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Venous Thromboembolism

Deep Venous Thromboembolism

Proximal DVTs have a higher risk of PE than distal DVTs. Proximal DVTs are those that affect the popliteal or femoral veins.

Treatment of DVT

Oral direct factor Xa inhibitors (e.g. rivaroxaban, apixaban) are a better choice than the traditional warfarin heparin combination. The factor Xa inhibitors work quickly, do not require monitoring of INR, and avoid the adverse effects and restrictions associated with warfarin use. Patients who are not candidates for factor Xa inhibitors include those with poor renal function and those with malignancy associated thrombosis.

Warfarin and heparin are the traditional anticoagulants used to treat DVTs. Unfractioned heparin or low molecular weight heparin (enoxaparin) must be given first as it acts quickly and works to combat the initial pro-coagulant effect of warfarin (due to the fact that warfarin first reduces protein C & S production before affecting other vitamin K-dependent factors). With this combination, INR must be monitored to ensure that a therapeutic goal range of 2-3 is achieved. Patients must be in this therapeutic range for the anticoagulant effect to be enough to prevent DVT complications such as pulmonary embolism. It takes approximately 4-5 days for this therapeutic range to be achieved.

Inferior vena cava (IVC) filters can be placed in patients for whom anticoagulation does not work (thromboembolism progresses or recurrence of DVT while on anticoagulants). IVC filters are also used for patients who are actively bleeding therefore cannot be given anticoagulants. IVC filters work by preventing embolization of thrombi from the lower limb to the lungs, thereby preventing PE. Filters are placed using a transvenous approach. For actively bleeding patients, a removable filter is typically used and removed once the patient is stabilized. Removable filters are preferred because if left in place filters can migrate or erode into surrounding tissue and can even result in a thrombus that surrounds the filter.

Thrombolytics are given when patients with PE who are hemodynamically unstable. They are also given to patients with massive DVTs with severe swelling or limb-threatening ischemia. If these patients do not improve with thrombolytics or if they have a contraindication to thrombolytics then consider thrombectomy (mechanical/ surgical) or an iliac stent.

Hyperhomocysteinemia

Homocysteine is an amino acid that when elevated can lead to venous thrombosis and atherosclerosis. It can result in patients developing DVTs.

Homocysteine is converted to cystathionine by cystathionine beta-synthase which requires vitamin B6 (pyridoxine) as a cofactor. The cystathionine is then converted to cysteine. Homocysteine can also be converted to methionine by methylenetetrahydrofolate reductase and methionine synthase and the reaction requires vitamin B12 and folate as cofactors.

Treatment involves vitamin B6 which helps convert excess homocysteine to cystathionine.

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