Warfarin Institute of America

DEDICATED TO YOUR HEALTH SINCE 2000

INFORMATION ABOUT ANTIPHOSPHOLIPID ANTIBODY (HUGHES) SYNDROME

This information reworked and updated by

Laurel K. Forrest

Pharm D. Candidate

University of Colorado Health Sciences Center

School of Pharmacy 

  What is Antiphospholipid Antibody Syndrome (APS)?

APS is a condition in which the body recognizes a normal component of the vascular system, namely phospholipids that line the inside of our veins and arteries, as foreign.  When the body discovers that a foreign substance is present, it ramps up to attack the foreign substance, thus triggering an immune response.  Here lies the problem.  Normally, an immune response is a good thing.  This is what allows us to fight off and get rid of nasty bugs that cause the flu and common colds etc.  In the case of APS, the immune system is mounting an inappropriate response and attacking a normal part of us.  This is why these types of diseases are called auto-immune diseases, because it’s an attack against self.

  International Consensus Statement of Classification Criteria for Antiphospholipid Syndrome (The Sapporo Criteria)

  To be diagnosed as having APS a person must have:

• Experienced a clot in either an artery or vein

• Miscarriage (if a female who has been pregnant)

• Anticardiolipin antibodies

• Lupus anticoagulant

What are the possible outcomes from having this condition?

      Patients with APS are at risk mostly for recurring venous or arterial thrombosis, also known as blood clots. These may occur in almost any location from the legs to the lungs to the brain. There are also reports of the occurrence of spontaneous abortion and decreased platelet count.

Is there a treatment for this condition?

      Therapy is usually directed at the prevention of a thrombotic event (prevention of blood clot formation).

Is this treatment necessary?

      Blood clots that form for instance in the leg, known as a deep vein thrombosis or DVT, can become mobile in the blood stream.  This clot may then travel to the lungs, causing what’s called a pulmonary embolism or PE.  Clots that form elsewhere may may travel to the brain and cause a stroke.

What treatment is recommended for the prevention of a blood clot?

      Patients with APS are usually started on Coumadin® or Jantoven,® also known by the generic name warfarin.

How does warfarin work?

      Warfarin works by inhibiting several steps in the clotting process, thereby decreasing the occurrence of clot formation.

Is there strong evidence to suggest the success of warfarin therapy in APS patients?

  Editor's Note:  I have monitored the warfarin for many people with this condition and I'm not in agreement with the conclusion that an INR of 2.0 to 3.0 is adequate.  I have seen several people who have clots every time their INR drops below about 2.5.  The people with this condition experience unpredictable fluctuations in their INR test results.  In other conditions for which people take warfarin (Coumadin, Jantoven), this can almost always be traced to unreliable dosing, adding or subtracting interacting medications, eating habits etc.  However, APL Syndrome people are very conscious of their medical condition and have generally ruled-out these causes for the fluctuating INRs.  This leaves us with the conclusion that it must be something in their blood that causes the test to be inaccurate. Many of these people also seem to be able to predict their INR level based upon how they feel.  I have not found people with any other condition who were capable of reliably predicting this. 

How long will I have to take warfarin?

        The optimal duration of warfarin therapy in APS patients is unknown.  Because there is such a high risk of a recurring thrombotic event, the general consensus is to treat patients that have APS and have had a clot, for an indefinite time period -- probably lifelong or at least until a better agent becomes available.   Dr. Rodger Bick, a well-respected hematologist, predicts that eventually all people with this condition will have a clot while on warfarin and require low-molecular-weight heparin therapy by injection.

 Is warfarin therapy safe?

© 2006 Laurel K. Forrest  Used by permission

  Since this has only been a recognized medical condition for about the past twenty years, there are few long-term, outcomes studies.  Recently the problem of why the INR does not give good results has captured the interest of researchers such as Dr. Maureane Hoffman.  This has led to going "back to the basics" such as rethinking the entire mechanism of how blood clots.  

  The clotting problem is so serious in APL that some authorities in the coagulation field have concluded that warfarin (Coumadin, Jantoven) is not a very effective drug in this condition.  However, in the US at least, it is about the only oral choice available.  The alternative choices are the injections unfractionated heparin (UF) and low-molecular-weight heparin (LMWH).  UF is even harder to control than warfarin (Coumadin, Jantoven).  LMWH is easier to control but costs in excess of USD 50.00 per day.  They also often leave unrelenting bruises giving rise to the term "eggplant belly" to describe the portion of the body where they are injected.  

