PATHOPHYSIOLOGY OF PERIPHERAL BLOOD CIRCULATION
Peripheral blood circulation (in arterioles, pre-capillaries, capillaries, Post-capillary venules and small veins, arterio-venous anastomoses) provides balance of nutrient substrates gases, metabolites, electrolytes and water in the system “blood tissue – blood”.
The typical types of the local microcirculation disorders are arterial and venous Hyperemia, ischemia, stasis, thrombosis and embolism.
Arterial hyperemia (Blood Circulation Pathology)
The term hyperemia means an increased volume of the blood in affected organ. Arterial hyperemin is an active increase of organ or tissue blood filling due to excessive blood inflow by arterial vessels. Active hyperemia occurs when arterial dilatation produces an increased inflow of the blood into capillary beds with opening of inactive capillaries. Neurogenic mechanisms or vasouctive substances release brings to it.
Types: Arterial hyoermia is divided into physiological (working) and pathological. In turn, pathological arterial hyperemia is divided into neurogenic and metabolic. In turn, neurogenic arterial hyperaemia divided into neurotonic and neuroparalytic.
Etiology: Etiological factors are physical (mechanical, heat, ultravioler radiation), chemical and biological (infectious, immune, emotional) which lead to the dilation of arterial vessels.
Pathogenesis: There are two types of arterial hyperemia according pathogenesis – neurogenic (of neurotonic and neuroparalitic type) and caused by local metabolic (chemical) factors.
1. Neurotonic arterial hyperemia develops due to activation of neurotonic mechanisms. At first Claude Bernard reproduced it by stimulation of chorda tympani (the branch of the facial nerve), containing parasympathetic vasodilating fibers in the vessels, which don’t have parasympathetic stimulation, hyperaemia is caused by sympathetic system (cholinergic, histaminergic and beta-adreneraic mechanisms). Sympathetic cholinergic nerves dilate the small arteries and arterioler skeletal muscles, facial muscles, mucous membrane of the cheeks, intestine. Acetylcholine is a mediator.
2. Neuroparalytic arterial hyperemia may be observed in clinic and experiment on animals after cutting of the vasoconstrictive fibers and nerves (sympathetic, adrenergic ones). Claude Bernard observed hyperemia and hyperthermia of the skin on a rabbit’s head (ear) on the side of cutting the cervical node of the sympathetic trunk. Their mediator is norepinephrine.
3. Metabolic arterial hyperemia is caused by biological active substances (BAS) of a different origin (cellular and plasmatic). ATP, ADP, adenosine, nonorganic ions, reduction of pO2 and increase of pCO2 in the blood and tissues has the same effects. In some cases prostaglandins E and A, which have a vasodilative effect upon arterioles, metarterioles, precapillaries and venules, cause hyperemia.
Manifestations: Manifestations of arterial hyperemia are morphological (microscopical), biochemical (metabolic), functional and clinical. The hydrodynamic pressure in arterioles, capillaries and veins is increased. Arterial hyperemia is always accompanied with swelling (tumor), but never edema.
The following visible clinical signs manifest arterial hyperemia:
· Redness of the affected part
· Enlargement of organ or tissue due to swelling (tumor)
· Increase of the tissue turgor
· Local hyperthermia
· Intensification of organ function.
Subjective unpleasant sensations are
Microscopical picture is characterized by
· Dilatation of small arteries, arterioles, veins, capillaries
· Increased number of the…………………………..vessels
· Acceleration of the blood flow
· Opening of the inactive capillaries Division of blood flow into two parts: – central flow of the blood cells and peripheral flow of plasma.
Metabolism intensifies locally due to increased supply with oxygen and substrates.
Significance: ‘In the majority of cases arterial hyperemia is accompanied with intensification of metabolism and organ’s function. However, the unfavourable outcome is also possible. Thus, dilation of sclerotic vessels can result in rapture and haemorrhage. It is especially dangerous in the brain. Arterial hyperemia is of a great significance in course of inflammation.
Venous hyperemia (congestion) – (Blood Circulation Pathology)
It is an increase of organ or tissue blood filling due to limitation of blood out flow by venous vessels. Contrary to arterial hyperemia which is active, the venous hyperemia (congestion or passive hyperemia) is a result of impaired venous drainage.
