Case Report ~ Discussion

1. Case Report ~ Discussion Antiphospholipid syndrome  pulmonary embolism ~ diagnosis and approach

2. Antiphospholipid Syndrome (APS) APS is characterized by • Recurrent venous or arterial thrombosis • Recurrent fetal loss • Thrombocytopenia • Presence of antibodies to phospholipid such as anticardiolipin antibody (aCL) and lupus anticoagulant (LA)

3. APS - Epidemiology • Prevalence of antiphospholipid antibodies in healthy population is 2% ~ 5% • For all the patient with APS – female : male = 2 : 1 • Mean and median ages of patients in most reports is 35 to 45 years old

4. APS - Pathophysiology • Alteration of endothelial cell function • Alteration of the coagulation regulatory system, erythrocyte and platelet • A cofactor, beta2 glycoprotein-I ,is required and enhances the binding of aCL to cardiolipid

5. APS – Diagnosis 1

6. APS – Diagnosis 2

7. APS – Clinical Manisfestation

8. APS – Thromboembolic Disease • Noninflammatory thromboembolic disease • All venous and arterial systems have been cited,including large,median and small vessels • Most common site and presentation v. : lower extremity in the femoral and popliteal system a. : embolic cerebrovascular accident and transient ischemic attack • The recurrent rate is high

9. APS – pulmonary complication • Pulmonary embolism and infarction • Pulmonary hypertension • Major pulmonary arterial thrombosis • Pulmonary microthrombosis • Adult respiretory distress syndrome • Intraalveolar pulmonary hemorrhage • Post partum syndrome

10. APS – pulmonary complication ~ Pulmonary embolism and infarction • Recurrent deep venous thromboses are the most common vascular occlusive events encountered in patient with antiphosphlipid antibody and these are accompanied by pulmonary embolism and infarction in 1/3 of cases

11. Pulmonary Embolism (PE) • the third most common cardiovascular emergency after myocardial infarction • Mortality rate untreated : 30% anticoagulant treatment : 10% • Nonspecific signs and symptoms ~ cannot be accurately diagnosed on clinical grounds

12. PE –Clinical Presentation and Differential Diagnosis • Clinical triad : dyspnea , pleuritic chest pain, and hemoptysis • Most common symptom : dyspnea • Uncommon manifestation include unexplained fever, arterial tachyarhythmias, wheezing

13. Diagnosis of PE - Assessment 1 Chest radiography • Many patients with PE have a normal chest radiography • radiologic abnormalities : nonspecific, cannot distinguished from other pulmonary disorder Electrocardiogram • Frequently normal or nonspecific • Useful in differentiating between PE and myocardial infarction

14. Diagnosis of PE – Assessment 2 Blood Gas Estimation • A normal arterial PaO2 does not exclude PE (PE patients : 10~15%) • A low arterial PaO2 is nonspecific and cannot be used to rule-in PE • Danger of hemorrhage following arterial puncture if the patient is treated with heparin or thrombolytic therapy • Of limited value in the diagnosis of PE

15. Diagnosis of PE ~ Pulmonary angiography 1 • The standard for diagnosing pulmonary embolism (diagnostic accuracy : 80 ~ 95%) • Relative contraindication : (1)significant bleeding risk - platelet > 75000 (2)allergy to the contrast medium (3)renal insufficiency  adequent hydration after angiography

16. Diagnosis of PE ~ Pulmonary angiography 2 Side effect • Flushing • Transient hypotension • Catheter – induced ectopic beats

17. Diagnosis of PE ~ Pulmonary angiography 3 • Increased risk of complication (1)acute or severe chronic pulmonary hypertension (2)right heart failure (3)resperatory failure • Reduced risk of complication : selective arterial injection and limiting amount of contrast medium (low osmolality)

18. Diagnosis of PE ~ Pulmonary angiography 4 • Mortality rate : 0.5 % • Mordality required intubation : 0.4% required dialysis : 0.3% • Limitation : expensive, invasive, has small but significant risks and requires experienced physicians and supporting staff • Most commonly ued when ventilation-perfusion scanning is nondiagnostic but clinical suspicion remains high

19. Diagnosis of PE ~ Ventilation – perfusion scintigraphy 1 • Most commonly used non-invasive technique with clinical suspicion • Perfusion lung scan : not specific enough for diagnosis of PE • Ventilation imaging : differentiate vascular occlusion from disorder of ventilation

20. Diagnosis of PE ~ Ventilation – perfusion scintigraphy 2 Segmental defect • Occlusion of a branch of a branch of the pulmonary artery • Wedge shape and pleural based • Conforms to segmental anatomy of the lung • Large (>75%), moderate(25~75%), small(<25%) Nonsegmental defect

21. Diagnosis of PE ~ Ventilation – perfusion scintigraphy 3 V / Q match • Both scintigrams are abnormal in the same area, defects of equal size V / Q mismatch • Abnormal perfusion in the area of normal ventilation or much larger perfusion abnormality than ventilation defect

22. Diagnosis of PE ~ Ventilation – perfusion scintigraphy 4 High probability • Segmental or lobar perfusion defect with normal ventilation Low probability of PE • Perfusion defect with matched ventilation abnormality

