Antiphospholipid syndrome (APS) is an autoimmune disease associated with increased risk of thrombosis due to the presence of procoagulatory antibodies. APS can manifest in isolation or alongside other autoimmune diseases such as systemic lupus erythematosus (SLE). Typical clinical manifestations include recurring venous, arterial, and/or microcirculation thrombotic events (e.g., DVTs, stroke, TIAs) and obstetrical complications (e.g., recurrent miscarriages, premature births). APS should be suspected in patients with a history of thrombosis or miscarriage; diagnosis is confirmed by the detection of serum antiphospholipid antibodies (e.g., lupus anticoagulant, anticardiolipin antibodies). Management of acute thrombotic events varies widely depending on the clinical manifestation (e.g., stroke, DVT). Long-term management of APS (e.g., systemic anticoagulation with warfarin or heparin) is determined by the patient's risk of future thrombotic complications. Additional pharmacotherapy may be indicated for certain manifestations. Catastrophic antiphospholipid syndrome (CAPS) is a rare but severe form of APS that requires immediate treatment.
- Formation of procoagulatory antiphospholipid antibodies
- Induction of a hypercoagulable state → ↑ risk of thrombosis and embolism 
- Capillaries: splinter hemorrhages
- Pregnancy-related: : recurrent miscarriages and premature births
- Nonthrombotic manifestations: may include valvular heart disease, neurocognitive disorders
- Consider diagnostic testing based on the presence of typical symptoms, e.g.:
- Obtain antiphospholipid antibody testing to confirm diagnosis.
- Consider testing for associated autoimmune diseases (e.g., SLE), neoplasms, and infectious diseases.
- Involve rheumatology early.
Thrombosis in APS is typically unprovoked (e.g., ), recurrent, and/or manifests in unusual sites (e.g., kidneys, liver, retina). It is most commonly seen in younger individuals (< 50 years of age) and in individuals with comorbid autoimmune diseases (e.g., SLE).
Routine laboratory studies 
Obtain for all patients; results are nonspecific but may support the diagnosis.
- CMP: may reveal and/or nephropathy
- Coagulation panel: prolonged aPTT (caused by lupus anticoagulant)
- Urinalysis: may show proteinuria, e.g., in patients with thrombotic microangiopathy
Antiphospholipid antibodies (aPL antibodies) 
Reserve testing for patients with characteristic clinical features to avoid false positives.
Lupus anticoagulant (LA): antibodies against certain phospholipids in cellular membranes; detection involves a three-step procedure
- Screening for phospholipid-dependent coagulation with either:
- Mixing study: The patient's plasma is mixed with normal plasma (which contains clotting factors).
- Confirmation of phospholipid dependence: Phospholipid is added.
- Anticardiolipin antibodies (IgG and IgM): antibodies against cardiolipin, a phospholipid in cellular membranes
- Anti-β2-glycoprotein antibodies (IgG and IgM): antibodies directed against the cardiolipin binding factor β2 glycoprotein I that have prothrombotic effects 
- Symptomatic patients: The presence of ≥ 1 type of aPL antibody supports the diagnosis.
- Asymptomatic patients
Additional studies 
- Nonclassic aPL antibodies: may further support the diagnosis
- Imaging studies
- Histopathology: may be needed to confirm thrombosis 
Management should be specialist-guided.
- Treat acute thrombotic events (e.g., DVT, MI). 
- Provide urgent management for CAPS in acutely ill patients with multiorgan failure due to thrombosis.
- Initiate long-term thromboprophylaxis.
- Provide supportive care.
- Consider for patients with no history of thrombosis who have:
- Recommended regimen: low-dose aspirin therapy
- Indication: APS with a history of thrombosis
- First-line: warfarin
- Treatment duration
Antiphospholipid antibodies can prolong the aPTT and consequently provide falsely elevated INR results, which may lead to inadequate anticoagulation. Consider measurement of factor X activity to confirm adequate anticoagulation. 
Thromboprophylaxis for APS during pregnancy 
- Patients without an APS diagnosis with positive aPL antibodies (with or without SLE): Consider low-dose aspirin therapy.
- Patients with an APS diagnosis
- Low-dose aspirin therapy PLUS heparin (LMWH or UFH)
- Patients require close monitoring and management by a team of specialists to reduce the risk of miscarriage and thrombosis.
Supportive care 
- Management of additional risk factors for thrombosis
- Patient counseling (e.g., about VKA treatment, contraceptives, hormone therapy)
- (e.g., healthy diet, physical activity)
- Management of complications (e.g., thrombocytopenia, nephropathy)
Management of catastrophic antiphospholipid syndrome 
- Suspect in acutely ill patients with thrombosis. due to
- Consider other .
- Diagnosis of CAPS is based on:
- Simultaneous involvement of ≥ 3 organs, systems, or tissues
- Confirmation of positive aPL antibodies
- Start treatment as soon as CAPS is suspected; do not wait for laboratory confirmation.
- Treatment is not standardized but may include the following: 
Diagnosis of CAPS is difficult because clinical presentation varies widely and approximately 50% of affected individuals have no history of positivity.