venous thromboembolism (vte) helbert rondon, md, facp, fasn assistant professor of medicine unm...
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Venous Thromboembolism(VTE)
Helbert Rondon, MD, FACP, FASN
Assistant Professor of Medicine
UNM Health Sciences Center
Outline
Epidemiology of VTEPhysiology of HemostasisPathogenesis of VTERisk factors for VTEPrevention of VTEClinical presentation, Diagnosis and Treatment of
DVT and PETesting for ThrombophiliaSuperficial Vein Thrombosis
Epidemiology of VTE
White RH. Circulation. 2003;107:I-4 –I-8
Physiology of Hemostasis
Inherited Acquired
Factor V Leiden mutation Prior VTE
Prothrombin gene mutation Immobilization-Bed rest-Extended travel
Protein C deficiency Trauma
Protein S deficiency Major Surgery
Antithrombin deficiency Presence of CVC
Dysfibrinogenemia Pregnancy
Drugs:-Oral contraceptives-Tamoxifen-Bevacizumab
Specific Diseases-Malignancy-Antiphospholid Antibody Syndrome-Paroxysmal Nocturnal Hemoglobinuria-Nephrotic syndrome-Heart failure-Inflammatory Bowel Disease
Risk Factors for VTE
Pathogenesis of VTE: Virchow’s Triad
Case #1
54 year-old man with PMH Liver cirrhosis is brought to ER c/o AMS and abdominal pain x 2 days
Vitals: BP=90/60, HR=100, R=21, T=38.9 CPhysical exam:
Abdomen: diffuse tenderness, caput medusae, ascites Rectal : brown stool, negative hemoccult Neurologic : Confusion, asterixis
Labs: WBC=18K, Hb=13.1, Plat=120K, INR=1.6, ammonia= 98
Peritoneal fluid: WBC=973, Neutrophils=67%
Which of the following is the most appropriate method of VTE prophylaxis
for this patient ?
A. Intermittent pneumatic compressionB. Graduated compression stockingsC. Enoxaparin 40 mg subcut BIDD. Enoxaparin 40 mg subcut daily PLUS
Intermittent pneumatic compressionE. VTE prophylaxis not needed
Prophylaxis for VTE
Assessment of VTE risk
Geerts WH et al. Chest 2008; 133:381S–453S
Pharmacologic agents for VTE prophylaxis
1. LMWH: Enoxaparin 40 mg subcut once daily2. UFH: Heparin 5000 units subcut BID or TID3. Fondaparinaux 2.5 mg subcut once daily4. ASA5. Warfarin
Mechanical methods of VTE prophylaxis
Intermittent pneumatic compressionGraduated compression stockingsVenous foot pump
Case # 2
65 year-old woman with a long standing history of left knee osteoarthritis comes to your office c/o left calf pain and swelling
Vitals: BP=130/70, HR=100, R=21, T=36.9 ⁰C
Physical exam (see picture): Left calf edema and tenderness No erythema or palpable chord (+) Homan’s sign
Labs: D-dimer = 100 ng/dL
Case # 2 (cont.)
What is the most likely diagnosis in this patient ?
A. LymphedemaB. Ruptured Baker’s cystC. Deep venous thrombosisD. Superficial venous thrombosisE. Cellulitis
Deep Venous Thrombosis (DVT)
Proximal vs. Distal Lower Extremity DVT
Characteristic Proximal Venous System DVT
Isolated Calf DVT
Veins involved - Popliteal- Superficial femoral
- Anterior tibial- Posterior tibial- Peroneal
% of all lower extremity DVT
70-80% 20-30%
Symptomatic 80% 20%
Cause of PE > 90% < 10%
Ultrasound Sensitivity 97% 73%
Clinical Manifestations of DVT
Calf swellingCalf tendernessCalf asymmetry greater than 1.5 cmPalpable cordDilated superficial veinsHomans’s signSkin erythemaAltered skin temperature
Diagnostic Accuracy of Physical Signs for DVT
Finding Sensitivity (%) Specificity (%) Likelihood Ratio if Finding
Present Absent
Inspection
Any calf or ankle swelling 41-90 8-74 1.2 0.7
Asymmetric calf swelling ≥ 2 cm difference
61-67 69-71 2.1 0.5
Swelling of entire leg 34-57 58=80 1.5 0.8
Superficial venous dilation 28-33 79-85 1.6 0.9
Erythema 16-48 61-87 NS NS
Superficial thrombophlebitis
5 95 NS NS
Palpation
Tenderness 19-85 10-80 NS NS
Asymmetric skin coolness 42 63 NS NS
