Transcript Venous Thromboembolic Disease

Venous Thromboembolism
(VTE)
Helbert Rondon, MD, FACP, FASN
Assistant Professor of Medicine
UNM Health Sciences Center
Outline
 Epidemiology of VTE
 Physiology of Hemostasis
 Pathogenesis of VTE
 Risk factors for VTE
 Prevention of VTE
 Clinical presentation, Diagnosis and Treatment of DVT and
PE
 Testing for Thrombophilia
 Superficial Vein Thrombosis
Epidemiology of VTE
White RH. Circulation. 2003;107:I-4 –I-8
Physiology of Hemostasis
Risk Factors for VTE
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
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 C
 Physical 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 compression
B. Graduated compression stockings
C. Enoxaparin 40 mg subcut BID
D. Enoxaparin 40 mg subcut daily PLUS Intermittent
pneumatic compression
E. 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.
2.
3.
4.
5.
LMWH: Enoxaparin 40 mg subcut once daily
UFH: Heparin 5000 units subcut BID or TID
Fondaparinaux 2.5 mg subcut once daily
ASA
Warfarin
Mechanical methods of VTE prophylaxis
 Intermittent pneumatic compression
 Graduated compression stockings
 Venous 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. Lymphedema
B. Ruptured Baker’s cyst
C. Deep venous thrombosis
D. Superficial venous thrombosis
E. 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 swelling
 Calf tenderness
 Calf asymmetry greater than 1.5 cm
 Palpable cord
 Dilated superficial veins
 Homans’s sign
 Skin erythema
 Altered 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
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
10-54
39-89
NS
NS
Palpation
Other tests
Homans’s sign
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 limb
 Lymphedema
 Venous insufficiency
 Baker’s cyst
 Cellulitis
 Internal 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 venography
Contrast venography (Gold standard)
Complications of DVT
 Acute pulmonary embolism
 Post-thrombotic syndrome
 Phlegmasia 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 Q12h
 UFH: 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 daily
 Initiate Warfarin together with LMWH, UFH or
Fondaparinaux on the 1st treatment day
 LMWH, 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 daily
 Target 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 anticoagulation
 Recurrent 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 rhythm
 CXR: emphysema, interstitial opacities, cystic
airspaces, small right upper lobe pneumothorax
 D-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 contrast
B. Order a 2D echocardiogram
C. Order a V/Q scan
D. Order a Pulmonary angiography
E. 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
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
Lung
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
Chest wall tenderness
11-17
79-80
NS
NS
Unilateral calf pain or swelling
9-29
89-95
2.3
NS
Other
McGee S. Evidence-Based Physical Diagnosis. 2nd ed. Philadelphia, PA: Saunders; 2007: 365-370
Laboratory
 ABG: hypoxemia, respiratory alkalosis
 High BNP and N-terminal pro-BNP levels
 Increased Troponin I
EKG
 Non specific ST-segment and T wave changes 




most common
Sinus tachycardia
RV strain
New incomplete RBBB
S1Q3T3 pattern
S1Q3T3 pattern
Chest X-ray
 Cardiomegaly (24%)  most common
 Pleural 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 NPV
 2D echocardiography
 Spiral (Helical) CT chest with IV contrast  test of
choice
 V/Q scan
 Pulmonary 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 Q12h
 UFH: 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 daily
 Initiate Warfarin together with LMWH, UFH or
Fondaparinaux on the 1st treatment day
 LMWH, 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 daily
 Target 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 Csection and 6 hours after vaginal delivery
 Continue anticoagulation for at least 6 weeks
postpartum
Thrombolysis in PE
 Indication: Hemodynamic instability
 UFH should be administered first and in full
therapeutic doses
 Alteplase 100 mg IV infusion over 2h
Indications for IVC filter placement in PE
 Absolute contraindication to anticoagulation
 Recurrent PE despite adequate anticoagulation
 Hemodynamic 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 ?