Antiphospholipid syndrome

Background

• APS definition (need 1 from each category):
  • Presence of at least 1 of the following: DVT, arterial thrombosis, or pregnancy morbidity (eg fetal loss, preterm)
  • Presence of at least 1 of the following antiphospholipid antibodies (aPL): lupus anticoagulant (LA), anticardiolipin (aCL), β2-glycoprotein-1 (β2-GP-1)

• APS can occur as a primary condition or in setting of underlying disease (eg SLE)
• Lifelong anticoagulation with warfarin, with the following target INRs
  • 2.0-3.0 for venous
  • 3.0 for arterial
  • 3.0-4.0 recurrent thrombosis
  • ASA plus warfarin for severe/refractory cases

Pathophysiology

• Currently accepted theory: Susceptible patients (eg SLE) develop aPL after infection. After development of aPL, “second hit” stress required to develop full-blown APS. aPL affects coagulation by interacting with protein C, annexin V, platelets, proteases, tissue factor, and impairing fibrinolysis
  • “Second hit” stressors: smoking, prolonged immobilization, pregnancy, exogenous estrogen, malignancy, nephrotic syndrome, hypertension, hyperlipidemia

Clinical Features

• Thrombocytopenia, increased PT/INR and aPTT
• Microangiopathic Hemolytic Anemia (MAHA)
• DVT/PE
• Fetal loss
• Heart valve disease
• aPL-nephropathy
• Stroke/TIA, other neuro symptoms
• Livedo reticularis

Differential Diagnosis

Microangiopathic Hemolytic Anemia (MAHA)

• Disseminated Intravascular Coagulation (DIC)
• Thrombotic Thrombocytopenic Purpura (TTP)
• Hemolytic Uremic Syndrome (HUS)
• HELLP syndrome
• Heparin-Induced Thrombocytopenia (HIT)
• Hereditary spherocytosis
• Paroxysmal nocturnal hemoglobinuria (PNH)
• Malignant hypertension
• Scleroderma
• Antiphospholipid Syndrome (APS)
• Other medical causes: malignancy, renal allograft rejection, vasculitides like polyarteritis nodosa and Wegener's granulomatosis
• Drugs: chemotherapy; Clopidogrel (Plavix) associated with TTP
• Nonvascular causes: prosthetic valve (more common with mechanical, more common at aortic valve), LVAD, TIPS, coil embolization, patched AV shunt, AVM

Management

• Anticoagulation (unfractionated heparin, LMWH, or warfarin)
  • No benefit in treatment or prophylaxis using ASA or plavix
  • Add hydroxychloroquine if patient has SLE
  • Warfarin contraindicated in pregnancy!
  • DOACs (such as rivaroxaban, apixaban, and dabigatran) have not been shown to be effective in APS
• IVIG, plasmapheresis, and steroids have not been proven to be of benefit in APS

Catastrophic APS Treatment

• Treat stress that precipitated catastrophic APS (eg infection), anticoagulation, high dose steroids
  • If evidence of microangiopathy (thrombocytopenia, MAHA), add IVIG and plasma exchange to above regimen

Disposition

• Acute complications, admission with hematology consult

Complications

• Catastrophic APS: widespread thrombotic disease with multiorgan failure precipitated by some stress (eg infection)