Venous Thromboembolism Notes

Venous Thromboembolism (VTE) Notes

Clinical Presentation

• VTE is the 3rd most common cardiovascular emergency after myocardial infarction and stroke
• Deep Vein Thrombosis (DVT) - swelling, pain on palpation
• Pulmonary Embolism (PE)

Risk factors for VTE

• Virchow's triad - Hypercoagulability, Stasis, Endothelial injury
• Hypercoagulability - pregnancy, post-partum period, oral contraceptive use, cancer, 
• Stasis - prolonged immobility e.g. post surgery, long travel (train/ bus/ airplane)
• Endothelial injury - cancer, obesity

Risk Stratification and Probability Scores

• Well's criteria for DVT
• Well's criteria for PE 
• Scoring criteria
• 3.0 points each for
• clinical symptoms of DVT
• other diagnosis less likely than PE
• 1.5 points each for
• HR > 100 bpm
• Immobilization (>3d) or surgery in the last 4 weeks
• Previous DVT/ PE
• 1 point each for
• hemoptysis
• malignancy
• Probability scores in traditional Wells criteria
• High > 6.0
• Moderate 2.0 to 6.0
• Low < 2.0
• Probability scores in modified Wells criteria
• PE likely > 4.0
• PE unlikely < 4.0

• Pulmonary Embolism Severity Index (PESI) -- 30 day mortality due to PE
• HR, BP, SaO2, Age, COPD, Cancer
• 
  

Investigations

• History and Physical Exam
• Initial tests - ECG, CXR, D-dimer (to rule out VTE in low-probability cases), Well's criteria
• Diagnostic tests - imaging studies to be ordered determined by Well's criteria, and anticoagulation based on imaging results and patient presentation (risk factors, severity, etc). 
• DVT - options include B-mode compression ultrasound, colour duplex ultrasound, ascending contrast venography, CT contrast venography
• PE - options include contrast pulmonary angiography, ventilation-perfusion lung scan, CT, pulmonary angiography, magnetic resonance pulmonary angiography, tests for DVT

Non-pharmaceutical therapies

• Graduated compression stockings
• Intermittent pneumatic compression devices - sleeves placed on the legs and inflated with a programmable pump
• Used mainly when risk of bleeding is high 

Medications

• Initial anticoagulation
• Adults -- Subcutaneous low molecular weight heparin (LMWH) or Fondaparinux or Unfractionated heparin (UFH) given for minimum of 5 days or until INR is >/= 2 for 24-48 hours. Concurrently begin Warfarin (vitamin K antagonist) PO. 
• Alternatively, direct-acting oral anticoagulants (DOACs) can be given. These work by inhibiting the active site of thrombin (dabigatran) or factor Xa (apixaban, edoxaban, rivaroxaban). Monotherapy with apixaban or rivaroxaban is just as effective as LMWH + Warfarin therapy. However, they are associated with risk of hemorrhage, but it is lower than with vitamin K antagonists. 
• Pregnancy -- first choice is LMWH, and if not available then UFH. These heparins do not cross the blood-placenta barrier. Use for 3 months, including 6 weeks postpartum. Fondaparinux can be used if either of the heparins is unavailable, but is not preferred. DAOCs and Warfarin should not be used in pregnancy. Warfarin is teratogenic. If delivery is in the first month of anticoagulation, then consider a retrievable IVC filter while LMWH is being held. 
• Postpartum -- Warfarin plus LMWH/UFH for about 6 weeks postpartum. Warfarin is safe during breastfeeding. 
• Anticoagulants
• Low molecular weight heparins - dalteparin, enoxaparin, nadroparin, tinzaparin
• Unfractioned heparin - heparin sodium
• fondaparinux - indirect factor Xa inhibitor
• Vitamin K antagonists - warfarin, acenocoumarol 

• Duration of anticoagulation - depends on risk of recurrence
• first episode with reversible/ transient risk factor -- 3 months 
• first episode of unprovoked distal DVT -- 3 months
• first unprovoked episode -- minimum 3 months
• cancer associated thrombosis -- until cancer is resolved, LMWH preferred. 

• Anticoagulation associated hemorrhage
• Heparin induced thrombocytopenia (HIT) -- Argatroban and danaparoid
• idarucizumab -- dabigatran antidote
• prothrombin complex concentrates and activated prothrombin complex concentrates for hemorrhage

• Thrombolytics -- alteplase. Rarely used for VTE. Reserved for patients with life- or limb-threatening thrombosis and no bleeding-related contraindications. 

Review Questions

• Initial management of venous thromboembolism in an adult?
• Option 1 - if distal DVT with mild/ moderate symptoms, watch and wait is an option. Repeat imaging at 1 week, and if no change consider repeating 1 week later. If significant clot extension is identified, treatment is required. If proximal DVT or high-risk patient it is better to start with an anticoagulant (option 2 or 3).
• Option 2 - subcutaneous injectable anticoagulant (fondaparinux/ LMWH/ UFH) plus Warfarin. Stop injectable anticoagulant when INR is 2 or more for 24-48 hours.
• Option 3 - oral direct anticoagulant (apixaban/ rivaroxaban)
• Continue anticoagulation for 3 months and longer if irreversible cause, second unprovoked episode, etc. 
• Initial management of VTE if patient has renal failure?
• SC UFH
• Initial management of VTE in a patient with cancer?
• SC LMWH (dalteparin)
• apixaban/rivaroxaban and other direct acting oral anticoagulants are contraindicated
• Chronic management of VTE in a patient with cancer?
• LMWH continued for 6 months, after which Warfarin may be used. Continue anticoagulation until cancer resolves. 
• Chronic management of VTE in an otherwise healthy patient?
• direct acting oral anticoagulants (apixaban, rivaroxaban) preferred over Warfarin which is preferred over LMWH. 
• A 32 year old woman arrives to the clinic because of right lower leg swelling. She recently came back from summer vacation in the Phillipines. She is otherwise healthy and only takes an oral contraceptive. 
• Most likely has DVT, the oral contraceptive and long travel are risk factors. 

References:

ACP online VTE guidelines presentation

https://www.acponline.org/system/files/documents/about_acp/chapters/la/vte_presentation-deitelzweig.pdf