STASE NEUROLOGI

Atherotrombosis

Oleh
Yuliet Iman Mega, S.Ked
FAA 111 0014

Pembimbing: dr. Bambang,Sp.S

KEPANITERAAN KLINIK BAGIAN/SMF
NEUROLOGI RSUD dr. DORIS
SYLVANUS/FAKULTAS KEDOKTERAN
UNIVERSITAS PALANGKA RAYA
MEI 2016
1
 Atherothrombosis
Thrombus adalah bekuan darah .

Atherothrombosis
Adalah suatu proses terjadinya bekuan
darah yang menyumbat aliran pembuluh
darah

Atherosclerosis Atherothrombosis
oklusi mendadak

serangan mendadak

Arteri coronaria di jantung arteri

di otak

Acute Infark Miokard Cerebro
Epidemiolgi
Thrombosis penyebab kematian
terbanyak di Amerika Serikat.
>2 juta orang meninggal setiap tahun

akibat thrombosis arteri atau vena atau

penyakit- penyakit yang ditimbulkannya
Jika dibandingkan dengan kematian akibat

kanker sebesar 5 5 0 .0 0 0 per tahun,

thrombosis menimbulkan kematian 4 kali
lebih banyak
 Kecenderungan yang sama dapat
dijumpai dinegaran- negara berkembang
termasuk Indonesia. Di Indonesia,
thrombosis (penyakit jantung koroner dan
troke) penyebab kematian nomor satu,
lebih sering dari penyakit infeksi/
Trombosis
Thrombosis :
1. arteri, disebut thrombosis arteri (arterial
thrombosis
2. vena disebut thrombosis vena ( venous
thrombosis ).

. Komponen thrombus arteri terdiri dari platelet

(thrombosit) diselingi oleh anyaman fibrin,
komponen eritrositnya sangat rendah sehingga
thrombus berwarna putih disebut sebagai
white thrombus .
. Komponen thrombus vena sebagian besar

terdiri dari sel darah merah disela- sela

anyaman fibrin, komponen thrombosit sangat
sedikit, thrombus berwarna merah disebut

PATOGENESIS THROMBOSIS
Lebih dari 100 tahun yang lalu Rudolph Virchow pada
tahun 1854 mengemukakan Virchow Triad, yang
prinsipnya sampai sekarang masih dianggap valid.
Berdasar teori Virchow triad, thrombosis timbul karena
tiga hal:
1. Kelainan dinding pembuluh darah (vascular injury).
2. Gangguan aliran darah (gangguan rheology)
3. Kelainan konstituen darah (hypercoagulable state).

Atherothrombosis is commonly found in more

than one arterial bed in an individual patient *

Cerebrovascular Coronary
disease disease
7.4%
24.7% 29.9%

3.3%

3.8% 11.8%

19.2%

Peripheral arterial
disease
* Data from CAPRIE study (n=19,185)
Coccheri S. Eur Heart J 1998; 19(suppl):
P1268.
 Major clinical manifestations
of atherothrombosis

Ischemic Transient
stroke ischemic attack

Myocardia Angina:
l infarction Stable
Unstable

Peripheral arterial
disease:
Intermittent claudication
Rest Pain
Gangrene
Necrosis

Adapted from: Drouet L. Cerebrovasc Dis 2002; 13(suppl 1): 16.

Manifestations of
Atherothrombosis

Stroke
TIA

Acute MI
Unstable angina
Prior MI
PCI/stenting
Atrial fibrillation

Intermittent
claudication
Peripheral
vascular
intervention

Teri J McDermott CMI 2003

TIA = Transient ischemic attack

MI = Myocardial infarction
PCI = Percutaneous coronary intervention
Identifying those at risk of atherothrombosis

Local factors
Elevated prothrombotic factors: fibrinogen, CRP, PAI-1
Blood flow patterns, vessel diameter, arterial wall structure

Systemic
conditions
Generalized Atherothrombosis History of
disorders manifestations vascular events
Obesity Hypertension
Diabetes (myocardial Hyperlipidemia
infarction, Hypercoagulable
stroke, vascular states
Homocystinemia
death)

Genetic Lifestyle
Genetic traits Smoking
Gender Diet
Age Lack of exercise

Yusuf S et al. Circulation 2001; 104: 274653. 2. Drouet L. Cerebrovasc Dis 2002;13(suppl 1):16.
The normal artery wall

Endothelial Leucocyte Endothelial Leucocyte

permeability migration adhesion adhesion

Ross (1999)
 The normal artery wall

Endothelialcells
Endothelial cells

ContractileVSMCs
Contractile VSMCs
Early atherosclerosis (I)
Endothelial dysfunction Lipid accumulates
Lipid accumulates inin
the intimal
the intimal space
space and
and
isis associated
associated with
with
abnormal endothelial
abnormal endothelial
cell function
cell function

Lipi
d
 Platelet adhesion and activation
Platelets adhering to Aggregation
Normal platelets damaged endothelium of platelets into
in flowing blood and undergoing activation a thrombus
A B C

