ACTA MEDICO-BIOTECHNICA 2009; 3:??-?? 9 Pregledni ~lanek / Review Avtor / Author Erih Teti~kovi~, Marija Menih, Jožef Magdi~ Ustanova / Institute Department of Neurology, University Clinical Center Maribor, Maribor, Slovenia SPREMLJANJE PRETOKA V MOŽGANSKIH ARTERIJAH S TCD TCD MONITORING OF CEREBRAL BLOOD FLOW Članek prispel / Received 22.03.2009 Članek sprejet / Accepted 09.09.2009 Naslov za dopisovanje / Correspondence Simona Kirbi{, dr. med. Univerzitetni klini~ni center Maribor, Klinika za interno medi- cino, Odd. za intenzivno terapijo Ljubljanska 5, 2000 Maribor, Slovenija Telefon: 00386-2-3212471 Mobilni: 00386-40-339136 Fax: 00386-2-3312393 E-po{ta: simona.kirbis@gmail.com Abstract Platelet inhibition with aspirin and systemic anticoagulation with un- fractioned heparin to reduce the incidence of recurrent thrombosis after primary coronary intervention (PCI) has been the standard of care for patients with acute coronary syn- drome (ACS) with ST elevation for some time. Eptifibatide is the platelet membrane glycoprotein IIb/IIIa in- hibitor that is often used. Bleeding complications occur most often at sites of vascular access and are more common in elderly patients. Alveo- lar hemorrhage with hemoptysis is a rare complication. We describe the case of a 43-year old smoker with an ST elevation myocardial infarction admitted for PCI. He was treated with standard anticoagulation and dual antiplatelet therapy before ad- mission. Hemoptysis began approxi- mately five minutes after the intrac- oronary application of eptifibatide at the end of the procedure. Supportive Izvleček Z antiagregacijskim in antikoagulan- tnim zdravljenjem za~nemo pri bol- nikih z akutnim koronarnim sindro- mom (AKS) z elevacijo ST veznice že pred primarno koronarno inter- vencijo (PCI). Eptifibatid je zavira- lec glikoproteinskih receptorjev IIb/ IIIa na membrani trombocitov in ga pogosto uporabljamo skupaj s stan- dardnim heparinom za prepre~evanje tromboz po PCI. Krvavitve so zaplet po PCI in se najpogosteje pojavijo na vbodnem mestu in so pogostej{e pri starej{ih bolnikih. Alveolarna krva- vitev je redek zaplet po kombinira- nem zdravljenju z antiagregacijskimi in antikoagulantnimi zdravili. Opi- san bo primer 43-letnega kadilca, ki se je zdravil zaradi miokardnega infarkta z dvigom veznice ST. Pred primarno PCI je prejel standardni heparin in dvojno antiagregacijsko terapijo. Kak{nih 5 minut po intra- koronarni aplikaciji eptifibatida so se pojavile hemoptize. Potrebna je bila Ključne besede: alveolarna krvavitev, hemoptize, eptifibatide, miokardni infarkt, primarna koronarna intervencija, antiagregacijsko zdravljenje. Key words: hemoptysis, alveolar hemor- rhage, eptifibatide, myocardial infarction, primary coronary inter- vention, antiplatelet therapy Impr ssum Avtor / Author Kirbiš Simona, Sinkovič Andreja Us anova / Institute Un verzitetni klinični center Maribor, Klinika za interno medicino, Oddelek za intenzivno terapijo, Maribor, Slovenija University clinical center Maribor, Clinic for Internal Medicine, Department of intensive care unit, Maribor, Slovenia Alveolarna krvavitev kot zaplet po kombiniranem zdravljenju z antiagregacijski- mi in antikoagulantnimi zdravili pri primarni koronarni intervenciji pri bolniku z akutnim koronarnim sindromom z elevacijo ST veznice – prikaz primera Alveolar hemorrhage after treatment with combined antiplatelet and anticoagula- tion therapy before and during primary coronary intervention in acute coronary syndrome with ST elevation – a case report Poročilo o primeru / Case report 10 ACTA MEDICO-BIOTECHNICA 2009; 3:??-?? Poročilo o primeru / Case report IntroductIon Platelet inhibition with aspirin and systemic anti- coagulation with unfractioned heparin (UFH) to reduce the incidence of recurrent thrombosis af- ter primary coronary intervention (PCI) has been the standard of care for patients with acute coro- nary syndrome (ACS) with ST elevation for some time. Eptifibatide is a cyclic heptapeptide inhibi- tor of the platelet membrane GP IIb/IIIa receptor and reduces the incidence of recurrent thrombosis when administered at the time of PCI (2). How- ever, it increases the risk of bleeding complica- tions, particularly at vascular puncture sites but also in intracranial, gastrointestinal and retro- peritoneal sites (3,4,5). Very rarely, pulmonary alveolar hemorrhage (AH) can occur. We pres- ent a patient with pulmonary AH after the use of combined anticoagulant and antiplatelet therapy with eptifibatide, UHF, clopidogrel and aspirin. case report A 43-year old smoker was admitted to our Univer- sity Clinic from a regional hospital with symptoms and signs of anterior ST elevation myocardial in- farction. On admission, the platelet count and coagulation profile were within normal limits and he was normotensive and in Killip class I heart failure. Before admission he received oral clopi- dogrel (600 mg), aspirin (500 mg), sublingual ni- trate and standard heparin (5000 IE) i.v. After 45 minutes of transport to our cardiac catheterization laboratory, primary PCI was performed. Coronary angiography revealed an obstruction in the proxi- mal part of the left anterior descending (LAD) coronary artery. He had immediate balloon angio- plasty with bare metal stent implantation, result- ing in TIMI 3 flow. During the procedure intra- coronary boluses of eptifibatide (2 µg/kg/minute) were administered twice, after which he became hypotensive (blood pressure 80/60 mmHg) and treatment with adrenalin and dopamine (up to 8 µg/kg/minute) was needed to