Pediatric Antiphospholipid Antibody Syndrome Medication

  • Author: Barry L Myones, MD; Chief Editor: Lawrence K Jung, MD   more...
 
Updated: Apr 16, 2012
 

Medication Summary

Very few studies have addressed the efficacy of any treatment protocol in antiphospholipid antibody syndrome (APS). Most are small retrospective analyses or anecdotal reports. Many prospective studies have included too few patients and have been hampered by a lack of homogeneity of test groups. The Sapporo criteria were established, in part, to ensure a uniform homogeneous test population in order to promote accurate prospective studies of treatment protocols for patients with antiphospholipid antibody syndrome.

Next

Antiplatelet agents

Class Summary

Aspirin inhibits prostaglandin synthesis, preventing formation of platelet-aggregating thromboxane A2. It is used in low doses to inhibit platelet aggregation and improve complications of venous stases and thrombosis. However, doses as low as 5 mg/kg appear to additionally inhibit prostacyclin, thus promoting a procoagulant state. No prevalence data on aspirin resistance in children has been reported. The effect of aspirin on platelet function can be assessed by optical platelet aggregometry or Platelet Function Analyzer (PFA-100). Ticlopidine does not inhibit cyclooxygenase and, in this way, differs from aspirin. It inhibits the primary and secondary phase of aggregation induced by adenosine 5'-diphosphate (ADP) and reduces platelet-derived growth factor. Ticlopidine may also impair platelet adhesion, resulting in prolonged bleeding time. Dipyridamole potentiates the inhibitory effects of aspirin on platelet aggregation.

View full drug information

Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin)

 

Used for antiplatelet effect. Inhibits prostaglandin synthesis, preventing formation of platelet-aggregating thromboxane A2. May be used in low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis.

View full drug information

Ticlopidine (Ticlid)

 

Used for livedoid vasculitis and thromboembolic disorders. Second-line antiplatelet therapy for patients who cannot tolerate or in whom aspirin therapy has failed.

View full drug information

Dipyridamole (Persantine)

 

Used for thromboembolic disorders to complement usual aspirin or warfarin therapy. Platelet adhesion inhibitor that possibly inhibits RBC uptake of adenosine, which is an inhibitor of platelet reactivity. In addition, may inhibit phosphodiesterase activity, leading to increased cyclic-3',5'-adenosine monophosphate within platelets and formation of the potent platelet-activator thromboxane A2.

Used alone or in combination with low-dose aspirin therapy as indicated above. Also used in combination with low-dose PO anticoagulant therapy (with or without aspirin) in children with mechanical prosthetic heart valves.

Previous
Next

Anticoagulants

Class Summary

Unfractionated intravenous heparin and fractionated LMW subcutaneous heparin are the choices for initial anticoagulation therapy. If warfarin is chosen as maintenance therapy, it is initiated and concurrently administered with heparin for several days until the international normalized ratio (INR) reaches the target range.

View full drug information

Heparin

 

Used for thromboembolic disorders. Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis. Used as a continuous infusion while initiating PO warfarin therapy.

View full drug information

Enoxaparin (Lovenox)

 

Used for thromboembolic disorders. Prevents DVT, which may lead to PE in patients undergoing surgery who are at risk for thromboembolic complications.

Enhances inhibition of factor Xa (preferentially) and thrombin (factor IIa) by increasing antithrombin III activity. The ratio of antifactor Xa to antifactor IIa activity is approximately 4:1 (1:1 for unfractionated heparin)

View full drug information

Warfarin (Coumadin)

 

Used for thromboembolic disorders. Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders.

Adjust dose to maintain an INR in the range of 2.5-3.5.

Previous
Next

Immunomodulators

Class Summary

Immune globulin is a purified preparation of gamma globulin derived from large pools of human plasma. It is composed of 4 subclasses of IgG antibodies, approximating the distribution of human serum. IgA-depleted products are also low in the IgG4 component.

View full drug information

Immune globulin intravenous (Sandoglobulin, Gammagard, Gamimune, Gammar-P, Gamunex)

 

Used for autoimmune diseases. Neutralizes circulating myelin antibodies through antiidiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).

Previous
Next

Vasodilators

Class Summary

These agents are used to lower elevated blood pressure, decrease vasospasm, or prevent ischemia. Niacin is also used to decrease hyperlipidemia.

View full drug information

Nitroglycerin ointment (Nitrol, Nitro-Bid)

 

Causes relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate production. The result is a decrease in blood pressure.

Onset of action for ointment is 20-60 min. Duration of effect is 2-12 h.

