PATIENT1. A 68-year-old male patient with known complaint of hypertension and hypothyroidism presented to the emergency department with acute onset of the left anterior chest pain with radiation to back associated with sweating and restlessness. At the presentation his vitals were Blood pressure -131/76 mmhg, Heart rate -78/minute, Oxygen saturation-100% at room air. On further evaluation with preliminary investigation ECG showed sinus rhythm with ST elevation in 1, aVL , v1-v3, and ST depression in II, III, AvL (FIGURE 2), Troponin I -1.2 ng/dl, NT- pro BNP- 518 pg /ml.
He was diagnosed as Anterolateral wall Myocardial infarction in Emergency department and treated with Aspirin, clopidogrel and atorvastatin loading dose, Inj Heparin 5000 IU. This is followed by thrombolysis with the reteplase 2 dose 18 mg 30 minutes apart with first dose given at the 4.27pm and second dose at 4.57 pm on November 3rd week.
After 30 minutes of the first dose BP falls from 131/76mmhg to 112/67 mmhg at 4.47pm minute then followed by 87/49mmhg at 4.57pm, 05.07 as 106/54mmhg resolved to 108/65 mmhg at 05.27pm. Patient monitored in the Cardiac ICU and at 10.00pm BP recorded as 127/74 mmhg. Patient needed no Ionotropic agents for the treatment of hypotension. So, the Casualty of the event is possibly due to Reteplase drug according to WHO casualty assessment. (Table I)
PATIENT2. A 55-year-old male patient came to the emergency medicine department with retrosternal chest pain with profuse sweating, shortness of breath and nausea. On examination initial blood pressure -116/81 mmhg, pulse rate-68/minute, oxygen saturation 79 % on room air and 92 % with 2liter/minute oxygen, on the respiratory system examination – bilateral basal crepitation present.
On further evaluation in the emergency department with investigations like ECG revealed changes ST elevation at V1-V3, ST depression in II, III, aVF diagnosed as anterior wall MI (FIGURE 3) treated with Aspirin, Clopidogrel, Atorvastatin loading dose, Inj heparin 5000 IU, Inj Pantoprazole and Inj Ondansetron. This is followed by thrombolysis with Reteplase two doses 30 minutes apart.
First dose given at 9.15 am and second dose at 9.45 am on last week November. After the first dose of reteplase noticed the BP fall as 98/56 mmhg after 30 minutes at 09.45 am and subsequently as continued as 100/56 mmhg at 9.55 am, 104/74 mmhg at 10:15 am. The patient symptomatically managed and improved. The Hypotension occurred secondary to the reteplase drug administration can possibly be attributed to Reteplase as per the casualty assessment done by WHO casualty assessment. (Table I)
Reteplase is the fibrine-specific thrombolytic agent of second-generation tissue plasminogen activator. It is less immunogenic and indicated for thrombolytic therapy for myocardial infarction prior to Percutaneous intervention or as an immediate intervention. It is given as two doses of reteplase 18 mg (10 IU) given as IV over 2 minutes and 30 minutes apart. It is noticed that patients receiving the reteplase on an average of 20-40 minutes after the first dose of reteplase presented with hypotension. But all occurred in the context of the myocardial infarction either as anterior wall MI, anterolateral wall MI. Concomitant medications were antiplatelets and statins for the loading of myocardial infarction.
Above both patients belonging to Indian (Asian ethnicity). A cross-sectional prospective study by Naser Aslanabadi et al published in the Journal of Research in Pharmacy Practice reviewed the adverse drug reaction profile associated with reteplase in acute ST elevation MI patients (20 in number) in the Iranian population noticed mainly ADR related to the cardiovascular and circulatory system as bradycardia, anaphylaxis, tachycardia, oedema reported. (5) In INJECT trial (randomized double-blind) comparing the streptokinase vs reteplase noticed incidences of hypotension with reteplase in 15.5% study population in the reteplase arm as compared to the 17.6% study population in streptokinase arm with a statistically significant difference in the incidence of hypotension as an adverse effect in the reteplase group (p <0.05).[6]. In a case report published in the American journal emergency medicine reviewed the 12 cases of anaphylaxis secondary to the IV thrombolytic agents including streptokinase, alteplase, reteplase, in which one patient anaphylaxis is related to reteplase. The probable case of hypotension secondary to the bradykinin and histamine related mechanism.[7]
On reviewing the clinical picture of each patient in the emergency care of myocardial infarction noticed as the fall in blood pressure in the patients reviewed in the above 2 cases irrespective of age, and irrespective of type of myocardial infarction and probably due to the drug induced hypersensitivity leading to the hypotension or release of immune mediators like histamine in the circulation leading to the hypotension in these patients.
In the above patients, the incidence of hypotension is possibly due to reteplase induced one. The reason for the reteplase-induced hypotension can be attributed to hypersensitivity reaction but needs further evaluation for other unknown molecular mechanism as due to the drug Reteplase as an off-target effect in specific population due to genetic variations. All patients are either anterior wall MI or anterolateral MI.
In the present case series, the mechanism for development of hypotension due to the reteplase one possible mechanism is the allergy or anaphylaxis (type 1 hypersensitivity reaction) due to release of inflammatory mediators in the circulation immediately or transiently after the infusion of reteplase. But any other mechanism other than the mentioned needed further evaluation.