This blog is part IV in a series of blogs covering the issues presented at the 2018 Dysautonomia International Conference in Nashville, Tennessee.
As if we needed another syndrome. Chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), fibromyalgia (syndrome), irritable bowel syndrome (IBS) are old-timers in the ME/CFS/FM world. In the last couple of years, mast cell activation syndrome (MCAS) and Ehlers Danlos Syndrome (EDS) joined the party. Sjogren’s Syndrome (SS), which was all over the Dysautonomia International conference, may be a late entry, and now it seems we can add antiphospholipid antibody syndrome (APS) – which is apparently very common in POTS – to the list of syndromes that play together in these interrelated diseases. It’s also another autoimmune disease.
In fact, Dr. Hughes, the U.K. rheumatologist who discovered the syndrome, said that if you’re dealing with POTS, you’re very likely dealing with APS, which is also called “Hughes Syndrome”, as well.
Antiphospholipid Antibody aka Hughes Syndrome
APS is not some niche researcher’s fantasy; it’s a well-recognized systemic autoimmune disease which increases the clotting factors in our blood, producing “sticky blood”, which then impedes blood flows.
APS occurs when increased levels of antibodies attack the phospholipids or fats in our cells and in the lining of our blood vessels. (You can have the antibodies without having the disease.)
Like other systemic autoimmune diseases, APS can cause a wide range of symptoms that seem disturbingly like those found in ME/CFS. They include chest pain, shortness of breath, pain, redness, warmth, and swelling in the limbs, cold hands, chronic headaches, upper body pain, nausea, brain fog (memory problems, can’t find way home, forget words), balance problems, heart valve problems and a lacy-looking red rash on the wrists and knees. (Notice no mention of post-exertional malaise, though.)
The NIH’s National Heart and Lung Institute reports that APS can cause many health problems including heart attack, stroke, pulmonary embolism and kidney damage. Dr. Hughes reported that APS is commonly found in teenage migraine, stroke, heart attack and teenage epilepsy but is often – more than 30 years after its discovery – undiagnosed.
It affects 1-5% of the population and more often strikes women than men. One third of strokes occurring in younger people (<50 years) are believed due to APS. If you suffer from migraines and cold hands, he suggested that you may have APS. If you have APS, it’s likely you have another autoimmune disease as well.
Dysautonomia, Postural Orthostatic Tachycardia Syndrome (POTS) and Antiphospholipid Antibody Syndrome (APS)
Most of the focus in APS has been on its connection to stroke, clots and pregnancy, but Schofield proposes that its effects on autonomic neuropathy (damage to the autonomic nerves) can be just as devastating.
Dr Schofield – who has pioneered research into APS and POTS – first published evidence of APS in POTS in a small 2014 study. (No ME/CFS or FM studies have been done – but see Dr. Berg’s work below.) A 2015 exercise study, which showed evidence of impaired aerobic capacity and autonomic control, suggested APS could also be misdiagnosed as chronic fatigue syndrome (ME/CFS).
A 100-person 2015 study found APS antibodies in 7% of POTS patients while Schofield’s 38-person 2018 study found that 76% of participants in a retrospective IVIG trial in autoimmune dysautonomia (many of whom had POTS) had APS antibodies.
In her 2014 study, “Autonomic neuropathy-in its many guises-as the initial manifestation of the antiphospholipid syndrome” Dr. Schofield outlines two ways APS might be smacking POTS patients. Either the clotting caused by APS is damaging the autonomic nervous system fibers lining the capillaries; or the antiphospholipid antibodies are binding to and damaging the small fiber neurons.
A POTS / ME/CFS Mimic?
Schofield and others have shown that APS antibodies can be found in POTS patients, but Dr. Hughes proposed that APS may be being misdiagnosed as POTS as well. APS can produce symptoms (dizziness, vertigo and other neurological symptoms) similar to those found in POTS. In fact, Hughes reported that some cases misdiagnosed as POTS cleared up when the anticoagulant therapy used in APS was introduced.
A 2015 exercise study which showed evidence of impaired aerobic capacity and autonomic control provided the intriguing suggestion that some people diagnosed with chronic fatigue syndrome (ME/CFS) might actually be suffering the effects of APS – a treatable disease.
Dr. Hughes first tries aspirin, then, if necessary, two weeks of low molecular weight heparin. If that doesn’t work out, he moves on to Coumadin – a harsher drug. The anticoagulant therapy does not cure APS but it can stop the clotting process and clear up the symptoms it causes. Hughes noted one “POTS” patient who did not respond to POTS medications but did respond to heparin and his POTS cleared up.
Dr. Schofield reported that anti-coagulation in combination with IVIG can result in “meaningful clinical improvement” in patients with autoimmune dsyautonomia.
Antiphospholipid antibody syndrome (APS) is an autoimmune disease which causes increased clotting
It’s primarily associated with stroke, heart disease and problems in pregnancy, but Dr. Schofield believes it may be contributing to dysautonomia’s such as POTS
Dr Schofield believes APS may be impeding blood flows in the small capillaries and/or contributing to the small fiber neuropathy found in POTS.
Because APS can cause similar symptoms to POTS and ME/CFS some people diagnosed with those diseases may actually have APS – which is treatable
Treatment involves anticoagulants such as aspirin, heparin or coumadin
Around 2000 Dave Berg published several studies suggesting that an APS-like condition was present in ME/CFS, FM, GWS and related diseases.
Berg produced a treatment protocol which used heparin and immune factors to remove the fibrin depositions and pathogens he thought were present
With Berg’s retirement interest in coagulation and ME/CFS faded but recent studies suggest red blood cell and coagulation problems may exist in fibromyalgia.
Positive antibody results in combination with the right clinical picture are enough to make a diagnosis.
