Clin Med Venous Thromboembolism Flashcards
Define venous thromboembolism
Blood clot, usually from the deep veins of the leg [also air, fat, tumor, foreign body] that occludes pulmonary vasculature
venous thromboembolism etiology
- major cause of death in the United States, with as many as 650,000 cases/yr
- > 400,000 diagnoses of PE are missed in the United States annually.
- most deaths from PE are due to failure to diagnose rather than failure to treat adequately
- two thirds of patients die within 1 hour of symptom onset; this is the golden hour
mortality in venous thromboembolism
- mortality is 15% w/i 3 mos after occurance
- in 25% of PE, initial manifestation is death
- 3rd leading cause of death among hospitalized pt
most important risk factors in venous thromboembolism
*Virchow’s Triad
-stasis
-venous injury/endothelial damage
-hypercoaguability
(most pts have multiple)
inherited risks for venous thromboembolism
- factor V Leiden
- prothrombin gene mutation
- low protein C, S and antithrombin
- family hx of VTE
acquired risk factors for venous thromboembolism
▪ Smoking* ▪ Obesity* ▪ Immobility* ▪ Age >40 years ▪ Malignancy ▪ Pregnancy ▪ Atherosclerosis* ▪ Trauma, surgery, hospitalization* ▪ Infection ▪ Long haul travel (plane or auto) ▪ Electronic leads, indwelling catheters ▪ Previous DVT ▪ Pelvic or long bone fractures ▪ APL antibody syndrome (venous or arterial) ▪ Hyperhomocysteinemia (venous or arterial)
pts in who there is a high clinical suspicion for underlying disorder
- PE not associated w/ acquired risk factor
- family hx
- can be after 1st event
What is initial eval of thrombophilia directed toward?
most common causes: ▪ Factor V Leiden ▪ Prothrombin gene mutation ▪ APL Ab syndrome ▪Hyperhomocysteinemia
less common:
-protein C&S def., ATIII def.
gas exchange abnormalities in the pathophys of embolus
- gas exchange abnormalities (R–>L shunt leads to hypoxemia and increased a-A gradient)
- VQ mismatch
- increased dead space
- respiratory alkalosis
respiratory alkalosis as a sign of PE
- often is a sign of increased dead space and impaired minute ventilation
- may suggest massive PE
hemodynamic abnormalities
▪ Depends on clot burden/size of embolus
▪ Increased vascular resistance/RV afterload
▪ May cause RV dilation, hypokinesis, tricuspid regurgitation, FAILURE
▪ Interventricular flattening, impaired LV filling
▪ Increased wall stress and ischemia
symptoms of venous thromboembolism
▪ Dyspnea ▪ Chest pain (often pleuritic) ▪ Apprehension ▪ Cough** ▪ Hemoptysis ▪ Syncope ▪ Palpitation ▪ Wheezing ▪ Leg pain ▪ Leg swelling
signs of venous thromboembolism
▪ Tachycardia ▪ Tachypnea ▪ Hypoxemia ▪ Accentuated S2 ▪ Fever ▪ Diaphoresis ▪ Cardiac murmur ▪ JVD ▪ Cyanosis ▪ Hypotension ▪ Signs of DVT ▪ Homan’s test - not reliable
d-dimer as lab test for venous thromboembolism
▪ Non-specific measure of fibrinolysis ▪ Measured by ELISA
▪ High sensitivity (positive in present of disease)
▪ High negative predictive value (disease is absent when test is negative) in the OUTPATIENT setting
when to use d-dimer
use in outpatient setting/ER, not inpatient test for ruling out PE
CXR in venous thromboembolism
- usually normal
- may show collapse, consolidation, small pleural effusion, elevated diaphragm
- uncommon findings
What are some examples of uncommon findings in imaging for venous thromboembolism
- Westermark’s sign: dilation of vessels proximal to clot
- Hampton’s hump: pleural based opacities w/ convex medial margins
diagnosis w/ ECG in venous thromboembolism
- may show complete or incomplete RBBB
- T wave inversions are anteriorly S1Q3T3 ***
- large S wave in lead 1
- Q wave w/ T wave inversion in lead 3
- sign of RV strain
- not as common
V/Q scan in venous thromboembolism
- old standard
- currently reserved for renal impairment, IV contrast allergy, pregnancy, chronic PE
how is V/Q can done?
