Stacey Graven, ACNP Vascular Surgery, Springfield Clinic Springfield, Illinois

VTE In September 2008, Surgeon General issued a “Call to Action to Prevent Deep Venous Thrombosis and Pulmonary Embolism” Recognized as significant public health problem Limited awareness about DVT -- < 1 in 10 Americans are familiar with DVT

Venous Thromboembolism Defined as DVT and/or PE Leading cause of preventable hospital deaths and maternity deaths in US Despite standard anticoagulation, 1/3 suffer recurrence within 10 years

Virchow’s Triad Three factors contributing to thrombus Hypercoagulability—hormone therapy, genetic disorder Interrupted blood flow/stasis--immobility, varicose veins Endothelial dysfunction/injury– shear stress, catheters-- PICC

Treatment for DVT Goals of treatment Prevent PE Reduce morbidity/mortality Reduce risk of recurrent DVT Reduce incidence of post-thrombotic syndrome

Anticoagulation Therapy Primary medical treatment of DVT since 1930’s Noninvasive Contradictions Intracranial bleeding Severe active bleeding Severe thrombocytopenia Recent major surgery

Anticoagulation Therapy Unfractionated heparin (IV Heparin) Low molecular weight heparin (enoxaparin/Lovenox) Factor Xa Inhibitor (rivaroxaban/Xarelto), (fondaparinux/Arixtra), (apixaban/Eliquis) Direct thrombin inhibitor (dabigatran/Pradaxa) Vitamin K antagonist (warfarin/Coumadin)

Clotting Cascade

Unfractionated Heparin IV Heparin Prevents extension of clot, reduces incidence of PE and recurrent thrombus Interacts with antithrombin III, body’s primary anticoagulant, to inhibit thrombin Inpatient setting, rapid onset Treatment of choice for end-stage renal disease Monitored with PTT Standard of care until LMWH

Low Molecular Weight Heparin Enoxaparin (Lovenox) and Dalteparin (Fragmin) Given daily or twice day SQ -- replacing IV Heparin Dosed based on body weight and renal function No routine lab monitoring, i.e. PTT Used in outpatient setting Administered 1 mg/kg/daily or 1.5 mg/kg BID SQ LMWH used to treat DVT in patient’s with malignancy. More effective than warfarin in preventing recurrent DVT/PE In event of major bleeding, Enoxaparin reversed with protime sulfate Deep Vein Thrombosis Treatment and Management. Kaushal, MD; Chief Editor: Brenner, MD

Factor Xa Inhibitors Rivaroxaban (Xarelto) Blocks Factor Xa which is responsible for thrombin formation First oral medication in this class Start 15 mg BID x 21 d, then 20 mg daily Avoid in patients with CrCl < 30 ml/min No routine labs No anecdote

Factor Xa Inhibitors Fondaparinux (Arixtra) Indicated in prevention of DVT post orthopedic surgery Daily dose, based on weight 2.5 mg – 10 mg SQ daily Used with caution in end-stage renal patients, if CrCl < 30 mL/min--high risk of bleeding No lab parameters used i.e.. PTT/PT No antidote

Factor Xa Inhibitors Apixaban (Eliquis) Recent indication for prevention of DVT – post op in hip and knee replacement surgery 2.5 mg po BID Not currently approved for treatment of DVT

Direct Thrombin Inhibitor Dabigatran (Pradaxa) April 2014, approved for treatment DVT but must have received 5-10 days of IV anticoagulation therapy prior to initiation If CrCL > 30 mL/min – 150 mg BID If CrCl mL/min – 75 mg BID Shown to be noninferior to warfarin in 3 month treatment of DVT and lower risk of bleeding No lab monitoring No anecdote

Vitamin K Antagonist Warfarin (Coumadin) Interrupts production of Vitamin K – coagulation factor produced by liver Effect delayed 72 hours Use other form of anticoagulation, ( IV heparin, enoxaparin) INR 2-3 recommended Low cost Anecdote- Vitamin K Diet consistent in Vitamin K intake

