Alwin Mathew

Introduction. A stroke is a neurological deficit caused by a lack of blood flow to an area of the brain. It is the second leading cause of death and the third leading cause of disability in adults.⁸ Neuroimaging is key to differentiate between ischemic and hemorrhagic strokes.⁴ Ischemic strokes are caused by an occlusion to the cerebral vasculature. Some causes include atrial fibrillation, embolism, and hypercoagulability.² Treatments include therapeutics and thrombectomy. FAST is used to identify strokes and the NIHSS Scale is used to determine stroke severity.⁷ Risk factors include previous cardiovascular disease, smoking, diabetes, and physical inactivity.¹ Early intervention is key for successful patient outcomes.⁹ Thrombi are formed by platelets activation.⁵ Alteplase, a thrombolytic agent, was studied to see its effect on platelets.⁶ Methods. Studies utilized human platelets to examine alteplase.⁶ Studies also looked at the rising cost of alteplase using historical data and comparisons of alteplase and tenecteplase, a genetically recombinant alteplase, on reperfusion of large vessel occlusions.^3,5,6 Tenecteplase and alteplase were both given to 100 patients who were eligible for thrombectomy.³ The primary measurement was reperfusion greater than 50% for the occluded vessels while secondary measurements was Rankin and NIHSS scale scores.³ Results. Alteplase greatly decreased the amount of platelet aggregation without changing levels of platelet receptors P-selectin, PAC-1, GPIbα, GPVI and αIIbβ3.⁶ When looking at the change in alteplase cost from 2005-2014, there was an increase cost of 11% while prescription drug costs increased 30%.⁵ When comparing tenecteplase against alteplase for reperfusion, tenecteplase patients had better function after treatment, while long term Rankin scale scores showed no significant different in recovery of independent function.³ Conclusions. Alteplase, while causing a decrease in platelet aggregation, does not directly affect platelets themselves and mainly functions by activating plasminogen into plasmin.⁶ The rising cost of alteplase is likely due to inadequate reimbursement rates to acute care hospitals, creating a market for a viable therapeutic alternative.⁵ Tenecteplase is shown to be noninferior to alteplase in regards to reperfusion of occluded vessels.³ While end outcomes are similar, tenecteplase allows for single bolus administration, due to an increased half-life, significantly speeding up treatment time.^{2, 3} Patients can immediately be rushed to thrombectomy after tenecteplase treatment while alteplase patients require multiple doses before surgery.³ Tenecteplase is cheaper than alteplase, allowing it to have wider market appeal.² Tenecteplase has higher fibrin specificity and increased resistance to plasminogen activator inhibitors, causing an increased in drug half-life.²

1. Baley-Spindel I, Villaseñor-Villalpando E, Márquez-Espriella C, Rivera-Salgado MI, Dávila-Díaz R. Perivascular Hyaluronidase With Alteplase as Treatment for Hyaluronic Acid Thrombosis. Aesthet Surg J. 2020;40(5):551-559. doi:10.1093/asj/sjz101
2. Campbell BCV, Khatri P. Stroke. Lancet. 2020;396(10244):129-142. doi:10.1016/S0140-6736(20)31179-X
3. Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018;378(17):1573-1582. doi:10.1056/NEJMoa1716405
4. Kamalian S, Lev MH. Stroke Imaging. Radiol Clin North Am. 2019;57(4):717-732. doi:10.1016/j.rcl.2019.02.001
5. Kleindorfer D, Broderick J, Demaerschalk B, Saver J. Cost of Alteplase Has More Than Doubled Over the Past Decade. Stroke. 2017;48(7):2000-2002. doi:10.1161/STROKEAHA.116.015822
6. Lu J, Hu P, Wei G, Luo Q, Qiao J, Geng D. Effect of alteplase on platelet function and receptor expression. J Int Med Res. 2019;47(4):1731-1739. doi:10.1177/0300060519829991
7. Morotti A, Poli L, Costa P. Acute Stroke. Semin Neurol. 2019;39(1):61-72. doi:10.1055/s-0038-1676992
8. Thrift AG, Thayabaranathan T, Howard G, et al. Global stroke statistics. Int J Stroke. 2017;12(1):13-32. doi:10.1177/1747493016676285
9. Yen HC, Jeng JS, Chen WS, et al. Early Mobilization of Mild-Moderate Intracerebral Hemorrhage Patients in a Stroke Center: A Randomized Controlled Trial. Neurorehabil Neural Repair. 2020;34(1):72-81. doi:10.1177/1545968319893294