Antiphospholipid Antibody Syndrome

Aka: Antiphospholipid Antibody Syndrome, Antiphospholipid Syndrome, Lupus Anticoagulant Disorder, APLA

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II. Pathophysiology

  1. Antiphospholipid Antibodies bind cell membrane phospholipids (including vascular endothelium)
    1. Antibody binding triggers inflammatory and prothrombotic changes
  2. Increases risk of recurrent thrombosis of any size vessel
    1. Core features include arterial thrombosis, venous thrombosis and Recurrent Pregnancy Loss
  3. Highly associated with Systemic Lupus Erythematosus (SLE)
    1. However, 60% of cases are not related to SLE

III. Risk Factors

  1. Rheumatologic Conditions
    1. Systemic Lupus Erythematosus (40% of cases)
    2. Rheumatoid Arthritis (20% of RA patients are APLA positive)
  2. Genetic predisposition
    1. Inherited Coagulopathy
    2. Various HLA markers
  3. Infections
    1. HIV Infection
    2. Leptospira
    3. Lyme Disease
    4. Syphilis
  4. Medications
    1. Chlorpromazine
    2. Phenytoin
    3. Procainamide
    4. Quinidine
  5. Other factors
    1. Recurrent Pregnancy Loss (20% are APLA positive)

IV. Associated Conditions

  1. Major clinical associations
    1. Venous thrombosis
      1. Deep Vein Thrombosis
      2. Pulmonary Embolism
    2. Arterial thrombosis
      1. Cerebrovascular Accident (CVA)
      2. Transient Ischemic Attacks
      3. Myocardial Infarction
      4. Gangrene
    3. Recurrent Pregnancy Loss
    4. Thrombocytopenia
    5. Hemolytic Anemia
  2. Other clinical associations
    1. Heart Valve abnormality (esp. mitral and aortic valves)
    2. Positive Coombs tests
    3. Livedo Reticularis
    4. Migraine Headaches
    5. Leg ulcers
    6. Myelopathy
    7. Chorea
    8. Pulmonary Hypertension
    9. Avascular necrosis

V. Labs

  1. Antiphospholipid Antibodies (APLA)
    1. Background
      1. Up to 10% of healthy patients are APLA positive at low titers
        1. However persistently high titers occur in less than 1% of healthy patients
      2. APLA positive status is based on at least 1 of 3 markers positive
        1. Positive tests should be confirmed with a second test at >=12 weeks after inital test
        2. Risk increases with the number of positive markers
    2. Anticardiolipin Antibody IgG and IgM (most sensitive test)
      1. IgG > 20 GPL is positive (>40 GPL are associated with increased thrombotic events)
      2. IgM > 20 MPL units is positive
      3. Possibly IgA positive
    3. Anti-B2-Glycoprotein I Autoantibodies
    4. Lupus Anticoagulant (most specific test, but Test Sensitivity only 20%)
  2. Other lab findings
    1. Partial Thromboplastin Time (PTT) prolonged
    2. Autoantibodies are present in 5% of healthy patients
    3. False PositiveVDRL (30-40%)
    4. Cytopenias
      1. Thrombocytopenia
      2. Anemia

VI. Diagnosis: Revised Sapporo Criteria (2006)

  1. Diagnosis requires at least 1 clinical AND 1 lab criteria
  2. Clinical Criteria (at least one required)
    1. Vascular Thrombosis (one or more events)
      1. Arterial thrombosis OR
      2. Deep Vein Thrombosis (but NOT Superficial Thrombophlebitis) OR
      3. Small vessel thrombosis
    2. Recurrent Pregnancy Loss
      1. Unexplained fetal death at >10 weeks OR
      2. Premature birth <34 weeks due to PIH or placental insufficiency OR
      3. Three of more serial Spontaneous Abortions <10 weeks without other cause (e.g. chromosomal, anatomic, hormonal)
  3. Lab Criteria
    1. At least 1 of 3 Positive APLA (at high titers) by two tests spaced at least 12 weeks apart

VII. Prevention: Thrombotic Complications

  1. Anticoagulation
    1. Warfarin
      1. Moderate to high dose (INR >2 to 3) is protective
      2. Low dose (INR <1.9) does not prevent thrombosis
    2. Low Molecular Weight Heparin (LMWH)
      1. May be used for APLA in pregnancy
    3. Aspirin
      1. Protects against pregnancy loss (in those with multiple losses)
      2. Does not protect against thrombosis
  2. Systemic Lupus Erythematosus and APLA positive
    1. Hydroxychloroquine
    2. Consider Aspirin prophylaxis
  3. Avoid factors predisposing to thrombosis
    1. Avoid Oral Contraceptive use
    2. Avoid Immobility
  4. Modify atherosclerotic risk factors
    1. Hyperlipidemia
    2. Tobacco Abuse
    3. Diabetes Mellitus

VIII. Complications

  1. See Associated Conditions above
  2. Catastrophic Anti-Phospholipid Antibody Syndrome (CAPS)

IX. Resources

  1. Not So Benign Antiphospholipid Antibody Syndrome (Hematologist)
    1. https://doi.org/10.1182/hem.V21.1.2024112

X. References

  1. Bustamante (2023) Antiphospholipid Syndrome, StatPearls, Treasure Island, FL [PubMed]
    1. https://www.ncbi.nlm.nih.gov/books/NBK430980/
  2. Levine (2002) N Engl J Med 346:752-63 [PubMed]

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Related Studies

Ontology: Antiphospholipid Syndrome (C0085278)

