VENOUS THROMBOEMBOLISM

 VTE is a potentially fatal disorder which results from clot formation within the venous
circulation and is manifested as deep vein thombosis or pulmonary embolism.
 DVT is rarely fatal but PE can result in death within minutes of symptom onset, before effective
treatment can be given.
 Blood clots can form in: Arms, legs, lungs
1. Venous thromboembolism (VTE) - Blood clot that forms in a vein
2. Deep venous thrombosis (DVT) - Blood clot in a deep vein
3. Pulmonary embolism (PE) - Blood clot in the lungs

EPIDEMIOLOGY
• 900,000 VTE incidences annually
 First VTE occurs in 100/100,000 persons annually
o Approximately 1/3 = PE, 2/3 = DVT alone
o Idiopathic condition in 25-50% patients
• Recurrence rate ~7% at 6 months (despite therapy)
• Death ~6% DVT, ~12% PE within 1-month diagnosis

ETIOLOGY
1. Blood stasis- Blood stasis favors clotting in part through reduced clearance of the elements
responsible for blood clot formation. Contraction of the calf and thigh muscles coupled with
one-way valves in leg veins fascilitate blood flow back to the heart and lungs, and thus
damage to venous valves and periods of prolonged immobility results in venous stasis.
2. Vascular injury- intact vascular endothelial cells separate flowing blood from vessel wall
components responsible for preventing blood loss through clot formation.
3. Hypercoagulability- inherited and acquired conditions and certain drugs, ie estrogen
containing contraception, estrogen replacement therapy, and selective estrogen receptor
modulators increases the risk of VTE.
PATHOPHYSIOLOGY
NORMAL CLOTTING

COAGULATION CASCADE

THROMBUS FORMATION
  Thrombus orginates in te soleal venous sinuses or valvular sinuses (calf vein).
 It may also orginate in the iliac or femoral vein.
 Renal veins, upper limb veins, right side of heart and in situ thrombosis in the pulomonary
circulation are other sites.
 Thrombus formation and propogation depends on the presence of abnormalities of blood
flow, blood vessel wall, and blood clotting components known collectively as Virchow’s
triad.

RISK FACTORS
a. Recent orthopedic/general surgery
b. Limited physical movement/immobile
c. stroke, heart attack, heart failure, paralyzed
d. Broken bone (leg, hip, pelvis)
e. Cancer
f. Blood circulation problems
g. Personal or family history of blood clots
h. Hormones (birth control, hormone replacement)
i. Obesity
j. > 60 years of age
k. Smoker
l. Implanted vascular access
m. Previous thromboembolism (high risk)
n. Anti-phospholipidsyndrome (high risk)
VTE RISK SCORE
• Assess patient specific risk factors
• Scores categorize the risk of that patient having a VTE
• Evidence-based standardized scoring systems
a. CapriniVTE Risk Score (surgical)
b. Rogers VTE Risk Score (surgical)
c. Padua VTE Prediction Score (non-surgical)
d. KucherVTE Risk Score (non-surgical)
CLINICAL PRESENTATION
•Depends on location of blood clot
•Deep Venous Thrombosis (DVT)
•Pulmonary Embolism (PE)
Symptoms of DVT: Leg or Arm
1. Unilateral swelling
2. Warmth, redness
3. Pain (Worsens when standing or walking)
Symptoms of PE: Lungs
1. Difficulty Breathing
2. Shortness of breath (SOB)
3. Chest pain (Worse with deep breaths)
4. Coughing (May cough up blood or bloody phlegm)
5. Rapid HR
6. Fainting/Dizziness

DIAGNOSIS
• Clinical assessment
• Elevated D-dimer*
• Diagnostic studies

VTE DIAGNOSTIC STUDY

DVT Venography- It is the gold standard for diagnosis of DVT. It is an invasive test
that involves injection of radiopaque contrast dye intoa foot vein.it is an
expensive and cause anaphylaxis and nephrotoxicity.
Compression ultrasound- Most commonly used. It is a non- invasive test that
can visualize clot formation in vein of the legs.
PE Pulmonary angiography- it is gold standard for diagnosis of PE. It is an
invasive test that involves injection of radiopaque contrast dye into pulmonary
artery.
Computerized tomography
Ventilation-perfusion (V/Q) scan- it measures the distribution of blood and
airflow in the lungs. When ther is mismatch between blood and airflow in one
area of the lung, there is high probability that the patient has a PE

