Mabel Labrada, MD Miami VA Medical Center

Mabel Labrada, MD Miami VA Medical Center

*1-Treatment for acute DVT with underlying malignancy is for 3 months. *2-Treatment of provoked acute proximal DVT can be stopped after 3months of treatment and removal of transient factor. *3-New oral anticoagulants are (dabigatran, rivaroxaban, edoxaban, and apixaban) are vitamin K antagonists. *4-Isolated distal DVT of the leg provoked by a transient risk factor should be treated indefinitely.

Acute DVT and importance of accurate diagnosis. Treatment guidelines for acute DVT. New oral anticoagulants versus Vitamin K antagonists. Acute DVT Treatment Algorithms. New evidence for acute DVT treatment.

*Acute DVT is a major problem that may lead to significant morbidity, mortality, and healthcare costs. *Approximately 1% of acute hospital admissions are for venous thromboembolism (VTE). *~900,000 cases of pulmonary embolism (PE) and deep venous thrombosis (DVT) per year. *60,000-300,000 deaths, most occurring in untreated patients. *2/3 rd of VTE cases are associated with a hospitalization within the prior 90days.

Decreased Blood Flow (Stasis) Thrombosis Inflammation of or Near the Blood Vessels (Endothelial Damage) Intrinsic Alterations in the Nature of the Blood Itself (Hypercoagulability/Thrombophilia)

RISK FACTORS *Immobilization (prolonged hospitalization/bed rest/travel) *Recent surgery *Obesity *History of VTE *Lower extremity trauma *Malignancy *Oral Contraceptives or hormone replacement therapy *Pregnancy or postpartum *Stroke *Presence of a central venous catheter

*Antithrombin Deficiency *Protein C Deficiency *Protein S Deficiency Primary (Inherited): *Factor V Resistance to Activated Protein C - Most are V Leiden *Prothrombin Gene Mutation (G20210A) *Elevation of Factors VIII, IX, XI *Decreased or Abnormal Plasminogen *Vascular Plasminogen Activator Deficiency *Excessive Plasminogen Activator Inhibitor *Homocystinuria /? Hyperhomocysteinemia *Abnormal Fibrinogen

Secondary (Acquired): * Antiphospholipid Syndrome * Immobilization / Coach class thrombosis * Perioperative State * Trauma * Pregnancy / Estrogen * Prosthetic Surfaces including Catheters * Other Disease States including: *Carcinoma / Malignancy *Nephrotic Syndrome *Vasculitis / Sepsis *Myeloproliferative Disorders *Heparin-Induced Thrombocytopenia (HIT) *PNH *Hyperviscosity *Behçet's Disease

*History: complete thrombosis history, including age of onset, location, and treatment; precipitating conditions/medications; family hx; * Symptoms: swelling, pain, and erythema of the involved extremity *Physical Exam: palpable cord (thrombosed vein), calf or thigh pain, unilateral edema, warmth, tenderness, and/or superficial venous dilation. Note: Homan s sign is unreliable *However, each of the above signs and symptoms is nonspecific and has low accuracy for making the diagnosis of DVT. *Further diagnostic testing is required to confirm or exclude the diagnosis of DVT.

*Best Used in Low Clinical Probability Settings *ELISA: Negative Predictive Value ~ 98 % When < 500 & Low Likelihood of VTE

*Prevent clot extension *Prevent acute Pulmonary Embolism *Reduce the risk of recurrent thrombosis *Limit late complications: *Post-thrombotic syndrome, chronic venous insufficiency, chronic thromboembolic pulmonary hypertension

*Anticoagulant therapy is indicated in patients with acute DVT: *PE will occur in approximately 50% of untreated patients. *Initial treatment should be started acutely *Multiple available options including vitamin K antagonists, unfractionated heparin, low molecular weight heparin, fondaparinux, or the new oral anticoagulants (dabigatran, rivaroxaban, edoxaban, and apixaban).

*Vit K antagonists (VKA), such as coumadin, have been the only available agents for decades. *Drawbacks: narrow therapeutic window, many food and drug interactions, risk of bleeding, need for repeated blood testing to ensure desired international normalized ratio (INR) with associated costs and burdens. *Newer anticoagulants have shown to be as effective than VKA in preventing thromboembolic events, have fewer drug interactions, no need for continuous monitoring, and may have fewer side-effects. * Drawback: reversibility * Except for Dabigatran, lack of an antidote in case of bleeding or emergency surgery is a major drawback.

FIGURE 1. Selected steps in the blood coagulation pathway. Sites of action of thrombin inhibitors and factor Xa inhibitors are denoted by blue slashes.

