Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
Venous Thromboembolism
Deep Venous Thrombosis
and Pulmonary Embolism
Venous disease
Veins
Tunica media
Intima
Adventitia
Internal
elastic membrane
Telangiectasis
Varicose veins
Oedema
Lipodermatosclerosis
Venous
leg ulcer
Varicose vein
What Is DVT?
Membrane adhesion Molecule expression
(ICAM-1, E-selectin,)
Venous valve
Venous wall
remodeling
Thrombophlebitis
Formation of a venous clot depends on the
presence of of at least of one of Virchows triad
factors
-venous stasis
-injury to vessel wall
-hypercoagulable state
Malignancy
Surgery
Trauma
Pregnancy
Oral contraceptives or
hormonal therapy
Immobilization
Inherited
thrombophillia
Patient Group
Presence of venous
catheter
Congestive failure
Antiphospholipid
antibody syndrome
Hyperviscosity
Nephrotic syndrome
Inflammatory bowel
disease
DVT Prevalence, %
Medical patients
General surgery
Major gynecologic surgery
Major urologic surgery
Neurosurgery
Stroke
Hip or knee arthroplasty,
hip fracture surgery
Major trauma
Spinal cord injury
Critical care patients
10 20
15 40
15 40
15 40
15 40
20 50
40 60
40 80
60 80
10 80
Pathophysiology
Thrombi usually form at the venous cusps of
deep veins where altered or static blood flow
causes clot formation
Alternatively,
clots form from
intimal defects
Clots are
composed from
fibrin, red cells and
platelets and cause
partial/complete
obstruction of vein
Pathophysiology
Postphlebitic syndrome (PPS) may
develop after the resolution of a DVT
PPS is due to valvular incompetence,
persistent outflow obstruction and
abnormal microcirculation.
Superficial Thrombophlebitis
Thrombosis can occur in any superficial vein
primarily the saphenous vein and its tributaries
Local pain, redness, and tenderness are
characteristic findings.
Mild cases can be treated with warm compresses,
analgesia and elastic supports
Severe cases can be debilitating and should be
managed by bed rest, elevation of extremity,
support stockings, and analgesia.
Antibiotics and anticoagulants are useful in septic
thrombophlebitis
Superficial Thrombophlebitis
Incidence of DVT from extension of a
superficial clot is 3%.
Most clots in great saphenous vein will
extend into a deep vein system in a week or
so thus a follow-up US is guaranteed
Definite treatment is ligation and excision of
affected vein.
Physical examination
Homans test: Dorsiflexion of foot elicits pain
in posterior calf. However, it must be noted
that it is of little diagnostic value and is
theoretically dangerous because of the
possibility of dislodgement of loose clot.
Pratts sign: Squeezing of posterior calf elicits
pain.
DVT D-Dimer
A positive quantitative
ELISA
Unfortunately a
positive d-dimer is not
helpful diagnostically
An imaging study is
needed
Warfarin
Recommended Prophylaxis
General surgery
Gynecologic surgery
Treatment
Bed rest, leg elevation and elastic stockings
are of unproven benefit in the management
of DVT.
Aggressive anticoagulation will prevent
extension of the clot.
Early ambulation after adequate
anticoagulation is a safe approach
Primary objective of treating DVT is the
prevention of pulmonary embolus
Treatment
Patients with negative ultrasound can safely
have a repeat ultrasound in a week without
anticoagulation
Risk of PE in these patients is near 0% and
risk of forming a DVT is 1%.
Anticoagulation is recommended for
patients with calf DVT who had PE/DVT,
immobile, have hypercoagulable state
Treatment - LMWH
Fondaparinux sodium (Arixtra) - works by
inhibiting factor Xa
Prophylaxis: 2.5 mg SC qd starting 6 h after
surgery for 5-11 d; may administer up to 24
additional days following hip fracture
Treatment:
<50 kg: 5 mg SC qd
50-100 kg: 7.5 mg SC qd
>100 kg: 10 mg SC qd
Initiate warfarin within 72 h and continue
fondaparinux for at least 5 d until oral
anticoagulant effect established (ie, INR 2-3)
Treatment - LMWH
Enoxaparin (Lovenox)
LMWH used in treatment of DVT and PE as well
as DVT prophylaxis.
