Acute Myocardial Infarction in the Young Presented by Glenn Michael L . Gayos M.D. MAKATI MEDICAL CENTER MEDICAL GRAND ROUNDS

OBJECTIVES: To present a case of acute myocardial infarction in the young. To discuss the etiology, approach, management to the young patient with myocardial infarction

GENERAL DATA: W.V. 35 YEAR OLD MALE FILIPINO MARRIED

CHIEF COMPLAINT CHEST PAIN

HISTORY OF PRESENT ILLNESS: One week PTA (+) CHEST PAIN on the anterior chest well described as heaviness with no radiation (+) Self medicated with Aspirin with relief of sxs Few Hours PTA (+) While watching television, Recurrence of CHEST PAIN on the left anterior chest wall described as heaviness with radiation to the back. Persisting for more than thirty minutes Severity of pain 10/10 (+) Difficulty in breathing

PAST MEDICAL HISTORY: CVD May 2008 (2 weeks PTA )with right sided residuals, medications prescribed but not taken (-) DM (-) HTN (-) allergies (-) CA

Personal Social History Family History Hypertension both sides (-) DM, (-) Cancer, (-) Thrombosis, (-) early stroke or MI Personal Social History 25 pack year smoking history Occasional alcoholic beverage drinker Denies history of drug intake or stimulants

REVIEW OF SYSTEMS (-) headache, (-) loss of consciousness (-)easy bruisability (-) rashes (-) easy fatigability, (-) palpitations, (-) abdominal pain (-) diarrhea no constipation (-) edema (-) rashes (-) caudication (-) arthralgia, (-) limitation of motion

Physical Examination on Admission Bp 130/80 HR 106 RR 24 Temp 37.5 W.T. 55 kg H.T. 163cm BMI 20 JVP 8-9 Conscious coherent in cardio-pulmonary distress Anicteric sclerae, pink palpebral conjunctivae no carotid bruits no neck vein distention no CLAD Equal chest expansion, No retractions, Equal fremitus clear breath sounds

Physical Examination on Admission Adynamic precordium tachycardic regular rhythm no murmurs distinct S1& S2 no S3 noted Flat soft non-tender abdomen Full and equal pulses no edema no cyanosis Neuro-examination =shallow nasolabial fold ®, 5/5 motor function on all extremities no sensory deficit

SALIENT FEATURES 35 year old male chest tightness of more than 30 minutes duration Diaphoresis CVD 2 weeks PTA Smoker 25 pack years Bp 130/80 HR 106 RR 24 Equal chest expansion Tachycardic Equal Pulses Shallow nasolabial fold R

AT THE EMERGENCY ROOM 12 Lead ECG, Chest x ray, serum electrolytes cardiac enzymes, CBC Urinalysis Nitroglycerine ISDN drip Enoxaparin Morphine ASA/ Clopidogrel 02 via nasal cannula Diazepam

WORKING DIAGNOSIS S-T elevation Myocardial Infarction Anterolateral Wall S/P Cerbrovascular Disease To consider Hypercoagulable State

Admitted under Cardiology Service Immediately Referred Patient to interventional cardiology for Primary PTCA Neuro Referral Recommendations: CT Scan CVD Infarct noted

REPERFUSION STEMI px presenting to hospital with PCI capability should treat with primary PCI within 90 mins of medical contact Intervention AHA 2007 STEMI ( MODIFIED RECOMMENDATION)CLASS, ASSENT-4 PCI

CATH LAB REPORT OF CORONARY ANGIO AND PCI Emergency left heart catherization with coronary angiography and percutaneous coronary intervention/stenting of left main coronary artery were done by percutaneous seldinger technique using 6f Judkins catheters via the right femoral artery with no difficulty or complications