Definition (NCI) A syndrome associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses, marked by the presence of antibodies directed against phospholipids.
Definition (MSH) The presence of antibodies directed against phospholipids (ANTIBODIES, ANTIPHOSPHOLIPID). The condition is associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses. In pregnancy it can cause abortion. Of the phospholipids, the cardiolipins show markedly elevated levels of anticardiolipin antibodies (ANTIBODIES, ANTICARDIOLIPIN). Present also are high levels of lupus anticoagulant (LUPUS COAGULATION INHIBITOR).
Definition (CSP) associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses; involves the presence of antibodies directed against phospholipids; cardiolipins show markedly elevated levels of anticardiolipin antibodies; present also are high levels of lupus anticoagulant; in pregnancy it can cause abortion.
Concepts Disease or Syndrome (T047)
MSH D016736
ICD10 D68.61
SnomedCT 201450008, 26843008, 19267009
LNC LP40278-1, LA15309-0
English Anti Phospholipid Syndrome, Anti-Phospholipid Syndrome, Syndrome, Anti-Phospholipid, Syndrome, Antiphospholipid, Anti-Phospholipid Antibody Syndrome, Antiphospholipid Antibody Syndrome, Anti Phospholipid Antibody Syndrome, Antibody Syndrome, Anti-Phospholipid, Antibody Syndrome, Antiphospholipid, Antiphospholipid Antibody Syndromes, Syndrome, Anti-Phospholipid Antibody, Syndrome, Antiphospholipid Antibody, APL - Antiphospholipid syndrom, APS-Antiphospholipid syndrome, antiphospholipid syndrome (diagnosis), antiphospholipid syndrome, Antiphospholipid Syndrome [Disease/Finding], Antiphospholipid Syndrome, anti phospholipids syndrome, anticardiolipin syndrome, anti phospholipid syndrome, anti-phospholipid syndrome, antiphospholipids syndrome, antiphospholipid antibody syndrome, Antiphospholipid antibody syndrome, Lupus Anticoagulant Disorder, Hughes Syndrome, Syndrome, Hughes, Antiphospholipid syndrome, APL - Antiphospholipid syndrome, APS - Antiphospholipid syndrome, Anticardiolipin syndrome, Antiphospholipid syndrome (disorder), syndrome; anticardiolipin, syndrome; antiphospholipid, anticardiolipin; syndrome, antiphospholipid; syndrome
Italian Sindrome da antifosfolipidi, Sindrome da anticorpi antifosfolipidici, Sindrome antifosfolipidica
Swedish Antifosfolipidsyndrom
Japanese ｺｳﾘﾝｼｼﾂｺｳﾀｲｼｮｳｺｳｸﾞﾝ, 抗リン脂質抗体症候群, 抗りん脂質症候群, 抗りん脂質抗体症候群, 抗リン脂質症候群, 抗燐脂質抗体症候群, 抗燐脂質症候群, 燐脂質抗体症候群
Czech syndrom antifosfolipidových protilátek, antifosfolipidový syndrom, Antifosfolipidový syndrom
Finnish Fosfolipidivasta-aineoireyhtymä
Russian FOSFOLIPIDNYKH ANTITEL SINDROM, ANTIFOSFOLIPIDNYI SINDROM, АНТИФОСФОЛИПИДНЫЙ СИНДРОМ, ФОСФОЛИПИДНЫХ АНТИТЕЛ СИНДРОМ
Croatian ANTIFOSFOLIPIDNI SINDROM
Spanish síndrome antifosfolípido (trastorno), síndrome antifosfolipídico, síndrome antifosfolipídico (trastorno), síndrome antifosfolípido, Síndrome de los Anticuerpos Antifosfolípidos, Síndrome Antifosfolipidico, Síndrome del Anticuerpo Antifosfolípido, Síndrome antifosfolípido, Síndrome Antifosfolípido
Polish Zespół antyfosfolipidowy, APS
Hungarian Antiphospholipid syndroma
Norwegian Antifosfolipidsyndrom
Portuguese Síndrome Antifosfolípide, Síndrome do Anticorpo Antifosfolípide, Síndrome dos Anticorpos Antifosfolípides, Síndrome antifosfolipídica, Síndrome Antifosfolipídica
Dutch anticardiolipine; syndroom, antifosfolipide; syndroom, syndroom; anticardiolipine, syndroom; antifosfolipide, antifosfolipidensyndroom, Antifosfolipidesyndroom, Syndroom, antifosfolipide-
French Syndrome des anti-phospholipides, Syndrome de Soulier, Syndrome des anticorps antiphospholipides (SAPL), Syndrome des anticorps antiphospholipides, Syndrome des antiphospholipides
German Antiphospholipidsyndrom, Antiphospholipid-Syndrom, Phospholipid-Antikörper-Syndrom
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Lupus anticoagulant disorder (C0311370)

Concepts Disease or Syndrome (T047)
ICD10 D68.62
SnomedCT 19267009
English lupus anticoagulant, lupus anticoagulant disorder, lupus anticoagulant disorder (diagnosis), Lupus anticoagulant disorder, Lupus anticoagulant syndrome, lupus anticoagulant syndrome, Lupus anticoagulant, Lupus anticoagulant inhibitor syndrome, SLE inhibitor syndrome, Lupus anticoagulant disorder (disorder)
Spanish anticoagulante lúpico (trastorno), anticoagulante lúpico, síndrome de inhibidor LES, síndrome de inhibidor anticoagulante lúpico
Derived from the NIH UMLS (Unified Medical Language System)

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