Limitations of Anticoagulation Limitations of anticoagulation – inhibits propagation but does not remove thrombus Despite anticoagulation….. 2-4% progress to PE Main adverse effects – bleeding and thrombocytopenia Deep Vein Thrombosis Treatment and Management. Kaushal, MD; Chief Editor: Brenner, MD

Complications of Anticoagulation Hemorrhagic events most common 3%-10% risk of major bleeding in first 3-6 months Bleeding risk increases over time of therapy Higher risk populations: > 65 yo with CVA, DM, CKD Treatment of hemorrhage in IV heparin use DC drug – short half-life FFP or Plt --not effective If severe hemorrhage – Protamine Deep Vein Thrombosis Treatment and Management. Kaushal, MD; Chief Editor: Brenner, MD

Complications of Anticoagulation Treatment of hemorrhage in LMWH Similar to IV heparin Half – life longer (4-6 hours) Protamine but only reduces drug’s effects by 60% Treatment of hemorrhage in warfarin DC drug Vitamin K, possible FFP if severe Deep Vein Thrombosis Treatment and Management. Kaushal, MD; Chief Editor: Brenner, MD

Duration of Anticoagulation First episode of DVT: 3-6 months Questions to answer: Malignancy? Higher risk of recurrent DVT Lifelong therapy recommended– LMWH more effective Provoked versus unprovoked? Pregnancy, post-op, immobility If provoked, consider shorter duration of therapy LMWH more effective during pregnancy Hypercoagulable disorder? Test for clotting disorder prior to initiation of anticoagulation, may require lifelong therapy

Duration of Anticoagulation Recurrent DVT? at least 1 year, possibly lifelong Considerations: Did DVT reoccur – while on anticoagulation? INR therapeutic? Patient compliance Numerous recurrent DVTs – Lifelong therapy despite circumstances Location of DVT --proximal versus calf vein Consider other treatment in proximal vein involvement--thrombolysis

Calf versus Proximal Veins

Anticoagulation in Calf Vein DVT If isolated symptomatic calf vein DVT 3 months anticoagulation therapy due to low risk PE If asymptomatic calf vein DVT Often do not treat with anticoagulation and monitor with ultrasound over days for extension of thrombus Requires ASA Patient must be compliant in follow-up

Thrombolysis Use of thrombolytic agent – “clot buster” Restore venous patency Improve long term daily functioning Indicated for proximal DVT— inferior vena cava, iliac, and femoral veins Prevent post thrombotic syndrome – swelling, pain ulcerations Indicated in phlegmasia causing limb ischemia, rare but serious complication Rutherford’s Vascular Surgery, 7 th edition, 2010

Thrombolysis Indicated in patients with low bleeding risk Indicated in patients with symptoms for < 14 days with good functional status Contraindicated in patients with active bleeding, CVA/trauma/neurosurgery in past 3 months Disadvantage – procedure often takes 1-3 days and long infusion times Rutherford’s Vascular Surgery, 7 th edition, 2010

Thrombolysis Administer thrombolytic (Alteplase,Urokinase, Streptokinase) via catheter inserted into vein– common iliac DVT

Thrombolysis Patent common iliac vein after thrombolysis

Thrombolysis for Proximal DVT Studies show that thrombolysis Reduced symptoms of extensive DVT At one year, normal valve function Disadvantage – long infusion times Average treatment time 72 hours ICU status Higher cost Bleeding risk

Unique Left Femoral DVT with Thrombolysis Treatment Hardware placed for left hip replacement in 1990’s. Two decades later, developed acute common femoral/popliteal DVT from vein compression RT screw Underwent thrombolysis

Left Femoral DVT Underwent balloon angioplasty for better patency of vein

Left Femoral DVT It was determined that the screw needed to be removed from the vein- to prevent recurrent DVT

Left Femoral Vein DVT Treated with lifelong Warfarin

Mechanical Embolectomy Popular adjunct to thrombolysis Goal to remove/reduce thrombus burden Reduce time of thrombolytic infusion, hospital stay

Mechanical Embolectomy Catheter j

IVC Filter Inferior Vena Cava Filter– designed to trap emboli, prevent passage of thrombi to pulmonary artery Used in patients have contraindication to anticoagulation (hemorrhagic CVA, head injury) to prevent PE Used in patients with proximal DVT who have short term contraindication to anticoagulation, such as undergoing major surgery ACCP Guidelines, 9 th edition. Inferior Vena Cava Filters for Acute PE and DVT.

