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Acute Coronary

Syndromes-Trombolitik
Terapi

dr. Murthado Sani


Jp (K), FIHA

Introduction

The term of ACS has been developed to describe


the collection of ischaemic conditions which occur
through Coronary Plaque Rupture

ACS includes:
[1] STEMI
[2] NSTEMI & Unstable angina

NSTEMI & Unstable Angina

UA/NSTEMI defines a syndrome in which the symptoms of CAD and


ISHD increase in frequency, occur with less physical activity (later at
rest), last longer or become more severe.

Clinically, it is difficult to distinguish between UA and NSTEMI based


on symptoms alone. The differentiating feature is that patients with
NSTEMI have abnormal blood enzymes (Troponin) proving that a
heart attack has occurred. For many patients, it takes 6-12 hours to
complete a series of blood enzyme tests to make this determination.

It is not necessary for an artery to be severely blocked in order for


unstable angina to occur.

Etiology
Key stages in the development of ACS
[1] Ischaemic cascade
[2] Plaque formation and rupture
[3] Coronary occlusion and MI
[4] Ventricular remodelling

[1] Ischaemic Cascade


A cascade of ischaemic events is triggered as
shown in the diagram
Perfusion Deficit

Diastolic Dysfunction
Systolic Dysfunction
ECG Changes

MI

Unstable Angina

TIME

[2] Plaque Formation and Rupture

Plaques composed of fibrous and fatty tissues formed within


the arterial wall.

The atheromatous plaques usually grow slowly as they have


a Fibrous Cap on their luminal surface.

Sometimes, the cap is breached and the softer plaque tissues


become exposed to the thrombotic factors in the blood.

The plaque suddenly increase in size, causing a critical


reduction in myocardial blood flow.

Plaque Rupture

Plaque Rupture & Thrombus


Formation
Plaque
Rupture &
Thrombus
Formation
Plaque

[3] Coronary Artery Occlusion and MI

Sudden Plaque Rupture and thrombus


formation to the extent where the coronary
artery becomes totally occluded causing MI.

If blood flow is not restored rapidly (within 6


hr.), the muscle dies and becomes scar tissue.

[4] Ventricular Remodelling

Once an area of the heart becomes scar tissue, the


myocardium becomes this, fibrosed and functionless

The remaining healthy myocardium hypertrophies and


becomes hyperdynamic in function in an attempt to
compensate for the dead area.

This increased activity ultimately leads to worsening


cardiac function and development of a dilated poorly
functioning ventricle.

Clinical Features

Central chest pain


Dyspnoea
Nausea/vomiting
Sweating
Beware of Atypical Presentation without classic
chest pain (pulmonary oedema, acute confusion) in
diabetics and elderly patients.

Investigate ACS case


[1] Immediate assessment [ECG].
[2] Admission tests
Cardiac markers.
Chest x-ray.
[3] Urgent coronary angiography (if indicated and
available).

[1] Immediate Assessment (ECG)

12-lead ECG is the most urgent investigation in a


patient with a suspected ACS.

ECG changes and in particular ST elevation or


new onset LBBB mandates immediate action.

[2] Admission Tests


1- Cardiac Markers

Cardiac markers are measured at an appropriate time interval.


Commonly measured markers of myocardial damage include:
Troponin I
Creatine kinase (CK)
Lactate dehydrogenase (LDH)
Aspartate transaminase (AST)
Cardiac markers are of no value in making a decision regarding
thrombolysis, as even the earliest markers may be undetectable for the
first 6-12 hours after the infarction.

Cardiac Markers

[2] Admission Tests


2- Chest x-ray

Chest x-ray is often normal in patients with ACS.


However it may show evidence of:
Aortic Dissection
Cardiomegaly
Pulmonary oedema

In case of STEMI, thrombolysis should not be


delayed while awaiting a CXR unless an Aortic
Dissection is suspected.

[3] Urgent Coronary Angiography

Cardiac catheterisation allows invasive assessment


of:
Coronary arteries.

