Thrombocytopenia in pregnancy
Definition
Thrombocytopenia is defined as a low platelet count of less than 150 ? 109ZL (83-85), but only counts of less than 100 ? 109ZL are clinically significant.
It is classified as mild—platelet count 100- 150 ? 109ZL; moderate— platelet count 50-100 ? 109/L; and severe—platelet count less than 50 ? 109/L. Platelet counts of less than 20 ? 109/L are associated with significant maternal and perinatal morbidity (86).
Incidence
Thrombocytopenia is the second commonest haematological disorder in pregnancy after anaemia. It affects 6- 10% of all pregnancies, and while some studies show a 10% decrease in platelet counts in the third trimester in normal pregnancy, the absolute count remains well within normal levels (87, 88). Approximately 8% of pregnant women will have a platelet count between 100 and 150 ? 109/L (2).
Causes
The main causes of thrombocytopenia are (1) gestational; (2) autoimmune—immune thrombocytopenic purpura, systemic lupus erythematosus, or APS; (3) hypertensive disorders, PET, and HELLP syndrome; (4) thrombotic thrombocytopenic purpura (TTP), haemolytic uraemic syndrome (HUS); (5) human immunodeficiency virus (HIV); and (6) bone marrow suppression.
Gestational thrombocytopenia
This is the commonest type of thrombocytopenia and accounts for 75% of cases of thrombocytopenia diagnosed in pregnancy (1). It usually occurs in the third trimester and is thought to be due to the increased platelet consumption and plasma volume expansion in pregnancy. It is a diagnosis of exclusion and the following criteria should be met for diagnosis:
• There is mild to moderate thrombocytopenia.
• The platelet count seldom falls below 70 ? 109/L.
• Patients are asymptomatic.
• It usually occurs in the third trimester and platelet levels are normal in the first trimester.
• Platelet levels normalise rapidly following delivery.
Gestational thrombocytopenia is distinguished from immune thrombocytopenic purpura based on the gestation at onset, the absence of symptoms, and normal platelet levels prior to pregnancy (89).
There are usually no adverse effects to the mother or fetus, and no intervention other than reassurance is required.
Immune thrombocytopenic purpura
This is caused by autoantibodies against platelet surface glycoproteins, which leads to platelet destruction by the reticuloendothelial system. The exact cause is unknown; the majority of cases are idiopathic but some cases could be secondary to chronic infections such as HIV or connective tissue disorders. The antibody is immunoglobulin G (IgG), and can therefore cross the placenta and cause fetal thrombocytopenia. Management of this condition in pregnancy is divided into a maternal care plan and a fetal care plan. Patients should be managed by obstetricians experienced in high-risk pregnancy with haematologist involvement (90).
Maternal care plan
• Platelet level should be checked every 4 weeks in the first and second trimester and more frequently in the third trimester to initiate treatment if required.
• Treatment should be initiated in the first trimester only if the platelet levels fall below 20 ? 109/L.
• Vaginal delivery is safe, and a caesarean section should only be performed for usual obstetric indications.
• A general guide is to maintain platelet levels above 20 ? 109/L for vaginal delivery, above 50 ? 109/ l for caesarean section, and above 80 ? 109/L for regional anaesthesia.
• Levels below 80 ? 109 in the third trimester generally require treatment to provide the patient the option of regional anaesthesia for delivery.
• Corticosteroids are the first-line treatment; different protocols exist but generally the dose is 1 mg/kg/day which will increase platelet levels in about 1-2 weeks. After 2 weeks of treatment, the dose can be reduced by 10-20% per week to the minimum dose effective at keeping platelet levels between 50 and 80 ? 109/L.
• Intravenous immunoglobulins (IVIGs) may be given as second line, and are reserved for women with platelet levels below 10 ? 109/L or women who do not respond to steroid therapy. They increase platelet count rapidly—within 6-72 hours—but the level is not sustained and falls rapidly within days returning to pretreatment levels within 4 weeks.
• Platelet transfusions are a last resort as they will increase antibody titres and they do not cause a sustained increase in platelet levels. They should be used as directed by a haematologist.
• Splenectomy can be performed if there is severe immune thrombocytopenic purpura and medical treatment has failed. If indicated, it should be performed in the first or second trimester, and women should subsequently be offered immunization against Haemophilus influenzae, pneumococcus, and meningococcus and given penicillin prophylaxis.
Fetal care plan
• Cord blood samples should be taken to measure platelet count.
• Bleeding complications are not as common as previously stated, and platelet levels rarely fall below 50 ? 109/L in neonates.
• The platelet level reaches its nadir between 2 and 5 days of life, so it is important to monitor neonates closely during this period.
• Treatment with IVIG is recommended if platelet levels are below 20 ? 109/L and a cranial ultrasound scan should be performed to rule out bleeding.
Thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome
The hallmarks of TTP and HUS are a microangiopathic haemolytic anaemia and thrombocytopenia. The incidence of both conditions is increased in pregnancy, and may be difficult to differentiate from each other and from other hypertensive disorders in pregnancy such as PET and HELLP syndrome.
Management
The absence of hypertension is the main differentiating factor between TTP/HUS and PET or HELLP syndrome. Making this distinction is imperative, as the ultimate treatment of hypertensive disorders of pregnancy is delivery; while in TTP and HUS delivery does not alter the course of the disease (91).
Treatment:
• Corticosteroids.
• Plasmapheresis and plasma exchange.
• Dialysis in patients with acute kidney injury.
• Neurological support for patients with seizures and further imaging to rule out other causes of seizures.
• The use of platelet transfusion is controversial; there have been some reports of deterioration and microthrombi formation with their use (92). However, a review did not demonstrate any evidence of complications from platelet transfusion (93). Current recommendations are that platelet transfusion should be reserved for the prevention or management of life-threatening haemorrhage.