Deep-vein thrombosis, treatment

Indications for treatment with streptokinase include acute occlusion of arteries, deep vein thrombosis, and pulmonary embolism. Streptokinase therapy in coronary thrombosis, which is the usual cause of myocardial infarction (54,71,72), has proved to be valuable. In this frequently fatal condition, the enzyme is adrninistered intravenously at a dose of 1.5 million units over 60 min, or given by intracoronary infusion at a 20,000- to 50,000-unit bolus dose followed by 2000 to 4000 units/min for 60 min therapy must be instituted as soon as practicable after the diagnosis of heart attack is made. For deep vein thrombosis, pulmonary embolism, or arterial occlusion, streptokinase is infused at a loading dose of 250,000 units given over 30 min, followed by a maintenance dose of 100,000 units over a 60-min period. 

Heparin and warfarin are widely used in the treatment of thrombotic and thromboembolic conditions, such as deep vein thrombosis and pulmonary embolus. Heparin is administered first, because of its prompt onset of action, whereas warfarin takes several days to reach full effect. Their effects are closely monitored by use of appropriate tests of coagulation (see below) because of the risk of producing hemorrhage. 

Streptokinase is administered by intravenous or intra-arterial infusion in the treatment of thrombo-embolic disorders, e g. pulmonary embolism, deep-vein thrombosis and arterial occlusiorrs. It is also used in acute myocardial irtfarclioa... 

Bates SM, Ginsberg JS. Clinical practice. Treatment of deep-vein thrombosis. N Engl J Med 2004 351 268-277. 

Lenalidomide was approved recently for the indication of myelodysplastic syndrome where the 5q deletion is present. Since lenalidomide is an analog of thalidomide, all the same precautions must be taken to prevent phocomelia. The time to maximum lenalidomide concentrations occurs 0.5 to 4 hours after the dose. The terminal half-life ranges from 3 to 9 hours. Approximately 65% of lenalidomide is eliminated unchanged in the urine, with clearance exceeding the glomerular filtration rate. To date, no pharmacokinetic studies have been done in patients with renal dysfunction. Lenalidomide is used in the treatment of myelodysplastic syndrome and multiple myeloma. Other side effects are neutropenia, thrombocytopenia, deep vein thrombosis, and pulmonary embolus. 

Lenalidomide is an immunomodulating agent related to thalidomide that was recently approved for the treatment of patients with multiple myeloma and myelodysplastic syndrome (MDS). Lenalidomide lacks the common side effects of thalidomide, such as constipation and peripheral neuropathy. Interim analyses of two phase III trials show that lenalidomide in combination with dexamethasone produces higher response rates than dexamethasone alone in relapsed and refractory myeloma. Adverse effects of lenalidomide include diarrhea, nausea, muscle cramps, hematologic side effects and deep vein thrombosis.42... 

Direct thrombin inhibitors such as hirudin, Hirulog, the peptide aldehyde efegatran, and peptidomimetic compound argatroban have undergone clinical trials. Their application in the prevention and treatment of deep vein thrombosis contin-... 

Sarasin, F.P. and H. Bounameaux, "Decision Analysis Model of Prolonged Oral Anticoagulant Treatment in Factor V Leiden Carriers with First Episode of Deep Vein Thrombosis," BMJ, 316, 95-99 (1998). 

Accumulation of homocystine in blood is associated with cardiovascular disease deep vein thrombosis, thromboembolism, and stroke dislocation of the lens (ectopic lens) and mental retardation. Homocystinemia caused by an enzyme deficiency is a rare, but severe, condition in which atherosclerosis in childhood is a prominent finding. These children often have myocardial infarctions before 20 years of age. Ail patients excrete high levels of homocystine in the urine. Treatment includes a diet low in methionine. The two major enzyme deficiencies producing homocystinemia are ... 

Fondaparinux is a synthetic pentasaccharide. It is used for the prevention of deep vein thrombosis in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and pulmonary embolism. 

Plasminogen, an inactive precursor, is activated to plasmin which as a protease is able to break down fibrin clots. The thrombolytic agents in use promote the conversion of plasminogen to plasmin at the site of a thrombus. Indications include post-myocardial infarction treatment. The thrombolytic must be administered within 6 hours for an optimal effect. Other indications are treatment of acute pulmonary thromboembolism, deep-vein thrombosis, acute arterial thrombosis and thromboembolism, as well as in the clearance of arteriovenous catheters and can-nulae. Agents are streptokinase, anistreplase, urokinase, alteplase, reteplase and tenecteplase. 

