Category Archives: POTS

What Dysautonomia Patients Should Know About Antiphospholipid Syndrome

Many patients have sent Dysautonomia International questions about the association between antiphospholipid syndrome and POTS, after an article appeared in the medical journal Lupus on this topic on February 25, 2014.  Dysautonomia International asked the first author of this article, Dr. Jill Schofield, to address some of the questions raised by the patient community in the following blog post.  Please note that this is not meant to replace advice given by your own physician.

What Dysautonomia Patients Should Know About Antiphospholipid Syndrome
by Jill R. Schofield, MD

We have recently published the first clinical association of postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope (NCS) and orthostatic hypotension (OH) with antiphospholipid syndrome (APS).  APS is also known as Hughes syndrome.  I was delighted to co-author this paper with Professor Graham Hughes, who first described antiphospholipid syndrome in 1983, Professor Yehuda Shoenfeld, considered by many to be the “father of autoimmunity” and Dr. Svetlana Blitshteyn, noted autonomic expert and member of the Dysautonomia International Medical Advisory Board.  You can view the abstract of the article here: Postural tachycardia syndrome (POTS) and other autonomic disorders in antiphospholipid (Hughes) syndrome (APS).  The journal requires a paid subscription to view the full article, but your physician should be able to access it.

What is APS?
APS is a complex autoimmune disorder that is associated with several different antiphospholipid antibodies.  These antibodies may be directed against clotting factors, platelets, and/or the cells that line blood vessel walls and they cause the blood to be too sticky. This results in an increased risk of blood clots in:

1) Arteries–causing most commonly stroke or heart attack.
2) Veins–causing deep vein thrombosis (DVT) of the legs and/or pulmonary embolus (PE) of the lungs.
3) Placenta–causing recurrent miscarriage, stillbirth or low birth weight babies.

In addition to an increased risk for blood clots, a number of other manifestations may occur in APS due to “sludging” of the blood. The list of these non-clotting manifestations is long and they are less well known to most physicians.  Some of these manifestations include migraine (which may be severe and refractory to usual treatments), memory loss, seizures and stress fractures. We have now demonstrated that POTS, NCS and OH may also occur as non-clotting manifestations of APS.

How is APS diagnosed?
The Sapporo criteria for the diagnosis of definite APS requires:

1. Clinical criteria: Thrombosis (blood clot) or very specific pregnancy complications (such as three or more miscarriages).

2. Laboratory criteria: Medium to high titer antiphospholipid antibodies on more than one occasion at least 12 weeks apart.

These criteria were designed for rigorous clinical research studies, not for diagnosis. Unfortunately, most practicing physicians believe they were designed for diagnosis and this has resulted in patients with low titer antibodies and/or non-clotting manifestations not being diagnosed with APS, when they do have the syndrome. My hope is that we can change this perception, because I believe that with earlier diagnosis, we can prevent the thrombotic events!

For our study, we used the following criteria:

At least one clinical manifestation of the syndrome (including the non-clotting manifestations) along with the presence of one or more of the antiphospholipid antibodies in any titer:

1) Anticardiolipin IgG and/or IgM
2) Beta 2 glycoprotein I IgG and/or IgM
3) Lupus anticoagulant

It is common to have only one of these antibodies, but some patients have two or even all three. Occasionally various infections might cause a transient elevation in one or more of these tests, so the diagnostic criteria require you to have one or more of these antibodies on more than one occasion at least 12 weeks apart.  Notably, many of the patients in our study had low titers of the APS antibodies.

The lupus anticoagulant test has a misleading name because it is not a test for lupus and it is associated with increased clotting, not decreased clotting as the name implies. APS, however, may occur along with lupus, as well as Sjogrens syndrome or rheumatoid arthritis. It may also occur on its own. Most APS experts are either rheumatologists, hematologists or obstetricians, but most physicians are familiar with these tests, they can be ordered at any lab and they are relatively inexpensive.

Once a diagnosis of APS is made, there is no indication to repeat the antibody tests.  APS is not known to just resolve, but the antibodies are known to wax and wane over time.  There are many stories of patients who have had their levels fall into the normal range when their physicians repeatedly tested their antibodies and when told they no longer had APS and could stop their blood thinners, they went on to develop stroke or other major clotting events.

Regarding imaging tests, CT or MRI scans are used to test for stroke or other blood clots in APS patients with suspicious symptoms and clots in this syndrome can be found in any blood vessel.    Some APS patients have “white spots” on brain MRI scans; these are felt to represent very tiny clots. Ultrasound is commonly used to test for blood clots in the legs when there is new leg pain and/or swelling.

