WASHINGTON, D.C.—Catastrophic antiphospholipid syndrome (CAPS) has all the makings of a physician’s nightmare—it’s hard to diagnose, it’s hard to manage, and it can kill—so a team approach and quick action are essential in treating the disorder, an expert said during a clinical review titled, “Catastrophic Antiphospholipid Syndrome,” here at the 2012 ACR/ARHP Annual Meeting, held November 9–14. [Editor’s Note: This session was recorded and is available via ACR SessionSelect at www.rheumatology.org.]
The disease—which involves sudden clotting on multiple fronts—is rare, but “unfortunately, the mortality rate is still very high,” said Doruk Erkan, MD, associate professor at Weill Cornell Medical College and associate physician-scientist at the Barbara Volcker Center for Women and Rheumatic Diseases, both in New York. A registry showed a short-term death rate of 33% for patients diagnosed between 2001 and 2005.
“This is a complex disease that requires a team approach,” Dr. Erkan said. “There is no single physician in the world in my mind who can manage these patients alone. And the rheumatologist is a critical team member.”
The Role of aPL
Understanding antiphospholipid syndrome (APS), he said, is essential to understanding CAPS. The updated Sapporo criteria for APS are at least one clinical event—either thrombois or pregnancy morbidity—and one positive antiphospholipid antibody (aPL) test.
He emphasized, though, that the clinical manifestations of aPL should be viewed as part of a spectrum; that thrombosis can be a product of several factors, not just aPL; and that not every positive aPL test result is clinically significant.
“We need to ask the question: Is this a clinically significant aPL profile? The answer is not yes or no,” he said. “It’s like reading an EKG. You need to look at several parameters,” like persistent positivity.
The CAPS definition, then, is thrombosis in three or more organs, and these events must occur simultaneously or within a week. There must be confirmation of microthrombosis by biopsy and confirmation of persistent aPL.
If a patient has only three of the four, then the disorder is classified as probable CAPS. So, if a patient meets the other criteria but only two organs are involved, or if the other criteria are met but occur over the course of more than a week but less than a month, it’s labeled probable CAPS. If the disorder can’t be confirmed with a biopsy or persistent aPL is not confirmed, it’s also classified as probable CAPS. The reason for this designation is “really to suspect the disease early and to treat the disease as soon as possible,” Dr. Erkan said.
He has also created what he calls “CAPS-like” designation, with recurrent events despite every conceivable treatment, thrombosis with bleeding, isolated microthrombosis with bleeding, and severe thrombocytopenia.
The only registry for CAPS data (www.med.ub.es/mimmun/forum/caps.htm), kept by the European Forum on Antiphsopholipid Antibodies, shows that only about half of patients had definite CAPS, while the rest were probable cases—the main reason for a lack of confirmation was having no biopsy.
The registry shows that 70% of patients with suspected CAPS are female, and about half have trigger factors, mainly infections and surgical procedures. CAPS most commonly affects the kidneys, lungs, and brain, according to the registry’s data.
Only about half of patients have a history of APS, “which creates another diagnostic challenge,” Dr. Erkan said.
There is some evidence that the presence of aPL makes thrombotic micro angiopathies clinically worse. For instance HELLP Syndrome—a condition during pregnancy involving breakdown of red blood cells, elevated liver enzymes, and a low platelet count—is more serious when the woman is also positive for aPL.
“If an aPL-positive patient develops HELLP syndrome, there is tendency to have an early onset less than 24 weeks,” Dr. Erkan said. “There’s a more severe clinical course. Many patients develop hepatic infarcts. And it does not get better with delivery. These patients require much more aggressive treatment.”
He added, “It’s very clear that if aPL is part of the picture, the prognosis is worse. And I believe this is true for the rest of the thrombotic microangiopathies,” although there is no systemic data on it.
A related phenomenon, known as the “thrombotic storm,” is about to be studied in a trial. Lead researcher Craig Kitchens, MD, of the University of Florida, Gainesville, has hypothesized that large clots produce a thrombotic storm by producing thrombin, decreasing fibrinolysis, increasing coagulation activation products, and speeding up consumption of natural anticoagulant products. They are now recruiting subjects to delve into the topic further.
Deciding on Treatment
Dr. Erkan said that if you’re a rheumatologist and get a call asking for help with a patient with multiple clots, the first question should always be: Is there a history of APS or aPL positivity?
If yes, and the picture looks CAPS-like, “jump on it right away, start treatment as soon as possible,” Dr. Erkan said—especially if there are no other thrombotic risk factors in play.
Some of the medications used in CAPS patients include anticoagulation, corticosteroids, intravenous immunoglobulin, plasma exchange, rituximab, and cyclophosphamide—but the approach depends on the clinical features, and there are no systematic controlled data.
Dr Erkan made the point that “major bleeding is a poor prognostic factor in CAPS patients, and anticoagulation should be started as soon as possible, sometimes despite minor bleeding.” However, the timing of the anticoagulation is a real challenge. Dr. Erkan and others studied APS patients who developed bleeding, and came to the conclusion that “whatever decision you make with respect to the timing of the anticoagulation, things can go wrong.”1 Starting too early can lead to more bleeding; too late, more thrombosis.
“There is no right answer,” he said. “Somebody needs to make a decision.” One compromise might be to start a very low dose and then increase it if the patient can tolerate it.
“One way or another, rheumatologists will see patients in intensive care who have multiple blood clots,” Dr. Erkan said. “Catastrophic APS should always be considered in these patients. Early diagnosis and aggressive treatment are absolutely essential to obtain a positive outcome.” He also stressed the importance of not overdiagnosing CAPS, especially when patient have other thrombosis risk factors and nonsignificant aPL profiles.
Thomas Collins is a freelance medical journalist based in Florida.
Reference
- Silverberg M, Erkan D, Lockshin MD. Hemorrhage in the antiphospholipid syndrome: The challenge of anticoagulation. Arthritis Rheum. 2003;46:S52.
