potential need for surgery or epidural anesthesia is considered. The American Society of Hematology (ASH) and the British Committee for Standards in Hematology General Hematology Task Force Guidelines consider treatment to be appropriate for severe thrombocytopenia or thrombocytopenia with bleeding. Treatment is recommended for women with a platelet count below 10,000/μL at any time during pregnancy. Because of the increasing potential for imminent delivery, treatment is also recommended for platelet counts of less than 30,000/μL in the second and third trimesters. There is no consensus in treatment of the asymptomatic patient in the first trimester with platelet counts between 10,000 and 30,000/μL. Therapies for ITP in pregnancy are similar to initial therapy for ITP in the nonpregnant state. Platelet transfusion is generally not indicated except in cases of severe hemorrhage or immediately before surgery or delivery owing to the very short period of response in platelet count.
Glucocorticoids, such as prednisone, are generally the first line of treatment. The mechanism of action of glucocorticoid is to block antibody production and to reduce phagocytosis of antibody-coated platelets by the reticuloendothelial system in the spleen. A typical starting dose is 1 mg/kg of prednisone based on the prepregnancy weight with taper once a response has been achieved. Unfortunately, the adverse effects of steroids are increased in pregnancy and include gestational diabetes, weight gain, bone loss, hypertension, placental abruption, and premature labor.
Intravenous immunoglobulin (IVIg) may also be used in steroid-resistant patients or as a first-line agent, sparing the adverse side effects of prednisone. IVIg can be administered for platelets less than 10,000/μL during the third trimester or less than 30,000/μL in presence of acute hemorrhage, or for improvement of platelet count several days before delivery. The therapeutic response to IVIg is attributable to several different immunologic mechanisms including blockade of splenic macrophages. High-dose IVIg of 2 g/kg over 2 to 5 days is effective in raising the platelet count rapidly over several days but the effects are transient, generally lasting 1 to 4 weeks. The disadvantages of IVIg are that it is more costly than prednisone and IVIg is a blood product with a theoretic risk of blood-borne infections. IVIg is also helpful in patients with secondary immune thrombocytopenia as seen in SLE and HIV.
In pregnant patients with ITP beyond the optimal second trimester for splenectomy, who fail steroids, and for whom IVIg has been ineffective or is not an option, intravenous anti-RhD may be considered. Anti-RhD is a pooled IgG product taken from the plasma of RhD-negative donors who have been immunized to the D antigen. Experience with its use in pregnancy is limited, however. Use of anti-RhD in the second and third trimesters in 6 of 8 patients resulted in a partial response with no major maternal or fetal complications noted. Anti-RhD immunoglobulin binds to maternal red blood cells. Presentation of antibody-bound red cells to Fc receptors in the spleen results in preferential splenic phagocytosis of the red cells rather than platelets. Response occurs in 75% of patients within 1 to 2 days with peak effect in 7 to 14 days and duration up to 4 weeks. Use of anti-RhD results in mild anemia. In a series reported by Michel and colleagues, there was only one instance in which the hemoglobin fell greater than 2 gm/dL. The direct antiglobulin test was positive in 3 of the 7 newborns but none were anemic or jaundiced. In a series of 120 patients treated with anti-RhD during pregnancy in 2009, only one infant had jaundice, which resolved on phototherapy. Anti-RhD therapy in ITP has been associated with acute hemoglobinemia or hemoglobinuria and subsequent acute renal insufficiency with 5 deaths reported of 121,389 nonpregnant patients treated.
Rituxan is classified as a category C drug in pregnancy and its use has been limited to pregnant patients with lymphoma. No fetal malformations have been reported, nor any immune deficits described, but information is limited.
Other agents used in the treatment of the nonpregnant patient with ITP, such as cytotoxic and immunsuppressive agents with potential teratogenic effects, are discouraged in pregnancy. Interpretation of the hazards in using these agents in pregnancy is complicated by the fact that they have been generally used in situations unrelated to ITP and in which multiple agents including radiation were also used. Use of cyclophosphamide (Category D), an alkylating agent, during pregnancy has resulted in birth defects. In humans, exposure during the first trimester is associated with multiple defects of the calvaria and craniofacial and eye malformations. Use after the first trimester is associated with less risk of congenital malformations but growth retardation, impaired hematopoiesis, and developmental delay are reported. Low-dose cyclosporin A has been used in pregnant patients with no documented defects in the infant immune system and with nonsignificant increases reported in congenital malformations, rate of prematurity, and low birth weight. Azathioprine (category D) has been used safely in female renal transplant patients who are pregnant. The human fetal liver lacks the enzyme inosinate pyrophosphorylase, which converts azathioprine to its active form and it is therefore protected from the drug even though it crosses the placenta. Neonatal hematologic and immune impairment have been reported in some exposed infants, however.
Splenectomy during pregnancy is reserved for severe refractory ITP and is generally performed in the second trimester owing to risks of inducing premature labor in the first trimester and obstruction of the surgical field by the gravid uterus in the third trimester. Remission is achieved in 75% of women initially. Splenectomy does not affect the incidence of neonatal thrombocytopenia or the transplacental passage of circulating maternal antiplatelet antibodies.
