Indications

The activation of the coagulation cascade is multifactorial. Clot formation can occur due to venous stasis, hypercoagulable states such as malignancy, or endothelial injury. These conditions activate the coagulation cascade, which ultimately leads to the development of a fibrin clot. Streptokinase is FDA approved in the treatment of acute ST-segment elevation myocardial infarction, arterial thrombosis or embolism, deep vein thrombosis, pulmonary embolism, and arteriovenous cannula occlusion. It is also on the WHO Model List of Essential Medicines (EML). It is not currently commercially available in the United States. Streptokinase was the first thrombolytic agent brought to the market to treat acute myocardial infarction. The ISIS-2 trial with more than 30000 patients demonstrated streptokinase’s ability to reduce mortality compared to the standard treatment. The research showed that streptokinase could lyse over 50% of a thrombus in 5 to 10 minutes.[1][2][3][4][5][6][7] 

Mechanism of Action

Streptokinase is a polypeptide derived from beta-hemolytic streptococci of Lancefield group C bacteria. It forms a complex with plasminogen, which then converts to the proteolytic enzyme plasmin. This process results in a cascade that ultimately leads to the lysis of fibrin clots. Streptokinase causes a systemic thrombolytic state that usually resolves within 48 hours of administration. The half-life of streptokinase is between 23 and 29 minutes; however, it has been reported as high as 89 minutes in some instances.[2][4][5][8]

Administration

Thrombolytic therapy should be initiated as soon as the symptoms are present and no later than 6 hours. Clinicians ought to pay special attention to the dosing of streptokinase. Dosing varies based on each specific pathological setting.

• Acute ST-segment elevation myocardial infarction: The recommended dose for streptokinase in the setting of acute ST-segment elevation myocardial infarction is 1.5 million units intravenously over 30 to 60 minutes.
• Pulmonary embolism: The recommended dose in the setting of pulmonary embolism is a loading dose of 250000 units intravenously over 30 minutes. This is followed by 100000 units per hour for 24 hours.
• Deep vein thrombosis: The recommended dose in the setting of deep vein thrombosis is a loading dose of 250000 units intravenously over 30 minutes. This is followed by 100000 units per hour for 72 hours.
• Arterial thrombosis or embolism: The recommended dose in the setting of arterial thrombosis or embolism is a loading dose of 250000 units intravenously over 30 minutes. This is followed by 100000 units per hour for 24 to 72 hours.
• Arteriovenous cannula occlusion: The recommended course of treatment for arteriovenous cannula occlusion is to instill 250000 IU of streptokinase in a 2 mL solution into the occluded cannula.

Peak plasma concentration reaches 175 U/ml while the volume of distribution is 1.10 L, and the clearance of streptokinase is 0.65 L/h. The GISSI study showed that administration within 1-hour of the symptoms resulted in a 47% reduction in mortality rates. While those who were administered IV streptokinase within 3 hours had a 23% reduction in mortality. Overall, administering Streptokinase within 6 hours of the onset of symptoms has been shown to reduce mortality. Recommendations are that aspirin is administered along with streptokinase as it has been shown to decrease mortality and reduce reinfarction rates.[4][5][9]

Adverse Effects

Allergic reactions and bleeding are common adverse events related to streptokinase. The GISSI study demonstrated a 3.4% incidence of minor bleeding. The ISSI-2 study demonstrates a 0.4% incidence of significant bleeding. Patients may experience transient bradycardia or hypotension, with an incidence of 10%. Streptokinase is derived from bacterial proteins and thus can result in allergic reactions. Allergic reactions have been noted in up to 4.4% of patients and may present with fever, shivering, or rash. In rare cases, anaphylaxis may occur, which appears to be IgE mediated. Patients who develop anaphylactic signs and symptoms should promptly discontinue treatment and receive epinephrine.[4][10]

Contraindications

The thrombolytic nature of streptokinase makes it contraindicated in patients with active internal bleeding, as it can worsen bleeding in some patients. It is also contraindicated in patients with severe uncontrolled hypertension, intracranial neoplasms, surgery within two months, recent stroke, and intraspinal surgery.

Streptokinase administered with extreme caution to those who have experienced recent trauma, coagulopathies or hematologic diseases, gastrointestinal bleeding, infective endocarditis, obstetric deliveries, diabetic hemorrhagic retinopathy, organ biopsies, or previous puncture of a non-compressible vessel. Streptokinase is a pregnancy Category C medication. The effects of streptokinase on a fetus are unknown, and pregnant patients should only receive streptokinase to prevent life-threatening injury.[4]

Monitoring

Due to streptokinase’s thrombolytic mechanisms of action, patients need monitoring for bleeding. The patient's thrombin time, prothrombin time, partial thromboplastin time, complete blood count, and any signs of bleeding demand careful surveillance. Patients also need monitoring for signs and symptoms of reinfarction or vessel occlusion. Re ports of nonfatal instances of reinfarction are between 2.8% and 6%. Patients should also receive monitoring for signs and symptoms of an allergic reaction, including fever, shivering, rash, or in rare cases, anaphylaxis. Patients who have recently had exposure to beta-hemolytic streptococci may be resistant to streptokinase therapy because it is a derivative of streptococci polypeptides.[4]

Toxicity

Streptokinase can precipitate an allergic reaction. Symptoms include fever, shivering, and rash. Patients in rare instances have developed nonfatal anaphylactic reactions. In cases of anaphylaxis, patients should be administered epinephrine immediately and discontinue streptokinase therapy. The toxicity of streptokinase is believed to be because it is a polypeptide derivative of beta-hemolytic streptococci bacteria.[4][10]

Enhancing Healthcare Team Outcomes

Streptokinase is a thrombolytic agent that is highly effective in its ability to lyse fibrin clots and restore blood flow to ischemic tissue. The healthcare provider team requires education on dosing, administration, and potential complications of this thrombolytic. This team may consist of paramedics, emergency room physicians, emergency room nurses, cardiologists, pharmacists, and other nurses. Due to streptokinase’s need to be administered over 30 to 60 minutes, providers need to have staff on hand who can allocate time and resources to ensure the medication is administered safely. This staffing includes nurses who will administer and monitor the drug, pharmacists who will have involvement in dosing and help decide if it is the appropriate therapeutic choice. Clinicians need to be able to confidently deliver the appropriate dose for each of the clinical indications noted.

Percutaneous coronary intervention and other minimally invasive clot-busting techniques are generally preferable to thrombolytic therapy. Intravenous thrombolytic therapy still plays a crucial role in rural areas and developing countries where procedures such as percutaneous coronary intervention are not readily available. Overall, streptokinase is a safe and efficacious means of lysing fibrin clots and may restore blood flow to vital organs to prevent end-organ damage due to ischemia. There are several thrombolytic therapies on the market today. Streptokinase should merit consideration when clinically indicated.[4][8] If used, it requires close coordination of an interprofessional team to obtain the best patient outcomes possible. [Level 5]