Studies Reveal Thrombotic Risks in Antiphospholipid Syndrome

CHICAGO – Understanding of the thrombosis risks associated with antiphospholipid syndrome has increased dramatically over the past 12 months, judging from the recent literature on the subject.

Dr. Joan T. Merrill told attendees at a seminar at the Midwest Rheumatology Summit that the annual incidence rate of thrombosis in patients with antiphospholipid antibodies was 1.86% in a prospective multicenter study of 258 patients reported this year (Ann. Rheum. Dis. 2011;70:1083-6).

"Almost 2% per year, and that kind of gets you to 20% at 10 years," said Dr. Merrill. "That’s pretty high, and that’s pretty scary." Hypertension predicts thrombosis, as does the lupus anticoagulant test and lack of thromboprophylaxis during high-risk periods such as post surgery or long airplane flights.

Autoantibodies directed against complement-like structures lead to inflammatory events, including cell-mediated events that lead to a prothrombotic state. "And then, just as you see in atherosclerosis ... when the winds are propitious, what you get is a thrombotic event," said Dr. Merrill, medical director of the Lupus Foundation of America and director of the clinical pharmacology research program at the Oklahoma Medical Research Foundation.

Risk factors for thrombosis are higher in people who have multiple antiphospholipid antibody types (Arthritis Res. Ther. 2011;13:R118). This can be a reason to order multiple tests if insurance providers challenge those tests, said Dr. Merrill. Higher-titer autoantibodies also increase the risk of thrombosis (Acta Obstet. Gynecol. Scand. 2011 July 5 [doi: 10.1111/j.1600-0412. 2011.01236.x]), and antibodies with higher avidity will increase the risk of thrombosis (Lupus 2011;20:1166-71).

The syndrome complicates pregnancy as well.

The odds of women with preeclampsia having anticardiolipin antibodies, versus pregnancy without preeclampsia, were statistically significant (odds ratio, 2.86; 95% confidence interval, 1.37-5.98) in a recent study (Obstet. Gynecol. 2010;116:1433-43), and the odds with severe preeclampsia were much higher (OR, 11.15; CI, 2.66-46.75).

Dr. Merrill advised keeping this increased risk in mind, "since we have lupus patients and we are probably more likely [to order the anticardiolipin screen] than the average obstetrician."

Patients with lupus or antiphospholipid syndrome also often have migraines, and a 2011 study found that patients with a history of migraines have increased thrombotic risk (J. Thromb. Haemost. 2011;9:1350-4). Dr. Merrill advised being aware that what appears to be a migraine in a patient with the antiphospholipid antibody might actually be a thrombotic event, especially if the patient is a young woman.

Significant barriers still exist to evidence-based recommendations, according to information presented last year at the 13th International Congress on Antiphospholipid Antibodies. The barriers include poor standardization of tests.

"Around the country, at different labs, you’re going to get different results. In my place in Oklahoma, I may not even be thinking the same people have lupus that you do," said Dr. Merrill.

Other barriers are a poor understanding of pathogenic risk, heterogeneous patients, and studies that are retrospective and not population based.

A case was made at the end of last year for thrombin inhibition in antiphospholipid syndrome (Acta Clin. Croat. 2010;49:469-77). This could be good news for patients, since current univalent thrombin inhibitors are oral agents, which spare the patient the pain of injecting low-molecular-weight heparin. However, low-molecular-weight heparin may be safe long term for patients with the antiphospholipid syndrome (Ann. Rheum. Dis. 2011;70:1652-4).

"There’s been discussion for many years about the role of statins in the antiphospholipid syndrome," said Dr. Merrill. In a laboratory setting, fluvastatin inhibited markers of a prothrombotic state (Ann. Rheum. Dis. 2011;70:675-82). "It doesn’t provide you with the clinical evidence we like to see, but it’s what we have so far," she said.

The Midwest Rheumatology Summit acknowledged educational grants from Abbott, Amgen, Centocor, Genentech, Human Genome Science, and UCB. Dr. Merrill acknowledged consulting for Human Genome Sciences, Lilly, EMD Serono, GlaxoSmithKline, and Pfizer; receiving grants from Pfizer and Genentech/Roche; and receiving speaker honoraria from Human Genome Sciences/GlaxoSmithKline and Lilly.

