Common
Risk Factors for thrombosis (clots)
Fibrinogen
Fibrinogen is
the precursor to fibrin, a protein that binds platelets together to form a
blood clot. It has a role in normal and
abnormal clot formation (coagulation) in the body. During coagulation, fibrinogen reacts with
thrombin, producing fibrin, which in turn creates an insoluble fibrin network
generally referred to as a scab.
Fibrinogen also promotes platelet aggregation
that can lead to diminished blood flow and reduced delivery of oxygen to the
body. Fibrinogen causes blood platelets
to bind together, initiating abnormal arterial blood clots.
In a study of cardiovascular laboratory tests
in 136 patients with acute stroke; 76 patients with comparable risk factors for
stroke; and 48 healthy controls. Statistical analysis found that prior stroke
and fibrinogen levels predicted new events in stroke patients. After 1 year, fibrinogen levels remained
elevated in stroke survivors. The researchers concluded that fibrinogen levels
are associated with increased risk of recurrent vascular events (Beamer et al.
Neurology 1998).
Homocysteine
Homocysteine is
a toxic compound formed in the body from the amino acid methionine. Several
studies have shown that homocysteine increases blood coagulation by inhibiting
tissue fibrinogen activators. The result
is increased levels of fibrinogen and fibrin (de Jong et al. 1998; Selhub et
al. 1998; Coppola et al. 2000; Durand et al. 2001; Kuch et al. 2001).
Atherosclerosis
Once symptomatic atherosclerosis has developed,
a person is at significant risk for stroke, heart attack, and peripheral
arterial occlusion. The occlusive event (stroke, MI, etc.) tends to develop at
sites of pre-existing narrowing (stenosis). Atherosclerotic plaques can rupture
and expose tissue factor-rich plaque contents to the blood, initiating thrombus
formation.
Inflammation
Chronic inflammation is associated with a
variety of chronic diseases, including cardiovascular disease. C-reactive protein (CRP) is a sensitive indicator of
inflammation that rises before the erythrocyte sedimentation rate. C-reactive
protein is a marker of systemic inflammation and unstable arterial plaque, both
of which are indictors of increased thrombotic risk.
An article in the journal Thrombosis Research
described a study of patients with acute thrombotic stroke prior to treatment.
The patients with elevated C-reactive protein also had significantly elevated
plasma levels of thrombin-antithrombin complex (T-AT Complex),
plasmin-antiplasmin complex, and D-dimer of fibrin. When compared to those with
normal levels, platelet aggregation induced by adenosine diphosphate (ADP) was
also significantly higher in patients with elevated CRP. The authors
hypothesized that the activation of the blood coagulation and platelet
aggregation system may be related to elevated CRP levels in stroke patients
(Tohgi et al. 2000). An article in by Libby in Scientific American May 2002
provides an excellent discussion of the link between chronic inflammation and
atherosclerosis and coronary artery disease.
In
vessels, reduction of inflammatory cytokines (such as TNF-a) also reduces
platelet aggregation and the tendencies toward thrombus formation.
Lipoprotein (a)
Lipoprotein (a) is
an altered form of LDL cholesterol that has a structure nearly identical to
plasminogen, a protein that forms plasmin. Plasmin dissolves fibrin.
Unfortunately, lipoprotein (a) inhibits the breakdown of fibrin by competing with
plasminogen. Lipoprotein (a) was found to be a key component in blood clots,
plaque formation and CHD (coronary heart disease) (Rath et al. 1989; Beisiegel
et al. 1990).
Linus Pauling's theory of heart disease focused
on the adverse effects of lipoprotein (a) on the cardiovascular system. Pauling
and Rath proposed that lipoprotein (a) acted as a surrogate (replacement) for
vitamin C ( Rath et al. 1990a). They also proposed that a deficiency of vitamin
C resulted in the increased production of lipoprotein (a) which both hardened
the arteries and caused blood clots (Rath et al. 1990b).
Hypothyroidism
The endocrine system is a complex mechanism in
which each organ in the endocrine system impacts the function of other organs.
A low-functioning thyroid (hypothyroidism) would
therefore impact other systems, including the cardiovascular system.
Hypothyroidism is associated with increased cholesterol levels,
atherosclerosis, and increased homocysteine (Carantoni et al. 1997; Diekman et al.
1998; Nedrebo et al. 1998; Hussein et al. 1999; Hak et al. 2000; Kahaly 2000;
Diekman et al. 2001). The effect of hypothyroidism on the blood clotting system
is currently controversial and is the focus of several studies (Chadarevian et
al 1998; Muller et al. 2001).
Platelet Adhesiveness
In the 1970s at the National
Heart Hospital
in London a
platelet adhesiveness index (PAI) was developed. In this test a blood sample
was taken and split into two portion. In
the first portion, the platelets were counted just as they would in routine
blood cell count. The second portion of
the sample was passed over glass beads and the resulting platelets
counted. The more platelets that stuck
to the glass beads, the lower the platelet count and the higher the platelet
adhesiveness index (PAI). If half the
platelets stuck to the beads, PAI was 50.
What was observed was patients who had survived a heart attack would
have a higher PAI (50 for example) and were at risk of death from a second
heart attack. Young women who never
suffer from MI had a low PAI (20) and yet had proper blood clots in wounds.
From
1960 - 1965 at the National
Heart Hospital,
a PAI test was performed on every patient.
Not a single patient with PAI less than 40 was seen at this hospital for
heart disease. Anyone with a PAI <40
was apparently not having heart attacks.
They reasoned that a great contribution to having a heart attack
(“myocardial infarction” or MI) may be due to blood clotting in coronary
arteries. This is in part why aspirin
use became promoted.
The idea of testing for platelet adhesiveness never
came to the USA,
but the idea of reducing platelet adhesion did become part of the approach to
heart diseased due to the financial influence of pharmaceutical companies. Today there are several drugs promoted to
reduce PAI, one of which is the drug dipyridamole (Persantine®). From the European Stroke Prevention Study it
was observed that ~90% of strokes are caused by blood clots in the blood
vessels of the brain (thrombotic strokes).
Patients who had had an indication of a stroke used aspirin alone and
there was little or no benefit. When dipyridamole 300mg was added to the
treatment, stroke deaths were reduced by 50%, heart attack deaths by 35% and
cancer deaths by 25%.
There are many things that reduce PAI better than
aspirin and perhaps Persantine. To list
a few: Vitamin E 400 IU/day, Vitamin B6 >40mg/day, EPA/DHA from fish
oil, purple grape juice at 10 oz/day, GLA in evening primrose oil (supposed to
reduce PAI better than anything else), the oils of onion and garlic, ground
ginger, etc.