Asymmetric skin warmth 29-71 51-77 1.4 NS
Palpable cord 15-30 73-85 NS NS
Other tests
Homans’s sign 10-54 39-89 NS NS
McGee S. Evidence-Based Physical Diagnosis. 2nd ed. Philadelphia, PA: Saunders; 2007: 614-619
Differential Diagnosis of DVT
Muscle strain, tear, or twisting injury to the leg
Leg swelling in a paralyzed limbLymphedemaVenous insufficiencyBaker’s cystCellulitisInternal derangement of knee
Diagnostic Tests for DVT
D-dimer (Very good NPV in the setting of low pretest probability)
Compression ultrasonography (Test of choice)Impedance plethysmography (indicated in
recurrent DVT)Magnetic resonance venographyContrast venography (Gold standard)
Complications of DVT
Acute pulmonary embolismPost-thrombotic syndromePhlegmasia cerulea dolens
Assessment of Pretest Probability of DVT
Scarvelis D et al. CMAJ 2006;175(9):1087-92
Diagnostic Approach to DVT
Scarvelis D et al. CMAJ 2006;175(9):1087-92
Treatment of DVT
LMWH: Enoxaparin 1 mg/kg subcut Q12hUFH: Heparin 80 units/kg (5,000 units) IV
bolus, then heparin 18 units/kg/hour (1,300 units/hour) IV infusion
Fondaparinaux 7.5 mg subcut once dailyInitiate Warfarin together with LMWH, UFH
or Fondaparinaux on the 1st treatment dayLMWH, UFH or Fondaparinaux for at least 5
days and until INR ≥ 2.0 for 24 hours
Treatment of DVT (cont.)
Start Warfarin 5 mg PO dailyTarget INR = 2.5 (range INR 2.0-3.0)Duration of Warfarin treatment for 1st episode
of unprovoked DVT or DVT due to a transient reversible factor: at least 3 months
Duration of Warfarin treatment for 2nd episode of unprovoked DVT or DVT due to a permanent factor (i.e. APAP): long-term
Indications for Thrombolysis in DVT
Phlegmasia cerulea dolens catheter-directed thrombolysis or surgical thrombectomy
Indications for IVC filter in DVT
Absolute contraindication to anticoagulationRecurrent DVT despite adequate
anticoagulation
Prevention of Post-thrombotic syndrome
Knee-high graduated compression stockings exerting a pressure of 30 to 40 mmHg at the ankle started ASAP and for at least 2 years
Case # 3
35 year-old woman with PMH asthma presents to ER complaining of sudden onset SOB
Vital signs: BP=132/78, HR=90, RR=25, T=36.4 C, O2 sat=89% on RA
Physical exam: Lungs: absent breath sounds and hyperresonance in right
anterior chest Extremities: no edema or erythema
EKG: normal sinus rhythmCXR: emphysema, interstitial opacities, cystic
airspaces, small right upper lobe pneumothoraxD-dimer: 100 ng/dL
ER physician is concerned about PE. What is the next step in the management of this
patient ?
A. Order a Spiral CT chest with IV contrastB. Order a 2D echocardiogramC. Order a V/Q scanD. Order a Pulmonary angiographyE. PE has been ruled out, treat pneumothorax
Acute Pulmonary Embolism (PE)
Symptoms of PE
Dyspnea at rest or with exertion (73%)Pleuritic chest pain (44%)Cough (34%)> 2-pillow Orthopnea (28%)Wheezing (21%)Hemoptysis (13%)Symptoms of lower extremity DVT (42%)
Stein PD et al. PIOPED II. Am J Med. 2007;120(10):871-9
Diagnostic Accuracy of Physical Signs for PE
Finding Sensitivity (%) Specificity (%) Likelihood Ratio if Finding
Present Absent
Vital Signs
Temperature > 38 ⁰C 1-9 78-97 0.4 NS
Pulse > 100/min 25-43 69-75 NS NS
Respiratory rate > 30/min 21 90 2.0 0.9
SBP ≤ 100 8 95 1.9 NS
Lung
Cyanosis 3 97 NS NS
Accessory muscle use 17 89 NS NS
Crackles 59 49 NS NS
Wheezes 3 89 0.2 1.1
Pleural friction rub 14 91 NS NS
McGee S. Evidence-Based Physical Diagnosis. 2nd ed. Philadelphia, PA: Saunders; 2007: 365-370
Diagnostic Accuracy of Physical Signs for PE
Finding Sensitivity (%) Specificity (%) Likelihood Ratio if Finding
Present Absent
Heart
Elevated neck veins 3 96 NS NS
Left parasternal heave 1 99 NS NS
