How Can We Lower Risk for Clot in Patients With Antiphospholipid Antibodies?
How Can We Lower Risk for Clot in Patients With Antiphospholipid Antibodies?
Danowski A, de Azevedo MN, de Souza Papi JA, Petri M
J Rheumatol. 2009;36:1195-1199
Antiphospholipid antibodies (aPLs) are associated with hypercoagulability and clotting, with various mechanistic studies suggesting a direct role of aPLs in the generation of clots; however, clinically apparent clots do not develop in all patients with aPLs. As such, there is a "2-hit hypothesis" to explain clots in patients with aPLs in whom aPLs predispose to clot, but some other factor may be present before a clinically apparent clot can develop.
These authors sought to identify factors that may be associated with clotting in 1 of 3 clinical scenarios: primary antiphospholipid antibody syndrome; antiphospholipid antibody syndrome associated with systemic lupus erythematosus (SLE); or aPLs and SLE, but no history of clotting or pregnancy loss. The authors performed a cross-sectional chart review of 122 patients (84% female) followed at the Hopkins Lupus Center and determined the association of various factors with clotting using as a control group the patients with aPL/SLE, but no clots. They found that the prevalence of clotting and pregnancy loss was highest in those with antiphospholipid antibody syndrome and SLE. Venous thromboses were associated with elevated triglycerides (level of triglycerides considered elevated not reported), hereditary thrombophilia (including protein C and S deficiency, antithrombin III, and factor V Leiden mutations), anticardiolipin antibody immunoglobulin G > 40 IU (enzyme-linked immunosorbent assay; INOVA Diagnostics), and the presence of lupus anticoagulant (modified dilute Russell's viper venom time). Arterial clots were associated with hypertension and elevated homocysteine. No significant associations were found for pregnancy loss.
This is a small but fascinating study seeking to identify factors that may be associated with clotting and pregnancy loss in patients with aPLs. Patients with antiphospholipid antibody syndrome with or without SLE can be difficult to treat, and anticoagulation alone may not prevent all clots, so it would be clinically useful to identify other factors that may be altered to decrease the risk for clotting or pregnancy loss in patients with aPLs. This study and others like it should help set the stage for prospective interventional trials with the goal to prove that modification of risk factors such as elevated triglycerides, lowering of aPL levels (perhaps through B-cell depletion), or treatment of hypertension leads to improved outcomes.
In the meantime, should we be treating elevated triglycerides and hypertension in patients with aPLs to decrease the risk for clotting? A proven answer to this question is not yet known, but given the established benefit of treating these conditions for prevention of cardiovascular disease in the general population, it may be worthwhile to consider treatment while awaiting conclusive studies.
Abstract
Determinants of Risk for Venous and Arterial Thrombosis in Primary Antiphospholipid Syndrome and in Antiphospholipid Syndrome With Systemic Lupus Erythematosus
Danowski A, de Azevedo MN, de Souza Papi JA, Petri M
J Rheumatol. 2009;36:1195-1199
Study Summary
Antiphospholipid antibodies (aPLs) are associated with hypercoagulability and clotting, with various mechanistic studies suggesting a direct role of aPLs in the generation of clots; however, clinically apparent clots do not develop in all patients with aPLs. As such, there is a "2-hit hypothesis" to explain clots in patients with aPLs in whom aPLs predispose to clot, but some other factor may be present before a clinically apparent clot can develop.
These authors sought to identify factors that may be associated with clotting in 1 of 3 clinical scenarios: primary antiphospholipid antibody syndrome; antiphospholipid antibody syndrome associated with systemic lupus erythematosus (SLE); or aPLs and SLE, but no history of clotting or pregnancy loss. The authors performed a cross-sectional chart review of 122 patients (84% female) followed at the Hopkins Lupus Center and determined the association of various factors with clotting using as a control group the patients with aPL/SLE, but no clots. They found that the prevalence of clotting and pregnancy loss was highest in those with antiphospholipid antibody syndrome and SLE. Venous thromboses were associated with elevated triglycerides (level of triglycerides considered elevated not reported), hereditary thrombophilia (including protein C and S deficiency, antithrombin III, and factor V Leiden mutations), anticardiolipin antibody immunoglobulin G > 40 IU (enzyme-linked immunosorbent assay; INOVA Diagnostics), and the presence of lupus anticoagulant (modified dilute Russell's viper venom time). Arterial clots were associated with hypertension and elevated homocysteine. No significant associations were found for pregnancy loss.
Viewpoint
This is a small but fascinating study seeking to identify factors that may be associated with clotting and pregnancy loss in patients with aPLs. Patients with antiphospholipid antibody syndrome with or without SLE can be difficult to treat, and anticoagulation alone may not prevent all clots, so it would be clinically useful to identify other factors that may be altered to decrease the risk for clotting or pregnancy loss in patients with aPLs. This study and others like it should help set the stage for prospective interventional trials with the goal to prove that modification of risk factors such as elevated triglycerides, lowering of aPL levels (perhaps through B-cell depletion), or treatment of hypertension leads to improved outcomes.
In the meantime, should we be treating elevated triglycerides and hypertension in patients with aPLs to decrease the risk for clotting? A proven answer to this question is not yet known, but given the established benefit of treating these conditions for prevention of cardiovascular disease in the general population, it may be worthwhile to consider treatment while awaiting conclusive studies.
Abstract
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