Pulmonary Thromboembolism

1. Pulmonary Thromboembolism Prof. Sevda Özdoğan MD Chest Diseases

2. Pathophysiology of Pulmonary Embolism Virchow Triade • Venous stasis • Vascular endothelial (wall) damage • Hypercoagulation

3. 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)

4. Acquired Risk Factors

5. Genetic Risk factors

7. Clinical features and Diagnosis • Clinical suspicion*** • Medical history: • To identify the patient at risk • Family history • Medical or acquired risk factors • Symptomatology:

8. Unexplained acute dyspnea • Tachypnea • Substernal chest discomfort • Pleuretic chest pain • Hemopthysis • Cyanosis • Shock / sencope • Asymptomatic • Physical findings: (nonspecific) 97%

9. 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)

10. Chest Radiography • Negative chest radiogram is a common presentation so does’t exclude the diagnosis • 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)

11. Pulmonary infarct Linear atelectasis, pleural effusion

12. 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)

13. 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 gradientis increased in almost all the patients

14. 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

15. 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

16. 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

17. 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

20. Partial filling defect in right middle lobe and lover lobe artery Wedge shaped infiltration on the right upper lobe posterior segment

22. 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

23. 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

24. 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

25. Suspected PE Low clinical suspect D dimer (-) exclude High clinical suspect D dimer (+) Treatment High probability/filling defect V-Q scan/ BT Hipotension Severe hypoxemia Nondiagnostic PE P.angio Stabile clinical condition No treatment PE (-) Bilateral lower extremity (USG, IPG, CV, MRI) DVT (-) or nondiag. Serial examination Or angio Treatment DVT (+) ATS Clinical Practice Quideline-1999

27. Deep Venous Thrombosis (DVT) • Compression ultrasound • Doppler ultrasonography • Venography (gold standard)

28. 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

29. 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

30. 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%.

31. Body Weight-Based Dosingof Intravenous Heparin • Initial dosing: Loading 80 U/kg  18 U/kg/hr (APTT in 6 hrs) APTT(s) Dose ChangeAdditional 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

32. 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

33. 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

34. Contraindications for heparin • Active hemorrhagia • Recent cerebrovascular hemorrhagia • History of major hemorrhagia from gastrointestinal, genitourinary or respiratory system

35. 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

36. 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)

37. 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

38. 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

39. 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

40. Indications for thrombolytic treatment • 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

41. Thrombolytics

42. 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

43. 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

44. 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

45. 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

46. 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

47. Non medical Prophylaxis • Graduated compression stockings • İntermittent pneumatic compression • Foot impulse pumps • Early mobilization Can be used for patients who have contraindications to anticoagulants.