Two types of antiphospholipid antibodies are found: 1) anticardiolipin antibodies (IgG, IgM, and IgA); and 2) something called the lupus anticoagulant, which is directed against beta-2-glycoprotein I (IgG, IgM, IgA) in the blood and prothrombin, and plays an important role in clotting.
Dr. Schofield, who is making something of a career of finding newer, more effective antibody tests in POTS, found that prothrombin-based antibody testing (aPSPT antiphosphatidylserine-prothrombin, aPT antiprothrombin) was far more effective in identifying possible APS patients in POTS.
Testing can also include a panel of blood clotting tests (dilute Russel Viper venom time (dRVVT), lupus aPTT, mixing studies, the hex phase phospholipid test, and the platelet neutralization procedure).
The “Sticky Blood” Chronic Fatigue Syndrome (ME/CFS) / Fibromyalgia Connection
Around the year 2000, several studies suggested that a kind of coagulatory offshoot of APS was happening in ME/CFS. Three studies, one of them very large, suggested that ME/CFS and fibromyalgia patients had hypercoagulated or thickened blood, which David Berg speculated was reducing nutrient and oxygen flows to their tissues.
Berg, who ran Hemex Labs, believed an infection was triggering – or had triggered – antibodies, which ultimately produced the thickened or sticky blood which was clogging up the small capillaries in the body.
Berg also believed his hypothesis could account for the fascia/trigger joint problems in fibromyalgia. In an interview with Dr. Mazlen found on the website “CFS Remission”, he described what he believed was going on:
“The inability to clean up the blood vessel walls once fibrin is formed…The model simply says…they (fibromyalgia patients) form antibodies to whatever their invading pathogen is, (then) the immunoglobulins knock off the protective proteins on the endothelial cell’s surface.
“This exposes phosphatidyl serine in the capillaries to the flowing blood, and that allows the coagulation proteins to bind and so all of a sudden we’re generating thrombin in the small vessels in the capillaries throughout the body.
“So, if we take a muscle and pull it down to a ligament or a tendon and wrap that with the fascia, that fascia is only 5 or 6 cells thick, that’s where the capillary blood flow is and so if you coat the insides of that capillary with fibrin, not a blood clot, but fibrin, then the nutrients and oxygen do not pass through to that ligament or tendon on the other side and all of a sudden it says “ouch” and we’ve got a trigger point, a defined trigger point as in fibromyalgia.”
Berg’s ME/CFS/FM Treatment Protocol
In a Town Hall meeting in 2000, Berg presented a treatment protocol designed to stop the coagulation problems and then clean up the infections he believed were hiding in the coagulated areas:
- Provide heparin for 6 months (Berg described heparin as an anticoagulant, anti-inflammatory, antiplatelet, vasodilator, and NO production increaser).
- Add Bromelain at the beginning for 4-6 months for patients that have an increased Lp(a) or PAI-1.
- Add Transfer Factor after 30 days of heparin for 2-3 months.
- Add antibiotics 30 days after heparin.
- Continue to use heparin for another 2 months, just in case. If there are still a few pathogens left after these therapies, they will attempt to reactivate the coagulation cascade again, to generate Soluble fibrin &/or fibrin deposition. So by continuing heparin, this will prevent cascade reactivation and the immune system will be able to clean up the remaining pathogens.
Berg sounded like he was on a roll. He had a protocol he thought would work and described a typical response to heparin:
“I swam three laps and then worked in my yard. Oh am I going to pay for it tomorrow but only with sore muscles that haven’t been used in so long. Today, when I came in the house I gave in to my urge that I’ve had for the last 2 days to go skipping down the hall. I did it 3 times. How funny I looked. Like a little kid just learning to balance and learning to skip. Now I have to retrain my muscles but my mind still remembers how. That little girl in me got the biggest kick out of skipping again and it’s been years.”
Berg’s retirement in the early 2000’s apparently ended further efforts to establish his findings. A small study (n=17) in 2006 failed to find evidence of hypercoagulation. From what I can tell, nothing more has been done. Pathogen tests since then have failed to find evidence of the infections Berg believed were present, but inflammation could conceivably do the trick, and possible blood issues have continued to pop up in ME/CFS, fibromyalgia and related diseases.
Two 2017 studies found evidence of increased red blood cell deformity and rapid platelet aggregation as well as increased platelet distribution width – a marker of coagulation – in fibromyalgia. A small 2018 Gulf War Syndrome study found evidence of red blood cell deformability issues.
Just as Berg thought with ME/CFS over 15 years ago, Dr. Schofield believes antibodies in POTS and other autoimmune autonomic diseases are blocking blood flow in the capillaries. Ron Davis’s group is exploring whether red blood cell deformability problems are having a similar effect.
Could red blood cells be causing problems in all these diseases? Anything that restricts blood flow in the capillaries could lead to hypoxia and hamper energy production. Vermoulen’s exercise test results suggested reduced oxygen availability was causing the energy production problems he found in ME/CFS. We should learn much more about this with Dr. Systrom’s studies which the Solve ME/CFS Initiative is helping to fund.
More on Berg
- Perhaps the best explanation of Dr. Berg’s hypothesis and findings can be found here.
- Find out more about David Berg and hypercoagulation on Ken Lassesen’s CFS Remission site.
2018 Dysautonomia International Conference Blogs
- 2018 Dysautonomia International Conference I: Small Fiber Neuropathy, POTS, MCAS and Vagus Nerve Stimulation
- The 2018 Dysautonomia Conference Pt. II: Could You Have a Spinal Fluid Leak? An ME/CFS, POTS, FM Perspective
- Dysautonomia International Conference Pt III: The Autoimmunity Revolution in POTS