What is antiphospholipid syndrome ?
Antiphospholipid syndrome (APS) is an autoimmune disorder that can cause pregnancy complications. It is a diagnosis based on the presence of specific antibodies in laboratory testing and a history of blood clots and/or certain pregnancy complications. Antiphospholipid antibodies include:
- Lupus anticoagulant (LAC)
- Anticardiolipin
- Anti-β 2-glycoprotein I
Patients typically have one or more of these antibodies transiently present. A diagnosis of APS requires that 2 of these antibodies be present or elevated on two different lab draws at least 12 weeks apart. Laboratory criteria include:
- Testing for LAC is reported as either positive or negative.
- Anticardiolipin IgG or IgM must be of medium or high titer. This means IgG or IgM must be >40 GPL or MPL or >99%.
- Anti-β 2-glycoprotein I IgG or IgM must be of medium or high titer or >99%.
When should someone be tested for APS?
Vascular thrombosis
- One or more clinical episodes of arterial, venous, or small vessel thrombosis, in any tissue or organ
OR
Pregnancy complications
- One or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation, with normal fetal morphology documented by ultrasound or by direct examination of the fetus
OR
- One or more premature births of a morphologically normal neonate before the 34th week of gestation because of eclampsia or severe pre-eclampsia, or features consistent with placental insufficiency
OR
- Three or more unexplained consecutive spontaneous pregnancy losses before the 10th week of pregnancy, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded.
When should testing for APS NOT be done?
A history of or current diagnosis of preterm severe preeclampsia and/or early onset placental insufficiency is not a reason to test for APS as there is insufficient evidence to support that screening for and treatment of patients with APS improves subsequent pregnancy outcomes. Patients with a diagnosis of hemolytic anemia, autoimmune thrombocytopenia, amaurosis fugax, livedo reticularis, systemic lupus erythematosus, and who have a false-positive rapid plasma reagin result should not be tested for APS as these conditions are clinical criteria for APS.
Arterial or venous thrombosis (blood clot)
Blood clots are the most common and serious complication of APS. Venous blood clots account for 65–70% of blood clots with the most common site being a lower extremity. Arterial blood clots are less common and can occur in atypical sites like the retinal, subclavian, digital, or brachial arteries. The risk of thrombosis is significantly increased in pregnancy with a 5–12% risk of thrombosis during pregnancy or the period of time right before or after childbirth.
Complications of APS in pregnancy
Pregnancy loss
APS can cause recurrent pregnancy loss at <10 weeks of pregnancy during the embryonic period or >10 weeks of pregnancy during the fetal period. Most losses due to APS occur during the fetal period. APS can also cause recurrent pregnancy loss (RPL), which is defined by two or more failed clinical pregnancies documented by ultrasound or histopathology. Overall, < 5% of patients will experience two consecutive miscarriages, and 1% experience three or more, making it a relatively rare condition in pregnancy.
Preeclampsia and Fetal Growth Restriction
APS is most strongly associated with severe preeclampsia occurring at < 34 weeks of pregnancy, but overall, 11–17% of patients with preeclampsia will test + for antiphospholipid antibodies. APS is also associated with hypertensive disorders of pregnancy and fetal growth restriction (FGR).
Other complications of APS
Autoimmune thrombocytopenia (low platelets)
- Occurs in 40–50% of individuals with APS.
- Treated the same as thrombocytopenia caused by Idiopathic Thromboctopenia (ITP).
Catastrophic APS
- Progressive thromboses and multiorgan failure.
- Severe illness can occur in the postpartum period and consists of cardiopulmonary failure, fever, as well as renal insufficiency, and multiple thromboses.
Other
- Autoimmune hemolytic anemia
- Livedo reticularis
- Cutaneous ulcers
- Chorea gravidarum
- Multi-infarct dementia
How are pregnancy and the postpartum period managed if there is a diagnosis of APS?
The management of pregnancy and the postpartum period will be affected if APS was diagnosed based on vascular blood clot(s) and laboratory testing. If there is a history of a blood clot, prophylactic anticoagulation with heparin throughout pregnancy and 6 weeks postpartum is indicated. If there is no history of a blood clot, the best treatment has not been determined. Prophylactic heparin anticoagulation use during pregnancy and 6 weeks of postpartum may be considered. If there is a history of pregnancy loss at >10 weeks, stillbirth at >20 weeks or any type of RPL, prophylactic doses of heparin and low dose aspirin during pregnancy and 6 weeks PP should be considered.
Antepartum fetal surveillance should be considered due to the potential risk of FGR and stillbirth in pregnancies with APS. This may include serial fetal growth ultrasounds, biophysical profiles, or nonstress testing.
ACOG Summary of Recommendations and Conclusions
The following recommendations are based on limited or inconsistent scientific evidence (Level B):
- Obstetric indications for antiphospholipid antibody testing should be limited to a history of one fetal loss or three or more recurrent embryonic or fetal losses.
- Testing for antiphospholipid antibodies should be performed in patients with a prior unexplained venous thromboembolism, a new venous thromboembolism during pregnancy, or in those with a history of venous thromboembolism but not tested previously.
- In patients with APS and a history of stillbirth or recurrent fetal loss but no prior thrombotic history, prophylactic doses of heparin and low-dose aspirin during pregnancy and 6 weeks of postpartum should be considered.
The following recommendations are based primarily on consensus and expert opinion (Level C):
- For patients with APS who have had a thrombotic event, most experts recommend prophylactic anticoagulation with heparin throughout pregnancy and 6 weeks postpartum.
- For patients with APS who have not had a thrombotic event, expert consensus suggests that clinical surveillance or prophylactic heparin use antepartum in addition to 6 weeks of postpartum anticoagulation may be warranted.
- For long-term management postpartum, patients with APS should be referred to a physician with expertise in treatment of the syndrome, such as an internist, hematologist, or rheumatologist.
- Patients with APS should not use estrogen-containing contraceptives.
Resources
ASRM Committee Opinion on the Evaluation and Treatment of Recurrent Pregnancy Loss