The PVD. org Venous Thromboembolism (VTE) Deep Vein Thrombosis
(DVT) & Pulmonary Embolism (PE) Evaldas Giedrimas, MD Duane
Pinto, MD
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The PVD. org Overview Etiology and Risk Factors of VTE Etiology
and Risk Factors of VTE Symptoms of DVT and PE Symptoms of DVT and
PE Evaluation and Pretest Probability Evaluation and Pretest
Probability Diagnostic Modalities Diagnostic Modalities Treatment
and Prevention Overview Treatment and Prevention Overview FDA
Approved Therapies FDA Approved Therapies Length of Treatment
Length of Treatment Unusual Site DVTs Unusual Site DVTs
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The PVD. org Etiology of VTE Virchows Triad: Virchows Triad:
Vascular injury Stasis Hypercoagulable state 1/1000 or 400,000 per
year 1/1000 or 400,000 per year increased incidence after age 60
increased incidence after age 60 30 day mortality is 30% (20% due
to PE) 30 day mortality is 30% (20% due to PE) Subsequent risk of
recurrent DVT 30 % within 10 years Subsequent risk of recurrent DVT
30 % within 10 years
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The PVD. org Etiology of VTE: PE 4th leading cause of death 4th
leading cause of death 3rd cardiovascular cause of death behind MI
and CVA 3rd cardiovascular cause of death behind MI and CVA 30-50%
from ileo-femoral DVTs and 10-20% from upper extremity DVTs 30-50%
from ileo-femoral DVTs and 10-20% from upper extremity DVTs
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The PVD. org Risk Factors of VTE Majority of VTEs occur in
non-surgical patients Majority of VTEs occur in non-surgical
patients Initial VTE event contributes to recurrence Initial VTE
event contributes to recurrence Non-surgical Non-surgical hospital
or nursing home confinement, malignancy, central venous catheter or
pacemaker, superficial venous thrombosis, and neurological disease
with extremity paresis IBD IBD Nephrotic syndrome Nephrotic
syndrome Renal vein involved in 35% of VTEs with nephrotic syndrome
Urinary excretion of anti-thrombin III, platelet hyperactivity,
elevated plasma viscosity Travel Travel Increased risk when travel
exceeds 10 hours Malignancy Malignancy Incidence of VTE ~ 11%,
after resection can increase to 40% Pancreas, GI tumors, ovary,
prostate, lung are thombogenicPancreas, GI tumors, ovary, prostate,
lung are thombogenic Trousseau's syndrome migratory
thrombophlebitisTrousseau's syndrome migratory
thrombophlebitis
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The PVD. org Risk Factors of VTE in Hospitalized Patients
Usually have more than one risk factor Usually have more than one
risk factor NYHA Class III/IV Heart Failure COPD exacerbation
Sepsis Advanced age History of prior VTE Cancer Stroke with limb
paresis Bed rest
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The PVD. org Risk Factors of VTE in Surgical Patients
Orthopedic surgery, hip/knee replacement, hip fracture surgery,
trauma surgeries with spinal cord injuries Orthopedic surgery,
hip/knee replacement, hip fracture surgery, trauma surgeries with
spinal cord injuries Cancer, congenital thrombophilia, prior
history of VTE, obesity, increasing age >60 years Cancer,
congenital thrombophilia, prior history of VTE, obesity, increasing
age >60 years
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The PVD. org Estrogen Associated Risk Factors for VTE During
Pregnancy Increases risk by 3-6x especially with increasing age
Increases risk by 3-6x especially with increasing age Incidence is
even across 3 trimesters Incidence is even across 3 trimesters
Especially high during 6 weeks after delivery Especially high
during 6 weeks after delivery Immobility and Obesity Prior VTE High
estrogen Venous stasis Pelvic trauma with delivery Acquired
hypercoagulability: elevated fibrinogen, von Wilebrand factor, and
factor VIII, and decreased natural anticoagulants (Protein S) Left
leg > Right leg ( left iliac compression by the right iliac
artery) Left leg > Right leg ( left iliac compression by the
right iliac artery)
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The PVD. org Estrogen Associated Risk Factors for VTE: OCP Use
Among women in 20-30s 3-6 x greater risk Among women in 20-30s 3-6
x greater risk Higher in Factor V Leiden or prothrombin mutation
carriers Higher in Factor V Leiden or prothrombin mutation carriers
Greatest risk 6-12 month after onset Greatest risk 6-12 month after
onset Proportional to the estrogen dose Proportional to the
estrogen dose Trans-dermal preparation carry less risk Trans-dermal
preparation carry less risk
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The PVD. org Symptoms of VTE Deep Vein Thrombosis (DVT) Deep
Vein Thrombosis (DVT) Sudden onset of pain, swelling, in one limb
