RISK FACTORS : SURGERY, ESPECIALLY ORTHOPAEDIC, MAJOR ABDOMINAL & THORACIC, IMMOBALIZATION, OCCULT CANCER, ORAL CONTRACEPTIVES USE, POSTPARTUM, OBESITY, ADVANCED AGE, ANTICARDIOLIPID ANTIBODIES ( LUPUS ERYTHEMATOSUS), TRAUMA TO LEG, CHF
Medical Care: Immediate full anticoagulation is mandatory for all patients suspected to have deep vein thrombosis (DVT) or pulmonary embolism (PE). Diagnostic investigations should not delay empirical anticoagulant therapy. Initial anticoagulation is performed with intravenous heparin, which activates antithrombin III to slow or prevent the progression of DVT and reduces pulmonary emboli. Heparin does not dissolve the existing clot. The patient should be started simultaneously on oral anticoagulation with warfarin. After a therapeutic dose of warfarin is established, heparin is discontinued and warfarin therapy is maintained.
" Thrombolytic therapy
o Thrombolytic therapy should be considered for patients who are hemodynamically unstable, patients who have right-heart strain, and high-risk patients with underlying poor cardiopulmonary reserve.
o Although most studies demonstrate superiority of thrombolytic therapy with respect to resolution of radiographic and hemodynamic abnormalities within the first 24 hours, this advantage disappears 7 days after treatment. Controlled clinical trials have not demonstrated benefit in terms of reduced mortality rates or earlier resolution of symptoms when currently compared to heparin.
o Until randomized clinical trials demonstrate a clear morbidity or mortality benefit, the role of thrombolytic therapy in the management of acute PE remains controversial. The currently accepted indications for thrombolytic therapy include hemodynamic instability or right ventricular dysfunction demonstrated on echocardiography.
" Goals of anticoagulation therapy
o The efficacy of heparin therapy depends on achieving a critical therapeutic level of heparin within the first 24 hours of treatment. The critical therapeutic level of heparin is 1.5 times the baseline control value or the upper limit of normal range of the activated partial thromboplastin time (aPTT).
o This level of anticoagulation is expected to correspond to a heparin blood level of 0.2-0.4 U/mL by the protamine sulfate titration assay and 0.3-0.6 by the antifactor X assay.
o Each laboratory should establish the minimal therapeutic level for heparin, as measured by the aPTT, to coincide with a heparin blood level of at least 0.2 U/mL for each batch of thromboplastin reagent being used.
o Heparin therapy generally is overlapped with warfarin for a minimum of 4-5 days.
o A weight-based heparin dosing nomogram is an effective approach for achieving adequate anticoagulation. An initial bolus of 80 U/kg is followed by an infusion of 18 U/kg/h. The heparin dose is further adjusted to maintain an aPTT in the therapeutic range.
" Low molecular weight heparin
o Low molecular weight heparins (LMWHs) have many advantages over unfractionated heparin. These agents have a greater bioavailability, can be administered by subcutaneous injections, and have a longer duration of anticoagulant effect.
o A fixed dose of LMWH can be used, and laboratory monitoring of aPTT is not necessary.
o Trials comparing LMWH to unfractionated heparin have shown that LMWH is at least as effective and as safe as unfractionated heparin.
o The studies have not pointed to any significant differences in recurrent thromboembolic events, major bleeding, or mortality between the 2 types of heparin.
o LMWH can be administered safely in an outpatient setting. This has lead to the development of programs in which clinically stable patients with PE are treated at home at substantial cost savings.
" Oral anticoagulant therapy
o The anticoagulant effect of warfarin is mediated by the inhibition of vitamin K-dependent factors, which are II, VII, IX, and X. The peak effect does not occur until 36-72 hours after drug administration, and the dosage is difficult to titrate.
o A prothrombin time ratio is expressed as an International Normalized Ratio (INR) and is monitored to assess the adequacy of warfarin therapy. The recommended therapeutic range for venous thromboembolism is an INR of 2-3. This level of anticoagulation markedly reduces the risk of bleeding without the loss of effectiveness. Initially, INR measurements are performed on a daily basis; once the patient is stabilized on a specific dose of warfarin, the INR determinations may be performed every 1-2 weeks or at longer intervals.
" Duration of anticoagulation
o A patient with a first thromboembolic event occurring in the setting of reversible risk factors such as immobilization, surgery, or trauma, should receive warfarin therapy for 3-6 months. In the absence of an identifiable risk factor, the first idiopathic thromboembolic event should be treated for a minimum of 6 months, and 3 months of anticoagulation is insufficient in this setting.
o Warfarin treatment for longer than 6 months is indicated in patients with recurrent venous thromboembolism or in those in whom a continuing risk factor for venous thromboembolism exists, including malignancy, immobilization, or morbid obesity.
o Patients who have PE and preexisting irreversible risk factors, such as deficiency of antithrombin III, protein S and C, factor V Leiden mutation, or the presence of antiphospholipid antibodies, should be placed on long-term anticoagulation.
Surgical Care:
" Inferior vena cava (IVC) interruption by the insertion of an IVC filter (Greenfield filter) is indicated in the following settings:
o Patients with acute venous thromboembolism who have an absolute contraindication to anticoagulant therapy, eg, recent surgery, hemorrhagic stroke, or significant active or recent bleeding
o Patients with massive PE who survived but in whom recurrent embolism will be invariably fatal
o Patients who have objectively documented recurrent venous thromboembolism, adequate anticoagulant therapy notwithstanding
" An ideal IVC filter should have the following characteristics:
o Easy and safe placement by percutaneous technique
o Biocompatible and mechanically stable
o Ability to trap emboli without causing occlusion of the vena cava
" One large trial has shown that during the first 12 days after insertion of IVC filters, significantly fewer patients had recurrent PE. However, following a 2-year follow-up, no significant differences in survival rates existed between the 2 groups. Furthermore, significantly higher rates of recurrent DVT occurred among patients who received an IVC filter. Other complications of IVC filters include proximal migration of the filter into the right heart chambers and perforation of the IVC.
Activity:
" Activity is recommended as tolerated.
ALTERNATIVE DRUGS:
β’ Thrombolytics [streptokinase, urokinase, tissue plasminogen activator (tPA)]. Streptokinase and urokinase
not commonly used due to risk of anaphylactic reactions and dosing difficulties.
β’ tPA is given in two ways: 0.6mg/kg over 15 minutes or the traditional 100mg given over 2 hours
PATIENT MONITORING :
After hospital discharge, prothrombin time should be prolonged to an INR range of 2.0 to 3.0. Warfarin should be continued 6 months. In patients with continuous predisposition to DVT, it should be continued indefinitely.
PREVENTION/AVOIDANCE :
Recognition of patients with multiple risk factors for deep venous thrombosis and implementation of prophylactic therapy including low dose heparin, warfarin or leg compression devices
POSSIBLE COMPLICATIONS :
β’ Pulmonary infarction
β’ Acute cor pulmonale
β’ Recurrent deep venous thrombosis or pulmonary embolism, post phlebitic syndrome
β’ Treatment failure requiring surgical venous interruption
β’ Major hemorrhage associated with PE thrombolysis occurs in 8%, incidence of intracerebral bleed is 2%
and is fatal in 50% of cases
EXPECTED COURSE/PROGNOSIS : With appropriate therapy hospital mortality is less than 5%. Long-term prognosis determined by coexisting disease(s).