Enhances inhibition of factor Xa and thrombin by
increasing antithrombin III activity. Slightly affects
thrombin and clotting time and preferentially
increases inhibition of factor Xa.
Average duration of treatment is 7-14 d.
Treatment
Patients with proximal DVT require
anticoagulation
Preferred treatment is LMWH over UFH
because of the ease of administration, more
predictable anticoagulant effect, lack of need
to monitor the anticoagulation effect, lower
incidence of major bleeding and HIT
LMWH has a preferentially inhibitory effect
on factor Xa.
Treatment - LMWH
Dalteparin (Fragmin) - Enhances inhibition of
factor Xa and thrombin by increasing antithrombin
III activity. In addition, preferentially increases
inhibition of factor Xa.
Abdominal surgery: 2500 IU SC qd for 5-10 d
High-risk patients undergoing abdominal surgery:
5000 IU SC qd for 5-10 d
Hip arthroplasty: 2500 IU SC 4-8 h following
surgery, then 5000 IU SC qd for up to 14 d
Treatment
Because of LMWH is cleared by the kidneys, it
should be avoided in outpatients with Cr >2.03
One need not to wait for the creatinine result
before initiating LMWH therapy.
The ability to discharge patients from the ED after
initial dose of LMWH is cost-effective, safe, practical
and acceptable practice as long as there is a secured
24 hr follow up with PCP.
Treatment
Indications for admission include inability to
ambulate, poor social support, unreliable
follow-up, difficulty with education with
drug administration, need for lysis or
invasive therapy, and an alternative serious
diagnosis under investigation or that
requires treatment(arterial ischemia,
cellulitis, pelvic mass)
Treatment
In pregnant pt who cannot have heparin, danaproid
should be used.
It is acceptable to start coumadin and LMWH
simultaneously.
Warfarin interferes with hepatic synthesis of vitamin
Kdependent coagulation factors.
2-10 mg/d PO
Dose must be individualized and adjusted to maintain
INR at 2-3.
Warfarin is contraindicated in pregnancy, active
bleeding, recent major surgery (thoracoabdominal,
nervous system, spine, eye)
LMWH does not interfere with the work up of a
possible hypercoagulable state compared with UFH.
Treatment
Thrombolysis for DVT is indicated for
extensive iliofemoral thrombosis and
upper extremity DVT in patients with
low risk for bleeding.
Treatment
If LMWH is contraindicated, use UFH as 80
units/kg bolus and then 18 units/kg/hr
Serious bleeding from LMWH cannot be
completely reversed with protamine which
has been associated with hypotension and
anaphylactoid reactions.
If a patient has contraindication to heparin
like in pt with HIT, you can use a thrombin
inhibitor like lepirudin
Treatment
Initial hematological testing at follow-up
includes factor V leiden, prothrombin
molecular tests, screening for
antiphospholipid anticoagulants and a
fasting homocysteine level.
Upon completion of the anticoagulation ,
further testing includes antithrombin III,
protein C, protein S, and factor VIII level
Thrombolytics
Urokinase - Direct plasminogen activator isolated
from human fetal kidney cells grown in culture. Acts
on endogenous fibrinolytic system and converts
plasminogen to enzyme plasmin. Plasmin degrades
fibrin clots, fibrinogen, and other plasma proteins. It
is nonantigenic but more expensive than
streptokinase, which limits its use. When used for
purely local fibrinolysis, it is administered as local
infusion directly into area of thrombus and with no
bolus.