There is little information on the effects of the thrombopoietin mimetics, romiplostim and eltrombopag, in pregnancy or the developing fetal bone marrow. A pregnancy registry has been developed for patients who become pregnant while on either of these agents.
Delivery
Vaginal delivery is the preferred method of delivery. Epidural anesthesia during labor in thrombocytopenic patients is controversial because of concern for epidural hematoma. There are several reports of successful use of regional anesthesia in patients with ITP who have platelet counts of less than 100,000/μL without bleeding complications. Current guidelines state that there is no contraindication to regional anesthesia in patients with platelet counts of greater than 100,000/μL. Individuals with platelet counts between 50,000 and 100,000/μL require careful individual assessment. Regional anesthesia is contraindicated in those pregnant patients with platelet counts below 50,000/μL.
Fetal platelet counts do not correlate with maternal platelet counts. Fortunately, 90% of fetuses of mothers with ITP do not have thrombocytopenia. Determination of fetal platelet count requires an invasive procedure such as fetal scalp vein sampling or cordocentesis. The safety of these procedures needs to be weighed against the likelihoods of significant thrombocytopenia and subsequent birth process–related intracranial hemorrhage. Fetal scalp vein monitoring is technically difficult and requires ruptured membranes and cervical dilatation to at least 3 cm. Contamination of the fetal blood sample with amniotic fluid frequently results in fetal platelet clumping and spurious lab results. Cordocentesis has a 1% to 2% complication rate with risk of cord hematoma and pregnancy loss. Several studies comparing vaginal delivery to cesarean section found no increased risk in intracranial hemorrhage after vaginal delivery even in infants with severe thrombocytopenia. Monitoring for neonatal thrombocytopenia is required for several days following delivery, as fetal platelet counts continue to drop after delivery with nadir 1 to 2 days after delivery in pregnancies complicated by ITP.
Preeclampsia
Preeclampsia is the second most frequent cause of thrombocytopenia in pregnancy, accounting for 21% of cases. Preeclampsia affects 3% to 14% of pregnancies and is the most common medical disorder of pregnancy. Thrombocytopenia develops in 50% of patients with preeclampsia, generally in the third trimester, and correlates with the severity of the disorder. Preeclampsia is a syndrome characterized by the onset of hypertension and proteinuria after 20 weeks of gestation in a previously normotensive woman. The diagnostic criteria for preeclampsia include hypertension (systolic blood pressure [BP] greater than or equal to 140 mm Hg and diastolic BP 90 mm Hg) and proteinuria (300 mg protein/24 hours). Preeclampsia is defined as either mild or severe. Preeclampsia may be of early onset (<34 weeks) or late onset (≥34 weeks) and may also occur during labor or in the postpartum state. The pathophysiologic mechanisms in preeclampsia are not fully understood but the placentation process appears to be abnormal (for review see Sankaralingam and colleagues ). Trophoblastic cells have been shown to have defects in expression of adhesion molecules, vascular endothelial growth factors, and their receptors. High levels of P-selectin and CD63 expression and increased levels of CD40 ligand are found in preeclamptic pregnancies. Feto-placental ischemia develops, leading to impaired prostaglandin synthesis and release. This contributes to the development of hypertension, reduced placental flow, vascular damage, and platelet activation clinically manifested by a decrease in platelet number and increased new fibrin generation. Angiogenic factors, such as vascular endothelial growth factor 1 (VEGF1), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1), are elevated in preeclampsia above normal pregnancy ranges, often before preeclampsia is recognized clinically. Measurement of these factors is currently limited to research settings. Risk factors for preeclampsia include nongestational diabetes, family history of preeclampsia, maternal age older than 40 years, and antiphospholipid sydrome. The recurrence rate of early severe preeclampsia is 25% to 65% and for mild preeclampsia is 5% to 7% in subsequent pregnancies.
Diagnosis
Preeclampsia is suspected with new-onset hypertension with systolic blood pressure greater than or equal to 140 mm Hg and diastolic blood pressure 90 mm Hg. Laboratory studies useful in the diagnosis of thrombocytopenia related to preeclampsia include a complete blood count, peripheral blood smear, serum creatinine, uric acid, and 24-hour urine protein collection if urine dipstick indicates greater than 1+ protein. Coagulation studies are generally normal and disseminated intravascular coagulation is absent unless the disorder is severe.
Management
Most cases of late-onset preeclampsia are handled entirely by the obstetrician. The management of the pregnant patient is directed at stabilization of blood pressure followed by delivery of the fetus. Because most cases of preeclampsia occur late in pregnancy after 34 weeks, at a time when the fetal lung is mature, immediate delivery of the infant is the optimal treatment. Decisions for delivery are otherwise based on the balance of maternal and fetal risks of which platelet count less than 100,000/μL is one criterion. Platelet transfusion may be necessary to support hemostasis for procedures or active bleeding but platelet survival is shortened. Some studies report that mild preeclampsia may respond to aspirin therapy, but this has not been confirmed. Neonatal thrombocytopenia is reported in preeclamptic deliveries;
however, all reported infants were preterm deliveries of which 2 had intracranial hemorrhage despite cesarean section delivery.
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