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DVT (See my separate notes on PE)
Sources: Toronto
January 2015
VENOUS THROMBOEMBOLISM
DEFINITION
• Thrombus formation and subsequent inflammatory response in a superficial or deep vein
o Superficial thrombophlebitis, deep vein thrombosis (DVT) and pulmonary embolism (PE)
• Thrombi propagate in the direction of blood flow (commonly originating in calf veins)
• More common in lower extremity than upper extremity
• Incidence ~1% if age >60 yr
• Most important sequelae are pulmonary embolism (~50% chance with proximal DVT) and chronic venous insufficiency
AETIOLOGY
Always mention: Virchow’s Triad (Must know well!)
1. Venous stasis
• Immobilization (post-MI, CHF, stroke, post-op, prolonged sitting during travel, immobilization of an extremity after
surgery/fracture)
o Inhibits clearance and dilution of coagulation factors
• Chronic venous insufficiency
• Heart failure (risk of DVT greatest with right heart failure and peripheral edema)
2. Endothelial damage
• Exposes endothelium to prompt hemostasis
• Leads to decreased inhibition of coagulation and local fibrinolysis
• Post-op injury
• Trauma
3. Hypercoagulability
• Inherited coagulopathies
§ Factor V Leiden (most common overall),
§ Prothrombin G20210A variant,
§ Inherited deficiencies of antithrombin III, protein C or protein S
• Acquired
§ Antiphospholipid antibodies (i.e. lupus anticoagulant, anti-cardiolipin antibody and anti-Beta2-glycoprotein-1
§ Hyperhomocysteinemia
§ Malignancy (especially adenocarcinomas. Lung, pancreas, colon, rectum, kidney and prostate)
§ Cancer/cancer treatment
§ Hormone related:
1. Pregnancy, post-partum
2. Exogenous oestrogen administration: OCP, HRT, SERMs
§ Blood dyscrasias (myeloproliferative neoplasms, especially PRV, ET),
§ PNH, hyperviscosity (multiple myeloma, polycythemia, leukemia, sickle cell disease)
§ Nephrotic syndrome
§ Major surgery (especially orthopedic, thoracic, GI and GU)
§ Major trauma (especially fractures of spine, pelvis, femur or tibia, spinal cord injury)
4. Venography is the gold standard, but is expensive, invasive and higher risk
INITIAL TREATMENT
Wayne Robinson, MBBS Class of 2015
1. Low molecular weight heparin (LMWH)
§ Administered SC, at least as effective as UFH with a lower bleeding risk
§ Advantages:
a. Predictable dose response and fixed dosing schedule;
b. Lab monitoring not required;
c. <1% HIT;
d. Safe and effective outpatient therapy!!!
§ Disadvantages: Only partially reversible by protamine, long-term use associated with osteoporosis
§ Renally cleared – must adjust dose in patients with renal dysfunction
6. Thrombolytic drugs (e.g. streptokinase, tPA) à RESERVED FOR ACUTE LIMB/LIFE-THREATENING THROMBOSIS, and
low bleeding risk
LONG-TERM TREATMENT
1. Warfarin:
§ Standard treatment; should be initiated with heparin overlap: Dual therapy for at least 5 days!! due to:
1. Initial prothrombotic state
2. Half life of vitamin K factors and
3. Risk of warfarin-induced skin necrosis
MUST KNOW: Duration of anticoagulant treatment (with warfarin unless otherwise noted):
o First episode DVT with transient risk factor: 3 mo
o First episode DVT without identifiable risk factor (idiopathic) or single inherited risk factor (e.g. Factor V Leiden): 6-12 mo
or indefinite therapy (controversial)
o First episode DVT with ongoing risk factor (e.g. cancer, antiphospholipid antibody) or >1 risk factor: consider indefinite
therapy
o Recurrent DVT (2 or more episodes): indefinite therapy
2. IVC filters
§ Temporary filter indicated ONLY IF distal acute DVT (<4 wk) with significant contraindications to anticoagulant
therapy (i.e. active bleeding)
§ Must remove once safe to do so as filter is pro-thrombotic in the long-term (anticoagulation if left in)
Special considerations
1. Pregnancy: treat with LMWH during pregnancy, then warfarin for 4-6 wk post-partum (minimum total anticoagulation time of 3-
6 mo) [WARFARIN CROSSES PLACENTA AND TERATOGENIC – causes “chondrodysplasia punctata”]
2. Surgery: avoid elective surgery in the first month after a venous or arterial thromboembolic event
§ Preoperatively: IV heparin may be used up to 6 h pre-operatively
§ Perioperatively: Surgery safe when INR <1.5; warfarin should be discontinued for at least 4 wk pre-operatively to
allow INR to fall
Wayne Robinson, MBBS Class of 2015
§ Postoperatively: IV heparin or LMWH can be used for anticoagulation (start 12 h after major surgery until therapeutic
INR reached after restarting warfarin)
§ For patients at high risk for thromboembolism (VTE <12 wk, recurrent VTE, lupus anticoagulant, atrial fibrillation with
prior stroke, mechanical heart valve), IV heparin or LMWH (bridging) should be given before and after the procedure
while the INR is below 2.0
Prophylaxis
Consider for those with a moderate to high risk of thrombosis without contraindications
§ Non-pharmacological measures include:
1. Early ambulation
2. Elastic compression stockings (TEDs)
3. Intermittent pneumatic compression (IPC)
§ Relative: mild-moderate neurologic diathesis or thrombocytopenia, brain metastases, recent major trauma, major abdominal
surgery within page 2 d, GI/GU bleed within 14 d, endocarditis, severe HTN (sBP >200 or dBP >120), recent stroke
Low-Molecular-Weight Heparin versus a Coumarin for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer
NEMJ 2003;349:146-153
Study: RCT comparing the efficacy of LMWH (dalteparin) with an oral anti-coagulant agent (coumarin) in preventing recurrent thrombosis in patients with cancer.
Conclusions: In patients with cancer and acute VTE, dalteparin was more effective than coumadin in decreasing the risk of recurrent thromboembolism without increasing the
risk of bleeding.
Conclusion: Prolonged treatment with vitamin K antagonists leads to a consistent reduction in the risk of recurrent VTE for as long as therapy is continued. Therapy should be
discontinued when the risk of harm from major bleeding (which remains constant over time) is of greater concern than the absolute risk of recurrent VTE (which declines over
time). No specific recommendation was made regarding optimal duration of treatment.