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 PaO 2 does not exclude PE (PE patients : 10~15%) A low arterial PaO 2 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. Diagnosis of PE ~ Ventilation – perfusion scintigraphy 5 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 )

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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