Coronary Angiography: Totally occluded Left Main Segment

CARDIAC CATHETERIZATION REPORT CORONARY ANGIOGRAPHY: Selective cannulation of the LCA with a 6F JL4 catheter shows a TOTALLY OCCLUDED LEFT MAIN SEGMENT. Selective cannulation of the RCA with a 6F JR4 cathter shows a very large and dominant vessel with two large patent posterior descending branches. PROCEDURE: Emergency left heart catheterization with coronary angiography and percutaneous coronary intervention/ stenting of left main coronary artery were done by percutaneous Seldinger technique using 6F Judkins catheter via the right femoral artery with no difficulty or complications. The patient tolerated the procedure well (IABP was on standby). CATHETERS USED: 6 F JL4 AND JR4 Cordis diagnostic catheters 6F XB 3.5 Cordis Vistabrite tip guide catheter CONTRAST USED: 130 ML Ultravist 370

PCI A 6F XB 3.5 Cordis Vistabrite tip guiding catheter was used to engage the left main. A 0.014” x 180 cm Cordis Supersoft Stabilitzer wire was used to cross the lesion and positioned into the distal LAD. A 2.0 (15 mm length) Terumo Ryujin rapid exchange balloon was then advanced across the lesion and then inflated at 12 atm for 23 seconds. A second balloon 3.0 x 15 mm Sprinter was used to further dilate the lesion at 12-14 atm for 11-33 seconds. Post balloon angiogram showed a residual stenosis of 40 – 50%. A Taxus 3.5 x 20 mm stent was then advanced across the lesion and deployed at 8 atm for 36 seconds. The delivery balloon was re-inflated at 14 atm for 13 seconds. Post-stent angiogram of the left main LAD showed no significant residual stenosis at the lesion site with TIMI-2 antegrade distal flow, no contrast staining and no loss of side branches. No significant change in the post-stenting angiographic results occurred after an observation period of 5 – 7 minutes. The procedure was terminated with the patient in stable condition.

CARDIAC CATHETERIZATION REPORT BALLOON INFLATION Lesion dilated: Left main-proximal LAD SITE Balloon/ Stent Size Duration (sec) Pressure (atm) Left Main LAD Ryujin balloon 2.0 x 15 mm 23 12 Sprinter balloon 3.0 x 15 mm 11 33 14 Taxus stent 3.5 x 20 mm 36 8 Delivery balloon 13

PTCA CONCLUSION Successful Primary PCI/stent deployment of the Left Main - LAD

Total Occlusion of Left Main Coronary Artery Rare occurrence with 2.6% frequency in one study Generally presents as pulmonary edema, cardiogenic shock, or sudden death PTCA feasible and effective procedure Effect of Primary Angioplasty on Total or Subtotal Left Main Occlusion Analysis of Incidence, Clinical Features, Outcomes, and Prognostic Determinants Hon-Kan Yip, MD; Chiung-Jen Wu, MD; Mien-Cheng Chen, MD; Hsueh-Wen Chang, PhD; Kelvin Yuan-Kai Hsieh, MD; Chi-Ling Hang, MD and Morgan Fu, MD

POST PTCA 30 minutes Post PTCA Patient had episodes of desaturation O2 inhalation increased to fio2 100 % (02 sat 80-90%) Patient intubated Pulmo referral done CXR post intubation revealed pulmonary congestion/ pulmonary edema ABG done

CHEST X-RAY (POST INTUBATION) BASELINE CXRAY CXRAY AFTER < 6 HOURS

AT THE TELEMETRY Episodes of non-sustained ventricular tachycardia Patient started on AMIODARONE for Post PTCA arrythmia INITIAL LOADING DOSE (150 mg) MAINTENANCE DRIP (900 mg x 24 hours) Patient admitted to Telemetry Unit Referral to Nephrology Service for renal prophylaxsis and decreased urine output CT angiography with renal prophylaxis done D-dimer 642.60 ng/ ml (<500 ng/ ml)