Etiology: Etiological factors of venous hyperemia are those, which narrow the lumen or tonus of veins. They may be exogenous and endogenous. They are: –
· Obstruction of veins with a thrombus or an embolus
· Compression of veins by tumor, enlarged uterus, in the region of inflammation by exudates
· Exudative pleuritis, hemothorax, pneumosclerosis, emphysema
· Cardiac left- or right- side ventricle failure
· Professional overloading (vertical position for a long time)
· Genetic predisposition to venous congestion (weakness of venous elastic apparatus, low tonus of the smooth muscle elements of the vascular wall).
Pathogenesis: The disorders are caused by a local lack of oxygen (dcoxygenation of hemoglobin, tissue hypoxia) and substrates. It leads to the tissue dis-metabolism. As a result, atrophic and dystrophic changes develop.
Viscosity of the blood increases as well as permeability of capillaries. Transudate is formed due to the high hydrostatic blood pressure. Congestion in capillary bed is closely related to edema development. therefore, congestion and edema usually, together (venous edema). Congestion leads to intravascular thrombosis.
Prolong venous congestion results in excessive growth of the connective tissue which substitutes the parenchyma (so-called cirrhosis).
Manifestations: Manifestations of venous hyperemia are morphological (microscopical), biochemical (metabolic), functional, clinical.
The following visible clinical signs manifest venous hyperaemia:
· Enlargement of organ or tissue due to swelling (tumor)
· Cyanosis as a result of hypoxia and accumulation of deoxydated haemoglobin
· Edems, due to high hydrostatic pressure and increasing permeability of the vessel wall due to unoxygenated condition
· Local hypothermia
· Subjective unpleasant sensation are swelling and pain
Microscopical picture is characterized by:
· Dilatation of small arteries, arterioles, veins, capillaries.
· Slowing of the blood flow due to increased viscosity of the blood
· Transudate formation
· Atrophic and dystrophic changes
· Excessive growth of the connective tissue
Metabolic disorders in venous hyperemia develop as a result of tissue hypoxia. Intermediate products of uncomplete oxygenation are accumulated. Local metabolic acidosis develops.
Significance: In the majority of the cases venous hyperemia has a negative value. It leads to disorder of the tissue metabolism and cause atrophic and dystrophic changes. The function of organ is disordered due to hypoxia, dystrophia, and cirrhosis.
However, during inflammation venous hyperenia is of a great significance providing emigration of leukocytes.
Ischemia (Blood Circulation Pathology)
It is a decrease of organ or tissue blood filling due to the limitation or complete stop of arterial blood inflow.
Types: Ischemia is divided into compressive, obstructive and angiospastic types. Every type of ischemia has its own etiology and pathogenesis.
· Compressive ischemia is a result of a mechanical effect on arteries (tumor, foreign body, ligature, etc.).
· Obstructive ischemia is a result of narrowing of a vessel lumen by thrombus, embolus or atherosclerotic process.
· Angiospiastic ischemia is a functional disorder. The essence of it is a derangement of motor (vaso-constrictive) apparatus of the vessels.
Etiology: Various agents can cause ischemia. Angiospastic ischemia develops as a result of stimulation of vasoconstrictor apparatus of Vessels or their …………… spasm caused by:
· Physical factors (cold, mechanical and another injury),
· Chemical agents,
· Biological factors (bacterial toxins),
· Emotional factors (fear, pain, rage) and pathologic reflex.
Duration and consequences of ischemia depend on such conditions. Which can modify an effect or etiological factors:
· Time of injuring effect,
· Type of ischemia,
· Condition of the collateral circulation.
· Functional state of organ or tissue.
Pathogenesis: mechanism of an angiospastic ischemia depends on permeability of smooth muscle cells membranes for Na+, Ca2+, K+ and Cl– ions. Neurogenous, adrenergic, histaminergic, serotoninergic, dopaminergic mechanisms play a role. Angiotensin II is one of the most potent vasoconstrictors. It effects smooth muscles cells directly causing depolarization as a result of increased Na+ Permeability. When Na+ ions accumulate in the muscle fibers of vessels, their sensitivity to vasoconstrictors (catecholamines, visopressin) and angiotens increases.
Injury of endothelium results in losing of its ability to produce the relaxative factors (NO). It leads to spastic reactions.
Angiospastic ischemia may have a conditioned reflex nature.
Ischemia leads to the oxygen deficiency (hypoxia).
Embolism (Blood Circulation Pathology)
It is a pathological process, which is characterized by travelling of free bodies (embolus) in the vessels. An embolus is a substance that circulates from one location in the body to another, through the bloodstream.
By origin embolus:
· Exogenous (air, gas, foreign bodies, bacteria etc..)