Platelet
thrombus
Platelets adhering
to subendothelial
Platelets space

Endothelial cells
Subendothelial space

Adapted from: Ferguson JJ. The Physiology of Normal Platelet Function. In: Ferguson JJ,
Chronos N, Harrington RA (Eds). Antiplatelet Therapy in Clinical Practice. London: Martin
Dunitz; 2000: pp.1535.
Atherothrombosis: a Life-threatening Disease

Atherothrombosis is a chronic, progressive, generalized and unpredictable disease

characterized by the formation of blood clots on top of established atherosclerosis

Plaque rupture1 Plaque erosion2

An atherothrombotic manifestation (like myocardial infarction, stroke, transient

ischemic attack, unstable angina, or peripheral arterial disease) in one vascular
territory means increased risk in all vascular beds 3
Atherothrombosis (cardiovascular and cerebrovascular disease) is one of the worlds
biggest killers4

1. Falk E et al. Circulation 1995; 92: 657671 4. World Health Organization. Cardiovascular diseases site.
2. Arbustini E et al. Heart 1999; 82: 269272 www5.who.int/cardiovascular-diseases/main.cfm?p=0000000424
3. Aronow WS, Ahn C. Am J Cardiol 1994; 74(1): 6465 (last accessed 24 January 2003)
Therupturedatheroscleroticplaque
followingfibrinolysis

DaviesandHo,
1998
 Pathophysiology
Atherosclerosis develops as a
chronic inflammatory response of
the arterial wall to endothelial
injury.
Lesion progression occurs through
interactions of modified lipoproteins,
monocyte-derived macrophages, T-
lymphocytes, and the normal
cellular constituent of the arterial
wall.
The contemporary view of
 Response-
to-injury
hypothesis
The following are
the steps
involved in the
hypothesis:
1. Chronic
endothelial
injury
2. Accumulati
on of
lipoproteins
3. Monocyte
adhesion to the
 Response-to-injury
hypothesis
1. Chronic endothelial injury

with resultant endothelial

dysfunction, causing increased
permeability, leukocyte
adhesion, and thrombosis
 Response-to-injury hypothesis
2. Accumulation of lipoproteins
(mainly LDL and its oxidized forms) in
the vessel wall. Low-density
lipoprotein molecules (LDL) becoming
oxidized (ldl-ox) by free radicals,
particularly oxygen free (ROS). When
oxidized LDL comes in contact with
an artery wall, a series of reactions
occur to repair the damage to the
artery wall caused by oxidized LDL.
Cholesterol can move in the
 Response-to-injury hypothesis
3. Monocyte adhesion to the
endothelium
followed by migration into the intima and
transformation into macrophages and foam
cells. The body's immune system responds
to the damage to the artery wall caused by
oxidized LDL by sending specialized white
blood cells (macrophages and T-
lymphocytes) to absorb the oxidized-LDL
forming specialized foam cells.
Unfortunately, these white blood cells are
not able to process the oxidized-LDL, and
ultimately grow then rupture, depositing a
greater amount of oxidized cholesterol into
the artery wall. This triggers more white
blood cells, continuing the cycle.
 Response-to-injury
hypothesis
4.platelet adhesion

5.factor release
. from activated platelet,
macrophages and vascular
wall cells, inducing SMC
recruitment, either from
the media or from the
 Response-to-injury
hypothesis
6. SMC proliferations and ECM
production.
Eventually, the artery becomes
inflamed. The cholesterol
plaque causes the smooth
muscle cells to enlarge and
form a hard cover over the
affected area. This hard cover
is what causes a narrowing of
 Response-to-injury
hypothesis
7. Lipid accumulation
both extracellularly and within cells
(macrophages and SMCs).
accumulation if lipid-containing
macrophages in the intima gives
rise to fatty streaks, with further
evolution, a fibrofatty atheroma
consisting of proliferated SMC,
 Atherothrombosis: A Generalized and
Progressive Disease

Atherothrombosis
Atherothrombosis

Unstable
angina ACS
MI
Ischemic
stroke/TIA
Atherosclerosis Critical leg
ischemia
Intermittent
claudication
CV death

