Thrombosis Factor

Proaccelerin Accelerator Globulin (Ac-G) V Factor V deficiency, (parahemophilia) Increased risk for thrombosis (Factor V Leiden) Extremely rare 7-10 0.025 Liver, megakaryocytes, endothelial cells 11-15 FA5 HUMAN... 

A mutation in the human Factor V gene plays a major role in causing thrombosis (Factor V Leiden mutation R506Q). The mutation (a G A transversion) that changes the amino acid arginine (codon CGA) to glutamine (cod i CAA) is located at codon 506. The site of this mutation is selected and amplified by PCR in furnishing a DNA of 224 base pairs of which a piece of the antisense sequaice is shown below ... 

Homocysteine arises from dietary methionine. High levels of homocysteiae (hyperhomocysteinemia) are a risk factor for occlusive vascular diseases including atherosclerosis and thrombosis (81—84). In a controlled study, semm folate concentrations of <9.2 nmol/L were linked with elevated levels of plasma homocysteiae. Elevated homocysteine levels have beea associated also with ischemic stroke (9). The mechanism by which high levels of homocysteine produce vascular damage are, as of yet, aot completely uaderstood. lateractioa of homocysteiae with platelets or eadothehal cells has beea proposed as a possible mechanism. Clinically, homocysteine levels can be lowered by administration of vitamin B, vitamin B 2> foHc acid. 

Deficiency of Factor VII is relatively rare and inherited as an autosomal recessive disorder. Deficiency of Factor VII has been reported to be associated with bond abnormal bleeding and thrombotic tendencies. Deep vein thrombosis and pulmonary emboli have been reported in affected individuals. There is a very high frequency of Factor VII deficiency in people with the Dubin-Johnson syndrome, which is a congenital disorder of Hver function. 

Kleinschnitz C, Stoll G, Bendszus M et al (2006) Targeting coagulation Factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J Exp Med 203 513-518... 

Supplements of 400 Ig/d of folate begun before conception result in a significant reduction in the incidence of neural mbe defects as found in spina bifida. Elevated blood homocysteine is an associated risk factor for atherosclerosis, thrombosis, and hypertension. The condition is due to impaired abihty to form methyl-tetrahydrofolate by methylene-tetrahydrofolate reductase, causing functional folate deficiency and resulting in failure to remethylate homocysteine to methionine. People with the causative abnormal variant of methylene-tetrahydrofolate reductase do not develop hyperhomocysteinemia if they have a relatively high intake of folate, but it is not yet known whether this affects the incidence of cardiovascular disease. 

We shall first describe the coagulation pathway leading to the formation of fibrin. Then we shall briefly describe some aspects of the involvement of platelets and blood vessel walls in the overall process. This separation of clotting factors and platelets is artificial, since both play intimate and often mutually interdependent roles in hemostasis and thrombosis, but it facifitates description of the overall processes involved. 

Hemostasis and thrombosis are complex processes involving coagulation factors, platelets, and blood vessels. 

RAJAVASHISTH T B, YAMADA H and MiSHRA N K (1995) Transcriptional activation of macrophage stimulating factor gene by minimally modified LDL Arteriosclerosis, Thrombosis and Vascular Biology 15, 1591-8. 

Selective inhibition of tumor necrosis factor-induced vascular cell adhesion molecule-1 gene expression by a novel flavonoid. Lack of effect on trascriptional factor NF-kB Arteriosclerosis, Thrombosis and Vascular Biology 16, 1501-8. 

Identify risk factors and signs and symptoms of deep vein thrombosis and pulmonary embolism. 

Table 7-1).17 Venous thrombosis is uncommon in the absence of risk factors, and the effects of these risks are additive. Conversely, even in the absence of symptoms, VTE should be strongly suspected in those with multiple risk factors. 

First episode of VTE secondary to a transient (reversible) risk factor Warfarin 3 Recommendation applies to both proximal and calf vein thrombosis... 

Heparin-induced thrombocytopenia A clinical syndrome of IgG antibody production against the heparin-platelet factor 4 complex occurring in approximately 1% to 5% of patients exposed to either heparin or low-molecular-weight heparin. Heparin-induced thrombocytopenia results in excess production of thrombin, platelet aggregation, and thrombocytopenia (due to platelet clumping), often leading to venous and arterial thrombosis, amputation of extremities, and death. 

Fig. 11.1. Atherogenesis is a persistent inflammatory response that occurs in response to conditions that cause endothelial damage (e.g., hypercholesterolemia and oxLDL). After endothelial cells are activated, they elaborate cytokines, chemokines, and other mediators that recruit mononuclear cells (monocytes and T lymphocytes) to extravasate into the vessel wall where they are activated and release additional proinflammatory factors. Macrophages are able to take up oxLDL via scavenger receptors causing them to differentiate into foam cells and form a fatty streak that progresses to an atheroma with a necrotic lipid core and a fibrous cap. Chemokines can lead to weakening of the fibrous cap and eventual plaque rupture leading to thrombosis and occlusion of the involved vessel.

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