· Endogenous (thrombus, amniotic fluids. Fat, tumor cells etc.)
There are three main types of embolism:
· Embolism of lesser (pulmonary ) circulation, pulmonary.
· Embolism of greater [systemic] circulation, systemic
· Embolism of portal vein.
Embolism of pulmonary circulation: Embolus that originates in the venous circulation, such as from deep vein thrombosis, travel to the right side of the heart to the pulmonary circulation and eventually causing pulmonary infarction and even death.
This syndrome characterized by:
1. Generalized spasm of vessels pulmonary circulation à acute hypertension into pulmonary circulation and develops acute insufficiency of right heart;
2. Abrupt decrease of blood pressure in systemic circulation, as result of decreasing cardiac output and general peripheral resistance;
3. Disorders of external respiration à develop of respiratory failure.
Embolism of systemic circulation: often is a thrombus, which is formed in the left side of heart (as result of coarctation of aorta, aortic aneurysm, fibrillation, operation on the heart and artificial valves), air or fat emboli
Consequences depend on thrombus location.
· Coronary artery à infarction of heart
· Renal artery à infarction of kidney
· Arteries of lower extremities à gangrene, etc.
Air embolism is usually due to accidental pumping of air into the venous circulation during injection or transfusion. If large amounts of air mixed blood enter the right atrium, a bloody froth is formed and the patient suffers may cardiac arrest. In deep-sea divers, inhaled air may dissolve into the plasma due to the cardiac pressure at great depths, only to reform into bubbles of gas (gas embolism) within the embolism Circulation if the diver comes to the surface too quickly. This decompression sickness and embolization of the bubbles of mainly nitrogen occlude small vessels, lending to widespread anoxia of Tissues and even death. Amniotic fluid embolism may occur rarely during childbirth, some of the amniotice (containing fetal cells from the skin surface) may enter the maternal circulation through the exposed and bleeding placental bed in the uterus. The material passes in the venous circulation to the lung capillaries and may cause acute alveolar wall damage and disseminated intravascular coagulation.
Retrograde embolism: embolism of a vein by an embolus carried in a direction opposite to that of the normal blood current after being diverted into a smaller vein: venous-embolism.
An arterial embolism may be caused by one or more clots. The clots can get stuck in an artery and block blood flow. The blockage starves tissues of blood and oxygen, which can result in damage or tissue death (necrosis). Arterial emboli often occur in the legs and feet. Some may occur in the brain, causing a stroke, or in the heart, causing a heart attack. Less common sites include the kidneys, Intestines, and eyes. Arterial fibrillation is a major risk factor for arterial embolism. The risk of an embolism increases when factors that tend to form clots are increased. Other risk factors include injury or damage to an artery wall and conditions that increase blood clotting (such as severely increased platelet count), another condition that poses a high risk for embolization (especially to the brain) is mitral stenosis. Endocarditis (infection of the inside of the heart) can also cause arterial emboli. A common source for an embolus is from areas of hardening (atherosclerosis) in the aorta and other large blood vessels. These clots can break loose and flow down to the legs and feet. Paradoxical embolization can take place when a clot in a vein enters the right side of the heart and passes through a hole into the left side. The clot can then move to an artery and block blood flow to the brain (stroke) or other organs. If a clot involves the arteries supplying blood flow to the lungs, it is called a pulmonary embolus.
Symptoms: Asymptomatic and symptomatic
· Symptoms may begin quickly or slowly depending on the size of the embo and how much it blocks the blood flow.
· Symptoms of an arterial embolism in the arms or legs may include:
· Cold arm or leg
· Decreased or no pulse in an arm or leg
· Fingers or hands feel cool
· Lack of movement in the arm or leg
· Muscle pain in the affected area
· Muscle spasm in the affected aren
· Numbness and tingling in the arm or leg
· Pale color of the arm or leg (pallor)
· Weakness of an arm or leg
· Blisters of the skin fed by the affected artery
· Shedding (sloughing) of skin
· Skin erosion (ulcer)
· Tissue death (necrosis; Skin is dark and damaged)
Symptoms of a clot in an organ vary with the organ involved but may include:
· Pain in the part of the bedy that is involved
· Temporarily deereased organ function
· Acute MI
· Infection in the affected tissue
· Scptic shock
· Stroke (CVA)
· Temporary or permanent decrease or loss of other organ functions
· Temporary or permanent kidney failure
· Tissue death (necrosis) and gangrene
· Transient ischemic attack (TIA)
STASIS (Blood Circulation Pathology)
Stasis – decrease or stop blood flow in capillaries, small arteries and venues Distinguish some types of stasis: ischenic, venotes, and capillar (primary). All are caused by accordingly ischemia and venous hyperemia.