23. Modified PIOPED Criteria High probability (>80%) 2 large mismatched segmental defects without radiographic abnormality Any combination of mismatched defects equivalent to the above (2 moderate = 1 large) Intermediate probability (20~80%) Low probability (<20%) Nonsegmental perfusion defect Any perfusion defect with a substantially larger radiographic abnormality Matched ventilation and perfusion defects with normal chest radiograph Small subsegmental perfusion defects Normal ( No perfusion defect ) Diagnosis of PE ~ Ventilation – perfusion scintigraphy 5

24. Diagnosis of PE ~ Ventilation – perfusion scintigraphy 6 Condition associated with V/Q mismatch • Acute or chronic PE • Other cause of embolism : drug abuse, iatrogenic • Bronchogenic carcinoma • Hypoplasia or aplasia of pulmonary artery • Vasculitis • Post radiation therapy • Mediastinal or hilar adenopathy with obstruction of pulmonary artery or veins • Swyer – James syndrme

25. Diagnosis of PE ~ Ventilation – perfusion scintigraphy 7 Determinining Clinical Likelihood of PE • Assessment of risk factor for venous thromboembolism (leg paralysis, bed rest, malignancy, CHF, presence of central venous catheter …) • Evaluation of symptoms and signs • Interpretation of preliminary investigation (eg. chest radiograph and electrocardiogram)

26. Diagnosis of PE ~ Ventilation – perfusion scintigraphy 8

27. Diagnosis of PE ~ Ventilation – perfusion scintigraphy 9 • In PIOPED, ventilation-perfusion scans 34% were read as low probability 39% were read as intermediate probability additional diagnostic studies must be pursued • After pulmonary angiography, PE (+) patients with low-probability : 16% patients with intermediate-probability : 33% • the interobserver disagreement for intermediate- and low-probability ventilation-perfusion scans was 25% and 30%, respectively

28. Diagnosis of PE ~ Spiral tomographic scan 1 • capable of imaging nearly the entire thorax during a single breath-hold intravenous contrast can be timed to arrive pulmonary vasculature • Sensitivity : 64 ~ 93 % Specificity : 89~100 % Especially when PE is involved the main, lobar, or segmental pulmonary arteries

29. Diagnosis of PE ~ Spiral tomographic scan 2 Advantage • High sensitivity and specificity • Visualize the clot • Indentify other disease states that can mimic PE (lung tumor, pleyral disease, pericardial disease)  provide alternative diagnosis • Cost : 1/6 ~ 1/8 angiography

30. Diagnosis of PE ~ Spiral tomographic scan 3 Limitation • Inability of spiral scanning to detect PE in subsegmental pulmonary arteries (sensitivity : 29%)

31. Diagnosis of PE ~ Spiral tomographic scan 4 Clinical guidelines • It should be used as a ”rule-in” modality, rather than a ”rule-out” procedure • if an alternative diagnosis is being considered in addition to pulmonary embolism, spiral CT scanning can provide new information that a ventilation-perfusion scan cannot.

32. Diagnosis of PE ~ D-dimer assay 1 • Rapid, noninvasive and inexpensive • Commonly found in the circulation when venous thromboembolism is present • Also found in other disease state (cancer, CHF, inflammatory condition)

33. Diagnosis of PE ~ D-dimer assay 2 • Two general methods of measuring D-dimers : ELISA method, latex agglutination • Elevated D-dimer fragments are too nonspecific for diagnosis of venous thromboembolism by themselves. With negative predictive values close to 100%, certain D-dimer assays have the potential to be the only screening test necessary to” rule out” venous thromboembolism.

34. Diagnosis of PE ~ D-dimer assay 3 • To be used in a diagnostic strategy, the details of the assay should be known : type (latex or ELISA), operating characteristics (sensitivity and negative predictive value), and outcomes of clinical studies supporting the particular assay. • Testing for D-dimers should be restricted to patients in whom clinical suspicion of venous thromboembolism is low or moderate.

35. Diagnosis of PE ~ MRI 1 • Helpful for the diagnosis of pelvic and thigh deep venous thrombosis • Acute, symptomatic, proximal deep vein thromboses : sensitivity approaching 100% • Less sensitive for detecting calf deep venous thrombosis • PE : can demonstrate an embolus directly as an intrvascular filling defect (sensitivity : < pulmonary angiography)

36. Diagnosis of PE ~ MRI 2 Advantage and Limitation

37. PE – Diagnostic Approach 1

38. PE – Diagnostic Approach 2

39. References 1 • Antiphospholipid-Thrombosis Syndromes / Haemostasis 1999 ; 29:100-110 • Antiphospholipid Syndrome / The journal of Family Practice, Vol.38, No.6(Jun), 1994 • Review: Antiphospholipid Antibodies and the Lung / The journal of Rheumatology 1995 ; 22:62-6

40. Reference 2 • The Diagnosis of Pulmonary Embolism / Haemostasis 1995 ; 25:72-87 • Non-invasive diagnosis of pulmonary aembolism / International Jounal of Cardiology 65(Suppl.1)1998 s83-s86 • Improving Detection of venous thromboembolism / Postgraduate Medicine vol.108, No.4, September15, 2000

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