Antiphospholipid Syndrome

KEY FEATURES

Essentials of Diagnosis

• Hypercoagulability; recurrent arterial or venous thromboses

• Thrombocytopenia is common

• Recurrent or late fetal loss

• Anticoagulation with warfarin is recommended over direct-acting oral anticoagulants (DOACs)

General Considerations

• Antiphospholipid syndrome (APS) can occur alone or in association with other autoimmune diseases (eg, systemic lupus erythematosus [SLE])

• The clinical features of APS are

  • Venous or arterial occlusions

  • Pregnancy complications

• Catastrophic APS

  • Occurs in < 1% of patients with antiphospholipid antibodies

  • Leads to diffuse thromboses, thrombotic microangiopathy, and multiorgan system failure

CLINICAL FINDINGS

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 symptoms and signs of APS include

  • Thrombocytopenia

  • Mental status changes

  • Livedo reticularis

  • Skin ulcers

  • Microangiopathic nephropathy

  • Pulmonary hemorrhage

  • Cardiac valvular thickening or vegetations

• Obstetric manifestations include

  • ≥ 3 consecutive pregnancy losses before 16 weeks’ gestation

  • Fetal deaths between 16 and 33 weeks’ gestation in the absence of pre-eclampsia or placental insufficiency or

  • Severe pre-eclampsia or placental insufficiency occurring before 34 weeks with or without fetal death

Differential Diagnosis

• Other genetic or acquired conditions associated with hypercoagulability must be excluded including

  • Activated protein C resistance/factor V Leiden

  • Protein C deficiency

  • Protein S deficiency

  • Antithrombin deficiency

  • Myeloproliferative cancers

  • Heparin-induced thrombocytopenia

  • Paroxysmal nocturnal hemoglobinuria

• Catastrophic APS has a broad differential diagnosis, including

  • Sepsis

  • Pulmonary-renal syndromes

  • Systemic vasculitis

  • Disseminated intravascular coagulation

  • Thrombotic thrombocytopenic purpura

DIAGNOSIS

• The American College of Rheumatology and the European League Against Rheumatism classify APS by assigning scores to assay test results and clinical findings

  • Positive antiphospholipid antibody test (lupus anti-coagulant, moderate-to-high titers of anti-cardiolipin or anti- β2-glycoprotein-I antibodies) within three years of clinical criteria weighted by presence, absence, or severity of

    • Venous embolism or venous or arterial thrombosis

    • Microvascular conditions, such as livedo racemosa, livedoid vasculopathy, aPL nephropathy, pulmonary or adrenal hemorrhage

    • Obstetric complications, such as fetal death or preeclampsia with severe features

    • Cardiac valve thickening or vegetations or

    • Thrombocytopenia

Laboratory Tests

• Patients have at least one of the following three antiphospholipid antibodies

  • Immunoglobulin G (IgG) or immunoglobulin M (IgM) anti-cardiolipin antibodies

    • IgG anti-cardiolipin antibodies likely more pathologic than IgM

    • Can produce a biologic false-positive test for syphilis (ie, a positive rapid plasma reagin but negative specific anti-treponemal assay)

  • IgG or IgM antibodies to β₂-glycoprotein 1

  • A "lupus anticoagulant" that prolongs the partial thromboplastin time test in vitro

    • Presence of ...