1) Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), results from blood clots forming in the veins. VTE is potentially fatal and is more likely to occur in immobilized patients, those with hypercoagulable disorders, or after trauma or surgery. 2) PE occurs when a clot breaks off and lodges in the lung arteries, partially or fully blocking blood flow. Patients with PE have a higher risk of recurrent VTE than those with DVT alone. 3) Treatment of VTE involves both prevention and acute phase treatment, with the goals of preventing PE/complications and reducing mortality and treatment side

1. Pharmacotherapy of
VTE
Gobezie T.
1

2. Introduction
 VTE results from clot formation in the venous
circulation and is mostly manifested as deep vein
thrombosis (DVT) and pulmonary embolism (PE)
 Venous thromboembolism (VTE) is a potentially fatal
disorder and most frequently occurs in patients who
Sustain multiple trauma,
Undergo major surgery,
Are immobile for a lengthy period of time, or
Have a hypercoagulable disorder
2

3. Pulmonary embolism
PE is a thrombus that arises from the systemic
circulation and lodges in the pulmonary artery or one
of its branches, causing complete or partial obstruction
of pulmonary blood flow
Propagating clots break loose and embolize to block
pulmonary blood vessels.
Patients with PE are more likely to suffer recurrent
VTE than patients with DVT alone
 9 out of 10 PE cases are due to DVT
 50% higher incidence in African Americans
compared to Caucasians

4. Venous thromboembolism
 In the normal vascular system, blood remains in a fluid
state, transporting oxygen, nutrients, plasma proteins,
and wastes
 If vascular injury is present, a dynamic series of
reactions involving a formation complex interplay of
thrombogenic and antithrombotic stimuli, which
 Result in the local formation of a hemostatic plug that
seals the vessel wall and prevents further blood loss
but does not spread to other areas of the vasculature
4

5. Virchows Triad (SHE)
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6. Pathophysiology [3]
 Three primary factors influence formation of pathological
clots:
A. Stasis of Venous circulation/abnormal blood flow
 Slowed blood flow in the deep veins of the legs
 Damage to venous valves, or increased blood viscosity.
 Prolonged periods of Immobility (traveling for long hour without
moving extremities),
 varicose veins, surgery (esp. hip/knee),
 vessel obstruction (late pregnancy, obesity),
 HF (LVD), aFiB
7

7. Pathophysiology [4]
B. Hyper-coagulable states
 Deficiency of protein C, S, or anti-thrombin
 Excess amount of factor VIII or XI
 Estrogens and selective estrogen receptor
modulators
 Cancer, sever illness (sepsis), dehydration, use
of estrogen (birth control pills), HIT, postpartum
periods
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8. Pathophysiology [4]
C. Endothelial (vascular) injury (direct or indirect)
 Trauma or injury to vessels (e.g. Surgery) and
 Major-orthopedic surgery
 Indwelling-venous devices (central line catheters, Iv
lines, heart valves)
 IV drug use (venipuncture)
 Medications
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9. Risk factors
10

10. Clinical presentation
 DVT
• Pain and tenderness
• Unilateral leg swelling
• Warmth and erythema
• Palpable cord
• Asymptomatic
 PE
• Pain (chest, back, shoulder,
upper abdominal), Palpitation
• SOB, cough, Tachypnea,
Tachycardia
• Syncope, Hemoptysis
• New cardiac arrhythmia
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11. Clinical presentation
 DVT  PE
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12. Diagnosis (DVT)
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13. Diagnosis (PE)
14

14. Cont….
 D-dimer is a degradation product of fibrin blood clots,
and its sensitivity > 80% for DVT and >95% for PE
Initial diagnostic evaluation with D-dimer testing alone
without obligatory imaging tests are very important
If D-dimer abnormally elevated, imaging tests are the next
step.
Although the D-dimer test is a very sensitive for clot
formation, elevated levels can result from a variety of
other conditions (e.g., recent surgery or trauma,
pregnancy, and cancer).
Therefore, a negative test can help exclude the diagnosis
of VTE, but a positive test cannot confirm the diagnosis.
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15. VTE Management
Desired outcomes
1. Prevent the
development of PE
and the post-
thrombotic
syndrome,
2. Reduce morbidity
& mortality
3. Minimize adverse
effects and cost of
treatment.
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16. Pharmacotherapy
Treatment VTE
involves;
1. Prevention
2. Acute Phase
Treatment
3. Secondary
prophylaxis
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17. Pharmacotherapy
VTE prevention
1. Compression
devices
 Graduated
compression
stockings
Intermittent
pneumatic
compression
2. Quit smoking
3. Anti-coagulation
therapy
Within 8 hours after
surgery?
4. Mobilizing patients
as soon as possible
after surgery
5. Moving legs
during long trips
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18. Pharmacotherapy
UFH
oMoA:
Inactivates thrombin
and factor Xa through an
antithrombin (AT)-
dependent mechanism
Route of
administration
• IV or SC
Dosing
• About 5000IU bid to
tid
Adverse effects
oHIT
Two types
• Type 1:1-4 days
• Type 2: 5-10 days
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19. Pharmacotherapy
LMWH
oMoA:
Activates antithrombin
III; binding inhibits
factor Xa.
Route of
administration
• Preferably SC
Dosing
• Enoxaparin:
• 1 mg/kg every 12 hrs
or 1.5 mg/kg q 24 hrs
• Dalteparin
• 100 U/kg every 12
hrs or 200 U/kg q
24 hrs
• Tinzaparin:
• 175U/kg q 24 hrs
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20. Pharmacotherapy
Fondaparinux sodium
• A selective inhibitor of
factor Xa.
• Approved in patients
undergoing orthopedic
(hip fracture, hip & knee
replacement) surgery
• For treatment of VTE
and PE.
VTE prevention,
o2.5 mg SC QD
starting 6-8hrs after
surgery.
Treatment of DVT
and PE:
o7.5 mg SC QD
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21. Pharmacotherapy
DIRECT
THROMBIN
INHIBITORS
oCapable of inhibiting
both circulating and
clot-bound thrombin
oIndicated anticoagulants in
patients with history of HIT
• Lepirudin
• Bivalirudin
• Desirudin
Warfarin
oVitamin K antagonist
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22. Pharmacotherapy
23

23. Acute VTE/PE t/t
1. PE with sever cardiopulmonary compromise or DVT
w highest risk of limb Loss: Thrombolytic tt ffed by
UFH/LMWH
2. PE with poor prognosis or DVT unstable for
outpatient tt:
 Hospitalize for anticoagulant tt &
 give Rivaroxaban/apixaban or LMWH/fondaparinux x5 days
 LMWH/fondaparinux x5 days then dabigatran/edoxaban or
LMWH/fondaparinux x5 days overlap with warfarin
 Use UFH x5 days overlapped with warfarin, if CrCl<30ml/min
3. For pnts with active bleeding or CI to anticoagulation:
IVC filtration until acceptable for anticoagulation, then
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24. Heparin
25

25. Heparins: Acute VTE
26

26. Warfarin: Acute VTE
Inhibits cyclic
interconversion of
vitamin K
During acute VTE
treatment
o Overlapped with
heparins for at least 4 - 5
days,
• Discontinue heparin
once the INR is within
the desired range for 2
consecutive days
• Target INR : 2-3
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27. Warfarin: Acute VTE
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28. Monitoring
29
UFH LMWH Fondaparinux Warfarin
CBC YES YES YES YES
aPTT YES N/A N/A
Anti-Xa levels
Obesity/pregnancy
N/A YES YES N/A
Serum Creatinine N/A YES YES N/A
INR 2-3 days
after initial
dose