Because clotting has a vocabulary of its own, I have included this
Clotting Glossary, to help you understand some of the terms found in
Typically clots are not called acute and chronic, but you are
correct that fibrin and calcium have roles in the process. Calcium,
also known as Factor IV, is necessary in the clotting scheme, but I?ve
not heard of clots becoming calcified, without an indwelling catheter
of some kind. (I would suppose this could theoretically happen, it
must not be common).
?There are many types of blood clots that can occur in the veins:
· Deep vein thrombosis (DVT) is a blood clot occurring in a deep vein.
· Pulmonary embolism is a blood clot that breaks loose from a vein and
travels to the lungs.
· Chronic venous insufficiency isn't a blood clot, but a condition
that occurs when damaged vein valves or a DVT causes long-term pooling
of blood and swelling in the legs. If uncontrolled, fluid will leak
into the surrounding tissues in the ankles and feet, and may
eventually cause skin breakdown and ulceration.
Blood Clotting Disorders
Blood clotting disorders are conditions that make the blood more
likely to form blood clots in the arteries and veins. These conditions
may be inherited (congenital, occurring at birth) or acquired during
life and include:
· Elevated levels of factors in the blood which cause blood to clot
(fibrinogen, factor 8, prothrombin)
· Deficiency of natural anticoagulant (blood-thinning) proteins
(antithrombin, protein C, protein S)
· Elevated blood counts
· Abnormal Fibrinolysis (the breakdown of fibrin)
· Abnormal changes in the lining of the blood vessels (endothelium)
Blood clots typically occur when a blood vessel has sustained damage,
through injury, or plaque formation. Platelets are the first to
arrive, sticking to the injured edge of the vessel. The platelets act
not only as a physical ?plug? but also release a substance that
attracts more platelets, effectively stopping the bleeding.
Next come clotting factors, which induce the production of fibrin ?
strands of protein that stick to the platelets, sealing the wound.
After a few days, the blood vessel injury heals and the clot
dissolves, with the help of other anti-clotting factors.
?When a wound occurs, several changes take place to minimize blood
loss. First, the blood vessel slows the flow of blood past the wound
site. Next, platelets collect at the wound site to form a plug.
Finally, fibrin clots form scabs to replace these temporary platelet
plugs. Fibrin clot formation is dependent on adequate function of
clotting factors. Multiple factors can prevent fibrin clot formation.?
?The platelets are tiny cellular elements, made in the bone marrow,
that travel in the bloodstream waiting for a bleeding problem to
develop. When bleeding occurs chemical reactions change the surface of
the platelet to make it ?sticky.? Sticky platelets are said to have
become ?activated.? These activated platelets begin adhering to the
wall of the blood vessel at the site of bleeding, and within a few
minutes they form what is called a ?white clot.? (A clump of platelets
appears white to the naked eye.)?
?The thrombin system consists of several blood proteins that, when
bleeding occurs, become activated. The activated clotting proteins
engage in a cascade of chemical reactions that finally produce a
substance called fibrin. Fibrin can be thought of as a long, sticky
string. Fibrin strands stick to the exposed vessel wall, clumping
together and forming a web-like complex of strands. Red blood cells
become caught up in the web, and a ?red clot? forms.
A mature blood clot consists of both platelets and fibrin strands. The
strands of fibrin bind the platelets together, and ?tighten? the clot
to make it stable.
In arteries, the primary clotting mechanism depends on platelets. In
veins, the primary clotting mechanism depends on the thrombin system.
But in reality, both platelets and thrombin are involved, to one
degree or another, in all blood clotting.?
?The platelets produce a substance that combines with calcium ions in
the blood to form thromboplastin, which in turn converts the protein
prothrombin into thrombin in a complex series of reactions. Thrombin,
a proteolytic enzyme, converts fibrinogen, a protein substance, into
fibrin, an insoluble protein that forms an intricate network of minute
threadlike structures called fibrils and causes the blood plasma to
gel. The blood cells and plasma are enmeshed in the network of fibrils
to form the clot. Blood clotting can be initiated by the extrinsic
mechanism, in which substances from damaged tissues are mixed with the
blood, or by the intrinsic mechanism, in which the blood itself is
traumatized. More than 30 substances in blood have been found to
affect clotting; whether or not blood will coagulate depends on a
balance between those substances that promote coagulation
(procoagulants) and those that inhibit it (anticoagulants).?