  Research is getting to the basics of how the antibodies increase the risk for blood clots by:

• Inhibiting the action of protein C - a natural anticoagulant that prevents the blood from clotting in the arteries and veins
• Inhibiting the action of antithrombin III - another natural anticoagulant
• Disrupting the annexin V shield - this is a protein that normally forms a shield around phospholipids to prevent their action in forming clots.  This speeds up the formation of clots and may be the most important feature of antiphospholipid antibody syndrome.
• Increasing the amount of tissue factor on cell surfaces - this is a substance that normally is released in an injury that starts the blood clotting reaction
• Interfering with the breakup of clots after they are formed

  Crowther et al. reported on the results of a randomized, double-blind study to determine whether an INR range of 2.0 to 3.0 or a INR range of 3.1 to 4.0 prevented recurrent blood clots in people with the Antiphospholipid Antibody Syndrome. They studied 114 people for a mean of 2.4 years. The lower-intensity group had 56 people while the higher-intensity group had 58 people. The groups were very similar except that the higher-intensity group was 48% female while the lower-intensity group was 71% female.

  In the high-intensity group 10.7% of the people had recurrent thrombosis. In the lower-intensity group, 3.4% of the people had recurrent clots. There were more major bleeding episodes in the higher-intensity group (3.6%) than in the lower group (2.2%)

  The authors concluded that setting the INR goal at 2.0 to 3.0 was appropriate for people with antiphospholipid antibody syndrome.

  There were several follow-up letters to the editor disputing the conclusion. I’m not sure that I agree with that conclusion either. There were eight people who had clotting events during the study. These were four deep vein thromboses (DVT), two heart attacks (MI), one pulmonary embolism (PE), and one stroke (CVA). Five of these eight events occurred when the INR was below 2.0. It seems to me that the more practical conclusion is that the INR should never be allowed to drop below 2.0 in people with this condition.

  This also seems to agree with the observations in my clinic. Over the past eight years, I have managed warfarin (Coumadin, Jantoven) therapy for about 100 people with antiphospholipid antibody syndrome. Many of these people will have DVTs when their INR drops below about 2.5. I have even seen one young woman who had a clot in the retinal vein of her eye, lost all vision in that eye and eventually had it removed due to the pain that it caused.  To read about this condition, click here.

  The main conclusion that I would draw for people with this condition to ALWAYS maintain an INR above 2.0.

References:

Crowther MA et al. A comparison of two intensities of warfarin (Coumadin, Jantoven) for the prevention of recurrent thrombosis in patients with antiphospholipid antibody syndrome. N Engl J Med 2003;349:1133-8.

The following are all letters to the editor about the above article:

Paul N

Kosinski C

Gelber A et al

Stern S

Crowther et al N Engl J Med 2003; 349:2568-70

Ortel TL. The Antiphospholipid Syndrome. Anticoagulation Forum Eighth National Conference on Anticoagulant Therapy.  Orlando FL May 6-7, 2005.

Wilson et al. Arthritis Rheum. 1999;42:1309

Lim W, Crowther M, Eikelboom J.  Management of Antiphospholipid Antibody Syndrome.  JAMA 2006; 295 (9):1050-57.

  The situation with this condition can be summed up by this quote:

      "Once upon a time the physician was hard put to distinguish between the true-positive blood test for syphilis and the biologic false-positive reaction...  There was rejoicing when the physician could happily proclaim that the patient had a biologic false-positive reaction and not syphilis...  Time has made it clear that ... antibodies appearing without apparent cause may be the harbinger of an autoimmune disease...  One cannot help wondering if the patient would be better off with syphilis."  -- Fiumara. N Eng J Med. 1963;268:402

Hughes Syndrome: An Interview with Two Patients

by

Linda Bee Lo, Pharm D Candidate

University of Colorado Health Sciences Center

School of Pharmacy

What is Hughes syndrome: history, symptoms, research. Hughes Syndrome. Available at: http://www.hughes-syndrome.org/what1.htm. Accessed September 27, 2004.

© 2004 Linda Bee Lo  Used by permission.

  Many people with APL are highly motivated to control what is happening with their bodies.  However, they are frustrated by the fact that so little is known about this condition.  To assist with this understanding, this page is devoted to resources for people with APL.  

    Here is also a list of useful sites collated by Jan Pankey, MD and Tina Pohlman for people with an interest in this syndrome:

http://www.hughes-syndrome.org Hughes Syndrome Foundation (United Kingdom). Basic information about APS. Membership available (newsletters, HSF booklets by Dr. Hughes and APS patients)

Online encyclopedia page with exhaustive links to APS information

Sticky Blood Explained, by Kay Thackray. Described by one of her doctors as "Coming from a patient, and coming straight from the heart." Kay had an APS-related heart attack at age 37. Available thru sticky.ewebis.com (see above).

Positive Options for Antiphospholipid Syndrome (APS): Self-Help and Treatment, by Triona Holden and Robert Roubey. Descriptions of problems caused by APS and ways of dealing with them. Available in bookstores, or can be ordered through online bookstores.

© 2001 - 2007  Lodwick Creations, LLC

Home                              Back to interactions list

Contact Mr. Lodwick at allodwick@earthlink.net

Last updated June 14, 2007