How common is APS?
APS is not rare.  It has been estimated to affect approximately 1 out of 100 people (1% of the population).  It is, however, underdiagnosed.

We do not know how many POTS, NCS or OH patients have APS, but Dysautonomia International recently funded a research project designed by Dr. Svetlana Blitshteyn to try to shed some light on the topic of autoimmune markers and autoimmune conditions in patients with POTS.  Dysautonomia International will make an announcement when Dr. Blitshetyn’s study results are released.

We also do not yet know how often autonomic disorders occur in APS patients.

Should all patients with POTS be tested for APS?
Because this is a newly described clinical association, we have a lot to learn.  At this time, I believe all POTS patients should be tested for APS; other physicians might disagree.  At the very least, I believe all POTS patients with any of the following should be tested for APS: migraine, memory loss, balance trouble, livedo reticularis, Raynaud’s phenomenon, history of miscarriage, another autoimmune condition, a family history of blood clots or a family history of autoimmune disease. These were the most common findings in the patients in our study.  Also, of note, three of the 15 APS patients included our study also had Joint Hypermobility Syndrome (JHS).

Raynaud-hand2                               Screen Shot 2014-03-04 at 7.34.04 PM
Raynaud’s Phenomenon                                               Livedo Reticularis

The reason I believe all POTS patients without an apparent cause should be tested for APS is that POTS caused by APS might improve with a trial of aspirin, clopidogrel, heparin, warfarin and/or IVIG.  Many of these agents increase the risk of bleeding, however, which makes many physicians not experienced with APS nervous about using them in APS patients who have not had a clotting episode.  Because APS is a very hypercoagulable condition, however, APS patients (even those on high doses of blood thinners) have a much greater risk of clotting than bleeding. Despite this, Professor Hughes believes that many APS patients have been under-treated due to physician concerns about bleeding.

Additionally, APS is a serious medical condition and early diagnosis can help reduce the risk of major complications.  If you have one or more of the APS antibodies, you are at an increased risk for blood clots. If you are aware you have one or more of these antibodies, you can reduce your risk of blood clots by avoiding cigarettes, birth control pills or hormone replacement therapy.  You can also be sure that if you have other vascular risk factors, such as high blood pressure, high cholesterol or diabetes, they are treated aggressively.  Aspirin has also been shown to reduce the risk of arterial events in patients with APS antibodies.  Additionally, Professor Yehuda Shoenfeld’s research has shown that vitamin D levels are low (less than 15 ng/ml) in half of patients with APS and that low levels are associated with an increased risk for clotting and non-clotting manifestations of the syndrome.  So it makes sense for these patients to also be treated with vitamin D.

How is APS treated?
In addition to the points made above, APS patients who have had an arterial or venous clotting event are generally treated with blood thinners (usually warfarin or heparin) for life.  There are also several newer oral anticoagulants, one of which is presently being studied in APS patients in London.  Until this data is available, these drugs are generally not recommended for most APS patients.  APS patients with recurrent miscarriages are treated with aspirin and usually heparin (warfarin is contraindicated in pregnancy) throughout their pregnancy and for at least 6 weeks after delivery.

Importantly, Professor Hughes has found over the years that many of the non-clotting manifestations of APS often improve significantly or may even be completely aborted with anti-platelet agents such as aspirin or clopidogrel, and/or warfarin or heparin.  He has also found this to be true for autonomic symptoms in some APS patients.  Two patients in our study with POTS that did not improve with standard APS treatments (despite improvement of other APS manifestations) improved significantly with regular intravenous immunoglobulin (IVIG) therapy.  Unfortunately, IVIG is very expensive and many insurance companies require more data than two case reports before approving its use for a specific indication.

Where can you find additional resources on APS?
Dysautonomia International has a brief explanation of APS on its website, as well as some links to APS related journal articles and non-profit organizations. You can find a physician experienced in APS by going to APSAction.org, an international organization started in 2010 to improve collaboration amongst APS experts and to facilitate APS research.  An excellent patient forum on APS is HealthUnlocked Hughes syndrome and Professor Hughes has written a great book for patients entitled, Understanding Hughes Syndrome: Case Studies for Patients.