View full drug information

Niacin (Niacor, Niaspan, Nicotinex, Slo-Niacin)

 

Also called nicotinic acid or vitamin B-3. Component of 2 coenzymes necessary for tissue respiration, lipid metabolism, and glycogenolysis; inhibits synthesis of VLDL. Used as a dietary supplement and as adjunctive treatment of hyperlipidemias, peripheral vascular disease, circulatory disorders, and treatment of pellagra.

Onset of action within 20 min (extended release within 1 h). Duration of effect 20-60 min (extended release 8-10 h). Half-life 45 min.

Previous
Next

Drugs with effects on vascular endothelium, platelets, red blood cells

Class Summary

These drugs appear to have multiple mechanisms in the prevention of thrombosis and vascular spasm. The exact mechanisms are largely unexplained, but the properties of these drugs include changes in RBC rheology, inhibition of platelet adhesiveness/activation, inhibition of TNF-alpha production, and decreases in neutrophil and endothelial cell activation.

View full drug information

Pentoxifylline (Trental)

 

Used in vascular disease. May alter rheology of RBCs, which, in turn, reduces blood viscosity. Improves peripheral perfusion and vascular spasm in Raynaud phenomenon and vasculopathy/vasculitis.

Other effects include inhibition of platelet adhesiveness/activation, inhibition of TNF-alpha production, and decrease in neutrophil and endothelial cell activation.

View full drug information

Hydroxychloroquine (Plaquenil)

 

Inhibits platelets, chemotaxis of eosinophils, and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions.

Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.

View full drug information

Cilostazol (Pletal)

 

Affects vascular beds and cardiovascular function. May improve blood flow by altering rheology of RBCs. Produces nonhomogenous dilation of vascular beds, with more dilation in femoral beds than in vertebral, carotid, or superior mesenteric arteries.

Cilostazol and its metabolites are inhibitors of phosphodiesterase III and, as a result, cyclic AMP is increased, which leads to inhibition of platelet aggregation and vasodilation.

Previous
Next

Platelet count enhancers

Class Summary

These agents are used to augment platelet recovery.

View full drug information

Vincristine (Oncovin, Vincasar PFS)

 

Mechanism of action for treatment of thrombocytopenia is uncertain. May involve a decrease in reticuloendothelial cell function or an increase in platelet production. However, neither of these mechanisms fully explains the effect in TTP and HUS.

View full drug information

Danazol (Danocrine)

 

Synthetic steroid analog with strong antigonadotropic activity (inhibits LH and FSH) and weak androgenic action.

Increases levels of C4 component of complement and reduces attacks associated with angioedema. In hereditary angioedema, danazol increases level of deficient C1 esterase inhibitor.

Previous
Next

Other therapy with multiple actions

Class Summary

Medications with vasodilatory and antiplatelet activity with specific usage in the treatment of pulmonary hypertension and/or healing of refractory skin ulcerations have been administered in patients with APS.[82, 83, 84]

View full drug information

Bosentan (Tracleer)

 

Endothelin-receptor antagonist indicated for the treatment of pulmonary arterial hypertension in patients with WHO class III or class IV symptoms to improve exercise ability and decrease rate of clinical worsening. Inhibits vessel constriction and elevation of blood pressure by competitively binding to the endothelin-1 (ET-1) receptors ETA and ETB in endothelium and vascular smooth muscle. This leads to a significant increase in the cardiac index (CI) associated with significant reduction in pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), and mean right atrial pressure (RAP). Due to teratogenic potential, can only be prescribed through the Tracleer Access Program (1-866-228-3546).

View full drug information

Epoprostenol (Flolan)

 

Prostacyclin, PGI2 analogue that has potent vasodilatory properties. Elicits immediate onset of action. Half-life is approximately 5 min. In addition to vasodilator properties (all vascular beds), also contributes to inhibition of platelet aggregation (activates intracellular adenylate cyclase and results in increased CAMP in platelets) and plays role in inhibition of smooth muscle proliferation.

View full drug information

Sildenafil (Viagra, Revatio)

 

FDA-approved for pulmonary hypertension. Promotes selective smooth muscle relaxation in lung vasculature possibly by inhibiting phosphodiesterase type 5 (PDE5). This results in subsequent reduction of blood pressure in pulmonary arteries and increase in cardiac output. Elicits vasodilation and inhibits platelet aggregation. Also aids in healing refractory skin ulcerations.

Previous
Next

Antilipemic Agent

Class Summary

Therapy for dyslipoproteinemia or hyperlipidemia may reduce vascular risk factors for thrombosis. In vitro and animal model evidence suggests decreased endothelial cell and granulocyte activation.[90, 87]

View full drug information

Atorvastatin (Lipitor)

 

The most efficacious of the statins at high doses. Inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase), which in turn inhibits cholesterol synthesis and increases cholesterol metabolism. Reports have shown as much as a 60% reduction in LDL-C. The Atorvastatin versus Revascularization Treatment study (AVERT) compared 80 mg atorvastatin daily to standard therapy and angioplasty in patients with CHD. While events at 18 mo were the same between both groups, the length of time until the first CHD event occurred was longer with aggressive LDL-C lowering. The half-life of atorvastatin and its active metabolites is longer than that of all the other statins (ie, approximately 48 h compared to 3-4 h).

