Hypercoagulation Linked to Chronic
Fatigue, Fibromyalgia, MS, Infertility, Chronic Illness
PART 1
Read these related articles:
Hypercoagulation
Linked to Chronic Fatigue, Fibromyalgia, MS, Infertility, Chronic Illness -
PART 2
Hypercoagulation & Heparin - A
Second Look.
Interview with David Berg
David
Berg is the Director and Cofounder, with Lois Hill Berg, of HEMEX Laboratories.
Along with Dr. Harold Harrison and several clinical collaborators, they have
developed the idea of the hypercoagulation/ immune system activation of
coagulation theory in chronic diseases, a proposed cause of Chronic Fatigue
Syndrome and Fibromyalgia, and have proposed an appropriate treatment that
reduces many related symptoms. Mr. Berg has a M.S. degree in clinical pathology
and laboratory medicine, and has been in practice for 35 years. HEMEX
Laboratories offers testing and consultative services relating to the
diagnosis, treatment, and monitoring of hematological, clotting and/or bleeding
disorders.
We first
became involved with research in chronic illnesses while we were performing re
search regarding hypercoagulability - related infertility in women with one of
the local infertility specialists here in Phoenix, AZ. We found that a
hypercoagulable state, presumably due to a coagulation protein defect, existed
in many women who were infertile and/or who had recurrent spontaneous
abortions. Our colleague Dr. Couvaras observed that when he put women on low
dose heparin in order to maintain pregnancy, some with CFS/FM-like symptoms,
pelvic pain, and migraine-like headaches had amelioration of their symptoms. He
asked us “Why?” As a result, we performed a retrospective study on 30
of these obstetric patients with chronic illness symptoms, and determined that
all had coagulation system activation. As the hypercoagulability was decreased
by heparin injections, the chronic illness symptoms diminished. This was the
first clue to the connection between coagulation and chronic illnesses. These
findings were published as a poster at the 1998 AACFS meeting in Cambridge, MA.
We
subsequently refined our test panel for low level activation of coagulation to
include Prothrombin fragment 1+2 (F1+2), thrombin/antithrombin complexes (T/AT)
and Platelet Activation by Flow Cytometry assays. Thus, the ISAC or Immune
System Activation of Coagulation panel consisting of fibrinogen (FIB), soluble
fibrin monomer (SFM), F1+2, T/AT, and PA by Flow was born. With our partner and
Medical Director, Dr. Harold Harrison and several clinical collaborators, we
then designed and conducted a prospective, multi-center, blinded, case control,
associative study of non-obstetric CFS/FM patients and controls, with centers
in New York, Houston, and Phoenix. When the code was broken, identifying
patients and controls, we were able to identify most of the CFS/FM patients
based on having two or more positive test results out of the five assays in the
ISAC panel. It was the first definitive evidence that, indeed, chronic
illnesses have a demonstrable basis in the blood coagulation system. This study
was published in the international journal Blood Coagulation &
Fibrinolysis, 1999, 10:435-438. In another associative cohort study published
in Blood Coagulation & Fibrinolysis, 2000, 11:673-678, we determined that
Gulf War illness has similar findings of low level activation of coagulation.
In
November, 1999, Dr. Joe Brewer (an Infectious Disease specialist in Kansas
City) and I developed a model of pathogen activation of the immune and
coagulation systems. The model proposes that the end result of such
pathogenmediated activation is increased blood viscosity due to 1) an
underlying coagulation regulatory protein defect, and 2) activation of the
coagulation system by the pathogen. As the blood viscosity increases, the
diminished blood flow creates hypoxia (lack of oxygen) and nutrient deprivation
within various areas of the body. This is like trying to start your car in
Wisconsin in the winter with 60- weight engine oil. This model explains the
multi-organ symptomatology and also explains why the low dose heparin therapy
is effective by increasing blood flow as the blood viscosity decreases. Thus,
patients gain relief from their symptoms with this therapy.
The model
states that coagulation activation generates thrombin, which converts
fibrinogen to soluble fibrin monomer (SFM). Soluble fibrin becomes deposited in
the micro-circulation (capillaries) as fibrin or fibrinoid-like deposition,
blocking oxygen and nutrients transfer to parenchymal tissues. Many pathogens
activate the immune system. These include viruses (such as EBV, CMV, HHV6 &
others), bacteria (mycoplasma, chlamydia, borrelia, etc), fungi (such as
candida), etc. These pathogens are anaerobes, i.e., they live and reproduce in
an oxygen deprived cellular matrix or environment. That’s why fibrin
deposition becomes important to the survival of the pathogens because it
produces decreased oxygen in cells and tissues. One of the biggest challenges
to a clinician is to figure out what pathogens are present in the patient, and
therefore the most appropriate therapies against these pathogens. The average
CFS/FM patient may have anywhere from one to seven pathogens that need
eradication.