JillSchofieldDr. Schofield is a Johns Hopkins trained internist who has developed an interest in APS over the last few years. She currently practices in Denver, Colorado but plans to develop a multi-disciplinary (i.e. involving physicians from many specialties) APS clinic in an academic environment and is currently exploring options for where best to do this.

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New evidence of autoimmunity in POTS!

IS POTS AN AUTOIMMUNE DISEASE?

Big news this week in POTS research! Researchers from the University of Oklahoma and Vanderbilt University have identified evidence of adrenergic receptor autoantibodies in a small group of POTS patients, suggesting that POTS may be an autoimmune condition in these patients. The study was published in the Journal of the American Heart Association (JAHA). JAHA is an official journal of the American Heart Association, so this is great news for POTS awareness!

To help patients better understand what this means, Dr. David Kem from the University of Oklahoma Health Sciences Center has kindly provided Dysautonomia International with a patient friendly explanation of this complex research. Before we get to Dr. Kem’s explanation, let’s go over the basics of adrenergic receptors and autoantibodies.

Adrenergic receptors are present on the surface of cells in many different parts of the body, including the heart, blood vessels, nerves, brain, lungs, bladder, gastrointestinal tract and elsewhere. There are two main types of adrenergic receptors in the body – alpha adrenergic receptors and beta adrenergic receptors. Within the alpha and beta types, there are many different subtypes (alpha-1, alpha-2A, alpha-2B, alpha-2C, beta-1, beta-2, etc.)

Think of adrenergic receptors like a TV antenna (if you are old enough to remember when TVs had antennas!). If the TV antenna picks up a signal, it transmits a message across the screen. In adrenergic receptors the “signals” are chemicals present in the body called catecholamines (primarily epinephrine and norepinephrine). The “message” is what the catecholamine tells the receptor to do. For example, constrict a blood vessel or make the heart beat faster.

adrenergic receptor

 

Image of an adrenergic receptor, which is stimulated by catecholamines.

 

 

Antibodies are proteins created by your own immune system to protect you from pathogens, like bacteria and viruses. The human immune system can make more than 1 trillion different antibodies, each one meant to protect us from a different pathogen. Unfortunately, sometimes the antibody formation process goes awry, and the antibodies created by your immune system can turn against your own cells. These trouble-making antibodies are called autoantibodies. Autoantibodies can attack, damage or interfere with the functioning of healthy tissues and cells in your body.

Now that we all know what adrenergic receptors and autoantibodies are, here is what Dr. Kem has to say about the adrenergic receptor autoantibodies recently found in POTS patients:

POTS occurs frequently, but not exclusively, in younger females and its onset is occasionally preceded by or associated with a viral-like illness. It is more than a minor annoyance for most patients and leads to significant life changes and limitations in normal life. Our present study (Autoimmune Basis for Postural Tachycardia Syndrome) has produced data supporting the idea that production of autoantibodies, circulating proteins that normally fight such infections, have instead interacted with critical site(s) on specialized cell membrane proteins which alter their normal cell function.

These autoantibodies interfere with the system which controls the ability of blood vessels to constrict, which is needed to prevent a drop of blood pressure as a person stands. In POTS patients, this inadequate response to standing leads to a generalized increase of activity in the body’s sympathetic nerve system, which frequently normalizes the blood pressure. This increased nerve activity, however, increases the heart rate which is a prominent symptom in POTS.

We have also discovered a second group of autoantibodies in some POTS patients which directly increase the heart rate.

The combination of these two autoantibodies appears to cause the abnormal heart rate response observed in all 14 POTS patients we have tested to date for these autoantibodies.  We have previously identified similar autoantibodies in individuals diagnosed with idiopathic orthostatic hypotension (Editor’s note: see Agnostic Autoantobodies as Vasodilators in Orthostatic Hypotension: A New Mechanism and Autoantibody Activation of Beta-Adrenergic and Muscarinic Receptors Contributes to an “Autoimmune” Orthostatic Hypotension).

These autoantibodies may explain why beta blockers aren’t always effective in treating the tachycardia seen in POTS, since beta blockers fail to completely block autoantibody activity on their protein receptor and they fail to alter the partial blockade of the autoantibodies on the arteriole blood vessels that initiate the orthostatic problem.

Confirmation of our findings will require testing a larger group of POTS patients for these autoantibodies. We hope to eventually develop treatments to block these autoantibodies, without blocking the target receptor proteins at the cell surface at the same time. Such agents are in development and within a few years may be applicable in POTS. This approach may prove useful in several other diseases which are caused by similar autoantibodies.