May modestly elevate HDL-C levels. Clinically, reduced levels of circulating total cholesterol, LDL-C, and serum TGs are observed.

Before initiating therapy, patients should be placed on a cholesterol-lowering diet for 3-6 mo; the diet should be continued indefinitely.

View full drug information

Pravastatin (Pravachol)

 

Effective in reducing circulating lipid levels and improving the clinical and anatomic course of atherosclerosis.

View full drug information

Simvastatin (Zocor)

 

Inhibits cholesterol synthesis and increases cholesterol metabolism.

Previous
Next

Biological response modulator

Class Summary

Targeted anti-B cell therapy has been used in the treatment of refractory idiopathic thrombocytopenic purpura (ITP) postsplenectomy. The use of this modality has been extrapolated to treatment protocols for antiphospholipid syndrome.[91, 92, 93]

View full drug information

Rituximab (Rituxan)

 

Indicated to reduce signs and symptoms for moderately-to-severely active rheumatoid arthritis in combination with methotrexate. For use in adults who have experienced an inadequate response to one or more TNF antagonist therapies. Antibody genetically engineered. Chimeric murine/human monoclonal antibody directed against the CD20 antigen found on surface of B-lymphocytes.

Previous
Proceed to Follow-up
 
 
Contributor Information and Disclosures
Author

Barry L Myones, MD  Associate Professor, Departments of Pediatrics and Immunology, Pediatric Rheumatology Section, Baylor College of Medicine; Director of Research, Pediatric Rheumatology Center, Texas Children's Hospital

Barry L Myones, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American College of Rheumatology, American Heart Association, American Society for Microbiology, Clinical Immunology Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

James M Oleske  MD, MPH, François-Xavier Bagnoud Professor of Pediatrics, Director, Division of Pulmonary Allergy Immunology and Infectious Diseases, Department of Pediatrics, New Jersey Medical School; Professor, Department of Quantitative Methods, University of Medicine and Dentistry of New Jersey

James M Oleske is a member of the following medical societies: Academy of Medicine of New Jersey, American Academy of Allergy Asthma and Immunology, American Academy of HIV Medicine, American Academy of Hospice and Palliative Medicine, American Academy of Pain Management, American Academy of Pediatrics, American Association of Pediatrics, American Association of Public Health Physicians, American College of Preventive Medicine, American Pain Society, American Public Health Association, American Society for Microbiology, American Thoracic Society, Arab Board of Family Medicine, Association of Clinical Researchers and Educators (ACRE), Infectious Diseases Society of America, Infectious Diseases Society of America, Infectious Diseases Society of New Jersey, Medical Society of New Jersey, National Association of Pediatric Nurse Practitioners, Pediatric Infectious Diseases Society, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David D Sherry, MD  Director, Clinical Rheumatology, Attending Physician, Pain Management, The Children's Hospital of Philadelphia; Professor of Pediatrics, University of Pennsylvania School of Medicine

David D Sherry, MD is a member of the following medical societies: American College of Rheumatology and American Pain Society

Disclosure: Nothing to disclose.

Daniel Rauch, MD, FAAP  Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine

Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine

Disclosure: Baxter Honoraria Consulting

Chief Editor

Lawrence K Jung, MD  Chief, Division of Pediatric Rheumatology, Children's National Medical Center

Lawrence K Jung, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Rheumatology, Clinical Immunology Society, and New York Academy of Sciences

Disclosure: Nothing to disclose.

References

  1. Myones BL, McCurdy D. The antiphospholipid syndrome: immunologic and clinical aspects. Clinical spectrum and treatment. J Rheumatol. Apr 2000;27 Suppl 58:20-8. [Medline].

  2. Cuadrado MJ, Hughes GR. Hughes (antiphospholipid) syndrome. Clinical features. Rheum Dis Clin North Am. Aug 2001;27(3):507-24, v. [Medline].

  3. Roubey RA. Antiphospholipid antibody syndrome. In: Koopman's Textbook of Arthritis and Allied Health Conditions. 14th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:1546-61.

  4. Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med. Mar 7 2002;346(10):752-63. [Medline].

