management of venous thromboembolism: key lessons · management of venous thromboembolism: key...
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Management of Venous Thromboembolism: Key Lessons
Vijaya Bhatt, MDDivision of Hematology-oncologyDepartment of Internal Medicine
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DisclosureAdvisory Board: Pfizer
Some therapies not yet FDA approved will be discussed.
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OutlineDuration of Anticoagulation Choice of Anticoagulation Thrombophilia testing IVC filter placement Outpatient versus inpatient therapyMiscellaneous
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Duration of Anticoagulation
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Case #1A 28-year old woman is seen in the clinic for “blood clot in the left leg”..
What do you want to know more?
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Key history: VTEDiagnosis: First episode/recurrent …
Site: distal/proximal lower/upper extremity ..
Provoked: Risk factors.
Symptoms of post-thrombotic syndromeFamily history of VTEBleeding eventsCurrent anticoagulationHistory of abortionCancer screening
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Case #1Left proximal DVT- 10 years agoShe was on OCP when she developed DVTNo bleeding on warfarin but does not like INR checks
Protein C deficiency at the time of DVT diagnosis-provoked DVT-estrogen level can influence protein C
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Risk factors-“Provoked VTE”Surgery, trauma, hospitalization, pregnancy…. cancer, inflammatory bowel disease, obesity..
OCP, estrogen-vaginal ring- IM high-dose progesterone ?Long distance travel (just flight)
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Overview of management-ACCP guidelines
CHEST2016;149(2):315-352
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Risk of VTE Recurrence•Surgery: 3% at 5 years
•Nonsurgical transient risk factor: 15% at 5 years
•Unprovoked: 30% at 5 years
•Cancer: 15% annualized risk
Isolated distal DVT: half the risk of proximal DVT/PE
2nd unprovoked proximal DVT/PE: higher (1.5-fold)
than 1st unprovoked event
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ANNUAL risk of MAJOR bleeding on anticoagulant
Low (no bleeding risk factors) 0.8%
Moderate (one bleeding risk factor) 1.6%
High (two or more bleeding risk factors): 6.5%
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Risk of bleeding Age >65 years or >75 yearsHistory of bleedingCancerRenal or Liver failure Thrombocytopenia or AnemiaPrevious strokeDiabetesAntiplatelet therapy/NSAIDS; Poor anticoagulant controlComorbidity and reduced functional capacityRecent surgeryFrequent fallsAlcohol abuse
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Duration of anticoagulation
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Dhakal Petal.Clin Appl Thromb Hemost.(2016)
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3-month anticoagulation1. Provoked VTE2. Distal or upper extremity DVT3. High risk of bleeding
Important to avoid interruption during first 3 months, particularly first month
VTE prophylaxis after 3 months if at risk
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Extended anticoagulationUnprovoked proximal DVT or PE
AND
Low risk of Bleeding
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Unprovoked Proximal DVT: Wants to stop anticoagulation After 3-months, risk-stratify especially in woman
DASH or HERDOO-2D-dimer and ?repeat USGHigh-risk thrombophilia
Low-dose aspirin if stop anticoagulation
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Clinical scoring systemDASH:-elevated D-dimer post anticoagulation-age <50 years-male sex-hormone use in women
A score of 1: recurrence rate of 3.1% per year
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Clinical scoring systemHERDOO-2:-hyperpigmentation, edema or redness of affected leg, -elevated D-dimer while on anticoagulation-obesity with body mass index >30-age 65 years or older.
Women with 1 risk factors: recurrence of 1.3% per yearMen: 9.9% or higher.
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Case #277/M, prior history of 2 provoked DVTs, off A/C but on aspirin 325 mg. He developed an unprovoked PE more recently. He was started on rivaroxaban, and aspirin 325 mg was continued.
History of hypertension, CKD, issues with balance, left side hearing deficit, right knee arthritis, left leg weakness and has had multiple falls.
