eMedicine Specialties > Pediatrics: General Medicine > Rheumatology

Antiphospholipid Antibody Syndrome: Follow-up

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
Contributor Information and Disclosures

Updated: Aug 4, 2009

Follow-up

Further Inpatient Care

  • Further inpatient care in patients with antiphospholipid (aPL) antibody syndrome (APS) is only on an as-needed basis for management of thrombotic events but may include the following:
    • Imaging studies
    • Medical therapy
    • Invasive procedures for thrombolytic therapy
  • Further inpatient care is indicated if a catastrophic antiphospholipid antibody syndrome (CAPS) occurs.

Further Outpatient Care

  • Interval care includes the following:
    • History and physical examination for signs and symptoms of thrombotic or vasospastic events
    • Laboratory testing for monitoring anticoagulant therapy, antiphospholipid antibody testing, and, in the case of secondary antiphospholipid syndrome, underlying disease activity
    • Imaging and Doppler studies for follow-up of previous thrombotic process
    • Dietary and lifestyle counseling

Inpatient & Outpatient Medications

  • Antiplatelet therapy, such as administration of aspirin, dipyridamole, hydroxychloroquine, ticlopidine, clopidogrel, or combinations of these agents
  • Vasodilator and/or antiplatelet therapy, such as pentoxifylline or cilostazol
  • Vasodilators, such as niacin or topical nitroglycerin (nitropaste)
  • Anticoagulation therapy, such as warfarin, heparin, or low molecular weight (LMW) heparin90,91,92
    • Warfarin sensitivity is conferred by the presence of a cytochrome oxidase P-450 mutation (CYP2C9) and can be associated with severe bleeding (*3 isoleucine to leucine in 10% of Caucasians; *4 asparagine to glutamine in 3% of African Americans).
    • The presence of an antiphospholipid antibody accentuates the prothrombotic state that exists when warfarin is withdrawn (because of low protein C synthesis and the presence of plasminogen activator inhibitors).
      • Abrupt withdrawal of warfarin by the physician or by the patient through noncompliance may result in a thrombotic event.
      • Coverage with LMW heparin during the period of warfarin withdrawal (approximately 3-5 d until protein C levels return to normal) may reduce this risk.
    • The prothrombin time (PT), standard partial thromboplastin time, or both may be prolonged in the presence of an antiphospholipid antibody, thus diminishing the accuracy of these assays in monitoring of the effectiveness of anticoagulant therapy.
    • The PT/international normalized ratio (INR) assays are also inaccurate in the presence of the lupus anticoagulant (LAC) and may provide results that vary according to the source of thromboplastin (manufacturer or lot-to-lot).
    • Chromogenic factor X levels and the prothrombin–proconvertin time more accurately reflect the level of anticoagulation in patients with a LAC who are on warfarin therapy.
    • The adequacy of therapy with LMW heparin should be assessed with a plasma anti–factor Xa assay, which measures the inactivation of factor Xa. Ideally, the sample should be drawn 3 hours post-injection, kept at 4°C, and processed as soon as possible.
    • Antiphospholipid antibody can bind to platelet factor 4 (PF4), and/or β2-glycoprotein I [GPI]) in the enzyme-linked immunosorbent assay (ELISA) test for heparin antibodies. A false-positive test in the presence of antiphospholipid antibody–associated thrombocytopenia may be falsely interpreted as heparin-induced thrombocytopenia (HIT), and anticoagulation may be inappropriately halted. Confusion may be avoided by obtaining this test prior to exposure to heparin.93
  • Immunomodulators, such as intravenous immunoglobulin or rituximab
  • Therapy for thrombocytopenia, such as steroids, danazol, dapsone, intravenous immunoglobulin (IVIG), or vincristine
  • Therapy for pulmonary hypertension: This may include epoprostenol (prostacyclin PGI2), bosentan (non-selective oral endothelin receptor antagonist), sildenafil (phosphodiesterase-5 inhibitor)78,79,80
  • Therapy for dyslipoproteinemia or hyperlipidemia: This may include statin drugs or niacin.86
  • Dietary supplementation with folic acid, vitamin B-12, or both for patients with hyperhomocysteinemia: See Medication and the therapeutic algorithm in Media file 5.

    One set of suggested algorithms for the workup an...

    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.

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    One set of suggested algorithms for the workup an...

    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.

Transfer

  • Patients with CNS, cardiovascular, or peripheral vaso-occlusive events may need to be transferred to facilities with appropriate support personnel, experience, and equipment.
  • Patients with catastrophic antiphospholipid antibody syndrome require admission to an ICU, high-level supportive care, and multiple consultative services.

Deterrence/Prevention

  • Adequate medical therapy
  • Patient education
  • Monitoring for new events
  • Monitoring for drug adverse effects and toxicity

Complications

  • Hemorrhage may occur as a result of overaggressive therapy.
  • Rethrombosis may occur as a result of inadequate therapy.
  • Catastrophic antiphospholipid antibody syndrome can lead to death (50% mortality rate).

