Blood thrombosis

Heparin has been used in medicine and surgery for nearly 40 years and in this time has maintained a well-earned reputation as an effective and safe drug [1]. I may claim a share in this as I was a member of the research team at the University of Toronto which developed heparin for clinical use. The major clinical uses of heparin are for the prevention of thrombosis and the prevention of clotting of blood. Thrombosis is the complex plugging of blood vessels which can occur in veins after operation and child-birth and can occur in arteries as the result of diet, age and stress. Clotting of blood is a serious problem in the use of heart-lung machines, artificial kidneys, etc. and the prevention of this by heparin is most important. My presentation reviews points about this drug which indicates its actions are due to its polyelectrolyte nature. 

R. G. Macfadane, in R. Biggs, ed.. Human Blood Coagulation, Haemostasis and Thrombosis, 2nd ed., Blackwell Scientific PubHcations, Oxford, 1976, pp. 1-31. 

General trends in radiopharmaceutical research emphasize the use of small peptides. These molecules, of which the agents mentioned for thrombosis localization are an example, exhibit rapid and specific binding, and rapid blood clearance, two important parameters for a successflil radiopharmaceutical. Peptides are readily labeled with Tc and lend themselves to formulation as lyophilized kits that can be rapidly and rehably reconstituted. Possible targets for these molecules are quite varied, ranging from atherosclerotic plaque to P-amyloid (for Alzheimer s disease), to a variety of somatic receptors the populations of which are increased or decreased in disease. 

In general, arterial thrombi are platelet-rich ( white clots ) and form at ruptured atherosclerotic plaques, leading to intraluminal occlusion of arteries that can result in end-organ injury (e.g., myocardial infarction, stroke). In contrast, venous thrombi consist mainly of fibrin and red blood cells ( red clots ), and usually form in low-flow veins of the limbs, producing deep vein thrombosis (DVT) the major threat to life results when lower extremity (and, occasionally, upper extremity) venous thrombi embolize via the right heart chambers into the pulmonary arteries, i.e., pulmonary embolism (PE). 

Thrombosis is an imbalance toward the clotting capacity of the blood that leads to vessel occlusion by a clot. The clot prohibits ftuther blood flow and can so cause pathological sequelae dependent on its localization. 

Erythropoietin (Eprex ) is physiologically produced in the kidney and regulates proliferation of committed progenitors of red blood cells. It is used to substitute erythropoietin in severe anemias due to end stage renal disease or treatment of cancer with cytostatic agents. Side effects include hypertension and increased risk of thrombosis. 

Thrombosis is the development of a thrombus , consisting of platelets, fibrin, red and white blood cells in the arterial or venous circulation. Platelet-rich white thrombi are found in the arterial system and can be prevented by antiplatelet drugs. 

Thrombosis is the formation of a clot. A thrombus may form in any vessel, artery, or vein when blood flow is impeded. For example, a venous thrombus can... 

The IV solutions of plasma expanders include hetastarch (Hespan), low-molecular-weight dextran (Dextran 40), and high-molecular-weight dextran (Dextran 70, Dextran 75). Plasma expanders are used to expand plasma volume when shock is caused by bums, hemorrhage surgery, and otiier trauma and for prophylaxis of venous thrombosis and diromboembolism. When used in die treatment of shock, plasma expanders are not a substitute for whole blood or plasma, but tiiey are of value as emergency measures until die latter substances can be used. 

Many serious health problems result from abnormally located blood clots heart attacks (clots in coronary arteries), pulmonary embolism (clots in the lungs), and peripheral arterial occlusion and deep vein thrombosis (clots in the limbs). Each year heart attacks alone afflict over a million people in the United States, and almost half of them die as a result. 

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. 

Hemostasis is the cessation of bleeding from a cut or severed vessel, whereas thrombosis occurs when the endothelium lining blood vessels is damaged or removed (eg, upon rupmre of an atherosclerotic plaque). These processes encompass blood clotting (coagulation) and involve blood vessels, platelet aggregation, and plasma proteins that cause formation or dissolution of platelet aggregates. 

In hemostasis, there is initial vasoconstriction of the injured vessel, causing diminished blood flow distal to the injury. Then hemostasis and thrombosis share three phases ... 

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. 

Roth GJ, Calverley DC Aspirin, platelets, and thrombosis theory and practice. Blood 1994 83 885. 

The chapter on plasma proteins, immunoglobulins, and blood coagulation in the previous edition has been split into two new chapters on plasma proteins and immunoglobuhns and on hemostasis and thrombosis. 

Section VI consists of discussions of eleven special topics nutrition, digestion, and absorption vitamins and minerals intracellular traffic and sorting of proteins glycoproteins the extracellular matrix muscle and the cy-toskeleton plasma proteins and immunoglobulins hemostasis and thrombosis red and white blood cells the metabolism of xenobiotics and the Human Genome Project. 

Early studies indicate that combined GP Ilb/IIIa inhibition with rt-PA thrombolysis may improve clinical and MRI outcomes after acute ischemic stroke, with an acceptable safety prohle. The dual targeting of platelets and hbrin by combination therapy may provide synergistic benefits, including increased arterial recanalization, reduced microvascular thrombosis, reduced arterial reocclusion, and less rt-PA-mediated blood-brain barrier injury and secondary activation of the coagulation system. 

Recommendations in this section may change based on the results from the recent EPO-3 trial (epoetin alfa versus placebo). A difference in red blood cell transfusion rates was not observed between groups. Epoetin alpha therapy improved survival in trauma patients. Epoetin alfa did not have a measurable clinical benefit in medical/surgical non-trauma patients. Epoetin alpha therapy was associated with an increased thrombotic event rate, particularly in patients not receiving pharmacological deep vein thrombosis prophylaxis. 

Convert to oral warfarin pharmacotherapy once the platelet count has returned to baseline values (preferably >100-150 x 109/L). Continue for at least 30 d in patients without evidence of thrombosis (optimal duration is not known but one author recommends at least 2-3 mo of warfarin Blood, 2003). Continue for at least 6 mo in patients with evidence... 

Portal hypertension is a consequence of increased resistance to blood flow through the portal vein. Increased resistance is usually due to restructuring of intrahepatic tissue (sinusoidal damage) but may also be caused by presinusoidal damage such as portal vein occlusion from trauma, malignancy, or thrombosis. A third (and the least common) mechanism is outflow obstruction of the hepatic vein. This latter damage is posthepatic, and normal liver structure is maintained. This chapter will focus on portal hypertension caused by intrahepatic damage from cirrhosis. 

Gastrointestinal bleeding can result from erosion of intestinal blood vessels by pancreatic enzymes or as a result of thrombosis. 

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