Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 19-18 Antiphospholipid Syndrome in Pregnancy For further information, see CMDT Part 20-09: Antiphospholipid Syndrome + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Hypercoagulability, with recurrent thromboses in either the venous or arterial circulation Thrombocytopenia is common Recurrent fetal loss Because recurrent events are common and often serious, lifelong anticoagulation with warfarin is recommended for patients with antiphospholipid syndrome (APS) +++ General Considerations ++ Primary APS is diagnosed in patients who have Venous or arterial occlusions Pregnancy complications 3 or more first trimester miscarriages Unexplained fetal death and premature birth before 34 weeks of gestation attributable to severe preeclampsia, eclampsia, or placental insufficiency Diagnostic antiphospholipid antibodies but no other features of systemic lupus erythematosus (SLE) Catastrophic APS Occurs in < 1% of patients with antiphospholipid antibodies Leads to diffuse thromboses, thrombotic microangiopathy, and multiorgan system failure + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Often asymptomatic until a thrombotic event or a pregnancy loss occurs Thrombotic events may occur in either the arterial or venous circulations and include Deep venous thromboses Pulmonary emboli Cerebrovascular accidents Budd-Chiari syndrome Cerebral sinus vein thrombosis Myocardial infarction Digital infarction Hemorrhagic infarction of the adrenal glands (due to adrenal vein thrombosis) Other thrombotic events Other symptoms and signs often attributed to the APS include Mental status changes Livedo reticularis Skin ulcers Microangiopathic nephropathy Cardiac valvular thickening or vegetations Pregnancy losses associated with APS include Three or more unexplained consecutive spontaneous abortions prior to 10 weeks' gestation One or more unexplained deaths of a morphologically normal fetus after 10 weeks' gestation Preterm delivery at less than 34 weeks' gestation due to preeclampsia or placental insufficiency +++ Differential Diagnosis ++ Exclusion of SLE and other autoimmune disorders is essential because these disorders may be associated with additional complications requiring alternative treatments Other genetic or acquired conditions associated with hypercoagulability must be excluded including Activated protein C resistance/Factor V Protein C deficiency Protein S deficiency Antithrombin deficiency Hyperprothrombinemia (prothrombin gene G20210A mutation) Increased Factor VIII activity Hyperhomocysteinemia Catastrophic APS has a broad differential diagnosis, including Sepsis Pulmonary-renal syndromes Systemic vasculitis Disseminated intravascular coagulation Thrombotic thrombocytopenic purpura + Diagnosis Download Section PDF Listen +++ +++ Laboratory Findings ++ Laboratory criteria include the identification of at least one of the following three antiphospholipid antibodies Anti-cardiolipin antibodies Anti-cardiolipin IgG or IgM antibodies are typically measured with enzyme immunoassays A "lupus anticoagulant" that prolongs the partial thromboplastin time test in vitro Although the lupus anticoagulant is detected by a prolongation of the partial thromboplastin time in vitro, paradoxically it is associated with a thrombotic tendency rather than a bleeding risk The Russell viper venom time (RVVT) is more sensitive test for the lupus anticoagulant The RVVT is prolonged in the presence of the lupus anticoagulant It does not correct with mixing studies but does with the addition of excess phospholipid An antibody causing a "biologic false-positive test" for syphilis In the "biologic false positive" variant of the antiphospholipid antibody, the rapid plasma reagin (RPR) is (falsely) positive, but specific anti-treponemal assays are negative In pregnancy At least one of the following antiphospholipid antibodies is detectable Lupus anticoagulant Anticardiolipin antibodies Anti-beta-2-glycoprotein 1 antibodies The diagnosis of APS requires two positive antiphospholipid antibody test results at least 12 weeks apart since transient positive results can occur + Treatment Download Section PDF Listen +++ ++ Treat nonpregnant patients with APS with warfarin to maintain an INR of 2.0–3.0 Patients who have recurrent thrombotic events at this level of anticoagulation may require higher doses of warfarin aiming for INRs > 3.0, but bleeding risk increases substantially Patients with APS should receive lifelong anticoagulation therapy Treatment of APS in pregnancy Warfarin is teratogenic and is not used Optimal treatment is unclear but generally involves administration of a heparin compound (unfractionated or low-molecular-weight heparin [LMWH]) in prophylactic amounts (5000–10,000 units subcutaneously twice per day for the former) and low-dose aspirin (81 mg) Although anticoagulation is particularly prudent in women with a history of thrombosis, there is also evidence that this management reduces the risk for spontaneous abortion in women with recurrent pregnancy loss from APS Treatment is typically continued through pregnancy and the early postpartum period for thromboprophylaxis, although it is unclear whether this approach decreases the risk of stillbirth or placental dysfunction LMWH is also commonly used for this indication (30–40 mg subcutaneously once per day); however, it is not clear that LMWH has the same effect on reducing the risk of recurrent abortion as unfractionated heparin The use of corticosteroids and intravenous immunoglobulin are of unclear benefit in these patients, and neither treatment is recommended In patients with catastrophic APS, a three-pronged approach is taken in the acute setting: Intravenous heparin High doses of corticosteroids Either intravenous immune globulin or plasmapheresis + References Download Section PDF Listen +++ + +Dufrost V et al. Increased risk of thrombosis in antiphospholipid syndrome patients treated with direct oral anticoagulants. Results from an international patient-level data meta-analysis. Autoimmun Rev. 2018 Oct;17(10):1011–21. [PubMed: 30103045] + +Sciascia S et al. Diagnosing antiphospholipid syndrome: 'extra-criteria' manifestations and technical advances. Nat Rev Rheumatol. 2017 Sep;13(9):548–60. [PubMed: 28769114] + +Tektonidou MG et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019 Oct;78(10):1296–304. [PubMed: 31092409] + +Unlu O et al. Catastrophic antiphospholipid syndrome: candidate therapies for a potentially lethal disease. Annu Rev Med. 2017 Jan 14;68:287–96. [PubMed: 28099080]