TREATMENT
NON-PHARMACOLOGICAL TREATMENT
IVC Filter – Percutaneous insertion of an Inferior vencava filter (IVC) is a minimally invasive
procedure performed using fluoroscopic imaging.
• Implanted in inferior vena cava
• Captures an embolism on its way to heart/lungs
• Allows blood flow around trapped clots
• Option when unable to take anticoagulants:
o Contraindicated
o Previous failure on therapy

PHARMACOLOGICAL TREATMENT

DRUGS ACTING ON COAGULATION CASCADE

Drugs for VTE

 Heparin
 Low Molecular Weight Heparins (LMWH) • Lovenox®, Fragmin®
 Factor XaInhibitors • Arixtra®, Xarelto®, Eliquis®, Savaysa®
 Vitamin K Antagonist (VKA) • Coumadin®
 Direct Thrombin Inhibitor • Pradaxa®
 Thrombolytic therapy
 Surgical removal

1. HEPARIN
MOA: acts on multiple sites of the normal coagulation system
- Combines with antithrombinIII to inactivate Factor Xa, which inhibits conversion of
prothrombin to thrombin
Side Effects: bleeding, heparin-induced thrombocytopenia (HIT)
DOSE: adjust to target activated partial thromboplastin time (aPTT) (60-85
sec) per nomogram
• IV: 80 U/kg (or 5000 U) x 1, then 1000 U/Hr
• S/C: 333 U/kg x1, then 250 U/kg Q12H

2. LOW MOLECULAR WEIGHT HEPARIN (LMWH)

MOA: higher activity with anti-factor Xathan anti-thrombin compared to heparin

DOSE:
• Enoxaparin: 1 mg/kg SQ Q12H <or> 1.5 mg/kg SQ Q24H
• Dalteparin: 100 units/kg SQ Q12H <or> 200 mg/kg SQ Q24H
DOSE ADJUST:
• CrCl<30 ml/min
• Anti-factor Xalevel: 0.5-1 units/mL

• Side Effects: bleeding, anemia, diarrhea, nausea, thrombocytopenia

3. FACTOR Xa INHIBITORS
• Injectable -Arixtra® (fondaparinux)
• Oral tablet -Xarelto® (rivaroxaban), Eliquis® (apixaban) ,Savaysa® (edoxaban) ,Future:
betrixaban

MOA: selectively inhibits active binding site for factor Xa on the coagulation cascade
Side Effects: hemorrhage, anemia, thrombocytopenia

• Fondaparinux (Arixtra®)

DOSE:
• 5 mg SQ Q24H (<50 kg)
• 7.5 mg SQ Q24H (50-100 kg)
• 10 mg SQ Q24H (>100 kg)

Caution: • Bleeding risk increased in renal impairment and BW < 50 kg

• Rivaroxaban

DOSE
• 15 mg PO BID x 21 days, then20 mg PO Daily
• CrCl< 30: Avoid use

• Patient Counseling
a. Take with food
b. Missed dose
 o If miss dose and taking BID-may take 2 doses at once! (max 2 tablets in one
day, 30 mg/24 hours)
o If miss dose and taking once daily-take as soon as remember on that day, do
NOT double dose
• Apixaban (Eliqius®)

DOSE
• 10 mg PO BID x 7 days, then 5 mg PO BID

• Patient counseling
a. With or without food
• Edoxaban
DOSE
• 60 mg PO Daily after 5-10 days parenteral anticoagulant
o Decrease dose to 30 mg PO Daily if: CrCL15-50 mL/min, ≤ 60 kg,
or certain P-gpinhibitors

4. VITAMIN K ANTAGONIST (VKA)

• Coumadin® (warfarin)
• Jantoven® (warfarin)
MOA: inhibits vitamin K-dependent clotting factors (factors II, VII, IX, X) and anticoagulant
proteins C and S

DOSE (patient specific):

• Start with 5 mg PO daily (alt: 10 mg load x2 days)
• Adjust to INR 2-3 (goal 2.5) for VTE

• Side Effects: hemorrhage, skin necrosis, systemic atheroemboli, hypersensitivity

5. DIRECT THROMBIN INHIBITOR

MOA: directly inhibits thrombin, which prevents conversion of fibrinogen to
fibrin
DOSE:
• 150 mg PO BID after 5-10 days of parenteral anticoagulation
• Adjust if CrCl< 30 ml/min or acute renal failure
Side Effects: bleeding, GI effects, hypersensitivity
Counseling Points
• Keep in original container
• Bottle is only good for 4 months after opening
• Swallow whole with full glass of water
6. SURGICAL REMOVAL
•Thrombectomy
•Embolectomy
o Reserved for massive PE

SPECIFIC THERAPY ACCORDING TO LOCATION

PE
DVT

TREATMENT STRATEGY-
TREATMENT ALGORITHM