Transcript Venous Thromboembolism: Treatment

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
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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
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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
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received 5-10 days of IV anticoagulation therapy prior
to initiation
If CrCL > 30 mL/min – 150 mg BID
If CrCl 15-20 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)
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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
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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
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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 10-14 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, 7th 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, 7th 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 veinto 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
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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, 9th 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 20-30 mmHg, 30-40
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, 1788- 1830
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
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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 2.0-3.0
 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??