CHICAGO – Understanding of the thrombosis risks associated with antiphospholipid syndrome has increased dramatically over the past 12 months, judging from the recent literature on the subject.

Dr. Joan T. Merrill told attendees at a seminar at the Midwest Rheumatology Summit that the annual incidence rate of thrombosis in patients with antiphospholipid antibodies was 1.86% in a prospective multicenter study of 258 patients reported this year (Ann. Rheum. Dis. 2011;70:1083-6).

"Almost 2% per year, and that kind of gets you to 20% at 10 years," said Dr. Merrill. "That’s pretty high, and that’s pretty scary." Hypertension predicts thrombosis, as does the lupus anticoagulant test and lack of thromboprophylaxis during high-risk periods such as post surgery or long airplane flights.

Autoantibodies directed against complement-like structures lead to inflammatory events, including cell-mediated events that lead to a prothrombotic state. "And then, just as you see in atherosclerosis ... when the winds are propitious, what you get is a thrombotic event," said Dr. Merrill, medical director of the Lupus Foundation of America and director of the clinical pharmacology research program at the Oklahoma Medical Research Foundation.

Risk factors for thrombosis are higher in people who have multiple antiphospholipid antibody types (Arthritis Res. Ther. 2011;13:R118). This can be a reason to order multiple tests if insurance providers challenge those tests, said Dr. Merrill. Higher-titer autoantibodies also increase the risk of thrombosis (Acta Obstet. Gynecol. Scand. 2011 July 5 [doi: 10.1111/j.1600-0412. 2011.01236.x]), and antibodies with higher avidity will increase the risk of thrombosis (Lupus 2011;20:1166-71).

The syndrome complicates pregnancy as well.

The odds of women with preeclampsia having anticardiolipin antibodies, versus pregnancy without preeclampsia, were statistically significant (odds ratio, 2.86; 95% confidence interval, 1.37-5.98) in a recent study (Obstet. Gynecol. 2010;116:1433-43), and the odds with severe preeclampsia were much higher (OR, 11.15; CI, 2.66-46.75).

Dr. Merrill advised keeping this increased risk in mind, "since we have lupus patients and we are probably more likely [to order the anticardiolipin screen] than the average obstetrician."

Patients with lupus or antiphospholipid syndrome also often have migraines, and a 2011 study found that patients with a history of migraines have increased thrombotic risk (J. Thromb. Haemost. 2011;9:1350-4). Dr. Merrill advised being aware that what appears to be a migraine in a patient with the antiphospholipid antibody might actually be a thrombotic event, especially if the patient is a young woman.

Significant barriers still exist to evidence-based recommendations, according to information presented last year at the 13th International Congress on Antiphospholipid Antibodies. The barriers include poor standardization of tests.

"Around the country, at different labs, you’re going to get different results. In my place in Oklahoma, I may not even be thinking the same people have lupus that you do," said Dr. Merrill.

Other barriers are a poor understanding of pathogenic risk, heterogeneous patients, and studies that are retrospective and not population based.

A case was made at the end of last year for thrombin inhibition in antiphospholipid syndrome (Acta Clin. Croat. 2010;49:469-77). This could be good news for patients, since current univalent thrombin inhibitors are oral agents, which spare the patient the pain of injecting low-molecular-weight heparin. However, low-molecular-weight heparin may be safe long term for patients with the antiphospholipid syndrome (Ann. Rheum. Dis. 2011;70:1652-4).

"There’s been discussion for many years about the role of statins in the antiphospholipid syndrome," said Dr. Merrill. In a laboratory setting, fluvastatin inhibited markers of a prothrombotic state (Ann. Rheum. Dis. 2011;70:675-82). "It doesn’t provide you with the clinical evidence we like to see, but it’s what we have so far," she said.

The Midwest Rheumatology Summit acknowledged educational grants from Abbott, Amgen, Centocor, Genentech, Human Genome Science, and UCB. Dr. Merrill acknowledged consulting for Human Genome Sciences, Lilly, EMD Serono, GlaxoSmithKline, and Pfizer; receiving grants from Pfizer and Genentech/Roche; and receiving speaker honoraria from Human Genome Sciences/GlaxoSmithKline and Lilly.

