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Pulmonary Thromboembolism
Prof. Sevda Özdoğan MD
Chest Diseases
Pathophysiology of Pulmonary
Embolism
Virchow Triade
1.
2.
3.
Venous stasis
Vascular endothelial (wall) damage
Hypercoagulation
Risk factors
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The risk factors for VTE can be both
genetic or acquired for a certain patient
Risk increase if age>40
hypercoagulability)
(Comorbidity, stasis,
Acquired Risk Factors
Risk Factor
Previous DVT, PE
Major surgery
Malignancy
Obesity
Trauma
Fracture (Hip, leg)
Pregnancy
MI
Congestive hearth
failure
Stroke
Estrogen treatment
Immobilization
Burns
Hypercoagulability
Stasis
Trauma
Genetic Risk factors
Genetic
Activated protein C (APC) resistance
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Factor V Leiden mutation
Positive in 21% of VTE patients
Antithrombin III deficiency
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Protein C and S (cofactor) deficiency
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Prothrombin G20210A
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Hyperhomocystinemia
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Autosomal dominant
Risk of VTE x5
Autosomal dominant
Risk od VTE x6
A single nucleotide change in
prothrombin gene results in
elevated prothrombin levels
Risk of DVT x5
Defects in enzymes of homocystein
disposal
Risk of VTE x2
Genetic
Increased Factor VIII

Blood group other than O
RR of DVT x2
Combination of the genetic risk
factors
RR for VTE x4.8
Clinical features and Diagnosis
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Clinical suspicion***
Medical history:
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To identify the patient at risk
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Family history
Medical or acquired risk factors
Symptomatology:
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Unexplained acute dyspnea
Tachypnea
Substernal chest discomfort
Pleuretic chest pain
Hemopthysis
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Cyanosis
Shock / sencope
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Asymptomatic
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Physical findings: (nonspecific)
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97%
Diagnostic approach
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Semptomatology and signs
Chest radiology
Arterial blood gas analysis (ABG)
Electrocardiography
Standard laboratory tests
Echocardiography (Cardiac and venous doppler of the
lower extremity)
D-Dimer
Spiral CT or Ventilation / perfusion scan
Pulmoner angiography (gold standard)
Chest Radiography
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Negative chest radiogram is a common presentation
so does’t exclude the diagnosis
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80% Abnormal chest radiograph but nonspecific
Early:
 Peripheral regional oligemia (Westermark’s sign) (7%)
 A prominant pulmonary hilus with little tapering of vessels
(Fleischner’s sign) (15%)
Later:
 Peripheral wedge shaped densities (Hampton’s hump) (35%)
 Plate like atelectasis
 Diaphragmatic elevation (%24)
 Pleural effusion (%48)
Pulmonary infarct
Linear atelectasis, pleural
effusion
Frontal chest radiograph obtained from a patient
with an acute pulmonary embolism. The left
pulmonary artery is enlarged (small arrow), and a
wedge-shaped peripheral opacity is present at the
left costophrenic angle (large arrow)
ABG Analysis
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Hypoxemia, hypocapnia and respiratory
alcalosis
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PaO2 <%80
PaO2 may be normal in submassive embolism if no
underlying pulmonary disease is present
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(A-a)O2 gradient is increased in almost all the
patients
ECG
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Abnormalities of ECG are nonspecific
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Acute right ventricular strain in massive embolism
Sinus tachicardia
Negative T wave and/or ST segment depression in leads
V1-3
S1Q3T3 patern (Deep S wave in lead D1, deep Q wave in
lead D3, inverted T waves in D3)
Right bundle branch block (complete or incomplete)
P-pulmonale
Changes can be similar to MI
Standard laboratory tests
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Nonspecific changes
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WBC can be slightly elevated
LDH, bilirubine can be slightly elevated
D-Dimer (fibrin degradation product) can be
elevated
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ELISA or Latex agglutination
Sensitivity % 95-97 but specificity is low
<500 ng/ml PE can be excluded if there is also low
clinical probability
Elisa is more sensitive but slow compared to Latex
ECHOCARDIOGRAPHY
(Doppler)
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Can be performed rapidly at the bedside
Features that suggest acute massive PE include
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A dilated, hypokinetic right ventricle
With the absence of right ventricular hypertrophy
Distortion of the interventriculer septum toward the left
ventricle
Tricuspit regurgitation the elevation of pulmonary artery
pressure
Identified trombi in the central pulmonary arteries
Absence of significant pathologic left ventricular conditions
Spiral Computed Tomography
Angiography (SCTA)
 May demonstrate or exclude other
abnormalities in the lung
 Bolus contrast is used for the visualization of
the pulmonary vasculature
 Filling defects are diagnostic
 Sensitivity and specificity is around 90% up
to subsegmental defects
Partial filling defect in right middle
lobe and lover lobe artery
Wedge shaped infiltration on the
right upper lobe posterior
segment
Ventilation-Perfusion
Scintigraphy
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Detection of the perfusion abnormalities subsequent to the
embolic event
Classically to display that a segment distal to an obstructing
embolus is not perfused but is still ventilated
99Tc is usually used for perfusion and 133Xe for ventilation
scaning. The two studies are analysed together.