- radioactive compound inhaled into lung; normal lung will be evenly distrubuted
- radioactive compound injected into vein; no injected material reaches region past PE
- “mismatch” of inhaled and injected compounds on the lung scan images = PE
CT scan used as diagnosis in venous thromboembolism
- new standard
- spiral CT/multislice
- data suggests that CT is as accurate as invasive angiography (gold standard)
- negative predictive value of 99%
MRI/MR angiogram as diagnosis in venous thromboembolism
- good at visualizing blood flow
- similar to invasive angiogram
diagnostic algorithm for venous thromboembolism
refer to slide 26 for flow chart
risk stratification
- anticoagulate first!
- hemodynamic stability
- elevated biomarkers (troponin, BNP)
- if BNP (brain naturetic peptide) is elevated consider ECHO
ECHO
▪ Insensitive for diagnosis but can risk stratify in pts with known PE
▪ In normotensive pts (hemodynamically stable) RV dysfunction is an independent risk factor for early death
▪ McConnell’s sign: regional RV dysfunction w/ free wall apical sparing is throughout to be specific for PE
Tx by anticoagulation
- initial anticoagulation w/ UFH or LMWH
- Unfractionated heparin (UFH)
Unfractionated Heparin
▪ Maintain PTT at 60-80 seconds
▪ Preferred in pts undergoing further therapy (can be reversed)
▪ Weight based nomogram effective for initiating therapy
▪ Can be reversed:
-Preferred in pts undergoing further therapy
-Use in pts with high bleeding risk
▪ Contraindicated in patients with hx of heparin induced
▪ Pregnancy and morbidly obese patient may need factor Xa monitoring
thrombocytopenia (HIT)
LMWH (Lovenox) Low molecular weight heparin
▪ More predictable response
▪ Dosed at 1mg/kg q12, given subQ
▪ Dose adjustments:
-Kidney disease – give q24 if creatinine clearance <30
-Pregnancy – usually need to monitor factor Xa; some need dose adjustment
▪ Obesity – usually will not dose over 100mg q12:
-May need factor Xa monitoring
oral agents for tx
-coumadin (Warfarin)
-Non vit. K oral agents (NOACs) : ▪ Apixaban (Eliquis) ▪ Rivaroxaban (Xarelto) ▪ Dabigatran (Pradaxa) ▪ Edoxavab (Savaysa)
Warfarin
▪ Vitamin K antagonist
▪ Diet can effect levels
▪ Dose response variation ▪ Dose determined by INR: therapeutic range INR is 2-3
▪ Must have concurrent therapy with UFH/LMWH for 5 days AND until INR >2 for 2 consecutive days
▪ Risk of bleeding
Apixaban (Eliquis)
▪ Factor Xa inhibitor
▪ No dosing adjustment for age or
renal disease (Dosing is adjusted when used for
atrial fibrillation)
▪ Use with caution in liver disease ▪ Lower incidence of bleeding
▪ 10mg BID x7 days, then 5mg BID
complications
Rivaroxaban (Xarelto)
▪ Factor Xa inhibitor ▪ Not easily reversible ▪ Low incidence of GI bleed and ICH ▪ Cannot use in renal disease ▪ 15mg BID for 21 days, then 20mg qHS: Must be taken with a large meal
Dabigatran (pradaxa)
▪ Direct thrombin inhibitor ▪ No dose adjustment for renal ▪ Must have 5 days of therapy with ▪ 150mg BID disease UFH/LMWH prior to initiation
Edoxaban (Savaysa)
▪ Factor Xa inhibitor
▪ Must have 5 days of therapy with UFH/LMWH prior to initiation
▪ Dose adjustments for renal disease
▪ 60mg once daily
Fondaparinux (Arixtra)
▪ ArgatrobanSynthetic pentasaccharide with anti-Xa activity
▪ No adjustments but cannot be used if CrCl <30 ▪ No risk of HIT
▪ 2.5mg subcutaneous injection once daily
Argatroban
▪ Direct thrombin inhibitor
▪ Used inpatient in the form of a drip
Thrombolytics
▪ Only use in case of hemodynamic instability* (rarely used)
▪ t-PA (Altepase): FDA approved for PE; 100mg infused over 2 hrs
▪ No difference in mortality or recurrent PE at 90 days when compared to UFH
▪ Remember contraindications for t-PA (active bleeding, surgery w/i last 30 days, allergy)
HIT (heparin induced thrombocytopenia)
▪ Formation of IgG against heparin platelet factor IV complex
▪ Both UFH and LMWH can cause this (Less with LMWH)