CHICAGO – Understanding of the thrombosis risks associated with antiphospholipid syndrome has increased dramatically over the past 12 months, judging from the recent literature on the subject.

Dr. Joan T. Merrill told attendees at a seminar at the Midwest Rheumatology Summit that the annual incidence rate of thrombosis in patients with antiphospholipid antibodies was 1.86% in a prospective multicenter study of 258 patients reported this year (Ann. Rheum. Dis. 2011;70:1083-6).

"Almost 2% per year, and that kind of gets you to 20% at 10 years," said Dr. Merrill. "That’s pretty high, and that’s pretty scary." Hypertension predicts thrombosis, as does the lupus anticoagulant test and lack of thromboprophylaxis during high-risk periods such as post surgery or long airplane flights.

Autoantibodies directed against complement-like structures lead to inflammatory events, including cell-mediated events that lead to a prothrombotic state. "And then, just as you see in atherosclerosis ... when the winds are propitious, what you get is a thrombotic event," said Dr. Merrill, medical director of the Lupus Foundation of America and director of the clinical pharmacology research program at the Oklahoma Medical Research Foundation.

Risk factors for thrombosis are higher in people who have multiple antiphospholipid antibody types (Arthritis Res. Ther. 2011;13:R118). This can be a reason to order multiple tests if insurance providers challenge those tests, said Dr. Merrill. Higher-titer autoantibodies also increase the risk of thrombosis (Acta Obstet. Gynecol. Scand. 2011 July 5 [doi: 10.1111/j.1600-0412. 2011.01236.x]), and antibodies with higher avidity will increase the risk of thrombosis (Lupus 2011;20:1166-71).

The syndrome complicates pregnancy as well.

The odds of women with preeclampsia having anticardiolipin antibodies, versus pregnancy without preeclampsia, were statistically significant (odds ratio, 2.86; 95% confidence interval, 1.37-5.98) in a recent study (Obstet. Gynecol. 2010;116:1433-43), and the odds with severe preeclampsia were much higher (OR, 11.15; CI, 2.66-46.75).

Dr. Merrill advised keeping this increased risk in mind, "since we have lupus patients and we are probably more likely [to order the anticardiolipin screen] than the average obstetrician."

Patients with lupus or antiphospholipid syndrome also often have migraines, and a 2011 study found that patients with a history of migraines have increased thrombotic risk (J. Thromb. Haemost. 2011;9:1350-4). Dr. Merrill advised being aware that what appears to be a migraine in a patient with the antiphospholipid antibody might actually be a thrombotic event, especially if the patient is a young woman.

Significant barriers still exist to evidence-based recommendations, according to information presented last year at the 13th International Congress on Antiphospholipid Antibodies. The barriers include poor standardization of tests.

"Around the country, at different labs, you’re going to get different results. In my place in Oklahoma, I may not even be thinking the same people have lupus that you do," said Dr. Merrill.

Other barriers are a poor understanding of pathogenic risk, heterogeneous patients, and studies that are retrospective and not population based.

A case was made at the end of last year for thrombin inhibition in antiphospholipid syndrome (Acta Clin. Croat. 2010;49:469-77). This could be good news for patients, since current univalent thrombin inhibitors are oral agents, which spare the patient the pain of injecting low-molecular-weight heparin. However, low-molecular-weight heparin may be safe long term for patients with the antiphospholipid syndrome (Ann. Rheum. Dis. 2011;70:1652-4).

"There’s been discussion for many years about the role of statins in the antiphospholipid syndrome," said Dr. Merrill. In a laboratory setting, fluvastatin inhibited markers of a prothrombotic state (Ann. Rheum. Dis. 2011;70:675-82). "It doesn’t provide you with the clinical evidence we like to see, but it’s what we have so far," she said.

The Midwest Rheumatology Summit acknowledged educational grants from Abbott, Amgen, Centocor, Genentech, Human Genome Science, and UCB. Dr. Merrill acknowledged consulting for Human Genome Sciences, Lilly, EMD Serono, GlaxoSmithKline, and Pfizer; receiving grants from Pfizer and Genentech/Roche; and receiving speaker honoraria from Human Genome Sciences/GlaxoSmithKline and Lilly.