In clinical practice the results of V/Q scintigraphy are
interpreted together with the clinical estimate of the likelihood
of acute PE
A normal V/Q virtually excludes clinically relevant PE
Patient with multiple embolisms in both lungs: segmental
mismatch defect in left lung was detected by both SPECT (A
and B) and planar scintigraphy (C and D). Defects are marked
by arrows in B and D. Subsegmental mismatch defects are
present in right lung. CT angiography found thrombotic clots in
branches of middle lobe artery and both lower lobe arteries
Pulmonary Angiography (gold
standard)
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Detects emboli in the subsegmental or even more
peripheral arteries
Unfortunately it is invasive and there is lack of
availability in an urgent investigation
Can be used if V/Q scan is nondiagnostic and the
clinical probability is high
 Mortality %0,5
 Major complications %0,4
Suspected PE
High clinical
suspect
D dimer (+)
Low clinical
suspect
V-Q scan/ BT
Nondiagnostic
D dimer (-)
exclude
High probability/filling defect
Hipotension
Severe hypoxemia
P.angio
Treatment
PE
Stabile clinical condition
Bilateral lower extremity
(USG, IPG, CV, MRI)
Serial examination
Or angio
PE (-)
No treatment
DVT (-) or
nondiag
.
DVT (+)
Treatment
ATS
Clinical Practice Quideline-1999
Deep Venous Thrombosis
(DVT)
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Compression ultrasound
Doppler ultrasonography
Venography (gold standard)
Treatment of PTE and DVT
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Supportive treatment
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Anticoagulant therapy
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Oxygen
Intravenous fluid
Vasopressor agents
Resuscitary measures depending on the clinical status of the
patient
Unfractionated heparin (UFH)
Low molecular weight heparin (LMWH)
Oral anticoagulants (Warfarin, rivaroxaban)
Thrombolytic treatment
Surgical treatment
UFH
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Binds to AT-III
Anticoagulant factors are secreted from
vascular endothelial cells
Inhibits platelet aggregation
Its effect is prophlactic for the
recurrences, not thrombolytic
Administration of UFH
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APTT monitorisation should be performed
5000 UI bolus + 25.000-35.000 UI/24 hr.
Or 1000 IU/hr continious iv infusion
aPTT check in 6 hours (x1,5-2,5), platelet
count in 3-5 days
Probability of recurrent VTE 5.4% and
major hemorrhagia 1.9%.