2D ECHOCARDIOGRAM (06/03/08) Concentric left ventricular hypertrophy with hypokinetic anterior interventricular septum, anterior and lateral left ventricle from mid to apex. Left ventricular ejection fraction is reduced, 56% (Teicholz) / 52 % (Simpson’s). Normal left atrial dimension. Normal right atrial and ventricular dimensions. Normal main pulmonary artery diameter. Normal diameter of aortic root and proximal ascending aorta (2.5 cm). Thickened margins of right and non-coronary cusps of aortic valve leaflets with normal mobility pattern. Normal mitral, tricuspid and pulmonic valves. Color Flow and Doppler study: Mitral regurgitation, mild. Tricuspid regurgitation, mild. Normal pulmonary artery pressure (by pulmonary acceleration time >110 msec). Normal left ventricular diastolic function indices (E/A ratio = 1.3; IVRT = 80 msec)

CT ANGIOGRAPHY 6/3/08 Bilateral marked pneumonic consolidation in both lower lobes as well as in the upper lung regions Normal Ct angiography of the pulmonary vessels including the thoracic aorta No evident pulmonary embolism

ECG POST PTCA 6/3/08 (1030H) ST Elevation Myocardial Infarction anterolateral wall elevation 6/3/08( 1330H) Acute St Elevation Myocardial Infarction MI 6/4/08 antero-septal wall myocardial infarction with reciprocal changes in the inferior leads

2020H non-sustained v-tach Magnesium Sulfate 4 gram in 50ml D5w x 30min Dopamine inotropic support

First Hospital Day Coffee ground/per NGT Enoxaparine discontinued Repeat Cardiac Enzymes Diagnostic Test Hypercoagulable Work-up Medications Dopamine / Dobutamine Furosemide 40mg Piperacillin Tazobactam Metoprolol Nicorandil

ECG on 1st HD

2nd HD Episodes of hypotension Bilateral Rales (base-mid) CXR increased congestion Episodes of Chest Pain Treatment Dopamine /Dobutamine Furosemide Increased NTG patch transfer of patient to ICU was done.

Continuous titration of Dopamine/ Dobutamine 3rd HD Episodes of Hypotension Persistence of pulmonary congestion Electrolyte abnormalities Continuous titration of Dopamine/ Dobutamine Increased Furosemide Correction with KCL

4th HD Repeat 2d Echo (6/7/08) Concentric left ventricular hypertrophy with segmental wall motion abnormality over left anterior descending artery distribution with preserved global systolic function, EF 59% Dilated aortic root aortic sclerosis, MR moderate, TR mild Improvement of thickening of anterior and lateral wall compared to (6/3/08)

6th HD Weaning Started via SIMV IV amiodarone shifted to Oral Tapering of Pressors Started CXR showed clearing of pulmonary congestion

7th HD Patient extubated NGT removed Clear liquid diet with 1.2L/day Tapering of Dobutamine Started

On the 10th HD Normal CXR Dobutamine tapered off Anti-Cardiolipin Results Warfarin 5mg initially Warfarin 2.5mg OD

On the 24th HD Discharged Stable and Improved Home Medications ASA 80 mg tablet 1 tablet daily Clopidogrel 75 mg tablet 1 tablet daily Nicorandil 10 mg tablet ½ tablet 2x a day Amiodarone 200 mg tablet 1 tablet 2x a day Cilostazol 100 mg tablet 1 tablet 2x a day Metoprolol 50 mg tablet ½ tablet 2x a day Atorvastatin 40 mg tablet 1 tablet once a day Warfarin (Coumadin) 5 mg tablet T – Th 2.5 mg tablet M W F ST SU

DISCHARGE DIAGNOSIS: Myocardial Infarction Left Main Segment KILLIP III Pulmonary Congestion S/P CVD Lacunar Infarct LMCA (May 2008) S/P PTCA (6/3/08) T/Connective Tissue Disease Anti-phospholipid Antibody Syndrome Suspect

DISCUSSION

DEFINITION Myocardial infarction (MI) is the irreversible necrosis of heart muscle secondary to prolonged ischemia. Detection of rise/fall of cardiac biomarkers together with evidence of myocardial ischemia with at least one Symptoms of ischemia ECG changes Pathologic Q waves in ECG Evidence of loss of viable myocardium or wall motion