Pain usually in the calf, crampy, bursting, worse with ambulation,
precedes swelling Bilateral presentation usually due to underlying
malignancy or hypercoagulable disorder Pulmonary Embolism (PE)
Pulmonary Embolism (PE) Abrupt onset of dyspnea, cough, syncope
Pleuritic chest pain
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The PVD. org DVT Evaluation and Pretest Probability Active
cancer - 1 pt Active cancer - 1 pt Paralysis or recent limb casting
1 pt Paralysis or recent limb casting 1 pt Recent immobility > 3
days 1 pt Recent immobility > 3 days 1 pt Local vein tenderness
1 pt Local vein tenderness 1 pt Limb swelling 1 pt Limb swelling 1
pt Unilateral calf swelling > 3 days 1 pt Unilateral calf
swelling > 3 days 1 pt Collateral superficial vein 1 point
Collateral superficial vein 1 point Alternative diagnosis likely
subtract 2 points Alternative diagnosis likely subtract 2 points
High probability = 3+High probability = 3+ Moderate = 1-2Moderate =
1-2 Low =
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The PVD. org PE Evaluation and Pretest Probability Clinical
symptoms of DVT 3 pts Clinical symptoms of DVT 3 pts Alternate
explanation less likely than PE 3 pts Alternate explanation less
likely than PE 3 pts Heart Rate > 100 1.5 pts Heart Rate >
100 1.5 pts Immobilization or surgery within 4 weeks 1.5
Immobilization or surgery within 4 weeks 1.5 Prior VTE 1.5 pts
Prior VTE 1.5 pts Hemoptysis 1 pt Hemoptysis 1 pt Malignancy 1 pt
Malignancy 1 pt High probability >6 High probability >6
Moderate = 2-6 Moderate = 2-6 Low
The PVD. org Treatment FDA approved therapy
Heparin/Unfractionated Heparin (cont.) Resistance Resistance 25% of
individuals who require > 35,000 units per day Non-specific
binding, high factor VIII and fibrinogen levels, antithrombin III
deficiency, increased heparin clearance, aprotinin and NTG use
Heparin Induced Thrombocytopenia (HIT) Heparin Induced
Thrombocytopenia (HIT) 50% drop in platelets or < 100,000
platelet count 5-7% of patients, 5-10 days after initiation 50%
pro-thrombotic event rate lasting 30 days after
discontinuation
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The PVD. org Treatment FDA approved therapy Warfarin Inhibits
vitamin K dependent pro-coagulation factors (II, VII, IX and X)
Inhibits vitamin K dependent pro-coagulation factors (II, VII, IX
and X) Also inhibits protein C and S synthesis which is associated
with pro-coagulability and reason for overlap with heparin therapy
Also inhibits protein C and S synthesis which is associated with
pro-coagulability and reason for overlap with heparin therapy 24
hour decrease in Factor VIII, Protein C 24 hour decrease in Factor
VIII, Protein C Followed by Factor IX on day 2, Factor X on day
3.5, Factor II on day 5 Followed by Factor IX on day 2, Factor X on
day 3.5, Factor II on day 5
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The PVD. org Treatment FDA approved therapy LMWH Small heparin
fragments (4000-6000 kD) still causes conformational change Small
heparin fragments (4000-6000 kD) still causes conformational change
Higher affinity for factor Xa than thrombin by anti-thrombin enzyme
Higher affinity for factor Xa than thrombin by anti-thrombin enzyme
Safe in a daily or BID dose based on weight Safe in a daily or BID
dose based on weight Similar and/or improved mortality, morbidity,
recurrence and side effect profile Similar and/or improved
mortality, morbidity, recurrence and side effect profile Effective
for PE treatment but needs initial inpatient monitoring Effective
for PE treatment but needs initial inpatient monitoring
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The PVD. org Treatment FDA approved therapy LMWH (cont.) HIT
HIT less than 1% Monitoring Monitoring Suggested in obese, pregnant
patients, prolonged therapy, especially with renal insufficiency
Anti-factor Xa level - 4 hours after last LMW heparin dose (goal
0.5-1.0 IU/ml BID & 1.0-2.0 for QD dose)
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The PVD. org Treatment FDA approved therapy Fondaparinux
Ultra-low molecular weight heparin Ultra-low molecular weight
heparin Synthetic pentasaccharide analog for ATIII activation
Synthetic pentasaccharide analog for ATIII activation Given SQ,
renal excretion (not for pts with CrCl
The PVD. org Unusual Site DVT Ovarian Vein Thrombosis Rare, but
often post-partum Rare, but often post-partum Etiology Etiology
R>L, due to tortuosity and multiple valves Suppurative pelvic
thrombophlebitis Presentation and Complications Presentation and
Complications Fever unresponsive to antibiotics PE, thrombus
extension into L renal vein or IVC Ureteral obstruction Low rate of
recurrent thrombosis and thromboembolism
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The PVD. org Unusual Site DVT Ovarian Vein Thrombosis (cont.)
