Antiphospholipid Syndrome

Antiphospholipid (APL) antibodies can be detected in as many as 1% to 5% of unselected individuals.1,2 These antibodies are a common acquired cause of increased thrombotic risk (currently obesity is the most common acquired cause of hypercoagulability.3-9 The term “antiphospholipid syndrome” (APS) refers to a spectrum of clinical conditions that is associated with the presence of antiphospholipid antibodies. Both clinical and laboratory features must be present for the diagnosis of APS to be made.8-10 Any one or more of the conditions discussed below can occur in patients with the antiphospholipid syndrome.

  • Venous Thrombosis. Antiphospholipid syndrome can be detected in approximately 10% of patients presenting with their first venous thrombosis.7Studies have shown that at least one thrombotic event occurs in approximately 30% of patients with persistent antiphospholipid antibodies.7Deep venous thrombosis (DVT) occurs in approximately 40% of individuals with primary APS. The risk is even greater in individuals with other acquired thrombotic risk factors such as pregnancy, prolonged immobilization, or oral contraceptive therapy as well as in those with autoimmune disorders.7,8Venous thrombosis may occur in other vascular beds in association with APS such as cerebral sinus or intra-abdominal.
  • Arterial Thrombosis. Arterial thrombosis in APS is less common than venous thrombosis but results in greater incidence of morbidity.1 The CNS is the most common site of arterial thrombosis with APS although coronary thrombosis has also been reported. More than 25% of patients with APS have evidence of arterial occlusions.1 Antiphospholipid antibodies can be detected in as many as 33% of patients with strokes prior to the age of 50, and it is observed in 7% to 10% of unselected stroke patients.1 The incidence of stroke in patients with antiphospholipid antibodies increases when other risk factors (such as hypertension, hyperlipidemia, or smoking) are present. Patients with antiphospholipid antibodies also suffer from an increased incidence of cerebral infarcts, severe vascular headaches, transient ischemic attacks, and visual disturbances.6
  • Infertility and Complications of Pregnancy. In pregnancy, antiphospholipid antibodies are associated with placental-vascular thrombosis as well as interference with the complement system that can lead to fetal demise, fetal growth retardation, premature delivery, and neonatal thrombosis. Fetal loss associated with APS typically occurs in the second trimester. Between 5% and 15% of cases of recurrent spontaneous abortion are linked to APS.1
  • Thrombocytopenia. Thrombocytopenia is reported in 30% to 50% of patients with primary APS, although this rarely causes bleeding; however, thrombocytopenia is not considered one of the primary diagnostic criteria for APS because it can be found in so many other conditions.7,8
  • Other Conditions. APS is sometimes associated with symptoms that can include vasculitic rashes, dermal necrosis of digits, livedo reticularis, nephropathy, arthralgias, pulmonary hypertension, chorea, migraine headaches to name a few.8,10,11
  • Catastrophic APS. Rarely, patients with antiphospholipid antibodies will suffer from multiple thrombotic occlusions simultaneously in an acute, life-threatening condition leading to multiorgan failure that is referred to as catastrophic APS.8,11

Antiphospholipid antibodies can be subclassified into several clinical categories:

  • APL in otherwise healthy individuals
  • APL associated with systemic lupus erythematosus (SLE), other autoimmune disorders, or malignancies
  • Drug-induced antiphospholipid antibodies

A variety of therapeutic drugs can induce the production of antiphospholipid antibodies

 

calcium channel blockers

chlorpromazine

hydralazine

hydantoin

isoniazid

methyldopa

phenytoin

phenothiazine

procainamide

quinine

quinidine

thorazine

various antibiotics

Individuals with drug-induced antiphospholipid antibodies that persist after the drug treatment is ended experience an increased risk of thrombosis.5

  • Infection-induced antiphospholipid antibodies7

Often observed during the convalescent phase of acute bacterial and viral infection

Often observed in individuals with syphilis

Generally not associated with an increased risk of clinical complications as these antibodies tend to be directed against phospholipid rather than phospholipid-binding proteins

Usually transient

Note: Because it is not possible to distinguish infection-induced antiphospholipid antibodies from clinically significant antiphospholipid antibodies, all patients who test positive for antiphospholipid antibodies should be retested after 12 or more weeks to rule out transient antibodies.10

Antiphospholipid antibodies can be detected indirectly with tests that are based on their effect on clot-based, in vitro coagulation assays (ie, lupus anticoagulants) or directly by solid-phase immunoassay.13 Due to the heterogeneity of antibodies associated with APS, both clotting and solid-phase immunoassay testing is recommend when APS is suspected.4,9

References

1. Jenson R. The antiphospholipid antibody syndrome. Clin Hemost Rev. 2001; 15(11):1-4.

2. Misita CP, Moll S. Antiphospholipid antibodies. Circulation. 2005 Jul 19; 112(3):e39-44.PubMed 16027261

3. Triplett DA. Coagulation abnormalities. In: McClatchey KD, ed. Clinical Laboratory Medicine. 2nd ed. Baltimore, Md: Lippincott Williams and Wilkins; 2002:1033-1049.

4. Brandt JT, Triplett DA, Alving B, et al. Criteria for the diagnosis of lupus anticoagulants: An update. On Behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardization Committee of the ISTH. Thromb Haemost. 1995; 74(4):1185-1190. PubMed 8560433

5. Bick RL. Antiphospholipid thrombosis syndromes. Clin Appl Thromb Hemost. 2001 Oct; 7(4):241-258. PubMed 11697705

6. Hirsh J, Anand SS, Halperin JL, et al. Guide to anticoagulant therapy. Heparin: A statement for healthcare professionals from the American Heart Association. 2001; 103(24):2994-3018. PubMed 11413093

7. Alving BM. The antiphospholipid syndrome: Clinical presentation, diagnosis, and patient management. In Kitchens CS, Alving BM, Kessler CM, eds. Consultative Hemostasis and Thrombosis. Philadelphia, Pa: WB Saunders; 2002:181-196.

8. Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med.2002; 346(10):752-763. PubMed 11882732

9. Carreras LO, Forastiero RR, Martinuzzo ME. Which are the best biological markers of the antiphospholipid syndrome? J Autoimmun. 2000; 15(2):163-172. PubMed 10968904

10. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost., 2006; 4(2):295-306. PubMed 16420554

11. Keeling D1, Mackie I, Moore GW, Greer IA, Greaves M. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol. 2012 Apr; 157(1):47-58.

12. Harris EN, Pierangeli SS, Gharavi AE. Diagnosis of the antiphospholipid syndrome: A proposal for use of laboratory tests. Lupus. 1998; 7(Suppl 2):S144-S148. PubMed 9814693

13. Schjetlein R, Wisloff F. An evaluation of two commercial test procedures for the detection of lupus anticoagulant. Am J Clin Pathol. 1995; 103(1):108-111. PubMed 7817935

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