Epidemiology Myocardial infarction (MI) under the age of 40 years accounts for around 3%-10% of cases of coronary artery disease. Incidence of MI is approximately 8 times lower in patients 18 to 45 years than in older patients

Clinical Presentation -Angina progressing rapidly to fully evolved myocardial infarction -Symptoms present less than 1 week duration -Rarely presents with classic presentation of worsening angina culminating in MI

Causes of MI the Young

Causes of MI in the Young Cocaine Abuse Atheromatous Coronary Artery Disease Coronary Artery Dissection/ Aneurysm Kawasaki’s, Takayasus Hypercoagulable State Anti-phospolipid Antibody Syndrome (primary/secondary) Factor V Leiden

Atheromatous Coronary Artery Disease 80% of acute myocardial infarction in the young The atheromatous process starts early CHD was found in 20% of men and 8% of women between the ages of 30 and 34 years of age Rom J Intern Med, January 2006 Ginghin et al

Non-Atheromatous Coronary Artery Disease Aortic Dissection Aneurysms, ectasia, and anomalous origin of coronary arteries Coronary artery aneurysms congenital or acquired secondary to Kawasaki’s disease in childhood

MI with Normal Coronary Arteries 1-12% occurence based on Coronary Angiography Typical patient is young, without any previous history of chest pain Mean age at largest series of MI in patients with normal coronary arteries patients, was 43 years and 43% were women. significantly less frequent angina prior to myocardial infarction. cardiovascular risk profile is lower than that of patients with CAD, Coronary Artery Spasm Hypercoagulable States Embolic Phenomena Embolic phenomena Paroxidical Phenomena Characteristics and Prognosis of Myocardial Infarction in Patients With Normal Coronary Arteries from CHESTPeter Ammann, MD; Sabine Marschall, MD; Martin Kraus, MD; Lucius Schmid, MD; Walter Angehrn, MD; Reto Krapf, MD and Hans Rickli, MD

MI related to substance Abuse Cocaine use is associated with various cardiac complications including MI. 48% of non-traumatic chest pain in the young associated with cocaine use 6% MI at ER. after various complications after cocaine use. Cardiovascular Complications of Cocaine Use Richard A. Lange, M.D., and L. David Hillis, M.D.

Hypercoagulable States PRIMARY SECONDARY Antithrombin deficiency Antiphospholipid syndrome Protein C deficiency Factor V Leiden Disorders of the fibrinolytic system Hypoplasminogenemia Abnormal plasminogen Plasminogen activator deficiency Factor XII deficiency Dysfibrinogenemia Others: elevation of factor VIII Abnormalities of coagulation and fibrinolysis Trosseau syndrome Nephrotic syndrome Abnormalities of the blood vessels and flow Venous stasis Homocystinuria Thrombotic thrombocytopenic purpura Abnormalities of the platelets Myeloproliferative disorders Paroxysmal hemoglobinuria Diabetes mellitus

Clotting Cascade

Factor V Leiden (resistance to APC) Site Venous, occasional arterial, Dx -APC resistance assay aPTT with exogenous APC / aPTT without APC Normal > 2.2 -modified APC-resistance assay. -FV leiden DNA-based analysis by PCR : Loss of principal aPC cleavage site on factor V protein→ Resistance to inactivation of Factor Va by APC

Anti-phospholipid Antibody Syndrome Autoimmune thrombotic disease. It is characterized by recurrent arterial or venous thrombosis, recurrent fetal loss or in-utero death and/or thrombocytopenia CVD most frequent thromboembolic manifestations MI with normal coronary arteries presence of AAS among young patients with AMI ranges from 14% to 21%, Rev Clin Esp.  2001; 201(3):118-21 (ISSN: 0014-2565) Seijas M ; Martínez Vázquez C ; Rivera A ; Rayo N ; Ordi-Ros J ; Nodar A ; Picón J

