Anti-phospholipid syndrome

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Anti-phospholipid syndrome

• Clinton Mitchell
• 5th year Haematology

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Anti-phospholipid syndrome

• defined as a venous thromboembolic event or
  unexplained miscarriage, plus repeatably positive
  anticardiolipin antibodies and/or lupus
  anticoagulant that are repeatably positive at
  least 6 weeks later.
• Disorder due to the presence of auto-antibodies
  which bind proteins that act as co-factors for
  phospholipids
• Successful coagulation involves
  phospholipid-dependent coagulation factors
• ß2-glycoprotein is thought to be one of the
  targets for these antibodies

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Historical origins

• It was clear from the beginning that, while the
  syndrome was associated with classical lupus, it
  was separable from it. For a distinct syndrome
  it most certainly is it occurs in ANA-negative
  SLE patients, atypical lupus patients and, as
  expected, individuals with no lupus at all.
• Graham Hughes (early 1980s)

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Anti-phospholipid syndrome

• This quote would mark the origin of the primary
  anti-phospholipid syndrome
• APS can occur in patients without evidence of any
  definable associated disease (primary APS)
• It may also occur in association with SLE or
  another rheumatic or autoimmune disorder
  (secondary APS)

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• In APS, as noted may detect either
  anticardiolipin antibodies (ACA) or lupus
  anticoagulant (LAC) or both. Thought to be
  measuring same thing two different ways.
• Important to distinguish between the antibodies,
  detected as ACA or LAC, and the syndrome called
  Aps.

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Epidemiology

• Antibodies can be found in as many as 50 of
  individuals with SLE and in 1-5 of the healthy
  population
• Anti-cardiolipin antibodies tends to occur more
  frequently in elderly individuals
• Actual frequency in the general population is
  unknown

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Risk factors

• There is no defined racial predominance for
  primary APS
• higher incidence among Maori and Pacific
  populations of SLE may contribute to an increased
  risk
• Female predominance exists, particularly for
  secondary APS
• APS occurs more commonly in young to middle-aged
  adults
• Genetic predisposition (one study showed a 33
  incidence rate)

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Aetiology

• Autoimmune disorder of unknown cause
• Search for possible triggers has uncovered a wide
  array of associated rheumatic or autoimmune
  diseases
• SLE 25-50
• rheumatoid arthritis 33
• ITP 30
• Infections (especially syphilis)

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Pathophysiology

• An alteration of the homeostatic regulation of
  blood coagulation occurs
• Other mechanisms (which may or may not be
  dependent on ß2GP1) include
• activation of platelets to enhance endothelial
  adherence
• activation of vascular endothelium (facilitates
  the binding of platelets and monocytes)

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Pathophysiology

• Other auto-antibody processes are thought to
  include
• production of antibodies against other
  coagulation factors (prothrombin, protein C, and
  protein S)
• reaction of antibodies to LDL (predisposing to
  atherosclerosis and myocardial infarction)

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Clinical presentation

• Clinical features include arterial and venous
  thromboses, recurrent miscarriages and
  thrombocytopaenia
• 20 of strokes occurring lt45 years may be
  attributable to APS
• 27 of women with gt2 miscarriages have APS
• Other features include VHD cutaneous
  manifestations (livedo reticularis) chorea,
  migraine and epilepsy

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Livedo reticularis

• Completely blanchable reticulated areas of
  erythema which may be red or blue depending upon
  the rate of blood flow through these vessels. In
  this case deep or incomplete obstruction of
  vessels is leading to impaired flow through the
  dermis, but this flow is sufficient to maintain
  the vascular integrity.

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Investigations

• Anti-cardiolipin antibodies are diagnostic
• ANA are usually negative
• Haemolytic anaemia, thrombocytopaenia
• which is paradoxically associated with an
  increased risk of thrombosis
• Normal ESR
• Prolonged APTT
• Patients may have a false positive VDRL syphilis
  test

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Management

• Prevention
• avoid smoking
• avoid oral contraceptives and HRT
• avoid any prolonged immobilisation
• lose weight
• exercise

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Management

• Low dose aspirin can be used for mild cases and
  primary prevention
• Warfarin is used in more severe cases (aiming for
  an INR gt3)
• Anti-platelet agents have not been extensively
  studied
• Hydroxychloroquine should be considered in
  patients with SLE
• consider fractionated heparin in pregnancy

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Sequelae

• Sequelae are related primarily to the risk of
  thrombosis
• recurrent miscarriage (aPA decrease levels of
  annexin V, a protein with potent anticoagulant
  activity found in the placenta)
• CVA, MI, renal failure
• Pulmonary HTN

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Prognosis

• Most individuals with primary APS lead normal
  healthy lives with appropriate medication and
  lifestyle modifications
• However, subsets of patients continue to have
  thrombotic events despite aggressive therapies
• Secondary APS carries a similar prognosis
• morbidity and mortality influenced by underlying
  autoimmune or rheumatic condition