  5. Lockshin MD. Antiphospholipid antibody syndrome. Rheum Dis Clin North Am. Feb 1994;20(1):45-59. [Medline].

  6. Cimaz R, Descloux E. Pediatric antiphospholipid syndrome. Rheum Dis Clin North Am. Aug 2006;32(3):553-73. [Medline].

  7. Petri M. Epidemiology of the antiphospholipid antibody syndrome. J Autoimmun. Sep 2000;15(2):145-51. [Medline].

  8. Welsch S, Branch DW. Antiphospholipid syndrome in pregnancy. Obstetric concerns and treatment. Rheum Dis Clin North Am. Feb 1997;23(1):71-84. [Medline].

  9. Hansen KE, Kong DF, Moore KD, Ortel TL. Risk factors associated with thrombosis in patients with antiphospholipid antibodies. J Rheumatol. Sep 2001;28(9):2018-24. [Medline].

  10. Harris EN, Pierangeli SS. 'Equivocal' antiphospholipid syndrome. J Autoimmun. Sep 2000;15(2):81-5. [Medline].

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

  12. Amigo MC, Khamashta MA. Antiphospholipid (Hughes) syndrome in systemic lupus erythematosus. Rheum Dis Clin North Am. May 2000;26(2):331-48. [Medline].

  13. Wilson WA, Gharavi AE, Koike T, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum. Jul 1999;42(7):1309-11. [Medline].

  14. Wilson WA, Gharavi AE, Piette JC. International classification criteria for antiphospholipid syndrome: synopsis of a post-conference workshop held at the Ninth International (Tours) aPL Symposium. Lupus. 2001;10(7):457-60. [Medline].

  15. Lockshin MD, Sammaritano LR, Schwartzman S. Validation of the Sapporo criteria for antiphospholipid syndrome. Arthritis Rheum. Feb 2000;43(2):440-3. [Medline].

  16. Wilson WA. Classification criteria for antiphospholipid syndrome. Rheum Dis Clin North Am. Aug 2001;27(3):499-505, v. [Medline].

  17. Miyakis S, Lockshin MD, Atsumi T. 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].

  18. [Guideline] Asherson RA, Cervera R, de Groot PG, et al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus. 2003;12(7):530-4. [Medline].

  19. Giordano P, Tesse R, Lassandro G, Fracchiolla D, Ranieri P, Lotito A, et al. Clinical and laboratory characteristics of children positive for antiphospholipid antibodies. Blood Transfus. Dec 22 2011;1-6. [Medline].

  20. Muscal E, Brey RL. Antiphospholipid syndrome and the brain in pediatric and adult patients. Lupus. Apr 2010;19(4):406-11. [Medline]. [Full Text].

  21. Cook MC. B cell biology, apoptosis, and autoantibodies to phospholipids. Thromb Res. 2004;114(5-6):307-19. [Medline].

  22. Esmon NL, Safa O, Smirnov MD, Esmon CT. Antiphospholipid antibodies and the protein C pathway. J Autoimmun. Sep 2000;15(2):221-5. [Medline].

  23. Meroni PL, Raschi E, Camera M, et al. Endothelial activation by aPL: a potential pathogenetic mechanism for the clinical manifestations of the syndrome. J Autoimmun. Sep 2000;15(2):237-40. [Medline].

  24. Meroni PL, Raschi E, Testoni C, et al. Antiphospholipid antibodies and the endothelium. Rheum Dis Clin North Am. Aug 2001;27(3):587-602. [Medline].

  25. Rauch J, Subang R, D'Agnillo P, Koh JS, Levine JS. Apoptosis and the antiphospholipid syndrome. J Autoimmun. Sep 2000;15(2):231-5. [Medline].

  26. Angles-Cano E, Guillin MC. Antiphospholipid antibodies and the coagulation cascade. Rheum Dis Clin North Am. Aug 2001;27(3):573-86. [Medline].

  27. Petri M. Pathogenesis and treatment of the antiphospholipid antibody syndrome. Med Clin North Am. Jan 1997;81(1):151-77. [Medline].

  28. Matsuura E, Kobayashi K, Tabuchi M. Accelerated atheroma in the antiphospholipid syndrome. Rheum Dis Clin North Am. Aug 2006;32(3):537-51. [Medline].

  29. Horita T, Atsumi T, Yoshida N, Nakagawa H, Kataoka H, Yasuda S. STAT4 single nucleotide polymorphism, rs7574865 G/T, as a risk for antiphospholipid syndrome. Ann Rheum Dis. Aug 2009;68(8):1366-7. [Medline].

  30. Pierangeli SS, Vega-Ostertag M, Harris EN. Intracellular signaling triggered by antiphospholipid antibodies in platelets and endothelial cells: a pathway to targeted therapies. Thromb Res. 2004;114(5-6):467-76. [Medline].

  31. Meroni PL, Raschi E, Testoni C, Tincani A, Balestrieri G, Molteni R, et al. Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta2-glycoprotein I) antibodies: effect on the proadhesive and proinflammatory phenotype. Arthritis Rheum. Dec 2001;44(12):2870-8. [Medline].

