Traditional therapeutic measures—including bed rest, continuous leg elevation, and elastic stockings—are of unproven benefit when used with anticoagulation in the management of a DVT. Aggressive anticoagulation will prevent extension of clot and allow for its lysis by the usual fibrinolytic pathways. Early ambulation with appropriate analgesia as needed after adequate anticoagulation with heparin is a practical and safe approach. PPS can be treated with periodic leg elevation, compression stockings, and pain medications as required.
Prevention of PE is the primary objective in treating DVT. Given the potential to propagate, a calf DVT should be followed closely with repeat duplex or IPG in 5 to 7 days after initial examination. (Some authorities suggest two repeat examinations at 2 and 7 days after first test. 7) The potential morbidity and cost of several months of anticoagulation is not justified for an isolated, nonextending calf DVT except in high-risk groups such as patients with a history of a previous proximal DVT or PE, significant cardiovascular comorbidity, a persistent hypercoagulable state, or poor ambulation.
Several recent studies have documented the accuracy of serial duplex examinations and the safety of withholding anticoagulation in patients clinically suspected of having DVT but with a normal initial ultrasound.47. A repeat duplex should be done in these patients at 5 to 7 days after initial exam or earlier if there is progression of symptoms or signs. The risk of a PE within 7 days of a normal duplex scan in patients with symptoms of DVT of the lower extremity is near zero. The probability of detecting DVT on a second ultrasound when there is a completely normal color-flow duplex scan from a few days earlier is approximately 2 percent. 27 Subsequent thromboembolism (typically nonfatal) within 3 months of two normal serial duplex studies occurs in about 0.6 percent of patients, which is comparable to the outcome in patients with normal venograms.7 It follows that withholding anticoagulation in patients with negative serial ultrasounds is safe, accurate, and cost-effective.
Proven proximal DVT requires immediate anticoagulation to reduce local morbidity and prevent thromboembolism. The initial choice of treatment is becoming a low-molecular-weight heparin (LMWHs), such as dalteparin, enoxaparin, or tinzaparin. These are weight-adjusted and given once or twice daily subcutaneously until oral anticoagulation reaches the therapeutic range (100 U/kg q12h or 200 U/kg q24h for dalteparin; 100/mg/kg q12h for enoxaparin; 175 U/kg q24h for tinzaparin based on actual body weight). The available LMWH agents are not interchangeable. These drugs have several advantages over unfractionated heparin, including a more predictable anticoagulant effect, ease of administration, longer half-life, lack of a need to monitor the anticoagulation effect, resistance to inhibition by activated platelets, and a lower incidence of major bleeding and heparin-induced thrombocytopenia. 289 LMWH has a preferential inhibitory effect on factor Xa rather than factor IIa (thrombin) and is at least as effective and safe as unfractionated heparin in the treatment of DVT or PE. -HI0 INR or PTT cannot be used to monitor the effect of LMWH and measuring factor Xa levels is expensive, not readily available, and unnecessary given the very predictable effect of these heparins. The ability to discharge most patients home after treatment with LMWH with next-day follow-up makes this the most cost-effective option. The treatment plan must be discussed with the continuing care physician, including follow-up in 24 h and institution of warfarin.
Despite the increasing use of LMWH, some patients will have indications for admission. These include the patient who is unable to ambulate, has poor social supports or unreliable follow-up, has difficulty with education for drug administration, needs lytic or invasive therapy, or needs to have an alternative serious diagnosis investigated or treated (e.g., arterial ischemia, cellulitis, or pelvic mass). The consequences of a suspected or known PE such as hemodynamic instability or significant comorbidity will also require in-hospital treatment. obviously, there must be a mechanism for providing the patient with the medication before discharge from the ED.
