Venous Thromboembolism Flashcards
Where is a proximal deep vein thrombosis (DVT) located?
above the knee
Where is a distal deep vein thrombosis (DVT) located?
calf
Define: pulmonary embolism (PE)
thrombus or other foreign substance which passes through the circulation and becomes lodged in the pulmonary vasculature
Define: thrombosis
combination of platelets and clotting factors involved in the formation of fibrin-rich blood clot
Define: embolus
small portion of clot breaks off and travels to another part of the vasculature
What makes up Virchow’s Triad?
-stasis
-vessel injury
-hypercoagulability
What is stasis?
abnormalities in blood flow (Afib, left ventricular dysfunction, best rest/immobilization, venous obstruction, obesity)
What is vessel injury?
-vascular injury/trauma/surgery
-presence of foreign material
What is hypercoagulability?
abnormalities in clotting components
What is the clinical presentation of deep vein thrombosis (DVT)?
-unilateral leg swelling with local tenderness or pain
-erythema (skin redness)
-leg warmth
-Horman’s sign
What is the clinical presentation of pulmonary embolism (PE)?
-dyspnea
-tachycardia
-chest pain
-hemoptysis
-cough
-tachypnea
-anxiety
-shock
-hypoxia
What are the risk factors for venous thromboembolism (VTE)?
-prior DVT/PE
-increasing age
-surgery
-heart failure
-acute MI
-obesity
-varicose veins
-estrogen use
-malignancy
-spinal cord injury
-CVA
-trauma
-acute infection
-pregnancy
-hypercoagulable state
-immobility (> 3 days)
What are the available treatment options for venous thromboembolism (VTE)?
-unfractionated heparin
-vitamin K antagonist (warfarin)
-low molecular weight heparin
-thrombin inhibitors
-factor Xa inhibitors
What is the MOA of unfractionated heparin (UFH)?
binds to antithrombin converting it from a slow inhibitor to a rapid inhibitor of thrombin
What is the prophylaxis dose of unfractionated heparin (UFH)?
5000 units subq every 8-12h
What is the treatment dose of unfractionated heparin (UFH) in VTE?
80 units/kg then continuous IV infusion of 18 units/kg/hr
What are the adverse effects of unfractionated heparin (UFH)?
-bleeding most common
-thrombocytopenia (low platelets)
-osteopenia (bone loss)
-hyperkalemia (high potassium)
What are the common sites of bleeding associated with unfractionated heparin (UFH) use?
soft tissue, GI, urinary tract, nose, oral pharynx, bruising at injection site
What is Type I Heparin Induced Thrombocytopenia (HIT)?
aka HAT (heparin-associated thrombocytopenia)
-non-immune mediated
-causes mild decrease in platelets
-occurs 2-3 days on therapy
-discontinuation of product is not necessary
What is Type II Heparin Induced Thrombocytopenia (HIT)?
-antibody mediated with significant potential to cause thrombosis, limb loss, and death
-platelets fall > 50% typically after 5 days of therapy initiation
-heparin must be stopped immediately
What is the treatment for type II Heparin Induced Thrombocytopenia (HIT)?
argatroban, bivalirudin, DOAC and transition to warfarin
What are the monitoring parameters for unfractionated heparin (UFH)?
-activated partial thromboplastin time (aPTT) for treatment doses only every 6-12 hours
-platelets every 2-3 days for 2 weeks or until treatment is stopped
-Hgb/hct for signs of bleeding
-signs/symptoms of bleeding
What are the contraindications for unfractionated heparin (UFH)?
-history of HIT
-active bleeding
-allergy
What can be used to reverse the effects of unfractionated heparin (UFH)?
take into account half life
-transfusion
-protamine (1mg -> 100 units UFH)
What is the MOA of low molecular weight heparin (LMWH)?
enhances activity of antithrombin III (factor Xa mostly)
What drugs are low molecular weight heparin (LMWH)?
enoxaparin (LOVENOX) and dalteparin
What is the treatment dose for VTE using LMWH, enoxaparin (LOVENOX)?
1mg/kg SubQ BID
What is the prophylaxis dose for VTE using LMWH, enoxaparin (LOVENOX)?
30mg subQ BID or 40mg subQ daily
If a pt has renal impairment (CrCl < 30mL/min), enoxaparin (LOVENOX) should be dosed at ___________.
-prophylaxis: 30mg subQ every 24h
-treatment: 1mg/kg subQ every 24h
What are the monitoring parameters for LMWH?
aPTT monitoring not required
-renal function
-hemoglobin/hematocrit
-signs of bleeding
What are the adverse effects of LMWH?
-bleeding
-thrombocytopenia
-injection site pain
What are the contraindications of LMWH?
-history of HIT (although risk is less severe)
-active bleed
-allergy
What can be used to reverse the effects of low molecular weight heparin (LMWH)?
-transfusion
-protamine IV
What are the advantages of LMWH over UFH?
-simplified dosing
-improved subQ bioavailability
-more predictable dose response
-longer t1/2
-reduced incidence of HIT
-pt may self-administer
What drugs are factor Xa Inhibitors?
fondaparinux
What is the prophylaxis dose for Fondaparinux?
2.5mg SubQ every 24h
What is the treatment dose of Fondaparinux for DVT?
- < 50kg: 5mg subQ every 24h
-50-100kg: 7.5mg subQ every 24h - > 100kg: 10mg subQ every 24h
What are the adverse effects of Fondaparinux?
-bleeding
-less thrombocytopenia incidence
-injection site reaction
What are the contraindications for Fondaparinux?
-ClCr < 30mL/min
-body weight < 50kg (for prophylaxis) and use caution in treatment doses
-active bleed
-can cross placenta so use caution in pregnancy
What Direct Oral Anticoagulants (DOACs) require use of parenteral agent before use?
dabigatran and edoxaban
What drugs are Direct Oral Anticoagulants (DOACs)?
-dabigatran
-rivaroxaban
-apixaban
-edoxaban
What Direct Oral Anticoagulants (DOACs) can be used for prophylaxis?
-dabigatran
-rivaroxaban
-apixaban
What drugs are Direct Thrombin Inhibitors?
-bivalirubin
-argatroban
What drugs are vitamin K antagonists?
warfarin
What is the MOA of Warfarin?
interferes with the hepatic synthesis of vitamin K dependent clotting factors (II, VII, IX, X) as well as proteins CS
How many days does it take to achieve full therapeutic effect of Warfarin?
5-7 days
What are the adverse effects of Warfarin?
-hemorrhage most common
-skin necrosis
-purple toe syndrome
What are the contraindications of Warfarin?
-risk of hemorrhage > potential benefits
-pregnancy (but safe in breast feeding
-alcoholism/drug abuse
-noncompliance (extensive monitoring)
-active bleed
What are the drug interaction of Warfarin?
-decreased effect of warfarin (cholestyramine, smoking, alcohol, increased vitamin K+ (greens: spinach, kale, cabbage))
note also hypothyroidism can decrease the effect of warfarin
-increased effect of warfarin (CYP2C9 inhibitors, 3A4 inhibitors, decreased vitamin K, heparin, LMWH, and antiplatelets (clopidogrel, NSAIDs, COX-2 inhibitors garlic, ginger)
note heart failure, hepatic dysfunction, and hyperthyroidism can increase the effect of warfarin