4400 U/kg IV bolus followed by maintenance
infusion at 4400 U/kg/h for 1-3 d
For regional thrombus-directed therapy, smaller
bolus of 250,000 U IV may be given followed by
infusion at 500-2000 U/kg/h
Thrombolytics
Streptokinase
Acts with plasminogen to convert plasminogen to
plasmin. Plasmin degrades fibrin clots as well as
fibrinogen and other plasma proteins. An increase in
fibrinolytic activity that degrades fibrinogen levels for
24-36 h takes place with IV infusion of
streptokinase.
250,000 U IV bolus followed by an infusion at
100,000 U/h for 1-3 d
Thrombolytics
Alteplase
A tissue plasminogen activator (tPA) produced by
recombinant DNA and used in the management of
acute myocardial infarction, acute ischemic stroke,
and PE.
100 mg IV over 2 h recommended for treatment of
massive PE
For DVT, an infusion of 0.5-1.5 mg/h utilizing
catheter-directed therapy has been used, depending
on local expertise
Treatment
Treatment
Thrombectomy is only indicated with ischemic
leg secondary to a massive venous clot like in
phlegmasia cerulea dolens.
In ED , pt adequately anticoagulated who present
with new thrombus or propagation should
receive LMWH
If the fail LMWH or there is a free-floating
thrombus an IVC should emergently inserted.
IVC filter is indicated for when anticoagulation
therapy is contraindicated, there is embolization of
DVT after 1-2 weeks of anticoagulation
Secondary ULDVT
Central venous catheters
Pacemakers
Higher incidence: Chemotherapy, TPN
via central lines
Improper placement of catheter tip
Incidence varies: 1-4% of all DVTs
Associated Conditions
Presence of a central venous catheter in
(72%)
Infection (28%)
Extrathoracic malignancy (22%)
Thoracic malignancy in (21%)
Renal failure (21%)
Prior lower-extremity deep venous
thrombosis (18%)
Marinella MA, Kathula SK, Markert RJ. Heart Lung. 2000 MarApr;29(2):113-7. Spectrum of upper-extremity deep venous thrombosis in
a community teaching hospital.
Clinical Features
Diagnosis
Duplex ultrasonography
Treatment Protocol
Treatment
Expectant management
Removal of offending agent
Anticoagulation (standard: heparin x 5-7
days, 3 mos of Coumadin)
Thrombolysis (streptokinase, urokinase,
TPA)
Surgery
SVC filter
SVC Filters
SVC Filters
Ascher, Enrico, Hingorani, Anil, Mazzariol, Fernanda, Jacob, Theresa, Yorkovich, William,
Gade, Prasad
Clinical Experience with Superior Vena Caval Greenfield Filters. Journal of Endovascular
Surgery 1999 6: 365-369
PULMONARY EMBOLISM
10
PE - PATOPHYSIOLOGY(1)
PE Epidemiology and Etiology
Embolus travels through the heart
and obstructs a blood vessel in the
lung
PE - PATOPHYSIOLOGY(3)
DIAGNOSIS
Based on:
Relevant SYMPTOMS & SIGNS
Associated RISK FACTORS
Probability of ALTERNATIVE
Diagnosis
OBJECTIVE Confirmation
PULMONARY EMBOLISM
What are the risk factors for
pulmonary embolism and or DVT
Risk factor
Age > 40 years
n = 1231
%
88.5
Obesity
Hx venous thromboembolism
Cancer
Bed rest > 5 days
Major Surgery
37.8
26.0
22.3
12.0
11.2
11
Risk factor
Multiple trauma
1.1
CHF
n = 1231
8.2
childbirth
1.1
Varicose veins
5.8
Myocardial infarction
0.7
3.7
96.3
Estrogen
2.0
76.0
Stroke
1.8
39.0
PULMONARY EMBOLISM
90% of clinically important PE results
from leg DVT
96% of patients with DVT or PE have one
or more risk factors
The risk increases in proportion to the #
of risk factors
Confirmed DVT(%)
11%
24%
36%
50%
100%
PULMONARY EMBOLISM
12
PULMONARY EMBOLISM
SYMPTOMS
Chest Pain
Apprehension
88%
- pleuritic
74%
-non pleuritic
14%
PULMONARY EMBOLISM
SYMPTOMS
Cough
Hemoptysis
Syncope
Dyspnea
59%
53%
30%
13%
85%
PULMONARY EMBOLISM
SIGNS
Tachypnea
Crackles
Tachycardia
Fever
Increased P2
Phlebitis
92%
58%
44%
43%
53%
32%
13
Diagnostic tests in PE
ECG FINDINGS
Sinus Tachycardia
T wave inversion
ST segment depression
Low voltage
L axis
S1 Q3 T3
ST elevation
R Bundle Branch Block
ECG FINDINGS
43%
40%
33%
16%
12%
11%
11%
11%
X-RAY FINDINGS
Diaphragm elevation
41%
Consolidation
40%
Pleural effusion
28%
X-RAY FINDINGS
Atelectasis
20%
Oligemia
15%
X-RAY FINDINGS
14
X-RAY FINDINGS
X-RAY FINDINGS
P.E.
