“Re-administering Streptokinase for

Recurrent ST-Elevation Myocardial Infarction:

Is there any possibility?”

A Case Report

Rizal R. Akbar1, Laksmi S. Agusta1, Ardian Rizal2

1General Practitioner of Wava Husada Hospital, Malang, East Java, Indonesia

2Cardiologist and Arrythmia Consultant, Wava Husada Hospital, Esat Java, Indonesia

Corresponding author : rizalrahmandaakbar@gmail.com

BACKGROUND

The pathophysiology of ST-segment elevation myocardial infarction (STEMI) entails

acute vulnerable plaque change that includes: plaque rupture, fissuring or erosion, all of which
could result in total arterial occlusion if stimulus for thrombus formation is potent and collateral
circulation is not well developed. Since morbidity and mortality due to myocardial infarction
closely correlate with its size, timely reperfusion of the infarct-related artery (either by
fibrinolysis or primary percutaneous coronary intervention [PCI]) is the mainstay of therapy to
preserve left ventricular function (the main predictor of survival in such cases). Streptokinase is
the most widely used fibrinolytic agent especially in economically burdened countries due to the
higher cost of the more effective recent generations of fibrinolytics such as tissue plasminogen
activator (t-PA).
Streptokinase is the most widely used thrombolytic agent, but a drawback to its use is the
widespread presence of anti-Streptokinase antibodies. The association of antibodies and an
immune reaction occurring following treatment with Streptokinase is well known, but the effect
of antibodies on the efficacy of Streptokinase has not been fully clarified.

CASE ILLUSTRATION

A 42-year-old Javanese male came to ER with sudden onset of heart-burning chest pain.
The pain was described in the center of the chest and radiate through the back and left arm since
3 hours prior to arrival, preceded by vomiting and diaphoresis. He regularly smoked 2 packs of
cigarettes per day. Past medical history was significant for hypertension with poor compliance of
treatment by consuming infrequent antihypertensive drugs. Any other prior medical treatments
were denied.

Physical Exam
 Physical examination revealed patient with Glasgow Coma Scale of 15, blood pressure of
177/85 mmHg, heart rate of 70 regular bpm, respiratory rate of 20 times per minute, and oxygen
saturation of 99%. Breath sounds were clear on the both lungs. Other physical examinations
showed unremarkable finding.
Complete blood count showed elevated WBC 12,640 /ul with shifting to the left pattern.
Renal function test within normal limit. Chest X-Ray revealed normal findings.
 ECG revealed ST segment elevations on lead II, III, aVF, V3R, V4R, V5R, V6R,
pathological Q waves in anteroseptal leads, and reciprocal downsloping ST segment depression
in lead I and aVL. These clinical and ECG findings irrefutably support the diagnosis of acute
inferior and right ventricular myocardial infarction with old anteroseptal myocardial infarction.

Treatment
After initial evaluation, the patient received loading dose of aspirin 320 mg and
clopidogrel 300 mg, followed by morphine 5 mg intravenous infusion, and was subsequently
offered to undergo primary PCI. The PCI option was later turned down, thus consequently led to
another treatment option by administering fibrinolytic agent using Streptokinase 1,500,000 IU
intravenous infusion over 60 minutes. Other drugs like captopril 12,5 mg, isosorbide dinitrate 5
mg, and atorvastatin 40mg, were also given as well.
This following picture shows the ECG pattern recorded 90 minutes after administeration
of streptokinase.
 After 90 minutes administration of streptokinase, a marked clinical improvement was
obtained by alleviating symptom of chest pain. Resolution of ST-segment elevation by more than
50% was also observed in the lead with maximum elevation compared with previous ECG.
These both criterias indicate a successful reperfusion.

Follow Up
Four days after discharge, the patient came to Cardiology Outpatient Center to undergo
another clinical examination performed by cardiologist. Prior medical records surprisingly
revealed previous history of anteroseptal ST-elevation myocardial infarction about 1 year ago
treated by similar fibrinolytic therapy using Streptokinase 1,500,000 IU intravenous infusion
over 60 minutes.