Please note that Dr. Kem and the other researchers involved are not able to test patient blood samples for these autoantibodies outside of a research setting at this time. There are very strict federal laws that prohibit them from doing so. If such a test becomes available to the public, Dysautonomia International will be shouting it from the roof tops. Imagine that – a blood test to help diagnose POTS ? We’re looking forward to it, but there is much work to be done.

Dysautonomia International is committed to funding additional research in this area as quickly as possible. We are optimistic that this will lead to a better understanding of POTS, better ways to diagnose it, and most importantly, better ways to treat it.

If you would like to support the next phase of this exciting new research, please consider making a donation to Dysautonomia International today.  You can make a difference in the lives of millions of people around the world living with POTS!

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Postural Orthostatic Tachycardia Syndrome vs. Postural Tachycardia Syndrome

POTS or PoTS? Postural tachycardia syndrome or postural orthostatic tachycardia syndrome? What is the correct term to use?

Dysautonomia International uses the term postural orthostatic tachycardia syndrome and the acronym POTS. That’s not to say that PoTS or postural tachycardia syndrome are wrong.  Both terms and acronyms are correct, but there are several reasons why Dysautonomia International uses the longer term.

1. The original term is “postural orthostatic tachycardia syndrome.”
The first article describing POTS was written by Mayo Clinic researchers Dr. Ronald Schondorf and Dr. Philip Low in 1993. They used the term “postural orthostatic tachycardia syndrome” and the acronym POTS.

2. Slightly more journal articles have been published using “postural orthostatic tachycardia syndrome.”
The literature is pretty closely divided, but as of today’s date, if you search on PubMed.gov, the online repository of 23 million medical journal articles abstracts from the US National Library of Medicine, you will find 262 abstracts if you search for the phrase “postural orthostatic tachycardia syndrome.”  If you search for the phrase “postural tachycardia syndrome” you will find 221 abstracts.

3. The general public much more commonly uses “postural orthostatic tachycardia syndrome.”
As of today’s date, a Google search for “postural orthostatic tachycardia syndrome” returns 194,000 results.  A Google search for “postural tachycardia syndrome” only returns 38,100 results.

4. POTS patients and their doctors are more likely to use “postural orthostatic tachycardia syndrome.”
Dysautonomia International asked a large international group of patients what term they used and what term their doctors used.  Over 90% of patients responded that they and their doctors used “postural orthostatic tachycardia syndrome” and POTS.

5. Most importantly, using the term “postural orthostatic tachycardia syndrome” may help patients get better medical care.
Including the “orthostatic” word helps a medical professional, who doesn’t know what POTS is, understand a basic principle; that the person who has POTS has an orthostatic problem. Most doctors and nurses, even if they have never heard of POTS, are aware of orthostatic hypotension and maybe even orthostatic intolerance, and they have been trained how to take orthostatic vitals. Including “orthostatic” in the name of the condition gives two big hints to medical professionals that may not know what to do with the POTS patient presenting in their ambulance, ER or medical office: (1) maybe this person needs to have their blood pressure and heart rate checked in different positions, (2) maybe we need to lay this person down to prevent a faint. A person unfamiliar with POTS would not be  reminded of these clues to the nature of the diagnosis if you simply call it “postural tachycardia syndrome.”

There is no right or wrong answer, but Dysautonomia International believes that anything we can do to help POTS patients obtain better medical care should be taken into consideration.

What term do you use?

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POTS Lecture at George Mason University

Dysautonomia International was asked by the George Mason University ACHIEVES Project to provide a lecture on Postural Orthostatic Tachycardia Syndrome (POTS) during a conference last November.  ACHIEVES is a collaboration between George Mason University and the Prince William County Public Schools that seeks to educate teachers, school nurses, coaches, and certified athletic trainers on health issues related to school aged children in sports.

Dr. Peter Rowe, noted POTS researcher and pediatric cardiologist from Johns Hopkins, once again graciously donated his time and talents to Dysautonomia International to provide a lecture on POTS during the ARCHIVES conference.

While watching the video, you may notice a sign on the podium that states “Preventing Sudden Death in School Aged Athletes.”  Please note that POTS is not associated with sudden death.  This was another topic covered at the same conference.

Dysautonomia International would like to thank the George Mason University ACHIEVES Project and Dr. Rowe for providing this excellect educational opportunity.

Postural Orthostatic Tachycardia Syndrome from Vimeo.

You can find other dysautonomia related videos on the Dysautonomia International Vimeo page.

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