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Antiphospholipid Syndrome Clinical Presentation

  • Author: Suneel Movva, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Jul 01, 2016
 

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
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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)
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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).
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Contributor Information and Disclosures
Author

Suneel Movva, MD Fellow in Rheumatology, Division of Rheumatology, Allergy and Immunology, Winthrop University Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Steven Carsons, MD Chief, Division of Rheumatology, Allergy and Immunology, Winthrop University Hospital; Professor of Medicine, Stony Brook University School of Medicine

Steven Carsons, MD is a member of the following medical societies: American College of Rheumatology, New York Academy of Sciences, Society for Experimental Biology and Medicine

Disclosure: Nothing to disclose.

Elise Belilos, MD Section Head of Rheumatology, Division of Rheumatology, Allergy and Immunology, Winthrop University Hospital; Assistant Professor of Clinical Medicine, Department of Internal Medicine, Stony Brook University School of Medicine

Elise Belilos, MD is a member of the following medical societies: American College of Rheumatology, Arthritis Foundation

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Lawrence H Brent, MD Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Janssen<br/>Serve(d) as a speaker or a member of a speakers bureau for: Abbvie; Genentech; Pfizer; Questcor.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Carlos J Lozada, MD Director of Rheumatology Fellowship Training Program, Professor of Clinical Medicine, Department of Medicine, Division of Rheumatology and Immunology, University of Miami, Leonard M Miller School of Medicine

Carlos J Lozada, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Received honoraria from Pfizer for consulting; Received grant/research funds from AbbVie for other; Received honoraria from Heel for consulting.

Acknowledgements

The authors gratefully acknowledge the contributions of Amiel Tokayer, MD.

References
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Antiphospholipid syndrome. Livedo reticularis.
Antiphospholipid syndrome. Arterial thrombosis resulting in ischemia and necrosis of the foot.
 
 
 
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