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, rivaroxaban)

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

* APTT check 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

Warfarin 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) 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 Early mobilizationCan be used for patients who have

contraindications to anticoagulants.