Stable
Stable angina/Intermittent
angina/Intermittent claudication
claudication
MI = Myocardial infarction
ACS = Acute coronary syndromes
Adapted from Libby P. Circulation 2001; 104: 365372
CV = Cardiovascular
Micrograph of an artery that supplies the
heart With significant atherosclerosis
and marked luminal narrowing
Kenichi Sakakura, MD, Masataka Nakano, MD, Fumiyuki
Otsuka, MD, Elena Ladich, MD, Frank D. Kolodgie, PhD
and Renu Virmani, MD. Pathophysiology of
Atherosclerosis Plaque Progression. Elsevier :
Australian and New Zealand Society of Cardiac. 2013
Kenichi Sakakura, MD, Masataka Nakano, MD, Fumiyuki
Otsuka, MD, Elena Ladich, MD, Frank D. Kolodgie, PhD
and Renu Virmani, MD. Pathophysiology of
Atherosclerosis Plaque Progression. Elsevier :
Australian and New Zealand Society of Cardiac. 2013
 Symptoms
Atherosclerosis develops gradually,
typically begins in early
adolescence, and is usually found in
most major arteries. There are
usually no atherosclerosis symptoms
until an artery is so narrowed or
clogged that it can't supply
adequate blood to your organs and
tissues. Sometimes a blood clot
completely obstructs blood flow, or
even breaks apart and causes blood
 Symptoms
Atherosclerosis symptoms depend on which
arteries are affected. For example:
Atherosclerosis in heart arteries, have
symptoms similar to
those of a heart attack, such as chest pain
(angina).
Atherosclerosis in the arteries leading to
brain, have symptoms such as sudden
numbness or weakness in your arms or legs,
difficulty speaking or slurred speech, or
drooping muscles in your face.
Atherosclerosis in the arteries in arms
and legs, produces decreased blood flow is
called peripheral artery occlusive disease
Symptom
s
The complicationsComplications
of atherosclerosis
depend on the location of the blocked
arteries. For example:
Coronary artery disease. When
atherosclerosis narrows the arteries close to
your heart, you may develop coronary
artery disease, which can cause chest pain
(angina) or a heart attack.
Carotid artery disease. When
atherosclerosis narrows the arteries close to
your brain, you may develop carotid artery
disease, which can cause a transient
ischemic attack (TIA) or stroke.
Stein Harald Johnsen, Signe Helene Forsdahl, Kulbir Singh, Bjarne Koster
 Peripheral artery Complications
disease. When atherosclerosis
narrows the arteries in your arms or legs, you may
develop circulation problems in your arms and legs
called peripheral arterial disease. This can make you
less sensitive to heat and cold, increasing your risk of
burns or frostbite. In rare cases, poor circulation in your
arms or legs can cause tissue death (gangrene).
Aneurysms. Atherosclerosis can also cause
aneurysms, a serious complication that can occur
anywhere in your body. An aneurysm is a bulge in the
wall of your artery. Pain and throbbing in the area of an
aneurysm is a common symptom. If an aneurysm
bursts, you may face life-threatening internal bleeding.
Although this is usually a sudden, catastrophic event, a
slow leak is possible. If a blood clot within an
aneurysm dislodges, it may obstruct an artery at some
 Tests
Doctors may find signsand diagnosis
of narrowed, enlarged
or hardened arteries during a physical
exam. These include:
A weak or absent pulse below the narrowed
area of the artery
Decreased blood pressure in an affected
limb
Whooshing sounds (bruits) over the arteries,
heard with a stethoscope
Signs of a pulsating bulge (aneurysm) in the
abdomen or behind knee
Evidence of poor wound healing in the area
where blood
 Tests and diagnosis
Depending on the results of the physical
exam, doctors may suggest one or
more diagnostic tests, including:
Blood tests.
Doppler ultrasound
Ankle-brachial index.
Other imaging tests.
Angiogram.
Electrocardiogram (ECG).
 Lifestyle and home
remedies
Lifestyle changes can help prevent
or slow the progression of
atherosclerosis.
Stop smoking.
Exercise most days of the
week.
Eat healthy foods
Manage stress
manage the condition of high
cholesterol, high blood pressure,
diabetes or other chronic disease
 Treatments and drugs
Lifestyle changes, such as eating a healthy diet
and exercising, are often the first line of
defense in treating atherosclerosis. But
sometimes, medication or surgical procedures
may be recommended as well.
Various drugs can slow or sometimes even
reverse the effects of atherosclerosis. Here
are some common choices:
Cholesterol medications. Aggressively
lowering low-density lipoprotein (LDL)
cholesterol, the "bad" cholesterol, can slow,
stop or even reverse the buildup of fatty
deposits in arteries. Boosting your high-density
lipoprotein (HDL) cholesterol, the "good"
cholesterol, may help, too. cholesterol

Treatments and drugs
Anti-platelet medications. Doctors may
prescribe anti- platelet medications, such
as aspirin, to reduce the likelihood that
platelets will clump in narrowed arteries,
form a blood clot and cause further
blockage.
Anticoagulants. An anticoagulant, such
as heparin or warfarin (Coumadin), can
help thin blood to prevent clots from
forming.
Blood pressure medications.
Medications to control blood pressure
such as beta blockers, angiotensin-
converting enzyme (ACE) inhibitors and
calcium channel blockers can help slow
Daftar Pustaka
Harrisons principle of internal medicine, 17th
edition.
Robbins basic pathology, 8th edition
Bick RL. Introduction to thrombosis: proficienct and

cost-effective approach to thrombosis.

Haematol/Oncol Clin N Amer 2003;17:1-8.
Deitcher SR, Rodgers GM. Thrombosis and

antithrombotic therapy. In: Greer JP, Foerster J,

Lukens JN, Rodgers GM, Paraskevas F, Glader th B,
editors. Winstrobes Clinical Hematology. 11 ed.
Philadelphia: Lippincott-Williams & Wilkins;
2004.p.1713-60.
TERIMA KASIH