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

• LITFL CCC — Lupus anticoagulants
• ICU Mind Maps — Antiphospholipid Syndrome (includes a useful management flowchart)
• Pulmonary Puzzler 002 — Not just a pulmonary embolism…

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

• PracticalHaemostasis.com — Antiphospholipid antibodies: introduction