  32. Ferrara DE, Swerlick R, Casper K, Meroni PL, Vega-Ostertag ME, Harris EN, et al. Fluvastatin inhibits up-regulation of tissue factor expression by antiphospholipid antibodies on endothelial cells. J Thromb Haemost. Sep 2004;2(9):1558-63. [Medline].

  33. Ferrara DE, Liu X, Espinola RG, Meroni PL, Abukhalaf I, Harris EN, et al. Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model. Arthritis Rheum. Nov 2003;48(11):3272-9. [Medline].

  34. López-Pedrera Ch, Buendía P, Aguirre MA, Velasco F, Cuadrado MJ. Antiphospholipid syndrome and tissue factor: a thrombotic couple. Lupus. 2006;15(3):161-6. [Medline].

  35. Redecha P, Franzke CW, Ruf W, Mackman N, Girardi G. Neutrophil activation by the tissue factor/Factor VIIa/PAR2 axis mediates fetal death in a mouse model of antiphospholipid syndrome. J Clin Invest. Oct 2008;118(10):3453-61. [Medline].

  36. Hughson MD, McCarty GA, Brumback RA. Spectrum of vascular pathology affecting patients with the antiphospholipid syndrome. Hum Pathol. Jul 1995;26(7):716-24. [Medline].

  37. Asherson RA, Cervera R, Piette JC. Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients. Medicine (Baltimore). May 1998;77(3):195-207. [Medline].

  38. Asherson RA, Cervera R, Piette JC. Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients. Medicine (Baltimore). Nov 2001;80(6):355-77. [Medline].

  39. Cervera R, Asherson RA, Font J. Catastrophic antiphospholipid syndrome. Rheum Dis Clin North Am. Aug 2006;32(3):575-90. [Medline].

  40. Cervera R, Bucciarelli S, Plasin MA, et al. Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of a series of 280 patients from the "CAPS Registry". J Autoimmun. May-Jun 2009;32(3-4):240-5. [Medline].

  41. Asherson RA, Piette JC. The catastrophic antiphospholipid syndrome 1996: acute multi-organ failure associated with antiphospholipid antibodies: a review of 31 patients. Lupus. Oct 1996;5(5):414-7. [Medline].

  42. Rosenzweig EB, Widlitz AC, Barst RJ. Pulmonary arterial hypertension in children. Pediatr Pulmonol. Jul 2004;38(1):2-22. [Medline].

  43. Moroni G, Ventura D, Riva P. Antiphospholipid antibodies are associated with an increased risk for chronic renal insufficiency in patients with lupus nephritis. Am J Kidney Dis. Jan 2004;43(1):28-36. [Medline].

  44. Nochy D, Daugas E, Huong DL, et al. Kidney involvement in the antiphospholipid syndrome. J Autoimmun. Sep 2000;15(2):127-32. [Medline].

  45. Amigo MC. Kidney disease in antiphospholipid syndrome. Rheum Dis Clin North Am. Aug 2006;32(3):509-22. [Medline].

  46. Daugas E, Nochy D, Huong du LT. Antiphospholipid syndrome nephropathy in systemic lupus erythematosus. J Am Soc Nephrol. Jan 2002;13(1):42-52. [Medline].

  47. Garcia-Martin F, De Arriba G, Carrascosa T. Anticardiolipin antibodies and lupus anticoagulant in end-stage renal disease. Nephrol Dial Transplant. 1991;6(8):543-7. [Medline].

  48. Tektonidou MG, Sotsiou F, Nakopoulou L. Antiphospholipid syndrome nephropathy in patients with systemic lupus erythematosus and antiphospholipid antibodies: prevalence, clinical associations, and long-term outcome. Arthritis Rheum. Aug 2004;50(8):2569-79. [Medline].

  49. Roldan CA, Shively BK, Lau CC, Gurule FT, Smith EA, Crawford MH. Systemic lupus erythematosus valve disease by transesophageal echocardiography and the role of antiphospholipid antibodies. J Am Coll Cardiol. Nov 1 1992;20(5):1127-34. [Medline].

  50. Turiel M, Sarzi-Puttini P, Peretti R, et al. Five-year follow-up by transesophageal echocardiographic studies in primary antiphospholipid syndrome. Am J Cardiol. Aug 15 2005;96(4):574-9. [Medline].

  51. 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].

  52. Cervera R. Recent advances in antiphospholipid antibody-related valvulopathies. J Autoimmun. Sep 2000;15(2):123-5. [Medline].

  53. Tenedios F, Erkan D, Lockshin MD. Cardiac manifestations in the antiphospholipid syndrome. Rheum Dis Clin North Am. Aug 2006;32(3):491-507. [Medline].