Prognosis

  • The long-term prognosis varies and depends on the tissue damage incurred and the organ system or systems affected. Clinical manifestations that are associated with a worse prognosis include the following:94,95,96
    • Pulmonary hypertension
    • Neurologic involvement (eg, CNS involvement, transverse myelopathy)
    • Myocardial ischemia
    • Nephropathy
    • Gangrene of the extremities
    • Catastrophic antiphospholipid antibody syndrome

Patient Education

  • Lifestyle counseling is indicated to educate patients and their families about the risk factors that are known to complicate the prognosis of patients with antiphospholipid antibody syndrome.
    • Dietary manipulation is recommended to prevent obesity, hyperlipidemia, and hypertension, starting at a young age, especially in patients with a family history of these problems.
    • Dietary manipulation is recommended to decrease consumption of methionine-containing foods that might increase homocysteine levels in patients carrying mutations of the gene that encodes for methylene tetrahydrofolate reductase mutation (MTHFR). Folate deficiencies need to be identified and corrected in these patients to control homocysteine levels.
    • Counsel adolescents about the potential risks of smoking tobacco in this setting. Provide smoking cessation programs for patients who already have started smoking.
    • In patients with a secondary antiphospholipid antibody syndrome, encourage compliance with medications for control of underlying disease processes, such as vasculitis and systemic lupus erythematosus (SLE).
    • Dietary counseling is indicated for patients on oral anticoagulants.
      • Maintenance of a consistent diet of foods containing vitamin K
      • Avoidance of foods and herbs with anticoagulant properties
    • Counsel patients regarding the risks of oral contraceptive use and the need for alternative methods of contraception.
  • Current information for patients and their families can be obtained from the excellent Web sites from the St. ThomasHospital in London (Hughes Syndrome, Hughes Syndrome Foundation, Heart Center Online for Patients).
  • For excellent patient education resources, visit eMedicine's Circulatory Problems Center and Stroke Center. Also, see eMedicine's patient education articles Blood Clot in the Legs and Stroke.

Miscellaneous

Medicolegal Pitfalls

  • Failure to recognize symptoms of venous or arterial thrombosis or ischemia 
  • Failure to recognize symptoms of inadequate therapy (rethrombosis) or therapy that is too aggressive (bleeding)
  • Failure to correctly interpret laboratory analyses
    • Overtreatment for the presence of a positive antibody titer alone without clinical symptoms
    • Undertreatment when laboratory test results are misinterpreted as negative in the presence of a clinical event
    • Undertreatment in the presence of thrombocytopenia and a false positive test for heparin-induced thrombocytopenia (HIT)

Special Concerns

  • Exercise restraint in ordering antiphospholipid (aPL) antibody testing in healthy, asymptomatic individuals with no known additional risk factors. In general, these patients are not treated because little direct evidence of increased risk of clinical events has been reported. However, insurance carriers (eg, life insurers, long-term care insurers) have scanned the literature and have subsequently assigned these individuals to a higher risk category.
  • Loss of transplanted organs due to thrombosis occurs at a high rate in patients with preexisting antiphospholipid antibodies.
 


More on Antiphospholipid Antibody Syndrome

Overview: Antiphospholipid Antibody Syndrome
Differential Diagnoses & Workup: Antiphospholipid Antibody Syndrome
Treatment & Medication: Antiphospholipid Antibody Syndrome
Follow-up: Antiphospholipid Antibody Syndrome
Multimedia: Antiphospholipid Antibody Syndrome
References
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Further Reading

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Keywords

anti-phospholipid antibody syndrome, Hughes syndrome, Hughes' syndrome, antiphospholipid syndrome, anti-phospholipid syndrome, APS, APLS, Sneddon syndrome, Sneddon's syndrome, thrombosis, primary antiphospholipid syndrome, PAPS, secondary antiphospholipid syndrome, antiphospholipid, aPl, deep venous thrombosis, arterial occlusive events, migraine headache, Raynaud phenomenon, transient ischemic attack, TIA, systemic lupus erythematosus, SLE, lupus anticoagulant, LAC, migraine headache, peripheral vasospasm, thrombocytopenia, anticardiolipin antibody, aCL antibody, cerebrovascular accident, myocardial infarction, endocarditis, pulmonary emboli, treatment, diagnosis

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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.

Medical Editor

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
James M Oleske, MD, MPH is a member of the following medical societies: Academy of Medicine of New Jersey, American Academy of Pediatrics, American Public Health Association, American Society for Microbiology, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

David D Sherry, MD, Director, Clinical Rheumatology, Attending Physician, Pain Management, The Children's Hospital of Philadelphia; Professor of Pediatrics, University of Pennsylvania
David D Sherry, MD is a member of the following medical societies: American College of Rheumatology and American Pain Society
Disclosure: Nothing to disclose.

CME Editor

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.

 
 
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