Hamptons
Hump
DIFFERENTIAL DIAGNOSIS
CHF
Asthma / COPD exacerbation
Pneumothorax
Pneumonia
Shock
Pleural disease
Chest wall Pain
P.E.
subsegmental
defect
DIFFERENTIAL DIAGNOSIS
Myocardial infarction
Pericarditis
1 or metastatic ca.
Hyperventilation syndrome
Infradiaphragmatic process
e.g. cholecystitis, splenic infarction
Compression Ultrasound or
Impedance Platysmography or
Intravenous Venogram
1st Test Compr. Ultrasound
15
Diagnosis: Objective
Confirmation
Pulmonary Angiogram
(GOLD STANDARD)
expensive
Technically more difficult requiring
skilled personnel
More risk for side effects
Not always available
VENTILATION /
PERFUSION SCANS
VENTILATION /
PERFUSION SCANS
Normal V/Q
Scan
16
High
Probability
V/Q Scan
VENTILATION /
PERFUSION SCANS
Non-High Probability
Ventilation perfusion defects that
did not qualify as
high or normal
D-dimer
A degradation product of of
crosslinked fibrin
High number of conditions that
activate coagulation & fibrinolysis e.g.
Surgery, inflammation, cancer
trauma.
17
PE Use of D-Dimer
Sensitive assay can exclude PE in low risk
patient
In patients with moderate pretest
probability only rapid quantitative ELISA
can adequately exclude PE
Patients judged to be high risk for PE
would still have a posttest PE probability
of 5-20% even after negative ELISA and
require further testing
Roy PM, Colombet I, Durieux R, et al. Systematic review and meta-analysis of strategies
for the diagnosis of suspected pulmonary embolism. BMJ. 2005;331(7511):259
PE Helical CT (CTA)
Negative CTA could safely exclude PE
in low risk patients
Negative LE US plus negative CTA
could exclude PE in moderate risk
patients
Eng J, Krishnan JA, Segal JB, et al. AJR 2004;183(6):1819-27. Roy PM, Colombet I,
Durieux P, et al. BMJ 2005;331(7511):259.
Spiral/Helical CT (SCT)
There are 3 SCT patterns:
1.
No PE seen and an alternate diagnosis
is found. This group does not require any
further investigation for VTE.
2.
Definite PE is detected in a segmental
or larger pulmonary artery.
3.
Patients with normal SCT, technically
inadequate scans, and scans that report
subsegmental PE are all considered
nondiagnostic. Further testing is required in
patients with these SCT patterns.
18
TREATMENT of PULMONARY
EMBOLISM
TREATMENT of PULMONARY
EMBOLISM
Heparin Nomogram
TREATMENT of PULMONARY
EMBOLISM
19
TREATMENT of PULMONARY
EMBOLISM
20