  54. Soltész P, Szekanecz Z, Kiss E, Shoenfeld Y. Cardiac manifestations in antiphospholipid syndrome. Autoimmun Rev. Jun 2007;6(6):379-86. [Medline].

  55. Yadav D, Chandra J, Sharma S, Singh V. Essential thrombocytosis and antiphospholipid antibody syndrome causing chronic budd-Chiari syndrome. Indian J Pediatr. Apr 2012;79(4):538-40. [Medline].

  56. Espinosa G, Cervera R, Font J, Asherson RA. Adrenal involvement in the antiphospholipid syndrome. Lupus. 2003;12(7):569-72. [Medline].

  57. Brey RL. Differential diagnosis of central nervous system manifestations of the antiphospholipid antibody syndrome. J Autoimmun. Sep 2000;15(2):133-8. [Medline].

  58. Frances C, Piette JC. The mystery of Sneddon syndrome: relationship with antiphospholipid syndrome and systemic lupus erythematosus. J Autoimmun. Sep 2000;15(2):139-43. [Medline].

  59. Muscal E, Brey RL. Neurologic manifestations of the antiphospholipid syndrome: integrating molecular and clinical lessons. Curr Rheumatol Rep. Jan 2008;10(1):67-73. [Medline].

  60. Muscal E, Brey RL. Neurological manifestations of the antiphospholipid syndrome: risk assessments and evidence-based medicine. Int J Clin Pract. Sep 2007;61(9):1561-8. [Medline].

  61. Bertolaccini ML, Hughes GR. Antiphospholipid antibody testing: which are most useful for diagnosis?. Rheum Dis Clin North Am. Aug 2006;32(3):455-63. [Medline].

  62. Carreras LO, Forastiero RR, Martinuzzo ME. Which are the best biological markers of the antiphospholipid syndrome?. J Autoimmun. Sep 2000;15(2):163-72. [Medline].

  63. Derksen RH, de Groot PG. Tests for lupus anticoagulant revisited. Thromb Res. 2004;114(5-6):521-6. [Medline].

  64. Exner T. Conceptions and misconceptions in testing for lupus anticoagulants. J Autoimmun. Sep 2000;15(2):179-83. [Medline].

  65. Galli M. Should we include anti-prothrombin antibodies in the screening for the antiphospholipid syndrome?. J Autoimmun. Sep 2000;15(2):101-5. [Medline].

  66. Gilman-Sachs A, Lubinski J, Beer AE, et al. Patterns of anti-phospholipid antibody specificities. J Clin Lab Immunol. Jun 1991;35(2):83-8. [Medline].

  67. Mcintyre JA, Wagenknecht DR. Anti-phosphatidylethanolamine (aPE) antibodies: a survey. J Autoimmun. Sep 2000;15(2):185-93. [Medline].

  68. Merrill JT. Which antiphospholipid antibody tests are most useful?. Rheum Dis Clin North Am. Aug 2001;27(3):525-49. [Medline].

  69. Petri M. Diagnosis of antiphospholipid antibodies. Rheum Dis Clin North Am. May 1994;20(2):443-69. [Medline].

  70. Pierangeli SS, Harris EN. Advances in antiphospholipid antibody testing. Clin Appl Immunol Rev. 2000;1:59-72.

  71. Rapizzi E, Ruffatti A, Tonello M, et al. Correction for age of anticardiolipin antibodies cut-off points. J Clin Lab Anal. 2000;14(3):87-90. [Medline].

  72. Tincani A, Allegri F, Balestrieri G. Minimal requirements for antiphospholipid antibodies ELISAs proposed by the European Forum on antiphospholipid antibodies. Thromb Res. 2004;114(5-6):553-8. [Medline].

  73. Tincani A, Balestrieri G, Allegri F, et al. Overview on anticardiolipin ELISA standardization. J Autoimmun. Sep 2000;15(2):195-7. [Medline].

  74. Triplett DA. Antiphospholipid-protein antibodies: laboratory detection and clinical relevance. Thromb Res. Apr 1 1995;78(1):1-31. [Medline].

  75. Triplett DA. Use of the dilute Russell viper venom time (dRVVT): its importance and pitfalls. J Autoimmun. Sep 2000;15(2):173-8. [Medline].

  76. Wong RC. Consensus guidelines for anticardiolipin antibody testing. Thromb Res. 2004;114(5-6):559-71. [Medline].

  77. Noda S, Ogura M, Tsutsumi A, Udagawa T, Kamei K, Matsuoka K, et al. Thrombotic microangiopathy due to multiple autoantibodies related to antiphospholipid syndrome. Pediatr Nephrol. Apr 2012;27(4):681-5. [Medline].