DIAGNOSTIC CRITERIA FOR APAS International Consensus Statement on an update of the classification criteria for definite Antiphospholipid Syndrome 2006. Clinical Criteria Laboratory Criteria • Vascular thrombosis – one or more episodes of arterial, venous or small vessel thrombosis in any tissue or organ. (confirmed by imaging, Doppler studies or histopathology) • Recurrent pregnancy loss. • Anticardiolipin antibody of IgG and/or IgM isotype on two occasions at least 12 weeks apart. • Lupus anticoagulant in plasma on two occasions at least 12 weeks apart. * Anti b2 glycoprotein I Antibody of IgG or IgM isotype in serum or plasma present on two occasions at least 12 weeks apart

ANTIPHOSPHOLIPID ANTIBODY SYNDROME

ALGORITHMIC APPROACH TO APAS

Management of Acute Myocardial Infarction Reperfusion (minimize total ischemic time) Restoration of balance between O2 supply and demand Pain Relief Prevention of Compilations

GOLDEN PERIOD

MEDICAL MANAGEMENT ANALGESIA- MORPHINE ASPIRIN BETA BLOCKERS ACE INHIBITORS/ ARB THIENOPYRIDINES

REPERFUSION Primary Invasive Strategy Fibrinolytic Therapy Goal Door To balloon time 90 minutes May give >12 hours Patients with caridogenic shock Primary PTCA Facilitated PTCA Rescue PTCA Fibrinolytic Therapy Door to needle time 30minutes May give within 12 hours of onset of symptoms Contraindications Hemorrhage Intracranial mass/stroke AVM Active bleeding 2007 Focused Update of the ACC/AHA

SECONDARY PREVENTION CONTROL OF MODIFIABLE RISK FACTORS SMOKING CESSATION WEIGHT LOSS EXERCISE Lipid and Sugar Management Anti-coagulation for Hypercoagulable States

PROGNOSIS IN THE YOUNG Better outcomes during medium and short term follow-up due to better baseline characteristics but may have higher long term morbidity and mortality Greater influence of Modifiable Risk factors towards prognosis Increased prevalence of smoking, hypertension and obesity in the young Acute Myocardial Infarction in Young Adults from American Heart JournalElvis Brscic, MD, et al

MODIFIABLE RISK FACTORS Observed that smoking, obesity, and hypertension more prevalent in young, high-risk, post-MI patients dyslipidemia and diabetes were less prevalent. Smoking and hypertension were associated with a differentially increased relative risk of adverse outcomes in younger patients. need for aggressive efforts at minimizing modifiable risk factors in young patients at risk for and after MI. High-risk Myocardial Infarction in the Young: The VALsartan In Acute myocardial iNfarcTion (VALIANT) Trial

APAS TREATMENT PROPHYLAXIS PREVENTION OF FURTHER THROMBOSES OF LARGE VESSELS Low dose Aspirin 80 mg tablet 1 tablet once a day Hydroxychoroquine (reported to decrease the titers of APLAS) According to American College of Chest Physicians  Low Molecular Weight Heparin followed by Oral anticoagulants (Warfarin) to maintain INR of at least 2.5 for 12 months or longer

RECOMMENDATIONS REPEAT ANTI-Cardiolipin Anti-body testing after 12 weeks Continue Clopidogrel and ASA for at least 14 days Rheumatology Follow-up Ant-coagulation

Thank You

ECG on admission

CXR On admission

Admission 17.0 47.9 17.17 3.3 COMPLETE BLOOD COUNT HB HCT RBC WBC LYMPH SEG PLT 17.0 47.9 6.0 17.17 70 20 286,000 Na K CREAT TROP I TCPK CPKMB CBG 140.0 3.3 1.0 0.0 64.0 0.6 162.0 PROTIME: 109.9% activity, 0.9 INR PTT: Patient 28.2 (25.1 – 33.9 sec) Control 29.1 seconds