Left ventricle.

Cardiac output.
Oxygen saturations.
Aorta.
Bypass grafts.
Intracardiac pressures.

With coronary angiography there is a possibility to


proceed into Primary Angioplasty

Coronary Angiography
Occluded
Proximal

Stent implantation
& patent RCA

RCA

Diagnostic Coronary Angiography with proceeding


Stent implantation into the proximal RCA
(Primary Angioplasty)

Diagnosis of STEMI

ECG ST segment elevation


New onset LBBB
Cardiac markers Troponin I
CK

Management of STEMI On
Admission

IV access
Oxygen
Aspirin 300 mg (and 75 mg daily thereafter)
Pain relief (opiate)
Sublingual GTN
Urgent Thrombolysis (unless contraindicated)
Primary Angioplasty
blockers
Insulin/glucose regimen if plasma glucose 11 mmol/L

Thrombolysis

The decision to consider thrombolysis depends upon:


A Good Clinical History for MI with an onset
within the last 12 hours.
ECG that shows evidence of acute STEMI or
new onset LBBB.

Where thrombolysis is indicated, aim to initiate treatment


within 20 min of presentation to hospital.

Thrombolytic Agents
Available Thrombolytic Agents
[1] Streptokinase
[2] tissue Plasminogen Activator (tPA)
Reteplase
Tenecteplase
Alteplase

for tPA Administration


Tissue Indications
Plasminogen
Activator (tPA)
(1) Streptokinase allergy
(2) Previous streptokinase treatment (5 days to 2 years)
(3) Hypotension
(4) Large anterior wall damage.
(5) New thrombus after streptokinase therapy (in 10 to 15%
of patients, usually within a few hours to days after
thrombolysis).

Contraindications to Thrombolysis

Recent stroke (2 months)


Previous haemorrhagic stroke (ever)
Recent head trauma (4 weeks)
Recent surgery including dental extraction (2 weeks)
Lumbar puncture (within 4 weeks)
Active peptic ulceration or other GI blood loss
Concurrent anticoagulation (unless INR <2.0)
Cont

Contraindications to Thrombolysis (Cont.)

Severe liver disease or clotting disorder


Pregnancy or <18 weeks postnatal
Acute pancreatitis
Aortic dissection
Active pulmonary disease with cavitation
Oesophageal varices
Cerebral neoplasm
Uncontrolled hypertension (BP >200/120)

Trombolitik pada Infark Miokard Akut

Infark Miokard Akut

ECG change in acute Myocardial infarction

R
P

> 2 mm

Q S
normal ECG
Fig. 16

ECG indicating AMI

HOMEOSTASIS
Definisi

Homeostasis adalah suatu keseimbangan fisiologis


antara sistem pembekuan darah dan sistem fibrinolitik
dengan tujuan mempertahankan keadaan cairan
darah dalam sistem sirkulasi.
Homeostasis dipertahankan oleh suatu sistem
keseimbangan yang luarbiasa antara jaringan
endotelium, sel-sel darah dan komponen plasma
sebagai aktivator pembekuan dan enzim-enzim
fibrinolitik, baik dalam bentuk prekursor maupun
dalam bentuk aktif sebagai enzim-enzim penghambat
Gangguan pada sistem keseimbangan ini merupakan
pemicu dan dapat menyebabkan respon yang
berhubungan dengan pembentukan thrombus atau
menyebabkan pendarahan.