Positivity of two or more tests in the ISAC panel occurs in more than
80% of all patients tested. However, the longer a patient has been ill (many
years), the less activation is needed by the pathogens for survival, and
therefore fewer tests may be positive. Someone who has been ill for 10 years or
more may only have one test positive in the panel. The ISAC panel also works
very well for monitoring anticoagulant therapy between 4-6 weeks after therapy
has started. It indicates whether or not there is enough heparin being given to
the patient, the overall patient improvement and the reaction of the body to
the pathogens, such as a Herxheimer-like reaction (relapse from infections or
reactivation of pathogens).
In
addition to the pathogens that can activate the immune system, metals (e.g.
mercury, lead, aluminum), exogenous toxins, chemicals, allergens, physical
trauma, vaccinations, and/or biological warfare agents can also activate the
immune system. This may lead to secondary infections, which may also trigger
coagulation activation. If the coagulation mechanism does not shut down
properly, then there is continued thrombin generation and soluble fibrin
formation, resulting in increased blood viscosity and decreased blood flow.
When you
look for a genetic basis in this model, one can test for seven different
regulatory proteins of the coagulation mechanism plus homocysteine in a panel
we call the HTRP (Hereditary Thrombosis Risk Panel). In July 2001, at the
International Society of Thrombosis and Hemostasis meeting in Paris, we
presented data from a retrospective study of over 400 chronically ill patients,
83% had one or more demonstrable coagulation protein defects. Forty percent of
the patients had a thrombophilia defect (decreased protein C, decreased protein
S, decreased anti-thrombin, APC resistance/factor V Leiden positivity, or
increased prothrombin/prothrombin gene mutation positivity). 39% of the
patients have defects in the fibrinolytic system (hypofibrinolysis due to
elevated lipoprotein (a) - Lp(a) and/or PAI1-plasminogen activator inhibitor-1.
21% of these patients had a defect in both the thrombophilia and
hypofibrinolysis marker groups. This means that not only do they form fibrin
easily, but also they are compromised in the ability to clean up the fibrin
deposition.
Let’s put this in plain English. When a pathogen(s) gains a
foothold, especially in the endothelial cells in the blood vessels (as well as
other cells), the bug(s) can be protected by the coagulation mechanism of
fibrin deposition on top of the infected cells. Half of the patients form
fibrin very fast, becoming fibrin(oid) deposition. Half of the patients have an
inability to clean up the fibrin, and therefore continue to have oxygen and
nutrient starvation of tissues for a long time. For example, if the fibrin
deposition occurs in a muscle, it says “ouch,” and you have a tender
point as in Fibromyalgia. If it is in the placenta, the placenta is compromised
by fibrin deposition and the baby aborts. As blood viscosity increases and
blood flow is reduced throughout the body, the patient becomes hypo-this and
hypo-that, such as hypothyroid, hypo-HPAaxis, hypo-estrogen, etc. The use of
low dose heparin restores blood flow throughout the body and hormones from the
endocrine system tend to normalize. Thus, the blood flow issue becomes one of
the most important issues of chronic illnesses. Unfortunately there is no easy
test to measure blood flow, only the effects of blood flow.
If you
consider the movie “Braveheart” (1000 AD) and you went to battle and
were wounded, you probably would have bled to death unless you clotted fast. By
clotting fast, you saved your own life and passed on this new trait to your
children. This hypothesis may explain how these coagulation defects were
genetically selected during the last 2000 years in Europe. Life expectancy back
then was only 30-40 years. With our life expectancy now of 80+ years, these
traits are no longer beneficial, but rather deleterious to our health. It was
the Spanish, French, British, Germans, Italians, Scandinavians, etc.
(Europeans) that colonized the Americas. This explains why most of the
chronically ill patients are white people of European decent. Therefore we have
a genetic basis in the coagulation system for chronic illnesses that is very
straightforward.
The model
of reduced blood flow from increased blood viscosity due to activation of
coagulation accompanied by a coagulation protein defect gives a scientific
basis for a contribution to the pathophysiology of chronic illness. It also
gives a measurable or quantifiable, objective aspect to testing the blood of
patients with these diseases. It is no longer “all in your head”, but
rather in your “blood.” It’s not rocket science, but a simple,
logical explanation for what’s going on in many chronically ill patients.
HEMEX Laboratories
provides testing services and consultative interpretations to clinicians and
physicians throughout the United States. For more information, technical
reprints, and/or patient information, please see their website at
www. hemex.com
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