If LMWH is not immediately available, a continuous infusion of unfractionated heparin can be started until LMWH is initiated or oral anticoagulation is therapeutic. Weight-adjusted dosing of 80 U/kg bolus followed by an infusion of 18 U/kg per hour will rapidly achieve a therapeutic activated partial thromboplastin time (aPTT). Traditional dosing of a 5000-U bolus followed by an infusion of 1000 U/h will result in subtherapeutic aPTT at 6 h in two-thirds of treated patients. If weight-adjusted dosing is not used, a higher bolus of 7500 to 10,000 U followed by an infusion of 1250 U/h or greater is recommended. The infusion is altered to keep the aPTT between 55 and 85 s (1.8 to 2.8 times normal). Close monitoring of patients is required to detect bleeding and heparin-induced thrombocytopenia and thrombosis. Serious bleeding due to LMWH is very unusual, but if it occurs, the anti-Xa effect cannot be reversed. Protamine can counteract the minor anti-thrombin effect of LMWH, but is not useful given its inability to effect factor Xa and its own inherent potential to cause bleeding.
oral anticoagulation with the vitamin K antagonist warfarin should be started on the same day as heparin for the treatment of a DVT. However, before its delayed effect of reducing prothrombin concentrations occurs, warfarin increases coagulability and thrombogenesis in the first 24 to 48 h owing to its early effect on reducing protein C levels.2 This has prompted some authors to suggest that warfarin should be started well after initiation of heparin when the aPTT is adequately prolonged, though it is common practice to start both drugs simultaneously. It is clear, however, that if heparin is discontinued early, when the International Normalized Ratio (INR) first becomes therapeutic, the patient is at risk of clot extension, since warfarin has induced a transient hypercoagulable state. The usual recommended loading dose of warfarin is 7.5 to 10 mg, which is twice the expected maintenance dose. Then the daily warfarin dose is adjusted to keep the INR between 2 and 3. Heparin can be discontinued when the INR is in the therapeutic range for at least two consecutive days.
Warfarin is associated with some serious adverse effects and should not be used in certain circumstances. The commonest risk of warfarin is bleeding. This is usually related to the degree of anticoagulation and typically responds to dose reduction. Skin necrosis secondary to warfarin occurs primarily in patients with a deficiency of protein C or protein S.2 The necrosis is due to thrombotic occlusion of small vessels, usually three to eight days after initiation of this drug. Warfarin is contraindicated in patients who are pregnant, have a serious or active bleeding diathesis, or have had very recent major surgery (thoracoabdominal, nervous system, spine, or eye). It causes fetal bleeding and is teratogenic, but neither unfractionated heparin nor LMWH crosses the placenta and both are safe for the fetus. LMWH is the preferred drug for the treatment of a DVT in pregnancy and warfarin can be safely started in the postpartum period even in breast-feeding women. 2
The duration of warfarin treatment has to be individualized and is dependent on a previous history of DVT or PE, reversibility of previous thromboembolic risk factors, the effectiveness of warfarin to resolve thrombosis, and on the risk of bleeding. oral anticoagulation for 3 to 6 months is associated with fewer recurrent thromboembolic events than shorter treatment regimens. There is no evidence that a longer course of warfarin is needed for patients with a PE. Despite adequate treatment of a DVT, there is a 6 percent risk of a recurrent DVT or PE during the first year and 13 percent over 5 years. Patients who present with a new or progressive clot despite adequate anticoagulation with warfarin need to be started on LMWH and investigated for a hypercoagulable state on an urgent outpatient basis. Warfarin resistance is not infrequently encountered in patients with metastatic disease.
The issue of initiating anticoagulation and interference with workup of possible hypercoagulability occasionally arises. Since LMWH does not alter the ability to investigate hypercoagulable states, there is no need to procure additional blood samples beyond routine coagulation studies in patients with a straightforward DVT. Further, acute-phase reactants themselves can alter blood results with an acute DVT/PE. Initiation of unfractionated heparin therapy is likely to interfere with the workup of hypercoagulability. However, such investigations for the underlying etiology of a DVT typically do not alter management. Thus, these patients can be investigated in 3 to 6 months, when anticoagulation is stopped. When a patient presents with a refractory or progressive clot despite warfarin and is treated with LMWH, further hematologic studies can still be carried out and extra blood from the ED can be held for further testing (factor V Leiden, antithrombin III, protein C and S levels, and antiphospholipid anticoagulants). If, for some reason, unfractionated heparin is used to treat a patient with DVT, then at least two extra blood tubes should obtained prior to initiation of treatment and held for further testing by the hematologist.
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