Antiphospholipid Syndrome Clinical Presentation

Updated: Sep 27, 2017
  • Author: Suneel Movva, MD; Chief Editor: Herbert S Diamond, MD  more...
  • Print
Presentation

History

Antiphospholipid syndrome (APS) is a heterogenous disorder in terms of clinical manifestations and range of autoantibodies. In 2006, revised criteria for the diagnosis of APS were published in an international consensus statement. [10] At least one clinical criterion and one laboratory criterion (discussed further in Lab Studies) must be present for a patient to be classified as having APS.

The clinical criteria consist of vascular thrombosis and pregnancy morbidity. Vascular thrombosis is defined as one or more clinical episodes of arterial, venous, or small-vessel thrombosis in any tissue or organ confirmed by findings from imaging studies, Doppler studies, or histopathology (see Histologic Findings).

Thrombosis may involve the cerebral vascular system, coronary arteries, pulmonary system (emboli or thromboses), arterial or venous system in the extremities, hepatic veins, renal veins, ocular arteries or veins, or adrenal glands. Investigation is warranted if a history of deep venous thrombosis (DVT, pulmonary embolism (PE), acute ischemia, myocardial infarction (MI), or stroke (especially when recurrent) is present in a younger individual (males < 55 y; females < 65 y) or in the absence of other risk factors.

Pregnancy morbidity is defined as the following:

  • One or more late-term (>10 weeks' gestation) spontaneous abortions
  • One or more premature births of a morphologically healthy neonate at or before 34 weeks’ gestation because of severe preeclampsia or eclampsia or severe placental insufficiency
  • Three or more unexplained, consecutive, spontaneous abortions before 10 weeks’ gestation

Laboratory criteria include any of the following (see also Lab Studies):

  • Medium to high levels of immunoglobulin G (IgG) or immunoglobulin M (IgM) anticardiolipin (aCL) Anti–beta-2 glycoprotein I
  • Lupus anticoagulant on at least two occasions at least 12 weeks apart

Testing for novel antibodies not recognized in the 2006 criteria can be considered if clinical suspicion is high, although in select cases they may not be commercially available.

Other antiphospholipid (aPL)–associated clinical features recognized by the 2006 consensus statement but not included in the criteria include cardiac valve disease, livedo reticularis, thrombocytopenia, nephropathy, and neurologic manifestations.

Thus, history of any of the following should raise the examiner's suspicion for APS:

  • Thrombosis (eg, DVT/PE, MI, transient ischemic attack [TIA], or stroke, especially if recurrent, at an earlier age, or in the absence of other known risk factors)
  • Miscarriage (especially late trimester or recurrent) or premature birth
  • History of heart murmur or cardiac valvular vegetations
  • History of hematologic abnormalities, such as thrombocytopenia or hemolytic anemia
  • History of nephropathy
  • Nonthrombotic neurologic symptoms, such as migraine headaches, chorea, seizures, transverse myelitis, Guillain-Barré syndrome, or dementia (rare)
  • Unexplained adrenal insufficiency
  • Avascular necrosis of bone in the absence of other risk factors
  • Pulmonary hypertension
Next:

Physical

Cutaneous manifestations include the following:

  • Livedo reticularis (see image below)
    Antiphospholipid syndrome. Livedo reticularis. Antiphospholipid syndrome. Livedo reticularis.
  • Superficial thrombophlebitis
  • Leg ulcers
  • Painful purpura
  • Splinter hemorrhages

Venous thrombosis–related findings include the following:

  • Leg swelling (DVT)
  • Tachypnea (pulmonary embolism)
  • Peripheral edema (renal vein thrombosis)
  • Abnormal funduscopic examination results (retinal vein thrombosis)

Arterial thrombosis–related findings include the following:

  • Abnormal neurologic examination results (eg, stroke)
  • Digital ulcers
  • Gangrene of distal extremities (see image below)
    Antiphospholipid syndrome. Arterial thrombosis res Antiphospholipid syndrome. Arterial thrombosis resulting in ischemia and necrosis of the foot.
  • Signs of myocardial infarction
  • Heart murmur (frequently aortic) or mitral insufficiency ( Libman-Sacks endocarditis)
  • Abnormal funduscopic examination results (retinal artery occlusion)
Previous
Next:

Causes

APS is an autoimmune disorder of unknown cause. The search for possible triggers has uncovered a wide array of associated autoimmune or rheumatic diseases, infections, and drugs that are associated with the LA or aCL antibodies. These associations may ultimately provide a clue to the etiology of APS. A considerable percentage of persons with certain autoimmune or rheumatic diseases also have aPL antibodies.

Common autoimmune or rheumatic diseases and the percentage of affected patients with aPL antibodies are as follows (note that these represent percentages of patients with aPL antibodies, rather than the clinical syndrome of APS [11] ):

  • SLE - 25-50%
  • Sjögren syndrome - 42%
  • Rheumatoid arthritis - 33%
  • Autoimmune thrombocytopenic purpura - 30%
  • Autoimmune hemolytic anemia - Unknown
  • Psoriatic arthritis - 28%
  • Systemic sclerosis - 25%
  • Mixed connective-tissue disease - 22%
  • Polymyalgia rheumatica or giant cell arteritis - 20%
  • Behçet syndrome - 20%
  • Infections
  • Syphilis
  • Hepatitis C infection
  • HIV infection
  • Human T-cell lymphotrophic virus type 1 infection
  • Malaria
  • Bacterial septicemia
  • Drugs
  • Cardiac - Procainamide, quinidine, propranolol, hydralazine
  • Neuroleptic or psychiatric - Phenytoin, chlorpromazine
  • Other - Interferon alfa, quinine, amoxicillin
  • Genetic predisposition
  • Familial association: Relatives of persons with known APS are more likely to have aPL antibodies. One study showed a 33% frequency.
  • HLA associations: An association has been found between aCL antibody and groups of individuals who carry certain HLA genes, including DRw53, DR7 (mostly people of Hispanic origin), and DR4 (mostly whites).
Previous