IVC Filter Temporary/removable filters are common – can remain in place permanently

IVC Filter Placed via catheter through femoral vein (groin) or jugular vein (neck) Short procedure time

Treatment Goal of DVT Reduce incidence of Post Thrombotic Syndrome Valves are dysfunctional due to thrombus Blood moves in both directions causing hypertension in venous system

Treatment Goal of DVT Post Thrombotic Syndrome (PTS) Late effects of proximal DVT Chronic pain Swelling Ulcerations Hyperpigmentation Present in 50% of proximal DVT after 2 years

Post Thrombotic Syndrome Ulcerations seen in PTS Treated with various wound products Compression stockings Leg elevation Skin grafting may be required Hyperbaric oxygen therapy

Compression Stockings Should be worn by ALL DVT patients Graduated compression increases deep venous flow by creating pressure on superficial veins Reduces post thrombotic syndrome by 50%

Compression Stockings Medical grade compression mmHg, mmHg, OTC Leg elevation “above level of heart” with stocking use Wear stockings during daytime hours Knee-high most popular

Treatment of PE Treatment is dictated by severity or clot burden Massive PE 5-10% --- hypotension, pulselessness Submassive PE 20-25% --- myocardial infarction w/o hypotension Low risk PE 70% --- no significant hemodynamic changes Circulation(2011) 123,

Treatment of PE Immediate anticoagulation with suspected PE– heparin reduces mortality from 30% to 10% ACCP Guidelines – UFH, LMWH, or fondaparinux plus oral anticoagulation (Warfarin) at time of diagnosis Discontinue UFH, LMW, or fondaparinux after INR is 2.0 for at least 24 hours Pulmonary Embolism Treatment and Management, Ouellette, MD; Chief Editor: Mosenifar

Treatment of PE Risk Stratification– need for thrombolysis? Based on severity, prognosis, and bleeding risk Thrombolysis recommended if… Hemodynamically unstable Hypotension, tachycardia, RV dysfunction, MI, poor respiratory status OR Hemodynamically stable with high risk for hypotension Thrombolysis contraindicated in massive PE if high risk for bleeding or severe renal failure-  then treatment is IV UFH Pulmonary Embolism Treatment and Management, Ouellette, MD; Chief Editor: Mosenifar

Thrombolysis Goals of thrombolysis in treatment of PE Reduce mortality Decrease RV pressure Prevent recurrent PE Improve gas exchange Thrombolytic agents Alteplase, Urokinase, Streptokinase, Reteplase

Embolectomy Catheter or surgical embolectomy Patients who remain unstable after thrombolysis or Patient with contraindications to thrombolysis

Inferior Vena Cava Filter ACCP Guidelines – recommend IVC placement if… contraindications for anticoagulation high risk for VTE recurrence

Duration of Anticoagulation Anticoagulation is essential for patients who survive PE Duration of treatment controversial At least 6 months to reduce risk of reoccurrence LMWH used concurrently with Warfarin for bridging until INR therapeutic When transitioning from IV heparin/LMWH to rivaroxaban/Xarelto ---no bridging needed

Long-term Considerations Removal IVC Filter Removal of IVC when PE risk is low, usually within 6 months when anticoagulation restarted after major surgery and mobility no longer impaired

Removal of IVC Filter Low risk procedure performed under fluoroscopy

IVC Removal

Take Home Points Prevention is key to reduce VTE incidence and mortality VTE is the #1 preventable death in hospital patients Every hospital patient should be risk-assessed for VTE Based on disease process and risk factors

Prophylaxis in Hospital Mechanical In hospital – pneumatic compression boots in bed Pharmacological LMWH – enoxaparin (Lovenox) 40 mg SQ daily or dalteparin (Fragmin) 5000 u SQ daily Fondaparinux (Arixtra) 2.5 mg SQ daily used after orthopedic surgery UFH (Heparin) 5000 u SQ every 8 hours Warfarin

Thank you Questions??