Download Primer Perkütan Koroner Işlem Sonrasında Clopidogrel Kullanımına

Primer Perkütan Koroner Işlem Sonrasında Clopidogrel Kullanımına Bağlı Diffüz Alveoler
Hemoraji
Adnan Kaya, Sami Ilhan, Mustafa Adem Tatlisu, Bayram Koroglu, Ahmet Oz
Dr. Siyami Ersek Göğüs Kalp ve Damar Cerrahisi Eğitim ve Araştırma Hastanesi, İstanbul, Türkiye
Antitrombotik ilaçlar stabil anjina pektoris ve akut koroner sendrom (Kararsız angina pektoris, ST
segment yükselmesiz MI, ST segment yükselmeli MI) ile başvuran hastalar için olmazsa olmaz ve en
uygun ilaç tedavisidir. Antiplatelet ve antikoagülan ilaçlar, akut koroner sendromda (AKS) ölüm ve
transmural miyokard infarktüsü insidansını azalttı.
Bu ilaçların trombüs oluşumunu engelleme ve trombositleri inhibe etme mekanizması ile benzer
şekilde kanama riskini artırırlar. Burada göğüs ağrısı ile kliniğimize başvuran ve anterior miyokard
infarktüsü tanısı konulan bir olgu sunulmuştur. Hastaya rutin klopidogrel 600 mg ve asetilsalisilic asit
300 mg oral başalndıktan sonra LAD’ye predilatasyon ve stent implantasyonu uygulandı. Klopidogrel
alınmasından iki saat sonra koroner yoğun bakım ünitesindeki takibinde kanlı balgam ve nefes darlığı
gelişti. Toraks yüksek rezonans bilgisayarlı tomografide diffüz alveoler hemoraji saptandı ve
klopidogrel kesildi. Klopidogrele bağlı diffüz alveoler hemoraji çok nadir görülen bir komplikasyon
olamakla birlikte bu ilacın ne kadar sıklıkta kullanıldığı düşünülürse tanı ve tedavinin önemi ortaya
çıkar.
Anahtar Kelimeler: Akut anteriyor myokard infarktüsü, klopidogrel kullanımı, diffüz alveolar hemoraji
Diffuse Alveolar Hemorrhagea Due to Clopidogrel Use in A Patient Who Has Undergone
Primary Percutaneouse Intervention
Adnan Kaya, Sami Ilhan, Mustafa Adem Tatlisu, Bayram Koroglu, Ahmet Oz
Dr. Siyami Ersek Cardiovascular Surgery Hospital, Istanbul, Turkey
Antithrombotic drugs are inevitable and most suitable drug therapy for the patients presenting with
stable angina pectoris and acute coronary syndromes (Unstable angina pectoris, Non-ST segment
elevation MI, ST segment elevation MI). Antiplatelet and anticoagulant drugs has reduced the
incidence of death and transmural myocardial infarction in acute coronary syndromes (ACS). Besides
their favorable effect to inhibit thrombus formation, platelet inhibition in ACS by the same mechanism
they increase bleeding risk. Here we present a case admitted to our institution with chest pain and in
whom anterior myocardial infarction was diagnosed. After routine antiplatelet therapy with asetilsalisilic
asit 300 mg per oral and clopidogrel 600 mg per oral the patient has undergone primary percutaneuse
intervention which ended with predilatation and stent implantation of LAD. After two hour of ingestion
clopidogrel the patient presented with bloody sputum and dyspnea in coronary care unit just after the
intervention. Thorax high resonance computerized tomography (HRCT) revealed diffuse alveolar
hemorrhagea in the case and clopidogrel stopped. Diffuse alveolar hemorrhagea due to clopidogrel is
a very rare major complication and as we take into consideration how commonly it is used, diagnosis
and management of this complication is crucial.
Key words: Acute anterior Myocard Infarction, Clopidogrel Use, Diffuse alveolar Hemorrhagea,
Complication
Introduction
The treatment combination of clopidogrel and aspirin reduces systemic ischemic events after
percutaneous coronary intervention (PCI) in high risk patients (1-2). Additional anti trombotic drugs like
GPIIb/IIIa inhibitors increase risk of minor and major bleeding as a side effect. Gastrointestinal
bleeding is especially showed in GPIIb/IIIa inhibitors as a major bleeding complication. Here we
discuss a patient who had a diffuse alveolar hemorrhage after primary percutaneous intervention
which was attributed to clopidogrel.
