Pulmonary Thromboembolism
Prof. Sevda Özdoğan MDChest Diseases
Pathophysiology of Pulmonary Embolism
Virchow Triade
1. Venous stasis2. Vascular endothelial (wall)
damage 3. Hypercoagulation
Risk factors
The risk factors for VTE can be both genetic or acquired for a certain patient
Risk increase if age>40 (Comorbidity, stasis, hypercoagulability)
Risk Factor Hypercoagulability
Stasis Trauma
Previous DVT, PE
Major surgery
Malignancy
Obesity
Trauma
Fracture (Hip, leg)
Pregnancy
MI
Congestive hearth failure
Stroke
Estrogen treatment
Immobilization
Burns
Acquired Risk Factors
Genetic Risk factorsGenetic
Activated protein C (APC) resistance
Factor V Leiden mutationPositive in 21% of VTE patients
Antithrombin III deficiency Autosomal dominantRisk of VTE x5
Protein C and S (cofactor) deficiency
Autosomal dominantRisk od VTE x6
Prothrombin G20210A A single nucleotide change in prothrombin gene results in elevated prothrombin levelsRisk of DVT x5
Hyperhomocystinemia Defects in enzymes of homocystein disposalRisk of VTE x2
Genetic
Increased Factor VIII RR for VTE x4.8
Blood group other than O RR of DVT x2
Combination of the genetic risk factors
Clinical features and Diagnosis
Clinical suspicion*** Medical history:
To identify the patient at risk Family history Medical or acquired risk factors
Symptomatology:
Unexplained acute dyspnea Tachypnea Substernal chest discomfort Pleuretic chest pain Hemopthysis
Cyanosis Shock / sencope
Asymptomatic
Physical findings: (nonspecific)
97%
Diagnostic approach
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 Negative chest radiogram is a common
presentation so does’t exclude the diagnosis
80% Abnormal chest radiograph but nonspecificEarly: 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)
Linear atelectasis, pleural effusion
Pulmonary infarct
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
Hypoxemia, hypocapnia and respiratory alcalosis PaO2 <%80 PaO2 may be normal in submassive embolism if no
underlying pulmonary disease is present
(A-a)O2 gradient is increased in almost all the patients
ECG Abnormalities of ECG are nonspecific
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 Nonspecific changes
WBC can be slightly elevated LDH, bilirubine can be slightly elevated D-Dimer (fibrin degradation product) can be
elevated 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) Can be performed rapidly at the bedside Features that suggest acute massive PE include
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 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)
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
ATSClinical Practice Quideline-1999
Suspected PE
V-Q scan/ BTHigh probability/filling defectTreatment
NondiagnosticHipotension Severe hypoxemia
P.angio PEStabile clinical condition
Bilateral lower extremity(USG, IPG, CV, MRI)
PE (-) No treatment
DVT (-) or
nondiag.Serial examinationOr angio DVT (+) Treatment
High clinical suspect
Low clinical suspectD dimer (+)
D dimer (-) exclude
Deep Venous Thrombosis (DVT)
Compression ultrasound Doppler ultrasonography Venography (gold standard)
Treatment of PTE and DVT Supportive treatment
Oxygen Intravenous fluid Vasopressor agents Resuscitary measures depending on the clinical status of
the patient Anticoagulant therapy
Unfractionated heparin (UFH) Low molecular weight heparin (LMWH) Oral anticoagulants (Warfarin)
Thrombolytic treatment Surgical treatment
UFH
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 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 Dosingof Intravenous Heparin Initial dosing: Loading 80 U/kg 18
U/kg/hr (APTT in 6 hrs)
APTT(s) Dose Change Additional Next APTT (h)
(x normal) (U/kg/h) Action
<35 (1.2 x) +4 Rebolus 80 U/kg 6 35-45 (1.2-1.5x) +2 Rebolus 40 U/kg 6 46-70 (1.5-2.3x) 0 0 6* 71-90 (2.3-3.0x) -2 0 6 >90 (<3x) -3 Stop infusion 1 h 6
* During first 24 hr, there after once a day
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 x2-2.5 (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
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 Reversible condition and the risk is high in prolonged use of
the drug Alopecia Cutaneous rush Hypersensitivity reactions
Urticeria, konjonctivitis, rhinitis, asthma, angioneurotic edema
Contraindications for heparin
Active hemorrhagia Recent cerebrovascular
hemorrhagia History of major hemorrhagia from
gastrointestinal, genitourinary or respiratory system
LMWH 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
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)
Low-Molecular-Weight Heparin
Rivaroxaban (New treatment) 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 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
Massive Pulmonary Embolism Hypotension Deep hypoksemia Right ventricular disfunction/iskemia Cardiovascular collapsThrombolytic treatment should be
performed immediatelyCan be performed in the first 14 days
ThrombolyticsDrug Loading dose Infusion dose Treatment
duration
Streptokynase250 000 IU
30 min100 000 IU/hr 24 hours
Urokynase4400 UI10 min
4400UI/kg/hr 12 hours
rt-PA- 100 mg
2 hours-
Complications Hemorrhagia (intracranial 1-2%) Fever, alergic reactions,nausea, vomiting, myalgia,
headache Contraindications
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 Reversible risk factor, first event, age<60 : 3-6 months
Reversible risk factor, first event, age>60: 6-12 months
First event, unknown risk factor: 6-12 months
Recurrent event: >12months- life long
Irreversible risk factor, first event: >12 months- life long
Vena Cava Filters
If there is a contraindication for anticoagulation If a complication due to anticoagulation occurs
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 Determined by the thrombotic risk of
the clinical situation in conjunction with the patients profile of risk factors Ortopedic surgery (post-traumatic) ICU Neurosurgery carry the highest risk
Prophylaxis 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
Non medical Prophylaxis Graduated compression stockings İntermittent pneumatic compression Foot impulse pumps Can be used for patients who have
contraindications to anticoagulants.
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