The main contraindications to oestrogen treatment are estrogen dependent tumors and previous deep vein thrombosis or embolus. 

A 23-year old pregnant woman who has been administered IV heparin for treatment of deep vein thrombosis has developed heparin-induced thrombocytopenia. Altering therapy by removing heparin and adding warfarin is not a viable option, because warfarin can cross the placenta and exert an anticoagulant effect in the fetus. Suggest a treatment approach. 

Contraindications Concomitant coumarin-type therapy when used in the treatment of breast cancer in high-risk women, history of deep vein thrombosis or pulmonary embolism in high-risk women... 

Unlabeled Uses Prevention of postoperative deep vein thrombosis (DVT), protection of aortocoronary bypass grafts, reduction of graft loss after renal transplant, treatment of intermittent claudication, sickle cell disease, subarachnoid hemorrhage, diabetic microangiopathy, ischemic heart disease... 

It is indicated in the prophylaxis and treatment of deep vein thrombosis in major surgery and pulmonary embolism, treatment of atrial fibrillation with embolisation, prophylaxis and treatment of peripheral arterial embolism. 

Before commencing the sessions the patients were assessed by physical examination and full medical history including age, sex, occupation, residence, special habits of medical importance with particular emphasis on the history of the underlying disease including duration of ulcer, mode of onset, ulcer pain, history of deep vein thrombosis or varicose veins, trauma, lump, varicosities, contact dermatitis and symptoms suggestive of ischaemia. Photographic reference of ulcer and ulcer area measurements were carried out at the commencement of treatment and during the follow up laser therapy, which continued for 6 months. 

A major focus of drug development has been to develop orally active anticoagulants that do not require monitoring. Rivaroxiban is the first oral factor Xa inhibitor to reach phase III clinical trials. The safety and efficacy of rivaroxiban appears to be at least equivalent, and possibly superior, to LMW heparins for prevention of deep vein thrombosis no routine monitoring is required. This drug is also in clinical trials for treatment of deep vein thrombosis and prevention of stroke in atrial fibrillation. 

The adverse effect profile of thalidomide is extensive. The most important toxicity is teratogenesis. Because of this effect, thalidomide prescription and use is closely regulated by the manufacturer. Other adverse effects of thalidomide include peripheral neuropathy, constipation, rash, fatigue, hypothyroidism, and increased risk of deep vein thrombosis. Thrombosis is sufficiently frequent, particularly in the hematologic malignancy population, that most patients are placed on some type of anticoagulant when thalidomide treatment is initiated. 

Vorinostat (Zolinza) is a histone deacetylase inhibitor that is approved for the treatment of cutaneous T-cell lymphoma in patients with progressive, persistent, or recurrent disease on or after two systemic therapies. The recommended dosing is 400 mg orally once daily. Adverse effects include pulmonary embolus, deep vein thrombosis, thrombocytopenia, anemia, and gastrointestinal disturbances. 

Estrogens with or without progestins should not be used for the prevention of cardiovascular disease. The Women s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 19 years of age) during 5 years of treatment with oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo.62... 

Gutt CN, Oniu T, Wolkener F, et al. Prophylaxis and treatment of deep vein thrombosis in general surgery. AmJSurg. 2005 189 14-22. 

Dedden P, Chang B, Nagel D, 1997. Pharmacy-managed program for home treatment of deep vein thrombosis with enoxaparin. Am J Health-Syst Pharm 54 1968. 

Fiessinger JN, Huisman MV Davidson BL, etal. Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis a randomized trial. J Am Med Assoc 2005 293 681-689. 

Eriksson H, Wahlander K, Gustafsson D, et al. A randomized, controlled, dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute deep vein thrombosis THRIVE I. J Thromb Haemost 2003 1 41 -47. 

Fondaparinux is a chemically synthesized pentasaccharide that mimics the antithrombin-binding site of heparin and LMWH. Its molecular size (1728Da) is too small to bind to thrombin molecules while it is bound to antithrombin, Therefore, it is a pure anti-Xa inhibitor. It binds very little to platelets, proteins, or endothelium and is excreted in the urine, It does not form a complex with PF4 or other positively charged molecules. It is not neutralizable by protamine sulfate, Recent clinical trials have resulted in FDA approval for prophylaxis of deep vein thrombosis in orthopedic surgery, It has been shown to be effective and safe for the treatment of pulmonary embolism (20,21) and ACS (non-ST-elevation Ml) (OASIS 5—Michelangelo Trial) (17). 

Buller HR, Davidson BL, Decausus H, et al. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep vein thrombosis a randomized trial. Ann Int Med 2004 140 867-873. 

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