Reasons of capillary stasis:
1. Physical (high – more than 80 ° C, and low less than – 7 ° C temperature)
2. Chemical (poisons, turpentine, mustard oil)
3. Biological (toxins of microorganisms)
Pathogenesis: Capillary stasis is caused by aggregation of blood cells, edema of Endothelium cells, blood flow decreased, clotting of blood as result of increase of permeability of vascular walls (under the action of histamine, serotonin, heparin). The final stage of stasis involves the process of aggregation and agglutination of the corpuscular elements of blood which results in blood thickening and its fluidity reduction. This process is activated by pro-aggregants, cations and high molecular weight proteins.
Manifestations of stasis:
· Reduction of the inner diameter in ischemic stasis;
· Increase of the lumen of vessels of microcirculation in congestive stasis;
· Increased number of aggregates of blood corpuscles in the luments and on their walls;
· Micro-hemorrhages (more often occur in congestive stasis)
The consequences of stasis: when agents are causing stasis are quickly withdrawn blood flow in the vessels of microcirculation is restored without entailing any noticeable changes in tissues. Prolonged stasis results in dystrophic changes in tissues (quite often to death of a tissue site or an organ).
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Thrombosis – is a life time process to produce of thrombus in the vessels lumen. A thrombus is a blood clot, consisting of platelets, fibrin and red and white blood cells, that forms anywhere within the vascular system, such as the arteries, veins, heart chambers or heart valves.
Three conditions, known as Virchow’s triad promote thrombus formation:
· Endothelial injury
· Alterations in laminar blood flow (slugging blood flow: changes in laminar flow, turbulence à arterial thrombosis, changes to stasis of flow à venous thrombosis)
· Increased coagulability or decreased activity of anti-coagulative and fibrinolytic systems.
There are two phases of blood clotting:
· Cellular: Cellular phase consist of adhesion, aggregation and agglutination of platelets.
· Plasmatic: Plasmatic phase consisting of several successive (consecutive, cascade) reductions, results of which is creation of fibrin.
Consequences of thrombosis – ischemia, necrosis, trophic disorders, recanalization, septic melting dissolution, calcification etc.
Coagulation is the process that leads to fibrin formation; This process involves controlled interactions between protein coagulation factors. Hemostasis is coagula tion that occurs in a physiological (as opposed to pathological) setting and results in sealing a break in the vasculature. This process has a number of components. inctual img adhesion and activation of platelets coupled with ordered reactions of the provem coagulation factors. Hemostasis is essential to protect the integrity of the vasculature. Thrombosis is coagulation in a pathological (as onnosed to nhysiological) setting reads to localized intravascular clotting and potentiallvocclusion ofa vessel. Therent an overiap between the components involved in hemostasis and thrombosis, butimes Salso evidence to suggest that the processes of hemostasis and thrombosis have sign nificant differences. There are also data to suggest that different vascular seting terial, venous, tumor microcirculation) may proceed to thrombosis by alrelem
chanisms, Exploitation of thesari Jectively target thrombosien within a damaged blood vesselitha first stage of wound healina liquid to a solid state. All situatione Virchow’s triad. Intact blor anof these differences could lead to therapeutic agents that. se Hathrombosis without interfering significantly with hemastasi andieisanrocess which causes bleeding to stop, meaning toke Hindi and blood vessel (the opposite of hemostasis is hemorrhage). It is the C ound healing. Most of the time this includes blood changing from d state.
All situations that may lead to hemostasis are portrayed by the rriad. Intact blood vessels are central to moderating blood’s tendencate endothelial cells of intact vessels prevent blood clotting with a heparin – likel ile and thrombomodulin an integral memorame proten expressed on the sur andothelial cells and serves as a cofactor for thrombin. Tiredices blood com Artv. comverting thrombin toamanticoagulant enzyme from a procoagulanten and prevent platelet aggregation with nitric oxide and prostacyclin. When en sothelial injury occurs, the endothelial cells stop secretion of coagulation and aggre nation inhibitors and instead secrete von Willebrand factor which initiate the main tenance of hemostasis after injury. Hemostasis has three major steps: ID vasoconstric tion. 2ytemporary blockage ora breakhya platelet plug, and 3) blood coagulation. or formation of a clot that seals the hole until tissues are repaired. | Molecule and thrombomodulin Steps ofmechanism Hemostasis occurs when blood is present outside of the body or blood vessels. Tt is the instinctive response for the body to stop bleeding and loss of blood.