achieve normoten- sion. Approximately five minutes after the second intracoronary bolus ofeptifibatide[edit okay?] the patient started to cough uncontrollably and mas- sive hemoptysis followed. He was admitted to the intensive care unit (ICU) with a blood pressure of 120/55 mm Hg and heart rate of 70/minute. Con- tinuous electrocardiographic and SaO2 monitor- ing was commenced and central venous and ar- terial catheters were inserted to measure arterial and central venous pressure invasively. The pa- tient was dyspneic, pale, and hypoxic with SaO2 91% on 100% oxygen (pO2 /FiO2 112). Endotra- cheal intubation and mechanical ventilation were required due to severe respiratory failure. Emer- gency bronchoscopy revealed diffuse pulmonary AH. During the procedure, several blood clots were removed and the patient received 1700 mL of packed red blood cells and 625 mL of fresh fro- intubacija, mehani~na ventilacija, transfuzija koncentri- ranih eritrocitov in ukinitev vseh antikoagulantnih sred- stev. Alveolarna krvavitev je življenje ogrožujo~ zaplet po PCI in zahteva intenzivno in hitro zdravljenje. care including endotracheal intubation, mechanical ven- tilation, transfusion of packed red blood cells and rever- sal of all anticoagulation. Alveolar hemorrhage is life- threatening but adequate intensive supportive measures can be life-saving. ACTA MEDICO-BIOTECHNICA 2009; 3:??-?? 11 Poročilo o primeru / Case report zen plasma within the first hour. Antiplatelet and anticoagulation therapy was discontinued and he was treated with protamine sulphate (25 mg i.v.). Within the next few hours iv. dopamine was re- placed by noradrenaline (up to 10 µg/kg/min) to maintain normal blood pressure. The signs and symptoms of abundant AH ceased after 12 hours of treatment. To prevent in-stent thrombosis, clopidogrel was administered on the second day and aspirin was added 5 days after admission to ICU. On the 13th day the patient was transferred back to the regional hospital dIscussIon Major and minor bleeding events may complicate the periprocedural course of patients who undergo primary PCI for ST elevation MI and receive com- bined antiplatelet and anticoagulation therapy, in- cluding a GP IIb/IIIa inhibitor. The signs and symp- toms of pulmonary AH are nonspecific. Hemoptysis and/or hemoptoe (spitting blood), together with pulmonary infiltrates on chest radiograph (ure 1) and arterial hypoxia, can be the consequences of a broad spectrum of clinical conditions such as pulmo- nary infection, pulmonary edema, aspiration pneu- Figure 1. Pulmonary alveolar infiltrates on the chest radiograph in our 43 year old smoker with ST – segment elevation myocardial infarction. Those infiltrates represent alveolar hemorrhage after the combined treatment with clopidogrel Aspirin, Heparin and eptifibatide. 12 ACTA MEDICO-BIOTECHNICA 2009; 3:??-?? Poročilo o primeru / Case report after intense antiplatelet and anticoagulation thera- py are not completely understood. In almost all re- ported cases the patients were smokers or ex smokers or had chronic obstructive pulmonary disease. An- other important risk for AH was pulmonary edema with increased pulmonary wedge pressure. Concor- dant with this, our patient was an active smoker and had cardiogenic shock with pulmonary edema dur- ing the primary PCI. We cannot be certain whether eptifibatide was re- sponsible for the AH in this case or whether it re- sulted from the cumulative effect of the antiplatelet and anticoagulation therapy. However, AH began immediately after the intracoronary bolus of eptifi- batide, so we can assume that it was the proximate cause. Our conclusions are that AH is a rare but poten- tially fatal complication after primary PCI for ST elevation myocardial infarction when combined an- tiplatelet and antithrombotic therapy are adminis- tered. Emergent support of respiratory function with intubation and mechanical ventilation in addition to temporary cessation of antiplatelet and antico- agulation therapy saves lives. monia, endobronchial malignancy and pulmonary thromboembolism. Alternatively, bloody expecto- ration can also mimic acute upper gastrointestinal bleeding, which can be excluded only with oesoph- agogastroduodenoscopy. In our case the final iden- tification of the bleeding site was possible only after the patient was intubated and bronchoscopy was performed, with the subsequent removal of massive blood clots. The severe respiratory compromise with a pO2/FiO2 112 was due to the combined effect of AH and con- comitant heart failure due to cardiogenic pulmonary edema. As in almost all reported cases of AH after combined antiplatelet and anticoagulation treat- ment, we observed normal platelet counts on admis- sion and after the PCI (3,4,5). Iskander et al in their retrospective analysis reviewed the incidence and risk factors of AH in the setting of either eptifibatide or abciximab therapy and ob- served that for patients treated with GP IIb/IIIa in- hibitors the risk for AH was significantly increased in comparison to the control group, and that this was particularly noticeable for eptifibatide (6). However, additional individual risks factors for AH references Silber S, Albertsson P, Aviles FF, Camici PG, Co-1. lombo A, Hamm C et al. Guidelines for percutane- ous intervention. The task force for percutaneous coronary interventions of the European Society of Cardiology. Eur Heart J 2005; 26:804–47 Popma JJ, Ohman EM, Weitz J, Lincoff AM, Har-2. rington RA, Berger P. 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