Common Risk Factors for thrombosis (clots)
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
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 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).
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
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.
reduction of inflammatory cytokines (such as TNF-a) also reduces platelet
aggregation and the tendencies toward thrombus formation.
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).
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).
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
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.