KESEIMBANGAN HOMEOSTATIK

Potensi pembekuan

Potensi fibrinolitik

Potensi penghambatan

Gangguan keseimbangan trombosis

Potensi fibrinolitik
Potensi pembekuan

Potensi penghambatan

PEMBENTUKAN TROMBUS
Lesi Endothelium
Pelepasan Tromboplastin
jaringan
Activasi sistem
pembekuan

Pembentukan fibrin

Paparan thd
jaringan

Aktivasi platelet

Adhesi platelet
Aggregasi platelet

Trombus

Permulaan aterosklero

Pembentukan plaque

Pembentukan trombu

Ruptur/robekan pada

75 %

Stenosis 100 %
trombus

Faktor-faktor penyebab
pembentukan
trombus

Gangguan aliran darah


Hiperviskositas
Hiperkoagulabilitas
Peningkatan perlekatan platelet
Peningkatan trombogenesitas
dinding pembuluh darah

Kesimpulan ttg dosis

Jenis lisis sangat tergantung dari


dosis yang diberikan
Dosis besar (1.5 juta IU/jam IV) akan
lebih menguntungkan dibanding
dosis kecil (50.000 IU/jam IV) dari
segi efek sampingnya

Indikasi

Utama : Infark Myokardium Akut (IMA =


AMI)
Lain : 1. DVT
2. Emboli pulmonum
3. Trombosis arteri perifer
4. Oklusi arteri kronik
5. Oklusi arteri dan vena retina

Dosis

IMA / DVT : 1.5 juta IU selama 60


menit IV

Pemberian streptase yang aman dan


efektif secara sistemik adalah melalui
IV pada pembuluh darah perifer
dengan menggunakan kecepatan
infus yang konstan.

Golden time : 6 jam

Kontraindikasi

Perdarahan aktif organ bagian dalam


Trauma kapitis, pembedahan
intrakranial dan intraspinal
Kanker intrakranial
Hipertensi berat
Gangguan pembekuan darah yang
tidak terkontrol
Alergi terhadap streptokinase

Flow chart for management of acute


MI
Emergency Care:

Confirm AMI / Combat Symptoms

History: Patient presenting with chest pain lasting > 15 min not rerponding
to sublingual nitroglycerine
Therapy: ASA (150 - 160 mg, to be chewed, Opioides (not intramuscular!)
Optional therapy: Antiemetics, Atropin, Naloxone, Nitrates,Beta-blockers,
Oxygen
Diagnosis: ECG (repeat, if equivocal) ST elevation or Bundle branch block

Early Care: Reopen coronary arteries (within first 12 hours)


Check: Contraindications (CI) against thrombolysis *
absolute CI***

relative CI***

Stroke
Recent major
trauma/surgery/head injury
(within preceding 3 weeks
Gastro-intestinal bleding within
the last month
Known bleeding disorder
Dissecting aneurism
Recent (> 5 days < 1 year)
treatment with Streptokinase or
Anistreptase **

Coumadin / warfarin therapy


Refractory hypertension (systolic
blood pressure > 180 mm Hg)
Transient ischemic attack in
precedinng 6 months
Pregnancy
Non-conpressable punctures
Traumatic resuscitation
Recent retinal laser treatment

Therapy: Thrombolysis
Streptase: 1.5 mio IU intravenously/ within 60 min. ***
* In case of existing CI consider alternative therapy e.g. primary PTCA
** CI specific for use of Streptokinase or SK-containing products
*** CI listed according to the European Guidelines (6). For the use of Streptase
compare the contraindications and precautions of the approved prescribing
information (cf. package insert)

Adjunctive therapy and success control: cf. (6)

Subsequent Care: Maintain patency / Improve prognosis


For recommendation cf. (6)

Fig. 24: Management of AMI

Monitoring

Perlu dilakukan monitoring terhadap :


1. TT/Trombin Time
2. PT/Protrombin Time
3. PTT/Partial Thromboplastin Time

Guidelines for thrombolytic


therapy according to risk
assessment
rtPA

Location:

Anterior MI

SK
or rtPA
Non-Anterior MI

Risk:

High*

Intermediate*

SK
Low*

Age < 75 Yrs

Age > 75 yrs

Complication:

Complicated
Inferior MI

Killip class 4
( Consider PTCA)

History

Prior CABG
Prior SK

Patient Age

* Risk factors for CV Death


at 6 Weeks post MI
Anamnesis
Female
Diabetes
Age>70
Prior MI

Initial Examination
ECG
Hypotension (<100mm Hg)
+ tachycardia (>100)
Atrial Fibrillation
Anterior MI
Rales > 1/3

