Thrombosis risk factors

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. 

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. 

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... 

Whereas (32 glycoprotein 1 ((J2-GPI) is the target of anticardiolipin antibodies, prothrombin is the antigen for most lupus anticoagulants. Both these antibodies are risk factors for both venous and arterial thrombosis. In addition, complications such as thrombocytopenia and recurrent miscarriages are manifestations of the so-called antiphospholipid syndrome (97). 

These findings suggest that CNT exposure should be evaluated as a potential cardiovascular risk factor. It should be noted, however, that no thrombosis or other adverse effects on the cardiovascular homeostasis were reported after intravenous injection in healthy animals, when this administration route was used for investigating the biokinetics of CNTs [119-126]. 

Risk factors for venous thromboembolism in pregnancy include increasing age, history of thromboembolism, hypercoagulable conditions, operative vaginal delivery or cesarean section, obesity, and a family history of thrombosis. 

Thrombolytic agents, 5 172t, 175-179 Thrombomodulin, 4 84, 88 Thrombosis, 4 83, 84 risk factors for, 4 90t Thromboxane, 4 103-104 Thromboxane A2, 4 85 Throttling devices, in refrigeration systems, 21 538... 

In a totally different field, studies were being carried out on children who had a deficiency of methionine synthase and an impaired ability to convert homocysteine to methionine, so that they had increased blood levels of homocysteine. It was noted that these children had an increased incidence of thrombosis in cerebral and coronary arteries. This led to a study which eventually showed that an increased level of homocysteine was a risk factor for coronary artery disease in adults. Since methionine synthase requires the vitamins, folic acid and B12, for its catalytic activity, it has been suggested that an increased intake of these vitamins could encourage the conversion of homocysteine to methionine and hence decrease the plasma level of homocysteine. This is particularly the case for the elderly who are undernourished (see Chapter 15 for a discussion of nutrition in the elderly). 

Cardiovascular disorders Estrogen and estrogen/progestin therapy have been associated with an increased risk of cardiovascular events (eg, Ml and stroke, venous thrombosis, PE [venous thromboembolism]). Manage risk factors for cardiovascular disease appropriately. 

A 25-year-old woman presents to the emergency department complaining of acute onset of shortness of breath and pleuritic pain. She had been in her usual state of health until 2 days prior when she noted that her left leg was swollen and red. Her only medication was oral contraceptives. Family history was significant for a history of "blood clots" in multiple members of the maternal side of her family. Physical examination demonstrates an anxious woman with stable vital signs. The left lower extremity demonstrates erythema and edema and is tender to touch. Ultrasound reveals a deep vein thrombosis in the left lower extremity chest computed tomography scan confirms the presence of pulmonary emboli. What are the likely risk factors in this woman—hereditary, acquired, or both What therapy is indicated acutely What are the long-term therapy options How long should she be treated Should this individual use oral contraceptives ... 

The increased risk of thromboembolism associated with atrial fibrillation and with the placement of mechanical heart valves has long been recognized. Similarly, prolonged bed rest, high-risk surgical procedures, and the presence of cancer are clearly associated with an increased incidence of deep venous thrombosis and embolism. Antiphospholipid antibody syndrome is another important acquired risk factor. Drugs may function as synergistic risk factors in concert with inherited risk factors. 

Treatment for established venous thrombosis is initiated with unfractionated or low-molecular-weight heparin for the first 5-7 days, with an overlap with warfarin. Once therapeutic effects of warfarin have been established, therapy with warfarin is continued for a minimum of 3-6 months. Patients with recurrent disease or identifiable, nonreversible risk factors may be treated indefinitely. Small thrombi confined to the calf veins may be managed without anticoagulants if there is documentation over time that the thrombus is not extending. 

The use of iloprost has been proposed in patients with systemic sclerosis, a disease that is often characterized by pulmonary hypertension and Raynaud s phenomenon. Three patients with systemic sclerosis who were treated with iloprost developed acute thrombotic events (3). In one case, intestinal infarction occurred 1 day after infusion of iloprost. In another patient the left kidney was not perfused 22 days after the last infusion of iloprost because of thrombosis of the left renal artery. The last patient, 9 months after the start of treatment with iloprost, and 5 days after the last infusion, had an anterolateral myocardial infarction. The authors commented that their observations did not allow them to conclude that there is a direct relation between infusion of iloprost and thrombotic events. However, they said that this possibility should be considered, and they suggested that risk factors for thromboembolism should be carefully evaluated in each patient with systemic sclerosis who is receiving iloprost. 

