Antiphospholipid Syndrome Clinical Presentation

  • Author: Elise Belilos, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Jan 19, 2012
 

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.[6] 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 are as follows:
    • Vascular thrombosis
      • 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 DVT, PE, acute ischemia, MI, or CVA (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
      • 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: Patients must have (1) medium to high levels of immunoglobulin G (IgG) or immunoglobulin M (IgM) anticardiolipin (aCL), (2) anti–beta-2 glycoprotein I, or (3) LA on at least 2 occasions at least 12 weeks apart. (See also Lab Studies.)

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 CVA, 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
    • Livedo reticularis (see image below)Antiphospholipid syndrome. Livedo reticularis. Antiphospholipid syndrome. Livedo reticularis.
    • Superficial thrombophlebitis
    • Leg ulcers
    • Painful purpura
    • Splinter hemorrhages
  • Venous thrombosis
    • Leg swelling (DVT)
    • Ascites (Budd-Chiari syndrome)
    • Tachypnea (PE)
    • Peripheral edema (renal vein thrombosis)
    • Abnormal funduscopic examination results (retinal vein thrombosis)
  • Arterial thrombosis
    • Abnormal neurologic examination results (eg, CVA)
    • Digital ulcers
    • Gangrene of distal extremities (see image below)Antiphospholipid syndrome. Arterial thrombosis resAntiphospholipid syndrome. Arterial thrombosis resulting in ischemia and necrosis of the foot.
    • Signs of MI
    • 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. Note that these represent percentages of patients with aPL antibodies, rather than the clinical syndrome of APS.[7]

  • Common autoimmune or rheumatic diseases and the percentage of affected patients with aPL antibodies
    • 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: Recent studies have revealed an association 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
Proceed to Differential Diagnoses
 
 
Contributor Information and Disclosures
Author

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, State University of New York at Stony Brook

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

Disclosure: Nothing to disclose.

Coauthor(s)

Steven Carsons, MD  Chief, Division of Rheumatology, Allergy, and Immunology, Professor of Medicine, Department of Internal Medicine, Winthrop University Hospital, State University of New York at Stony Brook

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

Disclosure: Nothing to disclose.

Specialty Editor Board

Carlos J Lozada, MD  Director of Rheumatology Fellowship Program, Professor, 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 and American College of Rheumatology

Disclosure: Pfizer Honoraria Speaking and teaching; Amgen Honoraria Speaking and teaching

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

Disclosure: Medscape Salary Employment

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, and American College of Rheumatology

Disclosure: Abbott Honoraria Speaking and teaching; Centocor Consulting fee Consulting; Genentech Grant/research funds Other; HGS/GSK Honoraria Speaking and teaching; Omnicare Consulting fee Consulting; Pfizer Honoraria Speaking and teaching; Roche Speaking and teaching; Savient Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; 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, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Additional Contributors

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

References

  1. Giannakopoulos B, Passam F, Rahgozar S, Krilis SA. Current concepts on the pathogenesis of the antiphospholipid syndrome. Blood. Jan 15 2007;109(2):422-30. [Medline].

  2. Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet. Oct 30 2010;376(9751):1498-509. [Medline].

  3. Girardi G, Redecha P, Salmon JE. Heparin prevents antiphospholipid antibody-induced fetal loss by inhibiting complement activation. Nat Med. Nov 2004;10(11):1222-6. [Medline].

  4. Lockshin MD. Update on antiphospholipid syndrome. Bull NYU Hosp Jt Dis. 2006;64(1-2):57-9. [Medline].

  5. Avcin T, Cimaz R, Silverman ED, Cervera R, Gattorno M, Garay S, et al. Pediatric antiphospholipid syndrome: clinical and immunologic features of 121 patients in an international registry. Pediatrics. Nov 2008;122(5):e1100-7. [Medline].

  6. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. Feb 2006;4(2):295-306. [Medline].

  7. Cohen D, Berger SP, Steup-Beekman GM, Bloemenkamp KW, Bajema IM. Diagnosis and management of the antiphospholipid syndrome. BMJ. May 14 2010;340:c2541. [Medline].

  8. Galli M, Luciani D, Bertolini G. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood. 2003;101(5):1827-1832. [Medline].

  9. Lambert M, Ferrard-Sasson G, Dubucquoi S, Hachulla E, Prin L, Hatron PY, et al. Diluted Russell viper-venom time improves identification of antiphospholipid syndrome in a lupus anticoagulant-positive patient population. Thromb Haemost. Mar 2009;101(3):577-81. [Medline].

  10. American College of Obstetricians and Gynecologists. Antiphospholipid syndrome. National Guideline Clearinghouse. Available at http://guideline.gov/summary/summary.aspx?doc_id=10928. Accessed May18, 2009.

  11. Ernest JM, Marshburn PB, Kutteh WH. Obstetric antiphospholipid syndrome: an update on pathophysiology and management. Semin Reprod Med. Nov 2011;29(6):522-39. [Medline].

  12. Klack K, de Carvalho JF. Dietetic issues in antiphospholipid syndrome. Rheumatol Int. Dec 23 2011;[Medline].

  13. Laskin CA, Spitzer KA, Clark CA, Crowther MR, Ginsberg JS, Hawker GA, et al. Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA Trial. J Rheumatol. Feb 2009;36(2):279-87. [Medline].

  14. Heilmann L, Schorch M, Hahn T, Adasz G, Schilberz K, Adiguzel C, et al. Pregnancy outcome in women with antiphospholipid antibodies: report on a retrospective study. Semin Thromb Hemost. Nov 2008;34(8):794-802. [Medline].