Body Weight-Based Dosing
of Intravenous Heparin
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Initial dosing: Loading 80 U/kg  18 U/kg/hr
(APTT in 6 hrs)
APTT(s)
(x normal)
Dose Change Additional
(U/kg/h)
Action
<35 (1.2 x)
35-45 (1.2-1.5x)
46-70 (1.5-2.3x)
71-90 (2.3-3.0x)
>90 (<3x)
+4
+2
0
-2
-3
Next APTT (h)
Rebolus 80 U/kg
Rebolus 40 U/kg
0
0
Stop infusion 1 h
* APTT check during first 24 hr, there after once a day
6
6
6*
6
6
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bed rest until heparin is therapeutic
elastic stockings until patient becomes
ambulatory ( post-thrombotic syndrome)
Oral anticoagulant can be given as warfarin
(Coumadin)5 mg/day on the first 24 hours,
when prothrombin time (PT) becomes x22.5 (INR 2-2.5)heparin can be stopped
Antidode of UFH is protamine sulphate
Antidote of warfarin is Vitamin K
Complications and side effects
of heparin
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Hemorrhagia (major % 0.5-3, fatal %0-0,8)
Thrombocytopenia
(The risk is lover in LMWH but if the condition occurs due to
autoantiplatelet antibodies it is a fatal complication. Heparin
should be stopped and an alternative anticoagulant (Hirudin etc)
should be given)
Osteopenia
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Reversible condition and the risk is high in prolonged use of the
drug
Alopecia
Cutaneous rush
Hypersensitivity reactions
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Urticeria, konjonctivitis, rhinitis, asthma, angioneurotic edema
Contraindications for heparin
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Active hemorrhagia
Recent cerebrovascular hemorrhagia
History of major hemorrhagia from
gastrointestinal, genitourinary or
respiratory system
LMWH
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Weight adjusted fixed dose subcutaneous
application is possible without laboratory
monitoring
Safer and better biopharmacology
HIT, osteopenia complications are less
As plasma half life becomes longer in renal
failure and morbid obesity anti Xa should be
monitored in this group
Low-Molecular-Weight Heparin
Drug
Treatment Dose
Ardeparin
130 anti-Xa U/kg bid
(Normaiflo)
Dalteparin
120 anti-Xa U/kg bid
(Fragmin, )
Enoxaparin
1-1.5 mg/kg bid
(Lovenox, Clexane)
(1 mg  100 anti-Xa units)
Danaparoid
(Orgaran)
Tinzaparin
175 IU/kg once a day
(Innohep)
Warfarin
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Oral agent
Inhibits the synthesis of protrombin, Protein
C, S,f II, VII, IX, X’un related to vitamin K
Plasma half life 42 hr
Monitorization PT(x2-3), INR(2-3)
5 mg/day is started in the first 24 hours of
treatment
Rivaroxaban (New treatment)
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Inhibitor of Factor Xa
Oral (Xarelto)
2x15 mg (3 weeks,) followed by 1x20 mg
Laboratory monitoring not needed
Plasma half life 5-9 hours
Dose should be reduced in renal failure
Side effects anemia, dizzinesss, vomiting,
hemoragia
Dabigatran
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Trombin inhibitor
Oral (Pradaxa)
2x150 mg
Laboratory monitoring not needed
Peak efficacy 1-4 hours after ingestion
Plasma half life 12-14 hr but can be longer in renal
failure, old age
No antidote!!
Can not be used in pregnancy,
Dyspepsia, hemoragia
Indications for thrombolytic
treatment
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Massive Pulmonary Embolism
Hypotension
 Deep hypoksemia
 Right ventricular disfunction/iskemia
 Cardiovascular collaps
Thrombolytic treatment should be performed
immediately
Can be performed in the first 14 days
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Thrombolytics
Drug
Loading dose
Infusion dose
Treatment
duration
250 000 IU
30 min
100 000 IU/hr
24 hours
4400 UI
10 min
4400UI/kg/hr
12 hours
-
100 mg
2 hours
-
Streptokynase
Urokynase
rt-PA
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Complications
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Hemorrhagia (intracranial 1-2%)
Fever, alergic reactions,nausea, vomiting, myalgia, headache
Contraindications
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Cerebral surgery or hemorrhagic attack within the last 2
months
Active intracranial disease
Uncontrolled hypertension
Hemorrhagic diathesis
Infective endocarditis
Pregnancy
Hemorrhagic rethinopathy
Pericarditis
Aneurism
Treatment duration
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Reversible risk factor, first event, age<60 : 3-6 months
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Reversible risk factor, first event, age>60: 6-12 months
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First event, unknown risk factor: 6-12 months
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Recurrent event: >12months- life long
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Irreversible risk factor, first event: >12 months- life long
Vena Cava Filters
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If there is a contraindication for anticoagulation
If a complication due to anticoagulation occurs
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Failure: new DVT or PE under treatment
Major or minor hemorragia
Trombocytopenia
Tissue necrosis
Drug reactions
For prophylaxsis
Thrombectomy, embolectomy are the other surgical
options
Primary Prevention
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Determined by the thrombotic risk of the
clinical situation in conjunction with the
patients profile of risk factors
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Ortopedic surgery (post-traumatic)
ICU
Neurosurgery carry the highest risk
Prophylaxis
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LMWH or UFH can be used in low doses
LMWH’s can be used preoperatively
safely
Prophylaxis should be continued up to 4
weeks after surgery (min 10-14 days)
Rivaroxaban 1x10 mg, Dabigatran
1x220 mg can be used
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Non medical Prophylaxis
Graduated compression stockings
 İntermittent pneumatic compression
 Foot impulse pumps
 Early mobilization
Can be used for patients who have
contraindications to anticoagulants.
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