Case Report
A 56-year-old male was referred to our tertiary cardiovascular and thoracic surgery center from an
emergency department of general hospital. On his arrival he had a strong retrosternal chest pain
which was radiating to left shoulder and both arms. In his medical history, he had HT treated with
angiotensin receptor blockers, DM treated with subcutaneous insuline injections. In 2005 he had been
amputated on his right foot under the knee because of diabetic foot. From this date asetilsalisilicasit
100 mg per orally once a day has started because of risk factors of coronary artery disease and
peripheral artery disease. In his physical examination blood pressure was 137/89 mmHg, heart rate
was 76 bpm, body temperature 37.1C and respiratory rate was 14/minute. Hemoglobin was 14.8 g/dL,
white blood cell count was 15.300/mm3 and platelets were 290.000 /mm3. Creatinine kinase
myocardial band(CK-MB) and troponin were positive. The electrocardiography revealed acute anterior
myocardial infarction with ST segment elevation from V1 to V4 in precordial leads. As soon as the
patient loaded with 600 mg clopidogrel and chewable aspirin 300 mg a diagnostic coronary
angiography was made. The coronary angiography revealed total occlusion of proximal LAD with no
antegrade and retrograde blood flow, a critical stenosis of distal right coronary artery( RCA) and
proximal and mid significant stenosis of circumflex artery. Percutaneous coronary intervention planned
to total occlusion of proximal LAD. After administration of 5,000 units of heparin the lesion passed
with wire and predilatation with 2x20 mm size balloon (Invader, Alvimedica) was made. A bare metal
stent of size 3X24 mm (Ephesos, Alvimedica) was implanted. LAD distal blood flow was TIMI-3 and
the intervention ended. The patient admitted to intensive coronary care unit after PCI which took one
hour with good hemodynamic parameters of 130/70 mmHg blood pressure and 73 bpm heart rate.
One hour later we were alerted by the nurses that the oxigen saturation of patient’s has dropped 72 %
by pulse oximetry and the patient started to cough. Rales in both lower segments of lungs were
present in physical examination. Bloody sputum was observed and arterial blood gas confirmed
decreased oxigen saturation to 70 %. The patients activated clotting time (ACT) was 227 seconds in
intervention room and was 201 seconds after bloody cough. Immediate chest X-ray at bed side
showed pulmonary edema like infiltration of both mid and basal segment of lungs. The patient took
ortopnea position in bed despite the right femoral sheath. 2D echocardiography at bed side showed
decreased ventricular performance (EF) to 30% with anterior and anteroseptal hypokinesia. Ruling out
acute mitral regurgitation and papillary muscular rupture, continuous positive air pressure (CPAP)
started and consultation of chest disease is demanded. 40 mg furosemide intravenous administered .
After 45 minutes on CPAP therapy finally the oxigen saturation of the patient increased to 86% which
was enough to transfer the patient to reveal computerized tomography of thorax which was ordered by
the consultant of chest disease. Thorax high resonance computerized tomography (HRCT)
demonstrated ARDS like bilateral ground glass opacities of lungs (Figure-1,2). Careful investigation of
CT revealed ground glass opacities of lungs were accumulated in the posterior sides of the lungs
(Figure-3) which was appropriate with the lying position of the patient. For the first time diffuse
alveolar hemorrhage was taught to be cause of the clinical compromise of the patient. Repeated
complete blood count (CBC) and activated clotting time testes were done. Hemoglobin dropped from
14.8 gr/dL to 11.1 gr/d L and the maximal ACT was 227 seconds which were obtained in the catheter
laboratory. Bronchoscopic examination showed clots and blood in the trachea and bronchial tree
without active bleeding which was conformation of diagnosis of diffuse alveolar hemorrhage one day
later. Clopidogrel was stopped as an etiologic agent of this complication. We followed up the patient
one week under aspirin and low molecular weight heparin (LMWH) without any more complication.
The patient was transferred to cardiovascular surgery for revascularization of CX and RCA.
Discussion
Diffuse alveolar hemorrhage is an active bleeding into the alveolar space. It is usually associated with
connective tissue disorders like microscopic poliangitis, Goodpasture’s syndrome, antiphospholipid
antibody syndrome, Wegener’s disease where the working mechanism of bleeding is injured vessel
walls due to immune reactions.
Diffuse alveolar hemorrhage which is associated to antithrombotic drugs is not common. As the
current guidelines suggest combination of different antithrombotic drugs in treatment of thrombosis for
their additive effect bleeding as a side effect become obvious.