There is a risk of thrombosis with estrogens, discussed in detail in the monograph on Hormonal contraception. Both superficial and deep complications can occur in either sex. Effects on clotting factors and renin are involved in one small study, men taking estrogens had increased concentrations of factor VII, factor VIII, and... 

In hormone replacement therapy, the risk of deep vein thrombosis is increased by a factor of 2-4 (35-37). The absolute increase in the treated population as a whole is low, with about one case of venous thromboembolism in 5000 women-years of use of hormone replacement therapy. However, in the subgroup with pre-existing risk factors, such as obesity, varicose veins, smoking, and a prior history of venous thromboembolism or superficial thrombophlebitis, the increase in risk from hormone replacement therapy can be substantial among these women are those with a genetic predisposition to thrombosis, generally due to some form of thrombophilia, such as deficiency of the coagulation inhibitors protein S, protein C, or anti thrombin III. In any of these subjects thrombosis can occur early in hormone replacement therapy. However, this tendency to early occurrence of deep vein thrombosis also seems to be present in all those who take hormone replacement therapy. 

There is also fairly strong evidence that immunological mechanisms play a role in thrombotic episodes associated with oral contraceptives, especially when they occur in the absence of risk factors for vascular disease (71), although this has been contested (72). In one series of reports on cerebral infarction, circulating immune complexes and/or specific antihormone antibodies were found in 15 of 20 patients (37). In a large series of women with venous or arterial thrombosis, anti-ethinylestradiol antibodies were absent in non-users but present in 72% of users they were also present in 33% of healthy oral contraceptive users without thrombosis (SEDA-16, 465). In half of the cases there were both anti-ethinylestradiol antibodies and a history of smoking were found jointly in half of the cases. 

Although the authors pointed to the absence of risk factors other than the drug, it must be remembered that cerebral venous thrombosis is a recognized complication... 

There have been several reports of arterial thrombosis associated with the use of desmopressin, including myocardial infarction (23-27). One of these reports concerned a case of fatal myocardial infarction in a blood donor in excellent health, with no risk factors and no signs of vascular disease (25). 

Tanis BC, Rosendaal FR. Venous and arterial thrombosis during oral contraceptive use risks and risk factors. Semin Vase Med. 2003 3 69-84. 

In view of the perceived benefit of aspirin in the secondary prevention of stroke and myocardial infarction, two large trials involving physicians as subjects were initiated to study the effect of aspirin in the primary prevention of arterial thrombosis. In the American study, 22,000 volunteers (age 40 to 84 years) were randomly assigned to take 325 mg of aspirin every other day or placebo. The trial was halted early, after a mean follow-up of 5 years, when a 45% reduction in the incidence of myocardial infarction and a 72% reduction in the incidence of fatal myocardial infarction were noted with aspirin treatment. However, total mortality was reduced only 4% in the aspirin group, a difference that was not statistically significant, and there was a trend for a greater risk of hemorrhagic stroke with aspirin. Thus, the prophylactic use of aspirin in an apparently healthy population is not recommended at this time, unless there are risk factors for cardiovascular disease. 

Elevated TAFI levels have been found in men with symptomatic coronary artery disease (142). TAFI is also reported to be a risk factor for deep venous thrombosis, A recent report on the high levels of TAFI in the acute phase of ischemic stroke revealed not only elevated levels but also an incremental increase in TAFI with the degree of neurologic deterioration (143). Therefore, the observation by Boffa et al. on the acute phase nature of this protein requires further validation, In addition, Juhan-Vague et al, stated that there is a correlation between TAFI levels and cardiovascular risk factors (144). Animal models may be needed to truly validate studies on TAFI upregulation and its relation to thrombosis. 

Common risk factors for developing branch retinal vein thrombosis (BRVT) and central retinal vein thrombosis (CRVT) include increased plasma fibrinogen, diabetes, decreased exercise, hypertension, and hyperviscosity (205). Sickle cell anemia, polycythemia vera, and other proliferative disorders may also lead to this syndrome. 

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