?Blood clots (fibrin clots) are the clumps that result from
coagulation of the blood. A blood clot that forms in a vessel or
within the heart and remains there is called a thrombus. A thrombus
that travels from the vessel or heart chamber where it formed to
another location in the body is called an embolus, and the disorder,
an embolism. For example, an embolus that occurs in the lungs is
called a pulmonary embolism.
Sometimes, a piece of atherosclerotic plaque, small pieces of tumor,
fat globules, air, amniotic fluid, or other materials can act in the
same manner as an embolus.?
Thrombi and emboli can firmly attach to a blood vessel and partially
or completely block the flow of blood in that vessel. This blockage
deprives the tissues in that location of normal blood flow and oxygen.
This is called ischemia and if not treated promptly can result in
damage or death (infarction or necrosis) of the tissues in that area.?
?Following damage to a blood vessel, vascular spasm occurs to reduce
blood loss while other mechanisms also take effect:
Blood platelets congregate at the site of damage and amass to form a
platelet plug. This is the beginning of the process of the blood
"breaking down" from is usual liquid form in such a way that its
constituents play their own parts in processes to minimise blood loss.
Blood normally remains in its liquid state while it is within the
blood vessels but when it leaves them the blood may thicken and form a
Blood clotting (technically "blood coagulation") is the process by
which (liquid) blood is transformed into a solid state.
This blood clotting is a complex process involving many clotting
factors (incl. calcium ions, enzymes, platelets, damaged tissues)
activating each other.?
?The end result of the clotting pathway is the production of thrombin
for the conversion of fibrinogen to fibrin. Fibrinogen is a dimer
soluble in plasma. Exposure of fibrinogen to thrombin results in rapid
proteolysis of fibrinogen and the release of fibrinopeptide A. The
loss of small peptide A is not sufficient to render the resulting
fibrin molecule insoluble, a proces that is required for clot
formation, but it tends to form complexes with adjacent fibrin and
A second peptide, fibrinopeptide B, is then cleaved by thrombin, and
the fibrin monomers formed by this second proteolytic cleavage
polymerize spontaneously to form an insoluble gel. The polymerized
fibrin, held together by noncovalent and electrostatic forces, is
stabilized by the transamidating enzyme factor XIIIa, produced by the
action of thrombin on factor XIII. These insoluble fibrin aggregates
(clots), together with aggregated platelets ( thrombi), block the
damaged blood vessel and prevent further bleeding.?
?Platelet aggregation and fibrin formation both require the
proteolytic enzyme thrombin. Clotting also requires:
· calcium ions (Ca2+)(which is why blood banks use a chelating agent
to bind the calcium in donated blood so the blood will not clot in the
· about a dozen other protein clotting factors. Most of these
circulate in the blood as inactive precursors. They are activated by
proteolytic cleavage becoming, in turn, active proteases for other
factors in the system.
?What essential function do gamma-carboxyglutamic acid residues endow
upon a protein? There appear to be two major effects:
· First, they enable the protein to bind to membrane surfaces. Much of
blood clotting is a result of blood-clotting proteins assembling into
a complex on the membranes of platelets and endothelial cells; within
these complexes, the factors can efficiently contact one another to
become activated and participate in clot formation. Additionally,
calcium is necessary for the blood clotting reaction.
The proposed mechanism involving carboxylation is that
gamma-carboxyglutamic acid residues strongly chelate calcium, and
positively-charged calcium forms ion bridges to negatively-charged
phosphate head groups of membrane phospholipids.
· Second, gamma-carboxyglutamic acid groups appear to participate in
forming the necessary structure of such proteins by forming
calcium-mediated intrachain interactions that link two
gamma-carboxyglutamic acids to a calcium ion (similar to disulfide
bridges, but much shorter).?
?A blood clot forms as a result of concerted action of some 20
different substances, most of which are plasma glycoproteins?
These are seen on a chart as well as an illustration of the intrinsic
and extrinsic pathways.
?The phenomenon of blood coagulation is traditionally distinguished
into two pathways. These pathways are the intrinsic and the extrinsic
pathways (Figure below). The intrinsic pathway is defined as a cascade
that utilizes only factors that are soluble in the plasma, whereas the
extrinsic pathway consists of some factors that are insoluble in the
plasma, e.g., membrane-bound factors (factor VII). However, the
boundary differentiating these two is becoming more and more blurred.?