Mayo Clinic AMI Guidelines

* Risk
Category
Low Risk:
Int Risk:
High Risk:

#
Factors
<1
2-3
>3

6 Week
Mortality
<3%
13%
17%

'Tailored' therapeutic approach to


thrombolytic therapy
Large

'High'intensity
regimen

'Medium' intensity
regimen

Expected
infarct size
(area at risk)

'Low' intensity
regimen
None

Small

12

Time of starting treatment after symptom onset (hours)

'High' intensity: accelerated rtPA or PTCA (if available)


'Medium' or 'Low' intensity: SK or rtPA (consider cost/effectiveness relation)

P robability of intracranial
haem orrhage (%)

Probability of intracranial haemorrhage in


patients with risk factors
4

Alteplase

3
2

all patients
1

Streptokinase
0
0

Risk faktors for intracranial haemorrhage

Fig. 20: Risk factors : age > 65 Years, < 70 kg body weight, hypertension

DEXA MEDICA TRAINING

CLINICAL STUDY

STREPTASE

Mortality reduction in ISIS2

Cumulative
Mortality
600 (No of patients)

Placebo13,2 %
ASA 10,7 %
SK 10,4 %
8,0 %
SK + ASA

500
400
300
200
100
0
0

14

21

28

Time (days)
Reduction of Mortality :
Cumulative Reduction:
Results of ISIS-2, mortality

SK = -25 %, ASA = -23 %


SK + ASA = -39%

35

In-hospital mortality in relation to interval


between onset of symptoms to lysis in the
GISSI trial

%%Mortality
Mortality

Interval
Interval
elapsed
elapsedinin
hours
hours

Number
Numberof
of
Patients
(n)
Patients (n)

Streptokinase
Streptokinase
group
group

Control
Control
group
group

PP

<1
<1

1277
1277

8.2
8.2

15.4
15.4

0.0001
0.0001

6094
6094

9.2
9.2

12.0
12.0

0.0005
0.0005

3649
3649

11.7
11.7

14.1
14.1

0.03
0.03

1352
1352

12.6
12.6

14.1
14.1

NS
NS

594
594

15.8
15.8

13.6
13.6

NS
NS

11712
11712

10.7
10.7
n=
n=5860
5860

13.0
13.0
n=
n=5852
5852

0.0002
0.0002

</=3
</=3
>3
>3- -66
>6
>6- -99
>9
>9- -12
12
Overall
Overall
reslts
reslts

Mortality and major clinical events


in the ISIS-3 trial
Event

SK
n=13,607

tPA
13,569

APSAC
13,599

Thrombolysis alone
20,375

(%)
10.5

Thrombolysis +
heparin
20,400
(%)
10.3

Death

(%)
10.6

(%)
10.3

Stroke:
any

1.04*

1.39

1.26

1.28

1.18

Stroke:
haemorrhagic

0.24*

0.66

0.55

0.56***

0.40

Bleeds:
any

4.5*

5.2

5.4

6.3***

3.9

Bleeds:
major

0.9

0.8

1.0

1.0***

0.8

Reinfarction

3.47

2.93**

3.55

3.16

3.47

Allergic
reactions

0.3

0.1**

0.5

0.3

0.3

Hypotension

6.7

4.4**

7.0

6.0

5.9

(%)
10.6

*
significantly lower than tPA and APSAC
** significantly lower than SK and APSAC
*** significantly higher than thrombolysis alone

ISIS-3 results in relation to treatment re

Kesimpulan

Penanganan AMI akan sangat berarti


apabila dilakukan sedini mungkin
pada saat terjadinya serangan.
Penggunaan dosis besar jauh lebih
menguntungkan
Dapat dikombinasi dengan
antikoagulan lain yang sesuai

Pesan

Penanganan AMI berpacu dengan


waktu, makin cepat makin baik.

Jadikan streptase sebagai terapi awal


setiap kejadian AMI

Kemasan Streptase