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.

*2/3rd of VTE cases are associated with a hospitalization within

the prior 90days.

*

*

“Decreased Blood Flow”

(Stasis)

“Inflammation of or Near the

Blood Vessels”

(Endothelial Damage)

“Intrinsic Alterations in the Nature of the Blood Itself”

(Hypercoagulability/Thrombophilia)

Thrombosis

*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

* Primary (Inherited):

*Antithrombin Deficiency

*Protein C Deficiency

*Protein S Deficiency

*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

*

* 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

Secondary (Acquired):

**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.

*