Hospital Medicine

Deep vein thrombosis; treatment

Deep Vein Thrombosis Treatment

I. What every physician needs to know.

Clinically relevant deep vein thrombosis (DVT) is the presence of a blood clot in one or more locations including the veins of the proximal venous drainage of the extremities, the deep veins associated with abdominal organs, the inferior and superior vena cava, and in rare instances, the venous collecting system of the brain. Thromboses are the physical result of an imbalance in the hemostatic system that leads to the formation of excessive clotting, often in the setting of sluggish blood flow and/or loss of vascular wall integrity ("Virchow's triad"). The associated finding of pulmonary embolism (PE) is nearly always a result of either partial or complete movement of a clot from a primary DVT site into the pulmonary arteries. DVT and PE often co-exist even though only one or the other may be clinically symptomatic.

III. Default Management.

The immediate goal of treatment is to effectively and immediately re-set the hemostatic system with the use of anticoagulant therapy so that new clots cannot be formed, and existing clots do not propagate. The long-term goal of therapy is to prevent clot recurrence. In rare cases there may be benefit to thrombolytic therapy. In patients who have an absolute contraindication to anticoagulation, vena caval interruption may be warranted.

A. Immediate management.

Prior to initiation of anticoagulation, obtain complete blood count (CBC) with platelet count, prothrombin time (PT), partial thromboplastin time (PTT), blood urea nitrogen (BUN), creatinine; consider testing for a hypercoagulable disorder in selected cases (for example, family history of venous thromboembolism, recurrent venous thrombosis, unusual location of the index clot), though there is lack of consensus regarding hypercoagulable testing.

Routine management

Immediate management of confirmed DVT, or for high level of clinical suspicion while awaiting diagnostic test results, begin with any of the three treatments below.

  • Dabigatran or edoxaban can be used after an initial period of unfractionated heparin, consistent with the protocol of clinical trials evaluating their efficacy in treatment of DVT.

  • Rivaroxaban and apixaban can be used without an initial period of unfractionated heparin, as the clinical trials validating their use did not use UFH prior to study drug administration.

  • Subcutaneous low molecular weight heparin (LMWH) using full anticoagulant dose, or Subcutaneous fondaprinux using full anticoagulant dose, or

  • Intravenous unfractionated heparin (UH) with monitoring to rapidly achieve activated PTT ratio >1.5. Recommend either: 1) bolus of 5,000U followed by at least 30,000U over the first 24 hours OR 2) 80U/kg bolus followed by 18U/kg/hour. Obtain frequent PTT levels to achieve full anticoagulation within 12-24 hours)

Preference for initial therapy may depend on a variety of factors including the anticipated site of care (inpatient versus outpatient therapy), bleeding risk, and patient preference.

If using warfarin, begin therapy on the first treatment day along with the parenteral anticoagulant. Do not use loading doses of VKA. Convert to VKA as a single agent after at least 5 days of overlap therapy with a parenteral anticoagulant, and only when INR is greater than 2.0 for at least 24 hours.

Special circumstances - massive clot

For selected patients experiencing massive acute proximal DVT, consider catheter directed thrombolysis, pharmacomechanical thrombolysis, and/or stent placement (if the appropriate level of expertise is available) to reduce acute morbidity and post-phlebitic complications. Patients should have symptoms present for <14 days, life-expectancy greater than 1 year and good performance status. These patients will still require anticoagulation for a period of time to prevent recurrence. In cases in which this is considered, consultation with a vascular surgeon or interventional radiologist is warranted.

Special circumstances - absolute contraindication to anticoagulation

For patients who have an absolute contraindication to anticoagulation and who have a lower extremity DVT, a vena caval filter is recommended. A retrievable filter is preferred. When risk of bleeding resolves, it is preferable to initiate anticoagulation and remove the filter if possible.

Vena caval filters are not otherwise recommended for use in the management of DVT.

B. Physical Examination Tips to Guide Management.

None

C. Laboratory Tests to Monitor Response to, and Adjustments in, Management.

Laboratory tests to monitor anticoagulation depend on the specific anticoagulant being used and the underlying comorbidities (see section IV).

D. Long-term management.

Intensity and monitoring of therapy

For patients taking VKA: Patients should be maintained between an INR of 2 and 3. Patients must undergo laboratory monitoring at regular intervals to maintain this therapeutic window. The frequency of monitoring should be determined for each individual. For patients on long-term anticoagulation with VKA, home monitors for point of care testing provide an alternative to frequent laboratory visits.

For patients taking direct oral anticoagulants, no routine laboratory monitoring is required. However, close outpatient follow-up is still required.

Choice of Agent

Recent guidelines help the clinician choose anticoagulant therapy. For patients without cancer, use of a direct oral anticoagulatnt (DOAC) is now recommended over VKA or LMWH therapy. For patients with cancer, LMWH is preferred over DOAC or VKA therapy.

Duration of therapy

For patients with DVT provoked by a transient or reversible risk factor (i.e., immobilization, surgery, oral contraceptives), continue anticoagulation at least 3 months beyond the removal of the risk factor.