Diagnosis often incidental Diagnosis often incidental Clinical
diagnosis during postpartum period or laparotomy CT is preferred,
with MRI, Ultrasound also used Therapy Therapy 7-10 day course of
heparin and antibiotics for post- partum OVT Excellent long-term
survival
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The PVD. org Unusual Site DVT Budd-Chiari Syndrome Rare Rare
Etiology Etiology of hepatic venous drainage most commonly due to
hepatic vein thrombosis Tumor (hepatocellular Ca, renal cell Ca,
Wilms tumor), primary veno-occlusive disease, congenital
obstruction, myeloproliferative disease, paroxysmal nocturnal
hemoglobinuria, pregnancy, OCP Presentation Presentation Can be
slow insidious to rampant progression of acute hepatic failure Type
1 IVC is occluded +/- hepatic veno-obstruction Type 2 occlusion of
major hepatic veins Type 3 fibrous obliteration of small
centrilobular intra-hepatic venules often during BMT
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The PVD. org Unusual Site DVT Budd-Chiari Syndrome (cont.)
Symptoms Symptoms Sinusoidal congestion, venous HTN, stasis,
hypoxia, hepatocyte necrosis, hemorrhage, parenchymal damage.
Diagnosis Diagnosis Doppler ultrasound, MRI, CT Therapy Therapy
Decompression, functional restoration, prevention of thrombus
propagation and recurrence Fibrinolytics: hemodynamic instability
after PE, catheter-directed lytic therapy has not been proven in
RCThemodynamic instability after PE, catheter-directed lytic
therapy has not been proven in RCT Anticoagulation is controversial
Surgical shunts can be helpful
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The PVD. org Unusual Site DVT Cerebral Venous Sinus Thrombosis
Young-to-middle aged womenYoung-to-middle aged women Etiology
Etiology Heterogeneous age group with heterogeneous risk factors
70% - Occur in superior sagittal and lateral sinuses Idiopathic,
hormone therapy, malignancy, venous malformation, post-operative,
infectious, dehydration, pregnancy, IBS, thrombophilia Presentation
Presentation Headache, focal neurological deficits, seizures, or
altered consciousness
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The PVD. org Unusual Site DVT Cerebral Venous Sinus Thrombosis
(cont.) Diagnosis Diagnosis CT- ~ 80% sensitivity and specificity ;
MRI more accurate yet still often incorrect Cerebral angiography
definitive diagnosis Therapy Therapy Heparin use but little
evidence for support of use, duration and dose
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The PVD. org Unusual Site DVT Retinal Venous Thrombosis
Atherosclerosis risk factors rather than VTE Atherosclerosis risk
factors rather than VTE Etiology Etiology Associated with HTN, DM,
CAD, connective tissue disease, malignancy, OCP use, IBS
Presentation Presentation Retinal arterial HTN, atherosclerosis,
causing retinal venous compression and stasis Visual loss 2 nd to
diabetic retinopathy Retinal hypertension, macular edema, vitreous
hemorrhage and glaucoma Therapy Therapy surgery, topical steroids,
cyclocryotherapy, photocoagulation