Antiphospholipid Syndrome

KEY FEATURES

Essentials of Diagnosis

• Hypercoagulability, with recurrent thromboses in either the venous or arterial circulation

• Thrombocytopenia is common

• Recurrent or late fetal loss

• Because recurrent events are common and often serious, lifelong anticoagulation with warfarin is recommended

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 often attributed to APS include

  • Thrombocytopenia

  • Mental status changes

  • Livedo reticularis

  • Skin ulcers

  • Microangiopathic nephropathy

  • Cardiac valvular thickening or vegetations

• Pregnancy losses associated with APS include

  • Unexplained fetal death after 10 weeks' gestation

  • One or more premature births before 34 weeks because of eclampsia, preeclampsia, or placental insufficiency

  • Three or more unexplained miscarriages before 10 weeks' gestation

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

Laboratory Tests

• Three types of antiphospholipid antibodies are associated are identified in APS

  • IgG or 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 the lupus anticoagulant is a stronger risk factor for thrombosis or pregnancy loss than is the presence of antibodies to either β₂-glycoprotein 1 or anti-cardiolipin

    • For women < 50 years old with a thrombotic stroke, odds ratio for having lupus anticoagulant is 43.1

    • 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

    • Tests for the lupus anticoagulant use phospholipid-dependent functional assays of coagulation, such as the Russell viper venom time (RVVT)

    • The RVVT is prolonged in the ...