Clopidogrel and glycoprotein IIb/IIIa inhibitors are recommended in the treatment of patients with
unstable angina pectoris and NSTEMI(3) and current treatment guidelines for ST elevation myocardial
infarction recommend that clopidogrel should be given for at least 12 months(4). DAH commonly
described in patients under glycoprotein IIb/IIIa inhibitors therapy. A study conducted by Ali et al (5)
found out the prevalence of pulmonary hemorrhage 0.5% for eptifibatide, 0.7% for abciximab, and
0.9% for tirofiban. Only 10 of the 5,382 patients (0.19%) who received abciximab in four clinical trials
developed pulmonary hemorrhage (6). Ikeda et al (7) reported a case of DAH after coronary stent
implantation in ST elevation myocardial infarction with aspirin and ticlopidine therapy and Kilaru et al
(8) reported the first case of DAH after placement of a coronary stent with clopidogrel therapy. When
the clinical situation of patient raises doubt of DAH conformation of the diagnosis with adjunct
laboratory tests and imagining must be done as soon as possible. Contrast enhanced chest CT scan
and bronchoscopic examination of air ways are preferred tools for diagnosis.
Here we present a case admitted to our institution with anterior myocardial infarction and in whom
DAH was diagnosed after two hours of 600 mg of clopidogrel ingestion. Here in this case this side
effect was attributed to clopidogrel because the patient was already taking aspirin and the activated
clotting time (ACT) was in normal therapeutic range. Yet the time interval from ingestion to bleeding
also is suggestive for clopidogrel associated DAH. This must be third case report of DAH associated
with clopidogrel use after Kilaru et al (8) and Kim et al(9) in the literature.
Conclusion
Diffuse alveolar hemorrhage (DAH) is a mortal bleeding complication of antithrombotic drugs if
misdiagnosed. Clinical findings like compromise in hemodynamic, dyspnea, arterial oxigen saturation
drop, hemoptysis, infiltration in chest X-ray, ARDS like chest CT findings, un explained hemoglobin
drop, utilization of antithrombositer or anticoagulant drugs may help making diagnose of DAH. DAH
as a complication of clopidogrel use is very rare to be found. If DAH is occurred, discontinuance of
causative drug is advised.
Acknowledgements
None
References
1. Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with
clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable
angina to prevent Recurrent Events (CURE) study. Circulation 2003;108: 1682-7.
2. Mehta SR, Tanguay JF, Eikelboom JW, et al. Double-dose versus standard- dose clopidogrel and
high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for
acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet 2010;376:123343.
3. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guidelines for the management of patients
with unstable angina and non-ST-segment elevation myocardial infarction. A report of the American
College of Cardiology/ American Heart Association task force on practice guidelines. J Am CollCardiol
2000;36:970–1062.
4. Kushner FG, Hand M, Smith SC Jr, et al. 2009 focused updates: ACC/ AHA guidelines for the
management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and
2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention
(updating the 2005 guideline and 2007 focused update) a report of the American College of
Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll
Cardiol 2009;54:2205-41.
5. Ali A, Hashem M, Rosman HS, Kazmouz G, Gardin JM, Schrieber TL. Use of platelet glycoprotein
IIb/IIIa inhibitors and spontaneous pulmonary hemorrhage. J Invasive Cardiol
2003;15(4):186-8.
6. Cohen SA, Effron MB. Abciximab and alveolar hemorrhage. N Engl J Med 1998;339:1861-1863
7. Ikeda M, Tanaka H, Sadamatsu K. Diffuse alveolar hemorrhage as a complication of dual
antiplatelet therapy for acute coronary syndrome. Cardiovasc Revasc Med 2011;12:407 11.
8. Kilaru PK, Schweiger MJ, Kozman HA, Weil TR. Diffuse alveolar hemorrhage after clopidogrel use.
J Invasive Cardiol 2001;13:535-7.
9. Kim, Y., Lim, J., Lim, J., Kim, S., Jung, T., & Choi, W. (2013). Pulmonary Alveolar Hemorrhage after
Clopidogrel Use for ST Elevation Myocardial Infarction. Korean Circulation Journal, 43(7), 497–499.
doi:10.4070/kcj.2013.43.7.497
Figure Legends
Figure-1; Coronal cut view of thorax contrast enhenced computerized thomogrphy showed diffuse ground
glass opacities of both lungs.
Figure-2; Transvers cut view of thorax contrast enhenced computerized thomography showed ground
glass opacities of posterior segment of lungs.
Figure-3; Sagittal cut view of thorax contrast enhenced computerized thomography showed ground glass
opacities of posterior segment of lungs.