?Vitamin K is required in the liver biosynthesis of the prothrombin
g-carboxyglutamic groups by participating in the carboxylation of the
g-carbon of glutamic acid. These carboxy groups are required for
binding calcium to prothrombin, which induce a conformation change in
prothrombin enabling it to bindi to co-factors on the phospholipid
surfaces during its conversion to thrombin by factor Xa, factor V, and
platelet phospholipids in the presence of calcium.?
?Atherosclerosis begins when cholesterol and other fatty substances
attach to and infiltrate the endothelial lining of coronary arteries.
These fatty deposits eventually form a large atherosclerotic plaque
that increases in size and juts out into the lumen of the artery. Even
plaques that may appear to be clinically insignificant can precipitate
a thrombotic event; indeed most thrombotic events are caused by small
plaques rupturing and resulting in an occlusive thrombus or blood
clot. Any plaque may rupture due to natural causes, such as shear
forces in the artery or gradual decay. Alternatively, rupture may
result from mechanical injury during a procedure such as percutaneous
transluminal coronary angioplasty (with or without stent
?When plaque rupture occurs, platelet adhesion, activation, and
aggregation follow. Plaque rupture exposes the endothelium (inner
lining) of the artery to the bloodstream. Platelets that come in
contact with the sub-endothelium will stick to it, binding to von
Willebrand factor (vWf), and begin to form a platelet monolayer that
covers the injured site, which protects against continued exposure of
the sub-endothelium and allows the healing process to begin. The
sub-endothelium also contains collagen, a potent platelet agonist,
which causes the bound platelets to activate and undergo a
conformational shape change. At this time, platelets will each express
70,000 - 100,000 glycoprotein (GP) IIb-IIIa receptors and release
internal pools of signaling agents, including ADP (adenosine
diphosphate), thromboxane A2, serotonin, and epinephrine into the
Please read the entire age for complete information. There are also
links to animated videos showing clot development.
?A fibrous, soluble protein called fibrinogen ("clot-maker") comprises
about 3% of the protein in blood plasma. Fibrinogen has a sticky
portion near the center of the molecule, but the sticky region is
covered by little amino acid chains with negative charges. Because
like charges repel, these chains keep fibrinogen molecules apart.
When a clot forms, a protease (protein-cutting) enzyme clips off the
charged chains. This exposes the sticky parts of the molecule, and
suddenly, fibrinogens (which are now called fibrins) start to stick
together, beginning the formation of a clot.
The protease that cuts off the charged chains is called thrombin. So,
just like the lobster clotting system, the heart of the reaction
involves just two molecules: fibrinogen and thrombin. But, unlike the
lobster, there's a lot more to this machine. It turns out that
thrombin itself exists in an inactive form called prothrombin. So it,
just like fibrinogen, has to be activated before it can start the
clotting process. What activates prothrombin? Here's where life gets
really interesting. Prothrombin, a protease itself, is activated by
another protease called Factor X which clips of part of the inactive
protein to produce active, clot-forming thrombin. OK, so what
activates Factor X? Believe it or not, there are still more proteases,
two of them, actually, called Factor VII and Factor IX, that can
switch on Factor X.?
The clotting cascade is a detailed and interesting study?far beyond
the scope of this question. There is a chart on this site that
illustrates the Intrinsic Pathway, or cascade.
Everything you wanted to know about clotting!:
?Degradation of fibrin clots is the function of plasmin, a serine
protease that circulates as the inactive proenzyme, plasminogen. Any
free circulating plasmin is rapidly inhibited by a2-antiplasmin.
Plasminogen binds to both fibrinogen and fibrin, thereby being
incorporated into a clot as it is formed. Tissue plasminogen activator
(tPA) and, to a lesser degree, urokinase are serine proteases which
convert plasminogen to plasmin. Inactive tPA is released from vascular
endothelial cells following injury; it binds to fibrin and is
consequently activated. Urokinase is produced as the precursor,
prourokinase by epithelial cells lining excretory ducts. The role of
urokinase is to activate the dissolution of fibrin clots that may be
deposited in these ducts.?
Formation of a clot-here you can see fibrin strands, red blood cells
and a few platelets
Looking through a partially occluded vein:
I hope this has adequately answered your question. If not, please,
before rating, request an Answer Clarification, before rating. I will
be happy to assist you further on this question, if possible.
