Coagulation venous thromboembolism

FIGURE 7-4. Coagulation cascade. AT, antithrombin HCII, heparin cofactor II TFPI, tissue factor pathway inhibitor. (Reproduced from Haines ST, Zeolla M, Witt DM. Venous thromboembolism. In ... 

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. 

Despite the variations that are found, the overall conclusion is that oral contraceptives cause an increase in coagulation factors I (fibrinogen), II, VII, IX, X, and XII, and a reduction in antithrombin III concentrations, which would be expected to predispose to venous thromboembolism, especially if not counterbalanced by an increase either in fibrinolytic activity or of other inhibitory proteins of the coagulation, such as protein C (70). 

The effect of continuously administered low-dose 17-beta-estradiol (E2) + norethisterone acetate (NETA) on coagulation and fibrinolytic factors has been studied in 120 menopausal women, using two dosage variations (1 mg of E2 with 0.25 mg or 0.5 mg of NETA) compared with placebo over a year (53). In either dose, the combination significantly lowered plasma concentrations of factor VII, fibrinogen, antithrombin, and plasminogen activator inhibitor-1 (PAI-1) compared with placebo. These changes appear favorable, since they may lead to increased fibrinolytic activity and could reduce the risk of coronary heart disease. However, antithrombin activity was also reduced, which may increase the risk of venous thromboembolism. 

Family history of venous thromboembolism, arterial disease or a known prothrombotic condition, e.g. factor V Leiden (pretreatment coagulation investigation is advised). 

Venous thromboembolism occurs when red bloods cells, fibrin, and to a lesser extent, platelets and leukocytes coagulate to form a thrombus within an intact cardiovascular system (9). A patient undergoing orthopaedic surgery incurs the greatest risk for VTE (10). Pulmonary embolism occurs when a segment of a thrombus within the deep venous system detaches itself from the blood vessel, travels to the lungs, and lodges within the pulmonary arteries. Both of these conditions, if not... 

Cardiovascular The main adverse effect of prothrombin complex concentrates is a risk of thrombosis, as patients taking oral anticoagulants have prothrombotic susceptibility factors [31, 33 ]. Reported thromboembolic complications include ischemic stroke, venous thromboembolism (venous thrombosis or pulmonary embolism), myocardial infarction, and disseminated intravascular coagulation [32 ]. 

Thrombosis in the dural sinuses or cerebral veins is much less common than cerebral arterial thromboembolism. It causes a variety of clinical syndromes, which often do not resemble stroke (Bousser and Ross Russell 1997). While ischemic arterial stroke and cerebral venous thrombosis share some causes (Southwick et al. 1986), others are specific to cerebral venous thrombosis (Table 29.1). A particularly high index of suspicion is required in women on the oral contraceptive pill (Saadatnia and Tajmirriahi 2007) and in the puerperium. In the past, cerebral venous thrombosis was strongly associated with otitis media and mastoiditis, lateral sinus thrombosis or otitic hydrocephalus, but the most common causes are now pregnancy and the puerperium, which cause 5-20% of the cerebral venous thrombosis in the developed world, the oral contraceptive pill, malignancy, dehydration, inflammatory disorders and hereditary coagulation disorders. No cause is found in around 20% of cases. 

The comprehensive review by Douglas provides a recent discussion of the clinically useful anticoagulants. Recent studies have shown heparin to be clearly effective in clinical states In which disseminated Intravascular coagulation was Indicated to be a pathologic factor.75 xhe most commonly employed oral anticoagulants are of the coumarin type such as warfarin and nicoumalone. The oral anticoagulants appear to be of value in the prevention of thromboembolic complications after myocardial infarction.9 76 However, anticoagulation therapy has been found to have no effect on death-rate in these patients.77 Warfarin has been shown to be effective in the prevention of postoperative venous thrombosis. 

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