During hemostasis three steps occur in a rapid sequence, Vascular spasm is the first response as the blood vessels constrict to allow less blood to be lost. In the second step, plate tets plug formation, platelets stick together to form a temporary seal to cover the break in the vessel wall. The third and last step is called coagulation or blood clotting Coagulation reinforces the platelet plug with fibrin threads that act as a “molecular glue. Platelets are a large factor in the hemostatic process. They allow for the creal tion of the” platelet plug “that forms almost directly after a blood vessel has been rup: tured. Within seconds of a blood vessel’s epithelial wall being disrupted platelets be gn to adhere to the sub – endothelium surface. It takes approximately sixiy setronds | umr the first fibrin strands begin to intersperse among the wound. After several mi – | une platelet plug is completely formed by fibrin. Hemastasis is maintained in the body via three mechanisms:
Vascular Spasm: – Damaged blood vessels constrict. Vascular spasm is the blood vessels’ first response to injury. The damaged vessels will constrict (vaso-constrict) which reduces the amount of blood flow through the area and limits the amount of blood loss. This response is triggered by factors such as a direct injury to vascular smooth muscle, chemicals released by endothelial cells and platelets and reflexes initiated by local pain receptors. The spasm response becomes more effective as the amount of damage is increased. Vascular spasm is much more effective in smaller blood vessels.
Platelet plug formation: – Platelets adhere to damaged endothelium to form platelet plug (primary hemostasis) and then degramilate. This process is regulated through thrombo-regulation. Platelet Plug Formation: Platelets play one of the biggest factors in the hemostatic process. Being the second step in the sequence they stick together (aggregation) to form a plug that temporarily seals the break in the vessel wall. As platelets adhere to the collagen fibers of a wound they become spiked and much stickier.
They then release chemical messengers such as adenosine diphospate (ADP), serotonin and thromboxane A2. These chemicals are released to cause more platelets to stick to the area and release their contents and enhance vascular spasm. As more chemicals are released more platelets stick and release their chemicals; creating a platelet plug and continuing the process in a positive feedback loop. Platelets alone are responsible for stopping the bleeding of unnoticed wear and tear of our skin on a daily basis.
The second stage of Hemostasis blood involving platelets that move throughout the blood. When the platelet find an exposed area or an injury, they begin to form what is called a platelets plug. The platelet plug formation is activated by glycoprotein called the Von willebrand factor (vWF), which is found in the body’s blood plasma. Platelets in the blood are activated, they then become very sticky so allowing them to stick to other platelets and adhere to the injured area.
There are a dozen proteins that travel along the blood plasma in an inactive state and are known as clotting factors. Once the platelet plug has been formed by the platelets, the clotting factors begin creating the platelet plug. When this occurs the factors begin to form a collagen fiber called fibrin. Fibrin mesh is then produced all around the platelet plug, which helps hold the fibrin in place. Once this begins, red and white blood cells become caught up in the fibrin mesh which causes the clot to become even stronger.
Blood coagulation: – Clots form upon the conversion of fibrinogen to fibrin, and its addition to the platelet plug (secondary hemostasis). Coagulation: The third and final step in this rapid response reinforces the platelet plug. Coagulation or blood clotting uses fibrin threads that act as a glue for the sticky platelets. As the fibrin mesh begins to form the blood is also transformed from a liquid to a gel like substance through involvement of clotting factors and pro-coagulants. The coagulation process is useful in closing up and maintaining or carrying the platelet plug on larger wounded area. The release of Pro-thrombin also plays an essential part in the coagulation process because it allows for the formation of a thrombus, or clot, to form. This final step forces blood cells and platelets to stay trapped in the wounded area. Though this is often a good step for wound healing, it has the ability to cause severe health problems if the thrombus becomes detached from the vessel wall and travels through the circulatory system; If it reaches the heart or brain it could lead to stroke, heart attack, or pulmonary embolism. However, without this process the healing of a wound would not be possible.
CLOTTING DISORDERS (Blood Circulation Pathology)
The normal balance between clot formation and breakdown can be changed by the presence of certain genetic or acquired defects leading to abnormal clot formation. Reason for the clot formation and breakdown processes to be unbalanced towards abnormal clot formation include blood vessels injury, venous stasis (lack of movement of the blood in the veins), and clotting disorders. These three factors make up Virchow’s triad. An alteration in any one of these three factors can lead to abnormal clotting.