Clotting factor cascade
blood clot scheme
blood clot formation
Calcium + clot formation
Clarification of Answer by
20 Sep 2005 20:59 PDT
Hi again Ekw70,
I'm still a bit confused as to what exactly you mean. Could you
share with me where you got the data showing that clots age per "acute
(<14 days), subacute (2weeks to 3 months) and chronic thrombus (>3
months) in terms of what the clots are made of."
I can find no evidence that clots are made of anythng different than
what was included in my answer. Did you check all the links?
I have found additional information, but I am not sure it is what
you are seeking. Whether a clot forms due to a vessel injury, or a
jagged peice of plaque, clots are made up of platelets, fibrin, red
blood cells, whose formation is facilitated by clotting factors. Small
clots are dissolved by anti-clotting factors, or therapy such as
heparin or other anti-coagulants. IF left alone, they increase in
?Most acute coronary syndromes are caused by acute thrombosis,
superimposed on a ruptured or eroded atherosclerotic plaque, with or
without concomitant vasospasm (1,2). Plaque rupture is not a rare
event. It is followed by a variable amount of hemorrhage into the
plaque and luminal thrombosis (often small and non-obstructive),
causing sudden and rapid, but often clinically silent, growth of the
?According to a study by researchers at the University of Pittsburgh
Medical Center (UPMC), a thin polymer coating on the inside of
coronary arteries may one day prevent blood clot formation called
acute thrombosis, following angioplasty.?
?Acute thrombosis occurs in five percent of patients who undergo
angioplasty and can lead to heart attack. This condition also may
necessitate repeat coronary intervention or bypass surgery.
The study attempted to determine if the polymer, polyethylene glycol
diisocyanate, could protect the damaged vascular wall from platelets
in the blood long enough for the inside of the artery to heal and
prevent the acute thrombosis process from beginning.?
?Venous thrombosis of the lower extremities is a common mechanism of
disease. Methods for detecting and diagnosing thrombus are Ultrasound
duplex imaging and compression of the veins.?
?Deep venous thrombosis (DVT) is the principal disease of the deep
system. The thrombus frequently originates in the cusps of valves. As
the clot progresses blood flow will restrict causing an increase in
venous pressure. The vein walls will stretch causing damage to the
valves. The entire clot or part of it can break loose and cause a
pulmonary embolism, which can be life threatening. Contributing
factors of DVT include venous stasis, trauma, hypercoagulation, age,
heart failure, and previous DVT.?
?Venous thrombosis in the superficial system (SVT) is not as
threatening as DVT. SVT can cause superficial phlebitis, an
inflammation of the vessels, resulting in a palpable cord throughout
?Image characteristics will appear differently along with each phase
of the thrombus. Fresh or acute thrombosis refers to clots that are
days up to two weeks old. Acute thrombus appears spongy in texture and
is poorly attached to the vessel wall. The vein will be distended
abnormally larger than usual. Venous distension helps to differentiate
between newly formed and older thrombus. Newly formed clot generates
low level echoes and may be anechoic. This will make imaging
difficult. The use of color Doppler will help indicate blood flow to
the vessel. A lack of flow indicates the presence of thrombus. The
subacute phase refers to clots that are weeks up to two months old.
The thrombus gradually becomes more echogenic. Retraction and lyses of
the thrombus will reestablish patency and occupy less of the vein
lumen. The vein becomes less distended and returns to a normal size.
The chronic phase refers to clots that are months to years old.
Chronic thrombus appears rigid in texture and is well attached to the
vessel wall. Echogenicity is strongly increased in this phase.
Echogenic intraluminal material may resemble plaque and cause acoustic
?In a 54-year-old man who suffered from chronic cardiac insufficiency
with terminal graded cyanosis on necropsy a foramen ovale late patens
was found with massive chronic thrombosis of the trunk and main
branches of the pulmonary artery above extensive partly ulcerous
atheromatous plaques. The thrombosis is considered autochthonous by
?It is generally accepted that platelet adherence to plaques on the
linings of arteries is part of the atherosclerosis cascade. Platelet
adherence is worsened by excess fibrin. Platelets release a
platelet-derived growth factor, causing the smooth muscle cells on the
walls of arteries to proliferate. The resultant smooth muscle cells
have an increased permeability to platelets and lipids, especially
LDL-cholesterol. As LDL increases, it penetrates further into the
arterial wall. Plaque forms in the arterial wall as a benign
neoplastic growth (a monoclonal mutation). Excess fibrin, free
radicals, chronic inflammation, homocysteine, oxidized LDL, and
environmental hydrocarbons, etc. aggravate this mutation.