ABG POST INTUBATION PO2 60.3 HCO3 21.6 PH 7.46 02 SAT 92 PCO2 26.4 BE -3.6 FIO2 100 PEEP MODE AC

DAY 2 Na K BUN CREAT CPKMB Mg 138.0 3.5 21.0 1.2 1123.2 1.9 HB HCT RBC WBC SEG LYMPH MONO PLTS 15.10 43.10 5.42 22.27 78 10 12 221,000

URINALYSIS COLOR YELLOW TRANSPARENCY HAZY PH 7.5 GRAVITY 1.01 PROTIEN NEGATIVE KETONES NITRITES ESTERASE BLOOD 3 RBC 255 EPITHELIAL 1 WBC 2 BACTERIA

HYPERCOAGULABLE Work up ANTI-CARDIOLIPIN IgG ANTI-CARDIOLIPIN IgM HOMOCYSTIENE 12.5 (5-15) Protein c 4.59 (4.62-4.94) Protein s 17 (13.5-24.1)

Hypercoagulable Work-Up Functional assay for antihrombin III, C , S Lupus anticoagulant Plasma homocysteine Antiphospholipid antibodies Clotting assay activated protein C resistance Factor V Leiden Prothrombin gene mutation

WORK-UP Anti-Cardiolipin Ig G 3 mpl(<15) Anti-Cardiolipin Ig M 6/16/08 ESR 43 ANA Negative CRP negative

Chest X-ray 6/3/08 normal 6/3/08 (post intubation) prominent pulmonary vasculature with pulmonary congestion E.T. 2 cm above the carina 6/5/08 progression of pulmonary congestion, still with pulmonary edema 6/9/08 complete clearing of pulmonary congestion

Diagnostics 6/3/2008 6/3/2008 6/4/2008 1250H 1646H D-dimer 642.6 6/3/2008 6/3/2008 6/4/2008 1250H 1646H D-dimer 642.6 CPK 0.6 1100 1123.2 cpkmb 64 18620 9810 trop I 0

ALGORITHMIC APPROACH TO APAS

ECG 6/3/08 (1030H) ST Elevation Myocardial Infarction anterolateral wall elevation 6/3/08( 1330H) Acute St Elevation Myocardial Infarction MI 6/4/08 antero-septal wall myocardial infarction with reciprocal changes in the inferior leads

Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report. Lupus.  2003; 12(7):518-23 (ISSN: 0961-2033) Lockshin M ; Tenedios F ; Petri M ; McCarty G ; Forastiero R ; Krilis S ; Tincani A ; Erkan D ; Khamashta MA ; Shoenfeld Y Hospital for Special Surgery, Barbara Volcker Center for Women and Rheumatic Diseases, New York, NY 10021, USA. LockshinM@hss.edu RECOMMENDATIONS: Valve abnormalities: anticoagulation is recommended for symptomatic patients with valvulopathy. Prophylactic antiplatelet therapy may be appropriate for asymptomatic patients (recommended by 13/17 experts in an independent review). Committee members disagreed whether corticosteroid therapy is helpful, but agree that distinguishing among presumptive valvulitis (valve thickening on echocardiogram), valve deformity and vegetations is important, as treatment implications may differ. Occlusive arterial disease (angina, myocardial infarction): the Committee recommends aggressive treatment of all risk factors for atherosclerosis (hypertension, hypercholesterolaemia, smoking) and liberal use of folic acid, B vitamins and cholesterol-lowering drugs (preferably statins). Hydroxychloroquine for cardiac protection in APS patients may be considered. The Committee also recommends warfarin anticoagulation for those who have suffered thrombosis in the absence of atherosclerosis, but recognizes that developing data may support the use of antiplatelet agents instead. Intracardiac thrombi: the Committee recommends intensive warfarin anticoagulation, and consultation with cardiac surgeons when appropriate. Ventricular dysfunction:

Summary The objective of this study was to highlight the need for investigation of antiphospholipid (aPL) antibodies in patients presenting with myocardial infarction (MI) and normal coronary arteries at angiography. We present five patients who were found to have had an MI without evidence of atherosclerosis. All had aPL antibodies and thus fulfilled the diagnosis of antiphospholipid syndrome (APS). Who did not have recurrent events on long-term anticoagulation maintaining an international normalised ratio of 3–4. This study suggests that APS is probably a major cause of MI in those with normal coronary arteries at angiography. It is an important diagnosis to make as they do not require anti-atherosclerotic treatment but appear, from this case series, to do well on high-dose warfarin. Further clinical studies are necessary to look at prevalence and best management in these patients.

