Editorial

Acute Pulmonary Embolism

Don’t Ignore the Platelet
Piotr Sobieszczyk, MD; Michael C. Fishbein, MD; Samuel Z. Goldhaber, MD

A
cute pulmonary embolism (PE) tetap merupakan keadaan darurat kardiovaskular yang ditakuti dan sering terjadi, dengan perkiraan kejadian
tahunan hampir 200.000 kasus di Amerika Serikat saja.1Meskipun kemajuan terapi,2Pendaftaran Emboli Kooperatif Internasional dari 2454
pasien3melaporkan kematian semua penyebab 90 hari yang sangat tinggi sebesar 17,4%. Penyebab kematian pada 45% pasien adalah PE itu
sendiri. PE berulang, fatal atau nonfatal, terjadi pada 8% pasien dalam 90 hari. Jelas bahwa strategi farmakologi terapeutik baru dengan
agen yang aman dan mudah digunakan diperlukan untuk mengurangi hasil yang merugikan dari penyakit umum ini. Bukti klinis dan
eksperimental menunjukkan bahwa antiplatelet agen, biasanya diabaikan dalam pengobatan PE, dapat memenuhi peran ini dengan
mencegah inisiasi dan propagasi dari trombus vena dan dengan meminimalkan konsekuensi fisiologis
yang merugikan dari PE
secara tradisional dikaitkan dengan warna merah sel darah dan "gumpalan merah" yang kaya
fibrin, sedangkan trombus arteri yang melapisi lesi aterosklerotik kaya akan trombosit,
sehingga tampak seperti "gumpalan putih". Namun, analisis morfologis yang hati-hati dari
trombus yang terbentuk di pembuluh darah mengungkapkan untaian pucat yang kusut dari
agregat trombosit dan fibrin di dalam massa sel darah merah.4Trombosit vena yang
diinduksi secara eksperimental Dts. bus di hadapan trombosit radiolabeled menunjukkan
akumulasi trombosit awal di "kepala" dari trombus vena.5,6Seiring bertambahnya usia
trombus, perolehan trombosit melambat dan bekuan menjadi "merah", terutama terdiri dari
fibrin dan eritrosit

Tromboemboli vena mengaktifkan trombosit, menyebabkan pelepasan agen vasoaktif seperti

serotonin, adenosin difosfat, prostaglandin, dan tromboksan A2.7–9PE menyebabkan
peningkatan ekskresi tromboksan B melalui urin2, penanda aktivasi trombosit pada fase
awal pembentukan trombus.10 Respons fisiologis terhadap aktivasi trombosit meliputi
hipertensi pulmonal, bronkokonstriksi, dan kegagalan ventrikel kanan.11 Konsekuensi yang
merugikan ini dihasilkan dari pengurangan

cute pulmonary embolism (PE) remains a dreaded
and frequent cardiovascular emergency, with an ical obstruction and local pulmonary vasoconstriction due to
estimated annual incidence of almost 200 000 cases
in the United States alone.1 Despite therapeutic advances,2 the
International Cooperative Embolism Registry of 2454 pa-
PE
tients3 reported a surprisingly high 90-day all-cause mortality
of 17.4%. The cause of death in 45% of patients was PE itself.
Recurrent PE, fatal or nonfatal, occurred in 8% of patients
within 90 days. It is clear that a novel therapeutic pharmaco-
logical strategy with a safe and easy-to-administer agent is
needed to reduce adverse outcomes from this common illness.
Clinical and experimental evidence suggests that antiplatelet
blood flow through the pulmonary vasculature due to mechan-
platelet-mediated release of humoral substances. Aspirin is a
potent inhibitor of thromboxane A2 synthesis, and antiplatelet
agents may reduce the adverse physiological response to
caused by humoral mediators.
Experimental evidence supports adjunctive antiplatelet ther-
apy for the treatment of PE. Pretreatment of rabbits with aspirin
before experimentally induced PE reduced mortality and atten-
uated tachycardia, pulmonary hypertension, and systemic arte-
rial hypotension. The likely mechanism is inhibition of prosta-
glandin and serotonin release by activated platelets.12,13 In a
agents, usually overlooked in the treatment of PE, may fulfill
bus in the presence of radiolabeled platelets shows early platelet
accumulation at the “head” of the venous thrombus.5,6 As the
thrombi age, acquisition of platelets slows and the clots become
“red,” predominantly composed of fibrin and erythrocytes.
Venous thromboembolism activates platelets, leading to re-
lease of vasoactive agents such as serotonin, adenosine diphos-
phate, prostaglandins, and thromboxane A2.7–9 PE causes in-
creased urinary excretion of thromboxane B2, a marker of
platelet activation in early phases of thrombus formation.10
Physiological responses to platelet activation include pulmonary
hypertension, bronchoconstriction, and right ventricular fail-
ure.11 These adverse consequences result from reduction of
The opinions expressed in this editorial are not necessarily those of the
editors or of the American Heart Association.
From the Cardiovascular Division, Brigham and Women’s Hospital,
Harvard Medical School, Boston, Mass (P.S., S.Z.G.); and the Department
of Pathology and Laboratory Medicine, UCLA Medical Center, Los Ange-
les, Calif (M.C.F.).
Correspondence to Samuel Z. Goldhaber, MD, Cardiovascular Division,
Department of Medicine, Brigham and Women’s Hospital, 75 Francis St,
Boston, MA 02115. E-mail sgoldhaber@partners.org
(Circulation 2002;106:1748-1749.)
© 2002 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
DOI: 10.1161/01.CIR.0000035277.48823.01
1748
canine model of PE, pretreatment with the cyclooxygenase
Remove it Now
Overall, antiplatelet therapy reduced the rate of venous throm-
boembolism. DVT was detected in 25% of patients treated with
an antiplatelet agent, compared with 34% of controls. The
Antithrombotic Trialists’ Collaboration reviewed data from
64 535 patients in 32 trials. Antiplatelet therapy (agents not
specified) significantly reduced the risk of clinically overt fatal
or nonfatal PE from 0.61% in controls to 0.46% in the treatment
arm.17
In the Pulmonary Embolism Prevention Trial of 13 356
patients with hip fractures, antiplatelet therapy was tested by
randomizing patients to low-dose aspirin (160 mg daily for 5
weeks) or placebo.18 Low-dose aspirin reduced the rate of fatal
PE by 58%, all PE by 43%, and symptomatic DVT by 29%.
Novel antiplatelet agents may provide additional safe and
effective treatment strategies for acute PE. Clopidogrel, a thien-
opyridine derivative, inhibits platelet aggregation by irreversibly
blocking the platelet ADP receptor. Clinical effectiveness of this
antiplatelet agent has been tested in 2 large clinical trials. The
Clopidogrel versus Aspirin in Patients at Risk of Ischemic
Events (CAPRIE) trial randomized 19 185 patients with known
atherosclerotic disease to either daily aspirin or clopidogrel.
After a mean follow-up of 2 years, patients treated with
clopidogrel had an annual risk of ischemic stroke, myocardial