Antiphospholipid Syndrome

Key Features

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

General Considerations

• The clinical features of primary antiphospholipid syndrome (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 thrombotic events

• Other symptoms and signs often attributed to the APS include

  • Mental status changes

  • Livedo reticularis

  • Skin ulcers

  • Microangiopathic nephropathy

  • Cardiac valvular dysfunction—typically mitral regurgitation—due to Libman-Sacks endocarditis

• 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

• Exclusion of other autoimmune disorders, particularly those in the SLE spectrum, is essential because such disorders may be associated with manifestations 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

Laboratory Findings

• Three types of antiphospholipid antibodies are associated with the APS

  • Anti-cardiolipin antibodies

    • IgG anti-cardiolipin antibodies are believed to be more pathologic than IgM

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

  • Antibodies to β₂-glycoprotein

  • 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 anticardiolipin

    • 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 ...