There are 2 types of clotting disorders. The first is a hereditary disorder that is inherited from one or both parent. The second is an acquired disorder, which a person is not born with, but that develops later in life.
Hereditary Clotting Disorders: The hereditary clotting disorders come in 2groups:
· Group 1: A lack of anti-clotting factors in the blood.
· Group 2: An increased amount of pro-clotting factors in the blood.
Group-1 disorders include anti-thrombin deficiency, protein C deficiency and protein S deficiency.
Group-2 disorders include activated protein C resistance (factor V Leiden mutation), prothrombin G20210A mutation and elevated levels of factors VIII, IX, and XI. In general, the Group 1 disorders are less common but more likely to cause abnormal clotting than Group 2 disorders.
A LACK OF ANTI-CLOTTING FACTORS IN THE BLOOD
Anti-thrombin deficiency: anti-thrombin is a natural blood thinner found in the body. It works to reduce clot formation. Over 100 gene mutations have been found that can lead to anti-thrombin deficiency. This disorder is inherited as an autosomal dominant trait, which means that if a person gets an abnormal gene from one parent and a normal gene from the other parent, they will have the disease.
Protein C Deficiency: Protein C is a natural anti-coagulant that is made primarily in the liver. During the clotting process, protein C is activated, and along with protein S acts as a blood thinner to keep the clotting process in check. Deficiency in protein C results in decreased ability to keep the clotting process in check, leading to abnormal clot formation.
Protein S Deficiency: Protein S acts with protein C to keep the body’s natural clotting process controlled. A low protein S level has similar effects as a low level of protein C.
AN INCREASED AMOUNT OF PRO-CLOTTING FACTORS IN THE BLOOD
Activated Protein C Resistance/Factor V Leiden Mutation: activated Protein C (APC) resistance refers to the resistance of factor V (one of the proteins in the blood that helps to regulate clot formation) to the activated protein C in the clotting reaction. Since activated protein C works on factors V to slow down the clotting reaction, resistance to this causes increased risk of clotting. The majority of APC resistance is due to the factor V Leiden mutation, which is a mutation in the gene that codes for Factor V.
Pro-thrombin Defects: Pro-thrombin Gene 20210A Mutation: the prothrombin G20210A mutation is an inherited defect of the gene prothrombin. Prothrombin is a protein in the blood that helps clot to form. A Person with this condition has high levels of prothrombin, which increases the risk abnormal clot formation.
Factors Elevations (Elevations in the levels of different proteins in the blood that participate in the clotting process): The elevation of coagulation factors V, VII, VIII, IX, X, and XI can occur. The association of these with increased risk of clotting is unclear, but persistently high factors levels are more common in patients with a history VTE.
Hyper-homocysteinemia: Hyperhomocysteinemia refers to an acquired or inherited elevation of the level of the amino acid homocysteine. Amino acids are the building blocks that make up proteins in the body. Homocysteine is one of several types of amino acids. Acauired acteinemia can occur with certain medical conditions, such as kidney failure, hypothyroidism, folate deficiency or vitamin B6 or B12 deficiency. Inherited hyper-homocysteinemia results from mutation in the genes coding for enzyme that break down homocysteine. These enzymes are methylene-tetrahydrofolate reductase (MANTHER), cystathione B synthase (CBS), or methionine synthase. Defects in these enzymes may or may not lead to hyper-homocysteinemia, depending on their severity. Hyperhomocysteinemia is associated with both artery and vein clotting problems. How hyper-homocysteinemia affects blood clotting is not fully known.
Anti-Phospholipid antibody syndrome (APS): Anti-phospholipid antibodies are a family of antibodies that are directed against proteins in the blood that are important for coagulation. These antibodies include the lupus anticoagulants and the anti-cardiolipin antibodies. Primary APS in cludes patients who have APS but do not have lupus or other autoimmune diseases. Secondary APS includes those patients with APS and systemic lupus erythematosus (SLE).
Heparin Induced Thrombocytopenia: Heparin induced thrombocytopenia (HIT) is a severe side effect of heparin therapy that can cause abnormal clotting. This condition occurs when a person’s body makes an antibody against the heparin and that antibodies also targets their platelets. The antibody binding to the platelets causes them to clump up, which forms a clot.