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Case #2
Increased risk of bleeding
STOP aspirin
Management of comorbidites: PT for balance and gait training
Reassess the risk and benefit.
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Choice of Anticoagulation
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Agents Situation
LMWH Cancer,liverdiseaseandcoagulopathy,pregnancy
VKA Creatinine clearance<30ml/min,poorcompliance
Edoxaban,dabigatran Requireinitialparentaltherapy
Dabigatran HigherriskofCADoverVKA
VKA,Apixaban HistoryofGIbleeding*
*Dabigatran,rivaroxaban,andedoxaban maybeassociatedwithmoreGIbleedingthanVKA.
CHEST2016;149(2):315-352
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Major bleeding events comparing NOACs versus VKAs
Chatree Chai-Adisaksopha et al. Blood 2014;124:2450-2458
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Fatal bleeding events comparing NOACs versus VKAs
Chatree Chai-Adisaksopha et al. Blood 2014;124:2450-2458
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Intracranial bleeding comparing NOACs versus VKAs
Chatree Chai-Adisaksopha et al. Blood 2014;124:2450-2458
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VKA versus NOACsCharacteristics Warfarin NOACsOnset/Duration Long ShortBridging Needed Noforapi/rivaroxabanInteractions Significant LimitedMonitoring INR NoneReversalAgents Yes Yes/approval pendingVTErecurrence Low LowBleeding Higher LowerCost Low High
Routeoral,onceortwicedailydoses
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Reversal of new anticoagulants•Hold 1-2 days before procedure•SUPPORTIVE CARE
•Oral factor Xa inhibitors (rivaroxaban, apixaban, edoxaban): Andexanet alfa
•Dabigatran: Idarucizumab
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Thrombophilia testing
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Thrombophiliaevaluation-Performed after careful consideration-Right timing-Right patient-Right tests
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“Unexplained” arterial thromboembolism
Even lower value of thrombophilia testing
?Therapeutic implications
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Thrombophilia evaluationAntithrombin activityProtein C activityFree protein S antigen and activityAntiphospholipid syndrome- acquired
PNH and MDS: alter management
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ThrombophiliaevaluationHeparin-induced thrombocytopeniaDisseminated intravascular coagulationThrombotic microangiopathyCatastrophic antiphospholipid antibody syndrome
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Cancer screening
Unprovoked VTE may be the first sign of an occult cancer.
Extensive screening with imaging and tumor markers is not of benefit.
Age and sex appropriate screening
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IVC filter
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IVC filterDecreases the risk of PE modestlyIncreases the risk of lower extremity DVT Filter-related complications such as migration.
Indication:– Acute, Proximal AND Lower extremity
DVT – Cannot tolerate anticoagulation.
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Home or early discharge (1) clinically stable with good cardiopulmonary reserve(2) no contraindications for anticoagulation(3) expected to be compliant and (4) feels well enough
Right ventricular dysfunction or increased cardiac biomarker levels: Hospitalization
(Grade2BACCP2016recommendations)
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Thrombolysis ACCP: anticoagulant alone over thrombolysis or catheter-assisted thrombus removal
Thrombolysis: low risk of bleeding and PE associated with hypotension.
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Superficial vein thrombosesSuperficial vein thromboses:
-5 cm or more -close to deep veins, or-underlying diseases such as cancer
Fondaparinux 2.5 mg for 6 weeks: FDA approved
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PICC associated DVT
PICC does not need to be removed3 months or more
Cancer-related thromboses: extended anticoagulant therapy
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Conclusion
• Provoked VTE or high-risk of bleeding: A/C for 3 months
• Unprovoked VTE, and low risk of bleeding: indefinite A/C
• Risk stratification for unprovoked DVT who want to stop
• NOACs vs. VKA: Lower risk of bleeding
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Conclusion
Limited role of thrombophilia testing or extensive cancer screening
Limited role of IVC filter
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