Antiphospholipid Syndrome

Reviewed and revised 14 September 2016 by Luke Collett and Chris Nickson

OVERVIEW

  • antiphospholipid syndrome (APS) is diagnosed by the occurrence of thrombosis or pregnancy morbidity in combination with detectable antibodies
  • APS is caused by a heterogeneous group of auto-antibodies directed against phospholipid binding proteins
  • Two main categories of antibodies:

(1) antibodies that prolong phospholipid dependent coagulation assays (lupus anticoagulants – LA) or
(2) antibodies that target cardiolipin (aCL) and/or β2-glycoprotein-I (anti-β2GPI)

  • APS can be primary (no associated disease) or secondary (e.g. occurring with another condition like SLE)

DIAGNOSTIC CRITERIA

Sapporo criteria — requires 1 clinical and 1 laboratory criterion:

Clinical

  • confirmed thrombosis (arterial, venous, or small vessel)
  • pregnancy morbidity (recurrent fetal loss before 10/40, unexplained fetal death at or beyond 10/40, premature birth from placental insufficiency, pre/eclampsia)

Laboratory (on 2 or more occasions at least 12 weeks apart)

  • direct (ELISA) — medium or high titre IgG or IgM antibodies against cardiolipin (aCL) or β2-glycoprotein-I (anti-β2GPI)
  • indirect — presence of antiphospholipid antibodies using at least 2 phospholipid dependent assays

LUPUS ANTI-COAGULANTS

  • antibodies that block phospholipids surfaces important for coagulation
  • increase APTT
  • prolonged APTT does not correct with a 1:1 mix of normal platelet-free plasma
  • correction of clotting time after addition of excess phospholipids confirms the presence of LA

-> result in acquired hypercoagulability due to poorly understood actions ? alteration of the regulation of haemostasis and endothelial cell injury

  • consensus guidelines recommend screening for LA with 2 or more phospholipid dependent coagulation tests:

(1) APTT
(2) dilute Russell viper venom time
(3) silica clotting time
(4) kaolin clotting time
(5) dilute PT
(6) textarin time
(7) taipan time

MANAGEMENT OF ANTIPHOSPHOLIPID SYNDROME

Asymptomatic

  • either no treatment or low dose aspirin

Thrombosis

  • warfarin (INR 2-3)
  • aspirin
  • LMWH
  • UFH
  • warfarin + aspirin
  • warfarin with higher INR target

Pregnancy

  • LMWH
  • UFH
  • aspirin

CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME

Overview

  • Subset of antiphospholipid syndrome (<1%)
  • distinguished by, severity, acute onset and multi-organ involvement
  • widespread small-vessel thrombosis results in multi-organ failure

Diagnosis

  • History of antiphospholipid syndrome and/or antiphospholipid antibodies
  • 3 or more organs/ tissues involved
  • Acute onset (< 1 week)
  • Biopsy confirming small vessel occlusion
  • Exclusion of other causes
    • DIC
    • Thrombotic microangiopathies eg TTP
    • HITTS
  • Trigger: infection, surgery, trauma, decrease in anticoagulation, medications, malignancy

Affected sites

  • Kidneys (~70%): AKI, malignant hypertension
  • Lungs: alveolar haemorrhage secondary to thrombosis
  • CNS: strokes
  • Heart
  • Skin
  • Arterial and venous thromboses

Treatment and

  • Combination treatment with steroids (methylprednisolone 1g/day), anticoagulation, plasma exchange (5 days), followed by IVIG
  • rituximab for refractory cases

Outcome

  • Mortality 30 – 50%
  • Low rate of recurrence

References and Links

LITFL

Journal articles

  • Westney GE, Harris EN. Catastrophic antiphospholipid syndrome in the intensive care unit. Critical care clinics. 18(4):805-17. 2002. [pubmed]

FOAM and web resources


CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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