For patients with unprovoked DVT, continue VKA anticoagulation at least 3 months. Recently updated guidelines suggest that for patients with a first unprovoked, proximal DVT with a low to moderate bleeding risk, prolonged anticoagulation is preferred to limited duration anticoagulation. For patients with an unprovoked proximal DVT who need to stop anticoagulation therapy and who can tolerate aspirin, aspirin is a recommended (though not an alternative to anticoagulation for patients who can tolerate it).

For patients with a second unprovoked DVT, recommend long-term VKA anticoagulation.

The recommendation of long-term anticoagulation carries risk of clinically significant bleeding and mandates that the treating physician frequently re-evaluate the patient's situational risks of both clotting and bleeding.

E. Common Pitfalls and Side-Effects of Management

All anticoagulants, by their design, carry significant risks of bleeding. UH can be reversed by protamine, warfarin can be reversed by Vitamin K, and there is now an antidote for Dabigitran; however, LMWH and fondaparinux have no specific antidote for immediate reversal. A reversal agent for anti-Xa inhibitors is expected to be approved by the FDA soon.

Some patients have additional risks of bleeding that may be unrecognized or ignored to great peril. Patients with thrombocytopenia, uremia or unrecognized liver disease (associated with coagulopathy), will be at high bleeding risk. In addition, patients taking prescribed or over the counter medicines containing aspirin or other anti-platelet drugs will have increased bleeding risk, and must be carefully monitored while on anticoagulants.

Patient education is paramount. Patients need to seek medical care when there are obvious signs of bleeding or trauma, and need to be particularly alert to possible head trauma and the early signs and symptoms of intracranial bleeding (nausea, vomiting, headache, dizziness, somnolence, etc.).

IV. Management with Co-Morbidities

Monitoring anti-Xa levels in patients anticoagulated with subcutaneous low molecular weight heparin and fondaparinux

While LMWH and fondaparinux can be used in most otherwise healthy patients without the need for monitoring, there are certain groups of patients (below) in whom it is essential that monitoring is used to assess efficacy and adjust dosing for optimal anticoagulant effect:

  • Elderly patients and young children.

  • Patients with renal or hepatic insufficiency.

  • Underweight or obese patients.

  • Pregnant patients.

  • Patients who had bleeding or recurrent clotting on standard dosing.

Anti-Xa lavels should be drawn 4 hours after the dose is given. In general, the target anti-Xa range is 0.6-1.0 IU/ml when LMWH is given every 12 hours, and 1.0-2.0 IU/ml when used once daily.

A. Renal Insufficiency.

LMWH and fondaparinux are cleared by the kidneys. For patients with renal insufficiency, there are approved dosage adjustments for LMWH (consult dosing guidelines); direct oral anticoagulants are generally avoided in patients with renal insufficiency.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

It is important to identify the provider who will be assuming responsibility for monitoring the patient’s anticoagulant therapy prior to hospital discharge, and arrange for communication between the inpatient and outpatient provider.

B. Anticipated Length of Stay.

Patients with low-risk DVTs who can tolerate oral therapy with a direct oral anticoagulant can be considered for hospital discharge, or even sent home from the emergency department, obviating the need for inpatient admission. However, patients with symptoms or other co-morbidities and functional limitations may require more prolonged admission. Of note, patients requiring IV UFH and transition to VKA will require a minimum admission of 5 days to ensure appropriate overlap therapy.

C. When is the Patient Ready for Discharge.

The patient is ready for discharge when the patient:

  1. Can manage administration of their anticoagulation therapy;

  2. Has received education on the use of VKA therapy including the goals of therapy, necessity of lab monitoring, interactions with foods and drugs, symptoms to watch for, how to immediately access the physician who will be directing their anticoagulation therapy, etc.;

  3. Has a written schedule for any appropriate testing and follow-up on leaving the hospital.

F. Prognosis and Patient Counseling.

Patients on long-term VKA therapy have a 1-5% annual risk of major bleeding.

Patients who have had an unprovoked DVT and who stop anticoagulation have a 10-30% risk of recurrent thrombosis, and a potentially higher risk during a "high-risk" situation.

If a patient who had an unprovoked DVT stops anticoagulation, recommend an aggressive approach to prophylaxis of clotting:

  • Maintain healthy lifestyle with ideal body weight, appropriate exercise.

  • Maintain good hydration.

  • Use venous support stockings to help prevent post-phlebitic syndrome.

  • Avoid hormone therapy with estrogen or progesterone.

  • Consider prophylaxis with LMWH, fondaparinux or UH for high risk situations such as long haul plane flights, periods of immobilization, pregnancy, etc.

VI. Patient Safety and Quality Measures

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

For any patient with a previous history of DVT, their risk of a second DVT is heightened. Use anticoagulant prophylaxis during high-risk situations (see above).

VII. What's the Evidence?

Kearon, C, Ekl, EA, Ornelas, J. "Antithrombotic Therapy for VTE Disease: Chest Guideline and Expert Panel Report". Chest. vol. 149. 2016. pp. 315-352.

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