  78. Khamashta MA. Primary prevention of thrombosis in subjects with positive antiphospholipid antibodies. J Autoimmun. Sep 2000;15(2):249-53. [Medline].

  79. Khamashta MA, Cuadrado MJ, Mujic F, et al. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med. Apr 13 1995;332(15):993-7. [Medline].

  80. Petri M. Management of thrombosis in antiphospholipid antibody syndrome. Rheum Dis Clin North Am. Aug 2001;27(3):633-42, viii. [Medline].

  81. Rai R. Obstetric management of antiphospholipid syndrome. J Autoimmun. Sep 2000;15(2):203-7. [Medline].

  82. [Best Evidence] Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. Nov 17 2005;353(20):2148-57. [Medline].

  83. Humpl T, Reyes JT, Holtby H. Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single-drug, open-label, pilot study. Circulation. Jun 21 2005;111(24):3274-80. [Medline].

  84. Rosenzweig EB, Ivy DD, Widlitz A. Effects of long-term bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol. Aug 16 2005;46(4):697-704. [Medline].

  85. Derksen RH, de Groot PG. Do we Know which Patients with the Antiphospholipid Syndrome Should Receive Long-term High Dose Anti-coagulation?. J Autoimmun. Sep 2000;15(2):255-259. [Medline].

  86. Wald DS, Bishop L, Wald NJ, et al. Randomized trial of folic acid supplementation and serum homocysteine levels. Arch Intern Med. Mar 12 2001;161(5):695-700. [Medline].

  87. Erkan D, Lockshin MD. New approaches for managing antiphospholipid syndrome. Nat Clin Pract Rheumatol. Mar 2009;5(3):160-70. [Medline].

  88. Lockshin M, Tenedios F, Petri M, McCarty G, Forastiero R, Krilis S. Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report. Lupus. 2003;12(7):518-23. [Medline].

  89. Levine SR, Brey RL, Tilley BC, et al. Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA. Feb 4 2004;291(5):576-84. [Medline].

  90. Belizna CC, Richard V, Thuillez C, Levesque H, Shoenfeld Y. Insights into atherosclerosis therapy in antiphospholipid syndrome. Autoimmun Rev. Nov 2007;7(1):46-51. [Medline].

  91. Takemoto CM. Rituximab for ITP: a long-term fix?. Pediatr Blood Cancer. Feb 2009;52(2):155-6. [Medline].

  92. Semple JW. ITP three R's: regulation, routing, rituximab. Blood. Aug 15 2008;112(4):927-8. [Medline].

  93. Marks SD, Patey S, Brogan PA, et al. B lymphocyte depletion therapy in children with refractory systemic lupus erythematosus. Arthritis Rheum. Oct 2005;52(10):3168-74. [Medline].

  94. Asherson RA, Chan JK, Harris EN, et al. Anticardiolipin antibody, recurrent thrombosis, and warfarin withdrawal. Ann Rheum Dis. Dec 1985;44(12):823-5. [Medline].

  95. Lawrie AS, Purdy G, Mackie IJ, Machin SJ. Monitoring of oral anticoagulant therapy in lupus anticoagulant positive patients with the anti-phospholipid syndrome. Br J Haematol. Sep 1997;98(4):887-92. [Medline].

  96. Moll S, Ortel TL. Monitoring warfarin therapy in patients with lupus anticoagulants. Ann Intern Med. Aug 1 1997;127(3):177-85. [Medline].

  97. Pauzner R, Greinacher A, Selleng K, Althaus K, Shenkman B, Seligsohn U. False-positive tests for heparin-induced thrombocytopenia in patients with antiphospholipid syndrome and systemic lupus erythematosus. J Thromb Haemost. Jul 2009;7(7):1070-4. [Medline].

  98. Alarcon-Segovia D, Perez-Ruiz A, Villa AR. Long-term prognosis of antiphospholipid syndrome in patients with systemic lupus erythematosus. J Autoimmun. Sep 2000;15(2):157-61. [Medline].

  99. Amigo MC. Prognosis in antiphospholipid syndrome. Rheum Dis Clin North Am. Aug 2001;27(3):661-9. [Medline].

  100. Erkan D, Asherson RA, Espinosa G, et al. Long term outcome of catastrophic antiphospholipid syndrome survivors. Ann Rheum Dis. Jun 2003;62(6):530-3. [Medline].