* New oral anticoagulants are alternatives to vitamin K antagonists for preventing and treating thromboembolic disease. * When oral anticoagulation is indicated, the choice of drug should be individualized. * Cost is an important consideration: direct costs of the new drugs are substantially higher than those of vitamin K antagonists and heparin, but cost-effectiveness may be comparable or superior to that of warfarin or enoxaparin when clinical efficacy and savings in avoiding coagulation tests are considered. * There is currently no conclusive evidence to determine which new oral anticoagulant drug is more effective and safe for long-term treatment, as head-to-head studies of the different medications have not yet been performed. However, there are factors to consider when choosing a drug: * Rivaroxaban and edoxaban can be taken once daily and may be better choices for patients who may have difficulties with compliance. * Dabigatran should be avoided in patients with dyspepsia because of gastrointestinal adverse effects. * Dabigatran should be avoided in patients at risk of myocardial infarction because of a possible additional increase in risk. * Many experts estimate that the new oral anticoagulants are not remarkably superior to vitamin K antagonists, and thus patients whose coagulation is well controlled and stable on a traditional drug would probably not benefit much from changing.

*Evidence supporting treatment of acute DVT * Recommendations: * Grade 1-Strong * Grade 2-Weak * Evidence: * Grade A-High * Grade B-Moderate * Grade C-Low * Evidence based on CHEST Guideline and Expert Panel Report 2016

*Provoked vs Non-provoked *Proximal vs Distal *First vs Recurrent

*PROXIMAL DVT or PE: minimum of 3 months of anticoagulation-(grade 1B) *Anticoagulation (AC): Dabigatran, rivaroxaban, apixaban, or edoxaban over VKA therapy-(2b) *For patients not treated with the newer anticoagulants, VKA is recommended over LMWH- (2C) *Following the 3mo all patients should be evaluated for the risk/benefit ratio of long-term therapy.

*PROXIMAL DVT or PE: 3 months with removal of transient factor -(Grade 1B) *PROXIMAL DVT or PE with Cancer: LMWH is recommended over VKA or other new AC-indefinitely or until remission- (Grade 2B)

*Isolated distal DVT of the leg provoked by a transient risk factor-3 months-(grade 1B) *Note: Duration of treatment of patients with isolated DVT is for who a decision has been made to treat with AC, however, no all patients who are diagnosed will be treated with AC. *In patients with acute isolated distal DVT of the leg and without severe symptoms or risk factors for extension: serial imaging of the deep veins for 2 weeks over anticoagulation (Grade 2C) or with severe symptoms or risk factors for extension then anticoagulation over serial imaging of the deep veins (Grade 2C).

*Unprovoked: over 3months with reassessment at periodic intervals (Grade 2B) * Indefinite treatment *In patients who have recurrent VTE on VKA therapy (in the therapeutic range) or on new oral anticoagulants and are believed to be compliant, recommendations are to switch to treatment with LMWH at least temporarily-(grade 2C)

*Aspirin for extended treatment of VTE: *Unprovoked proximal DVT or PE: *Patients that have stopped anticoagulation and have no contraindication to ASA, recommendations are for ASA over no ASA to prevent recurrent VTE (Grade 2B).

*IVC Filter in Addition to Anticoagulation for Acute DVT or PE: *In patients with acute DVT or PE who are treated with anticoagulants, recommendations are against the use of an inferior vena cava (IVC) filter- (Grade 1B).

*The new oral anticoagulants have favorable pharmacologic properties and similar efficacy and safety as vitamin K antagonists. *The new agents are indicated for treatment of deep vein thrombosis and pulmonary embolism. *Except for dabigatran, lack of an antidote in case of bleeding or emergency surgery is a major drawback. *Length of treatment varies for acute DVT presentations.

*1-Treatment for acute DVT with underlying malignancy is for 3 months. *2-Treatment of provoked acute proximal DVT can be stopped after 3months of treatment and removal of transient factor. *3-New oral anticoagulants are (dabigatran, rivaroxaban, edoxaban, and apixaban) are vitamin K antagonists. *4-Isolated distal DVT of the leg provoked by a transient risk factor should be treated indefinitely.

*Goodacre S. In the clinic. Deep venous thrombosis. Ann Intern Med 2008; 149. *Roca B., Roca M. The new oral anticoagulants: Reasonable alternatives to warfarin. Cleveland Clinic Journal of Medicine 2015; 82: 847-853. *Antithromobtic Therapy for VTE Disease. CHEST Guidelines and Expert Panel Report 2016; 315-352. *Heit JA. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol 2008; 28-370. *Approach to the diagnosis and therapy of lower extremity deep venous thrombosis. Uptodate 2016.