Antiphospholipid syndrome pathophysiology

Jump to navigation Jump to search

Antiphospholipid syndrome Microchapters



Historical Perspective




Differentiating Antiphospholipid syndrome from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis


Diagnostic criteria

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray



Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies


Medical Therapy


Primary Prevention

Secondary Prevention

Case Studies

Case #1

Antiphospholipid syndrome pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides


American Roentgen Ray Society Images of Antiphospholipid syndrome pathophysiology

All Images
Echo & Ultrasound
CT Images

Ongoing Trials at Clinical

US National Guidelines Clearinghouse

NICE Guidance

FDA on Antiphospholipid syndrome pathophysiology

CDC on Antiphospholipid syndrome pathophysiology

Antiphospholipid syndrome pathophysiology in the news

Blogs on Antiphospholipid syndrome pathophysiology

Directions to Hospitals Treating Antiphospholipid syndrome

Risk calculators and risk factors for Antiphospholipid syndrome pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Feham Tariq, MD [2]


Antiphospholipid syndrome (APS) is an autoimmune disease in which antiphospholipid antibodies (anti-cardiolipin antibodies and lupus anticoagulant) react against proteins that bind to anionic phospholipids on plasma membranes. This syndrome can be classified into primary (no underlying disease state) and secondary (in association with an underlying disease state) types. The underlying mechanism of APS mediated by the antibodies is mainly mediated via their affect on the coagulation cascade which subsequenlty leads to increased vascular tone of thrombosis. CAPS is a subclass of APS that results in development of a catastrophic illness characterized by progressive, severe arterial and venous thrombosis in multiple organs, often leading to death.


The pathogenesis of antiphospholipid syndrome is as follows:[1][2]

Primary APS

This type of APS has no other associated condition.

Secondary APS

The type of APS which occurs secondary to an underlying disease. The diseases and conditions associated with APS are as follows:[3][4][5]

Autoimmune diseases Infections Drugs Malignancy
  • Systemic lupus erythmatosus(SLE)
Bacterial infections:

Viral infections:

Parasitic infections:

Tumors of the following organs can cause APS:


Types of antiphospholipid antibodies

The following antiphospholipid antibodies are found in the plasma of patients:

Antiphospholipid antibodies Percentage
Anticardiolipin antibody 31%
Lupus anticoagulant (LA) 23-47%
Anti-beta-2 glycoprotein I 20%

Mechanism of action

The mechanism by which clinical manifestations occur in APS is mainly mediated by the antibodies which is as follows: [9][10][11][12][13][14][15]

Vascular thrombosis

Increased vascular tone:

Another effect of aPL is increased vascular tone which subsequently results in the following manifestations:

Role of Antiphospholipid Antibodies:

These antibodies have the following mechanism of action:[16][17][18][18]

  • Anti-beta-2 glycoprotein I antibody enhances the anticoagulant function of protein S by interfering its binding to its inhibitor C4b binding protein.
  • They bind negatively charged phospholipids and inhibit contact activation of the clotting cascade and platelet activation.
  • Another mechanism by which antiphospholipid antibodies create a prothrombotic state is by developing acquired activated protein C resistance.

Cellular mechanism

The underlying cellular mechanism involved in the pathogenesis of APS in as follows:[19][20][21]


  • Microparticles are found in the plasma of patients with APS in elevated levels.[22][23]
  • These are cell surface fragments released from the damaged, apoptotic and dying cells.
  • They lead to cell activation and subsequently lead to a prothrombotic state in the plasma.

Catastrophic Antiphospholipid Antibody Syndrome (CAPS)

  • CAPS is a subclass of APS that results in development of a catastrophic illness characterized by progressive, severe arterial and venous thrombosis in multiple organs, often leading to death.
  • Classification criteria for CAPS is as follows:
Classification criteria for CAPS
1. Evidence of involvement of three or more organs, systems, and/or tissues
2. Development of manifestations simultaneously or in less than a week
3. Confirmation by histopathology of small vessel occlusion in at least one organ or tissue
4. Laboratory confirmation of the presence of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, and/or anti-beta2-glycoprotein I antibodies)
Definite CAPS
  • Requires all four criteria
Probable CAPS
  • All four criteria, except for only two organs, systems, and/or sites of tissue involvement or
  • All four criteria, except for the laboratory confirmation at least six weeks apart due to the early death of a patient never tested for aPL before the catastrophic APS or
  • Criteria 1, 2, and 4 above or
  • 1, 3, and 4 and the development of a third event in more than a week but less than a month, despite anticoagulation

Genetic association

Antiphospholipid antibody syndrome is associated with the following genetic mutations:[24][25]

Gross Pathology Findings

Microscopic Pathology Findings

Histologic studies of skin or other involved tissues reveal the following:


  1. Negrini S, Pappalardo F, Murdaca G, Indiveri F, Puppo F (2017). "The antiphospholipid syndrome: from pathophysiology to treatment". Clin Exp Med. 17 (3): 257–267. doi:10.1007/s10238-016-0430-5. PMID 27334977.
  2. Giannakopoulos B, Krilis SA (2013). "The pathogenesis of the antiphospholipid syndrome". N Engl J Med. 368 (11): 1033–44. doi:10.1056/NEJMra1112830. PMID 23484830.
  3. Taraborelli M, Leuenberger L, Lazzaroni MG, Martinazzi N, Zhang W, Franceschini F; et al. (2016). "The contribution of antiphospholipid antibodies to organ damage in systemic lupus erythematosus". Lupus. 25 (12): 1365–8. doi:10.1177/0961203316637431. PMID 26945023.
  4. Conti F, Ceccarelli F, Perricone C, Leccese I, Massaro L, Pacucci VA; et al. (2016). "The chronic damage in systemic lupus erythematosus is driven by flares, glucocorticoids and antiphospholipid antibodies: results from a monocentric cohort". Lupus. 25 (7): 719–26. doi:10.1177/0961203315627199. PMID 26821965.
  5. Love PE, Santoro SA (1990). "Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Prevalence and clinical significance". Ann Intern Med. 112 (9): 682–98. PMID 2110431.
  6. McNeil HP, Chesterman CN, Krilis SA (1991). "Immunology and clinical importance of antiphospholipid antibodies". Adv Immunol. 49: 193–280. PMID 1853785.
  7. Safa O, Crippa L, Della Valle P, Sabbadini MG, Viganò D'Angelo S, D'Angelo A (1999). "IgG reactivity to phospholipid-bound beta(2)-glycoprotein I is the main determinant of the fraction of lupus anticoagulant activity quenched by addition of hexagonal (II) phase phospholipid in patients with the clinical suspicion of antiphospholipid-antibody syndrome". Haematologica. 84 (9): 829–38. PMID 10477458.
  8. Triplett DA (1998). "Many faces of lupus anticoagulants". Lupus. 7 Suppl 2: S18–22. PMID 9814666.
  9. Bick, RL, et al. Antiphospholipid and thrombosis syndromes. Sem Thromb and Hemostasis 1994;20:3. PMID 8059232
  10. Cervera, R, et al. Clinicopathologic correlations of the antiphospholipid syndrome. Sem Arth and Rheum 1995;24:262. PMID 7740306
  11. Kampe, CE. Clinical syndromes associated with lupus anticoagulants. Sem Thromb and Hemostasis 1994;20:16. PMID 8059230
  12. Asherson, RA. The catastrophic antiphospholipid antibody syndrome. J Rheum 1992:19:508. PMID 1593568
  13. Ruffatti, A, et al. A catastrophic antiphospholipid antibody syndrome: the importance of high levels of warfarin anticoagulation. J Int Med 1994;325:81.PMID8283165
  14. Neuwelt, CM, et al. Catastrophic antiphospholipid syndrome: Response to repeated plasmapheresis. A&R 1997;40:1534. PMID 9259436
  15. Bermas, BL, et al. Prognosis and therapy of antiphospholipid antibody syndrome. UpToDate 1997.
  16. Merrill JT, Zhang HW, Shen C, Butman BT, Jeffries EP, Lahita RG; et al. (1999). "Enhancement of protein S anticoagulant function by beta2-glycoprotein I, a major target antigen of antiphospholipid antibodies: beta2-glycoprotein I interferes with binding of protein S to its plasma inhibitor, C4b-binding protein". Thromb Haemost. 81 (5): 748–57. PMID 10365749.
  17. Shapiro SS (1996). "The lupus anticoagulant/antiphospholipid syndrome". Annu Rev Med. 47: 533–53. doi:10.1146/ PMID 8712801.
  18. 18.0 18.1 Male C, Mitchell L, Julian J, Vegh P, Joshua P, Adams M; et al. (2001). "Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus". Blood. 97 (4): 844–9. PMID 11159506.
  19. Morel O, Jesel L, Freyssinet JM, Toti F (2005). "Elevated levels of procoagulant microparticles in a patient with myocardial infarction, antiphospholipid antibodies and multifocal cardiac thrombosis". Thromb J. 3: 15. doi:10.1186/1477-9560-3-15. PMC 1266401. PMID 16219103.
  20. Pericleous C, Giles I, Rahman A (2009). "Are endothelial microparticles potential markers of vascular dysfunction in the antiphospholipid syndrome?". Lupus. 18 (8): 671–5. doi:10.1177/0961203309103062. PMID 19502261.
  21. Williams FM, Parmar K, Hughes GR, Hunt BJ (2000). "Systemic endothelial cell markers in primary antiphospholipid syndrome". Thromb Haemost. 84 (5): 742–6. PMID 11127848.
  22. Dignat-George F, Camoin-Jau L, Sabatier F, Arnoux D, Anfosso F, Bardin N; et al. (2004). "Endothelial microparticles: a potential contribution to the thrombotic complications of the antiphospholipid syndrome". Thromb Haemost. 91 (4): 667–73. doi:10.1160/TH03-07-0487. PMID 15045126.
  23. Ambrozic A, Bozic B, Kveder T, Majhenc J, Arrigler V, Svetina S; et al. (2005). "Budding, vesiculation and permeabilization of phospholipid membranes-evidence for a feasible physiologic role of beta2-glycoprotein I and pathogenic actions of anti-beta2-glycoprotein I antibodies". Biochim Biophys Acta. 1740 (1): 38–44. doi:10.1016/j.bbadis.2005.02.009. PMID 15878739.
  24. Brouwer JL, Bijl M, Veeger NJ, Kluin-Nelemans HC, van der Meer J (2004). "The contribution of inherited and acquired thrombophilic defects, alone or combined with antiphospholipid antibodies, to venous and arterial thromboembolism in patients with systemic lupus erythematosus". Blood. 104 (1): 143–8. doi:10.1182/blood-2003-11-4085. PMID 15026314.
  25. Nojima J, Kuratsune H, Suehisa E, Kawasaki T, Machii T, Kitani T; et al. (2002). "Acquired activated protein C resistance is associated with the co-existence of anti-prothrombin antibodies and lupus anticoagulant activity in patients with systemic lupus erythematosus". Br J Haematol. 118 (2): 577–83. PMID 12139749.

Template:WH Template:WS