Loud P2 19 84 NS NS
New gallop (S3 or S4) 30 89 NS NS
Other
Chest wall tenderness 11-17 79-80 NS NS
Unilateral calf pain or swelling
9-29 89-95 2.3 NS
McGee S. Evidence-Based Physical Diagnosis. 2nd ed. Philadelphia, PA: Saunders; 2007: 365-370
Laboratory
ABG: hypoxemia, respiratory alkalosisHigh BNP and N-terminal pro-BNP levelsIncreased Troponin I
EKG
Non specific ST-segment and T wave changes most common
Sinus tachycardiaRV strainNew incomplete RBBBS1Q3T3 pattern
S1Q3T3 pattern
Chest X-ray
Cardiomegaly (24%) most commonPleural effusion (23%)Elevated hemidiaphragm (20%)Pulmonary artery enlargement or
Fleischner’s sign (19%)Atelectasis (18%)Parenchymal pulmonary infiltrates (17%)Westermark’s sign (rare)Hampton’s hump (rare)
Elliot CG et al. ICOPER. Chest. 2000;118(1):33-8
Westermark’s sign
Hampton’s hump
Diagnostic tests for PE
D-dimer Good NPV2D echocardiographySpiral (Helical) CT chest with IV contrast
test of choiceV/Q scanPulmonary angiography (Gold standard)
Spiral CT Chest with IV contrast
V/Q scan
Pulmonary Angiography
Assessment of Pretest Probability of PE
Kearon C. CMAJ 2003;168(2):183-94
Diagnostic Approach to PE (Helical CT)
Agnelli G et al. N Engl J Med 2010;363:266-74
Diagnostic Approach to PE (V/Q scan)
Treatment of PE
LMWH: Enoxaparin 1 mg/kg subcut Q12hUFH: Heparin 80 units/kg (5,000 units) IV
bolus, then heparin 18 units/kg/hour (1,300 units/hour) IV infusion
Fondaparinaux 7.5 mg subcut once dailyInitiate Warfarin together with LMWH, UFH
or Fondaparinaux on the 1st treatment dayLMWH, UFH or Fondaparinaux for at least 5
days and until INR ≥ 2.0 for 24 hours
Treatment of PE (cont.)
Start Warfarin 5 mg PO dailyTarget INR = 2.5 (range INR 2.0-3.0)Duration of Warfarin treatment for 1st episode
of unprovoked PE or PE due to a transient reversible factor: at least 3 months
Duration of Warfarin treatment for 2nd episode of unprovoked PE or PE due to a permanent factor (i.e. APAS): long-term
Treatment of DVT/PE during Pregnancy
During pregnancy: - LMWH as for treatment of regular DVT/PE- Anti-Xa level target of 0.6 to 1.0 IU/mL - Warfarin is contraindicated during pregnancy
Switch to UFH as for treatment of regular DVT/PE, stop 4-6 h prior to delivery
LMWH or UFH should be started 12 hours after C-section and 6 hours after vaginal delivery
Continue anticoagulation for at least 6 weeks postpartum
Thrombolysis in PE
Indication: Hemodynamic instabilityUFH should be administered first and in full
therapeutic dosesAlteplase 100 mg IV infusion over 2h
Indications for IVC filter placement in PE
Absolute contraindication to anticoagulationRecurrent PE despite adequate
anticoagulationHemodynamic or respiratory compromise
that is severe enough that another PE may be lethal
Complications of PE
Chronic thromboembolic pulmonary hypertension
Screening for Thrombophilia
Indications:- 1st unprovoked DVT or PE before age 50- History of recurrent DVT or PE- 1st degree relatives with documented DVT or PE before
age 50
Screening tests:- Factor V leiden- Prothrombin gene mutation- Antiphospholipid antibodies- Antithrombin deficiency- Protein S deficiency- Protein C deficiency
Screening for Thrombophilia (cont.)
Timing of screening:- Acute thrombosis by itself can transiently reduce the
antithrombin and occasionally protein C and protein S levels
- Heparin can produce up to a 30 % decline in antithrombin
- Warfarin produces a marked reduction in protein C and protein S
- For the reasons above, test for thrombophilia at least 2 weeks after completing the initial 3 months of warfarin therapy following a DVT or PE
Superficial Venous Thrombosis
Treatment: LMWH (prophylaxis dose) for at least 4 weeks
Questions ?