Ct scan 6/3/08 Suggestive lacunar infarct in the left temporo-parietal subcortical area Unremarkable Ct scan examination of the rest of the brain

BETA-BLOCKER Oral B-blockers should be given in the first 24 hours IV B-blockers may be given at time of presentation Contraindications 1) signs of heart failure, 2) evidence of a low output state, 3) increased risk* for cardiogenic shock, 4) relative contraindications to beta blockade (Level of Evidence: B) 2007 AHA STEMI (MODIFIED RECOMMENDATION) CLASS I

Clopidogrel recommended to administer loading dosse of Clopidogrel 300mg Clopidogrel 75 mg daily + ASA in STEMI px regardless of whether they undergo reperfusion with fibrinolytic therapy (at least 14 day Long term maintenance therapy with clopidogrel 75mg daily is reasonable for STEMI patient

Lipid Control HDL >50 in females > 40 in males LDL 100> in non diabetics, 70>in diabetics and high risk patients Increase Omega 3 intake Promotion of daily physical activity High Serum Cholesteryl Ester Transfer Rates and Small High-Density Lipoproteins Are Associated With Young Age in Patients With Acute Myocardial Infarction

Kawasaki generalized vasculitis of unknown etiology vasculitis is most severe in medium-sized arteries but can also occur in veins, capillaries, small arterioles, and larger arteries. In severely affected vessels, the media develops inflammation with necrosis of smooth muscle cells. leading to aneurysms. Vessel wall becomes narrowed or occluded due to stenosis or a thrombus. Cardiovascular death usually occurs from a MI secondary to thrombosis of a coronary aneurysm or from rupture of a large coronary aneurysm

Takayasu’s Disease chronic, progressive, inflammatory, occlusive disease of the aorta and its branches Takayasu arteritis is heterogeneous. Most patients present with systemic and vascular symptoms; erythrocyte sedimentation rate is elevated in most Classification criteria (3 of 6 criteria are necessary), a Age of 40 years or younger at disease onset Claudication of the extremities Decreased pulsation of one or both brachial arteries Difference of at least 10 mm Hg in systolic blood pressure between arms Bruit over one or both subclavian arteries or the abdominal aorta Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the upper or lower extremities

6/3/08 1125.9 6/4/08 1073.5 6/5/08 -253 6/6/08 -350 6/7/08 -390 6/8/09 -150 40mg q12 40mg q 12 40mg q 6 40mg/od

Figure 1. The Clotting Cascade. Coagulation is initiated by the exposure of blood to tissue factor bound to cell membranes. Tissue factor interacts with factor VIIa to convert factor IX to factor IXa and factor X to factor Xa (only the activated forms are shown). Factor IXa converts factor X to factor Xa. Factor Xa generates factor IIa (thrombin) from factor II (prothrombin). Each of these reactions takes place on an activated cell surface. Once factor IIa is generated, it cleaves plasma fibrinogen to generate fibrin. The tissue-factor-pathway inhibitor forms a quaternary structure with tissue factor, factor VIIa, and factor Xa (shown in blue). The thrombomodulin–protein C–protein S pathway (shown in yellow) inactivates factors Va and VIIIa. Antithrombin III inactivates factors XIa, IXa, Xa, and IIa (shown in orange) in a reaction that is accelerated by the presence of heparan sulfate. In the fibrinolytic pathway, tissue- type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) convert plasminogen to plasmin. Once generated, plasmin proteolytically degrades fibrin (