  15. Ramos-Casals M, Brito-Zerón P, Muñoz S, Soto MJ. A systematic review of the off-label use of biological therapies in systemic autoimmune diseases. Medicine (Baltimore). Nov 2008;87(6):345-64. [Medline].

  16. Lockshin MD. Update on antiphospholipid syndrome. Bull NYU Hosp Jt Dis. 2008;66(3):195-7. [Medline].

  17. D'Cruz D. Renal manifestations of the antiphospholipid syndrome. Curr Rheumatol Rep. Feb 2009;11(1):52-60. [Medline].

  18. [Best Evidence] Ruffatti A, Del Ross T, Ciprian M, Nuzzo M, Rampudda M, Bertero MT, et al. Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicentre, retrospective follow-up study. Ann Rheum Dis. Mar 2009;68(3):397-9. [Medline].

  19. Asherson RA, Cervera R, Piette JC, et al. Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine (Baltimore). Nov. 2001;80(6):355-377. [Medline].

  20. Cervera R, Piette JC, Fornt J. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46(4):1019-1027. [Medline].

  21. Derksen RH, Khamashta MA, Branch DW. Management of the obstetric antiphospholipid syndrome. Arthritis Rheum. Apr 2004;50(4):1028-39. [Medline].

  22. Erkan D, Lockshin MD. New treatments for antiphospholipid syndrome. Rheum Dis Clin North Am. Feb 2006;32(1):129-48, x. [Medline].

  23. Fessler BJ. Thrombotic syndromes and autoimmune diseases. Rheum Dis Clin North Am. May 1997;23(2):461-79. [Medline].

  24. Galli M. Non beta 2-glycoprotein I cofactors for antiphospholipid antibodies. Lupus. Oct 1996;5(5):388-92. [Medline].

  25. Goldberg SN, Conti-Kelly AM, Greco TP. A family study of anticardiolipin antibodies and associated clinical conditions. Am J Med. Nov 1995;99(5):473-9. [Medline].

  26. Harris EN. Antiphospholipid syndrome. In: Klippel JH, Dieppe PA, eds. Rheumatology. 2nd ed. London, UK: Mosby; 1998:7.35.1-7.35.6.

  27. Hojnik M, George J, Ziporen L, Shoenfeld Y. Heart valve involvement (Libman-Sacks endocarditis) in the antiphospholipid syndrome. Circulation. Apr 15 1996;93(8):1579-87. [Medline].

  28. [Best Evidence] Lim W, Crowther MA, Eikelboom JW. Management of antiphospholipid antibody syndrome: a systematic review. JAMA. Mar 1 2006;295(9):1050-7. [Medline].

  29. Lockshin M. Antiphospholipid antibody syndrome. In: Kelley WR, Harris ED, Budd RC, Genovese MC, Firestein GS, Sergent JS, Sledge CB, Ruddy S, eds. Kelley's Textbook of Rheumatology. 7th ed. Philadelphia: WB Saunders; 1248-57.

  30. McNeil HP, Chesterman CN, Krilis SA. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol. 1991;49:193-280. [Medline].

  31. Pittoni V, Isenberg D. Apoptosis and antiphospholipid antibodies. Semin Arthritis Rheum. Dec 1998;28(3):163-78. [Medline].

  32. Ravelli A, Martini A. Antiphospholipid antibody syndrome in pediatric patients. Rheum Dis Clin North Am. Aug 1997;23(3):657-76. [Medline].

  33. Rosove MH, Brewer PM. Antiphospholipid thrombosis: clinical course after the first thrombotic event in 70 patients. Ann Intern Med. Aug 15 1992;117(4):303-8. [Medline].

  34. Ruiz-Irastorza G, Egurbide MV, Aguirre C. High impact of antiphospholipid syndrome on irreversible organ damage and survival of patients with systemic lupus erythematosus. Arch Intern Med. 2004;164(1):77-82. [Medline].

  35. Salmon JE, Girrardi G. The role of complement in the antiphospholipid syndrome. Curr Dir Autoimmun. 2004;7:133-148. [Medline].

  36. Sanna G, Bertolaccini ML, Cuadrado MJ. Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies. J Rheumatol. 2003;30(5):985-992. [Medline].

  37. Sebastiani GD, Galeazzi M, Morozzi G, Marcolongo R. The immunogenetics of the antiphospholipid syndrome, anticardiolipin antibodies, and lupus anticoagulant. Semin Arthritis Rheum. Jun 1996;25(6):414-20. [Medline].

  38. Simantov R, LaSala JM, Lo SK, et al. Activation of cultured vascular endothelial cells by antiphospholipid antibodies. J Clin Invest. Nov 1995;96(5):2211-9. [Medline].

  39. Wallace DJ. The use of chloroquine and hydroxychloroquine for non-infectious conditions other than rheumatoid arthritis or lupus: a critical review. Lupus. Jun 1996;5 Suppl 1:S59-64. [Medline].

  40. Zanon E, Saggiorato G, Ramon R. Anti-prothrombin antibodies as a potential risk factor of recurrent venous thromboembolism. Thromb Haemost. 2004;91(2):255-8. [Medline].

 
Previous
Next
 
Antiphospholipid syndrome. Livedo reticularis.
Antiphospholipid syndrome. Arterial thrombosis resulting in ischemia and necrosis of the foot.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.