 
Previous
Next
 
Palmar livedo reticularis associated with antiphospholipid antibody syndrome may range from a lacy, flat, reticulated pattern to a more confluent, nonblanching, slightly raised rash (secondary to extravasation of RBCs and plasma).
Livedo reticularis of the upper and lower extremities in a 15-year-old adolescent with primary antiphospholipid antibody syndrome. The pattern is lacy, flat, and nonblanching. The purplish hue is from stasis in the small vessel beds.
Muddy discoloration and mild diffuse swelling of the fingers observed as part of the Raynaud phenomenon, which is associated with antiphospholipid antibody syndrome. At room temperature, this patient still has decreased capillary refill and cold fingers despite treatment with pentoxifylline. The discoloration extends proximally onto the palms and turns blue-purple when exposed to cold.
Linear splinter hemorrhages are found under the nails of fingers and toes. These may be solitary or multiple and appear intermittently.
One set of suggested algorithms for the workup and treatment of patients with antiphospholipid antibody syndrome. This should not be considered dogmatic because laboratory evaluation is not standardized and treatment remains empiric and controversial. Laboratory testing is not recommended in healthy asymptomatic individuals with no risk factors and a negative family history.
Occlusion of the right middle cerebral artery in a 3-year-old child with severe headache and hemiparesis associated with anticardiolipin antibodies.
Organizing thrombus in an aortic valve in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE) and recurrent thrombotic events. The authors acknowledge the help of Hannes Vogel, MD, in preparing this image.
High-power degenerating aortic valve in a patient who has positive test results for antiphospholipid antibody and lupus anticoagulant and who has systemic lupus erythematosus (SLE) and recurrent thrombotic events. The authors acknowledge the help of Hannes Vogel, MD, in preparing this image.
Trichrome stain of a thrombus in the intestinal serosa in a patient who has positive test results for antiphospholipid antibody and lupus anticoagulant and who has systemic lupus erythematosus (SLE) and catastrophic antiphospholipid antibody syndrome (CAPS). The authors acknowledge the help of Hannes Vogel, MD, in preparing this image.
Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE), World Health Organization (WHO) class IV lupus nephritis, and acute renal failure. Top: Thrombosed kidney vessels (periodic acid-Schiff [PAS], original magnification X40). Bottom: Thrombosed kidney vessels (PAS, original magnification X20). Lumen is filled with eosinophilic fibrin with overlying injured endothelial cells. The authors acknowledge the help of Karen W. Eldin, MD, in preparing this image.
Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE), World Health Organization (WHO) class IV lupus nephritis, and acute renal failure. Top: Thrombosed kidney vessel (hematoxylin and eosin [H&E] stain, original magnification X20). Lumen is occluded with fibrin. A perivascular stromal reaction with degenerating inflammatory cells is observed. Bottom: Thrombosed kidney vessel (H&E stain, original magnification X20). Lumen is occluded with fibrin. The authors acknowledge the help of Karen W. Eldin, MD, in preparing this image.
Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE), World Health Organization (WHO) class IV lupus nephritis, and acute renal failure. Thrombosed kidney vessel with recanalization (arrows) (Jones stain, original magnification X20). Architectural distortion in the surrounding stroma is observed. The authors acknowledge the help of Karen W. Eldin, MD, in preparing this image.
Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE) and thrombocytopenia. Livedo reticularis of the upper extremities, which developed as petechiae in the classic lacy, reticular pattern, is observed.
Livedo reticularis of the upper extremities, which developed as petechiae in the classic lacy, reticular pattern and evolved as a confluent, nonblanching, slightly raised purpuric rash in the same reticular pattern.
Digital infarctions in a patient with systemic lupus erythematosus with antiphospholipid syndrome (APS) and long-standing Raynaud symptoms. Multiple and repeated digital infarctions are depicted, resulting in ulcerations and scarring. Scars and hyperpigmentation are also seen on the palmer aspect of hands and fingers.
A patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. Extensive involvement of all digits is noted, some with distal infarction and dry gangrene, others healing with residual eschar (and undermining epithelialization), and some with re-epithelialization and scarring. Healed superficial epidermal damage and desquamation is also present.
A patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. Eschar is still present on first digit bilaterally. More superficial lesions are shown here, with evolution and healing of lesions on all other toes.
CAPS, Bone Infarction - MRI (High Resolution Proton Density and STIR images) and Nuclear Bone Scan - Patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. MRI shows multiple infarctions in the distal tibia, tarsal bones and metatarsal bones (extensive bone marrow edema and increased T1 with fat saturation signal in the calcaneus bones). Flow and early blood pool images of technetium 99m bone scan show increase in activity in both heel regions with focal areas of decreased activity in the center of each calcaneus.
A patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. The technetium 99m bone scan reveals irregular multifocal areas of tracer accumulation within the left ventricle of the heart suggestive of myocardial infarction and altered calcium deposition. Irregular cutaneous and subcutaneous uptake is noted in multiple areas of the torso and upper arms (as well as in the upper thighs). High-resolution CT scanning of the chest reveals extensive calcification involving the myocardium, the mitral and tricuspid valve annuli, the aortic valve annulus, the proximal right coronary artery, and the left main coronary artery.
 
 
 
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.