In the free radical hypothesis, lipid peroxides damage the arterial
walls, further enhancing wall permeability, as well as additionally
increasing the oxidation of lipids, especially LDL. These free
radicals invade the arterial wall and activate cell proliferation and
abnormal cell duplication. The newly mutated cells migrate into the
arterial wall and induce plaque formation. This cell proliferation
increases the surrounding clot growth or thrombus formation. T-cell
antibodies regulate this process. The resulting lesions are
atheromatous plaque. The surrounding thrombi form primarily from
modified smooth muscle cells, LDL, and fibrin.
Naturally occurring thrombolytic enzymes that dissolve clots are
generated in the endothelial cells of blood vessels. As people age,
production of these enzymes slows and the blood is more prone to
coagulation. This results in clotting. However, clots can form at any
?Endothelial injury can expose collagen, causing platelet aggregation
and tissue thromboplastin release that, when stasis or
hypercoagulability is present, trigger the coagulation mechanism. Many
factors may contribute to venous thrombosis: injury to the endothelium
of the vein, eg, from indwelling catheters, injection of irritating
substances, thromboangiitis obliterans, and septic phlebitis;
hypercoagulability associated with malignant tumors, blood dyscrasias,
oral contraceptives, and idiopathic thrombophlebitis; and stasis in
postoperative and postpartum states, varicose thrombophlebitis, and
the thrombophlebitis that complicates prolonged bed rest of any
chronic illness, heart failure, stroke, and trauma.?
?Most venous thrombi begin in the valve cusps of deep calf veins.
Tissue thromboplastin is released, forming thrombin and fibrin that
trap RBCs and propagate proximally as a red or fibrin thrombus, which
is the predominant morphologic venous lesion (the white or platelet
thrombus is the principal component of most arterial lesions).
Anticoagulant drugs (eg, heparin, the coumarin compounds) can prevent
thrombi from forming or extending. Antiplatelet drugs, despite
intensive study, have not proved effective for prevention.?
?Dr. Mark Fisher, director of the UCI Stroke Center, and colleagues
found that in the carotid artery, the primary source of blood to the
brain, plaques form lesions that support the growth of the
stroke-causing blood clots, which can either block the artery or break
off and travel into the brain.?
??plaque can build up in the walls of your arteries. Cholesterol,
calcium, and fibrous tissue make up this plaque. As more plaque builds
up, your arteries narrow and stiffen. This process is called
atherosclerosis, or hardening of the arteries. Eventually, enough
plaque builds up to reduce blood flow through your carotid arteries,
or cause irregularities in the normally smooth inner walls of the
Definition of thrombosis:
"Thrombosis: The formation or presence of a blood clot in a blood
vessel. The vessel may be any vein or artery as, for example, in a
deep vein thrombosis or a coronary (artery) thrombosis. The clot
itself is termed a thrombus. If the clot breaks loose and travels
through the bloodstream, it is a thromboembolism. Thrombosis,
thrombus, and the prefix thrombo- all come from the Greek thrombos
meaning a lump or clump, or a curd or clot of milk. See entries also
to: Cavernous sinus thrombosis; Renal vein thrombosis. And see: Deep
Vein Thrombosis and Pulmonary Embolism."
"A disease that persists for a long time. A chronicdisease is one
lasting 3 months or more, by the definition of the U.S. NationalCenter
for Health Statistics. Chronic diseases generally cannot be prevented
byvaccines or cured by medication, nor do they just disappear.
Eighty-eightpercent of Americans over 65 years of age have at least
one chronic healthcondition (as of 1998). Health damaging behaviors -
particularly tobacco use,lack of physical activity, and poor eating
habits - are major contributors tothe leading chronic diseases."
I feel you may be thinking of chronic thrombosis in the sense that the
disease lasts a long time. Should the clot last a ong time, it is
still composed of the same matter - cells, fibin, clotting factors,
Please let me know if you require further research. I too would like
to know what you have so far, as it may give me further clues as to
what information you need.