DISCUSSION

Thrombolysis has been accepted practice since 1988. The risks associated with repeat
Streptokinase therapy will soon become a major clinical problem, as the numbers of patients
presenting with a second infarct, having had initial thrombolytic treatment with Streptokinase,
increases. There is little information regarding the effect of repeat thrombolytic therapy with
Streptokinase for repeat infarction.
Patients with AMI, as diagnosed by clinical symptoms, and ST segment elevation must
receive fibrinolytic medicines with the minimum of dosage. A realistic aim is to inject the bolus
of fibrinolytics within 10 min from STEMI diagnosis. Thrombolytic therapy should not be
administrated to patients who arrive with infraction after more than 12 hours. Streptokinase is
one of fibrinolytic therapy regimens which has the advantages of low cost and availability in
Indonesia. However, this therapy consumption had the golden time of three hours; its efficacies
decrease dramatically afterwards, and become absolutely useless after 12 hours.
The use of thrombolytic has significantly improved the management of patients with
acute myocardial infarction but available molecules remains imperfect regarding restoration of
normal coronary patency in about half the cases, risks of reocclusion, and risk of bleeding.
Streptokinase, which is the least expensive agent, has disadvantages as do the other
thrombolytics.
Previous studies of the effect of specific antibodies on the action of Streptokinase have
yielded conflicting results. Clinical failure of the activation of the fibrinolytic system by
Streptokinase has been reported due to the presence of a high titre of anti- Streptokinase
antibodies. In vitro clot lysis studies have demonstrated a significant reduction in the activation
of plasminogen by Streptokinase between days 6 and 21 following Streptokinase therapy, a time
when antibody titres are known to be high. On the other hand, a study of the effect of antibodies
on the action of Anisolated Plasminogen Streptokinase Complex (APSAC) found that a
significant proportion (22%) of subjects had sufficient concentration of anti- Streptokinase levels
to bind all of the Streptokinase present in a dose of APSAC (1 x 106 U of SK). At the average
level of anti- Streptokinase found, 29% of the dose could be bound. Despite this binding, only a
modest inhibitory effect on the fibrinolytic effect of APSAC was demonstrated in vitro. Other
authors, however, have demonstrated increasing reduction of Streptokinase activity in vitro, as
the 'Streptokinase resistance' titre increased. The differences in these studies may reflect the
differences between APSAC and Streptokinase; the former, Streptokinase-plasminogen complex,
may not be as easily inactivated as Streptokinase alone. Secondly, the sera studied by the earlier
group were from patients before treatment with APSAC or from normal control subjects.
Re-exposure of the antigen (Streptokinase) to the immune system would increase the
affinity of the antibody for its antigen, and be more likely to exhibit an inhibitory effect on
Streptokinase. The pharmaceutical companies which market Streptokinase advise therapy should
not be repeated between 5 days and 6 months or within 1 year of the initial treatment, because of
the risk of an immune reaction in the presence of high titres of antibodies. The efficacy of
thrombolysis would also be uncertain within this period. Moreover, Indonesian Heart
Association guideline 2018 for ACS said that receiving Streptokinase is specificly
contraindicated for the patients who have previously been thrombolysed with Streptokinase or
Anistreplase.
 Streptokinase, an immunogenic bacterial protein, has another feature: administration of
Streptokinase leads to an immunitory response with the production of specific anti-streptokinase
antibodies. These anti-streptokinase antibodies may interfere with the future administration of a
compound containing Streptokinase either by inducing an allergic response or by neutralising the
Streptokinase and making it ineffective. Moreover, anti-streptokinase antibodies, the result of
previous streptococcal infections, are present in the circulation. Although the prevalence of anti-
streptokinase antibodies in the general population, especially coronary patients at risk of
myocardial infarction, is not well known and their potentially harmful effects are even less well
known. In particular, the platelet aggregant effect in vitro of these antibodies in the presence of
Streptokinase was not taken into account in the trials studying the influence of anti-streptokinase
antibodies in the results of thrombolysis by Streptokinase. The anti-lytic effect of anti-
streptokinase antibodies is well documented. For this reason, many guidelines for ACS is not
recommended to readminister Streptokinase in patients who have previously been thrombolysed
with a product containing Streptokinase.
In contrary, this case has represented that repeat administration of streptokinase was
unproven to bring any detrimental effects. Patient also exhibited an improved clinical condition
and succesful reperfusion targets. A study conducted by Buchalter, et al using immunoglobulin
assay to investigate streptokinase resistance by measuring anti-streptokinase antibody showed
that streptokinase resistance develops early after treatment and is still present in 75% of patients
after 24 months. This study supports evidence that, even in slight proportion, the efficacy and
safety of streptokinase readministration might be considered as possible.

Conclusion:

This case report highlights the safety and efficacy of undeliberate re-administration of
streptokinase in patient presenting with ST-Elevation Myocardial Infarction. However, careful
consideration of clinician should be attained as the vast majority of present guidelines do not
recommend any readministration of fibrinolytic treatment regarding the possible adverse effects.
Further research of this finding should be conducted.

Keywords: Vascular disease, Myocardial Infarction, Streptokinase

References
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