▪ If suspected stop all heparin containing products
when to screen for HIT
- when platelets drop by >50% within 2 weeks of therapy
- Must check serotonin release assay to conform dx
What drug to start in the incidence of HIT
▪ Start direct thrombin inhibitor
- Argatroban
- ondaparinux (Arixtra)
- lepirudin
invasive procedures for embolus
- surgical embolectomy
- catheter directed embolectomy (angiovac)
- IVC filter
surgical embolectomy
▪ Only used for hemodynamic instability AND with contraindication to anticoagulation
▪ Requires a specialized center
▪ Can be effective
▪ Small published numbers
Catheter directed embolectomy (AngioVac)
▪ Emerging as effective therapy with fibrinolytics cannot be used
▪ Can be performed up to 5 days after event
IVC filter
-go in through femoral and place filter in IVC
▪ 5% risk of recurrent pulmonary embolus, especially after 6 months
▪ Continue anticoagulation if possible
▪ Remove after 2 months
▪ Complication of leg swelling can occur
How to determine which anticoagulation to use?
- CHEST 2016 guidelines: anticoag therapy for 3 mos* unless otherwise indicated
- recommend using newer agents such as NOACs over Warfarin in the tx of VTE not associated w/ cancer
In what diseases/history is a LMWH the recommended agent for tx?
- cancer
- pregnancy
- liver disease (NOACs contraindicated)
In what diseases/history is Warfarin the recommended agent for tx?
- renal disease
- GI bleed (or Apixaban)
In what diseases/history is a UFH the recommended agent for tx?
-if thrombolytics used initially
In what diseases/history are NOACs that don’t require monitoring the recommended agent for tx?
in noncompliance
if the 1st thromboembolic event in the context of a reversible risk factor, what is the duration of therapy?
3 mos
Case: Idiopathic first thromboembolic event.
What is the duration of tx?
▪ Treat for 3 months
▪ Further therapy at discretion of clinician:
-Risk factors include age, sex, d-dimer (men have 75% increased risk of recurrence; women 15%)
Case: recurrent VTE
What is the duration of tx?
▪ Treat for >3 months if bleeding risk is low to moderate
▪ May consider prolonged therapy and evaluate yearly
In the presence of continuing risk factors, what is the duration of tx?
treat indefinitely
risk stratification flow chart
refer to slide 43
recommendations for using Warfarin
▪ Heparin therapy should be continued for at least 5 days
▪ Oral anticoagulation should be overlapped with heparin for 4-5 days
▪ Heparin and Warfarin can be initiated simultaneously: dc heparin on day 5-6 if INR has been therapeutic for 2 consecutive days
▪ Discontinue heparin on day 5-6 if INR has been therapeutic for 2 consecutive
▪ Longer periods of initial heparin therapy is considered in the case of massive PE or iliofemoral thrombosis
recommendations for IVC filters
▪ No longer recommended in pt on anticoagulation: Only used when anticoagulation is contraindicated
▪ Should be removed if possible
What to add to tx after stopping anticoagulation
consider adding ASA if no contraindication
general tx in low risk PE
-treat at home vs early hospital discharge (3 days):
▪ Controversial
▪ Clinically stable with good cardiopulmonary reserve
▪ Pt has no contraindication to NOAC
▪ Consider the patient
Tx when there is a recurrence of VTE while on anticoagulation
▪ New recommendation is to treat with Lovenox for one month
▪ Evaluate reasons for failure (compliance, new active malignancy, true recurrence)
▪ If recurrent VTE in a cancer patient, increase Lovenox dose by ¼ or 1/3
how to prevent thromboembolism in inpatient setting
▪ LMWH: -40mg subQ once daily -30mg subQ once daily if CrCl <30 -30mg subQ BID if BMI >40 ▪ UFH ▪ Graded compression stocking (TED hose) ▪ Sequential compression devices (SCDs)
prognosis of thromboembolism
▪ Depends on underlying cause rather than PE itself
▪ Good outcomes when diagnosed early and treated adequately
▪ Perfusion defects resolve in most
