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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 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

    • Thrombocytopenia in the presence of persistent antiphospholipid antibodies but not 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

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

    • 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

Laboratory Findings

  • Three types of antiphospholipid antibodies are associated with this syndrome:

    • 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 ...

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