Alteplase acts by –
**Core Concept**
Alteplase is a recombinant tissue plasminogen activator (tPA) used for the treatment of acute ischemic stroke and pulmonary embolism. It works by catalyzing the conversion of plasminogen to plasmin, thereby dissolving blood clots.
**Why the Correct Answer is Right**
Alteplase specifically binds to the kringle domain of plasminogen, which is a high-affinity binding site. This binding induces a conformational change in plasminogen, allowing it to be activated to plasmin by a serine protease. Plasmin then breaks down fibrin clots into soluble fibrin degradation products (FDPs), effectively dissolving the clot. This process is mediated by the urokinase-type plasminogen activator receptor (uPAR) on the surface of endothelial cells.
**Why Each Wrong Option is Incorrect**
**Option A:** Alteplase does not work by inhibiting platelet aggregation, as it does not affect the platelet-derived growth factor (PDGF) pathway.
**Option B:** Alteplase does not act as a vasodilator, as its primary mechanism is not through the release of nitric oxide or the activation of endothelial nitric oxide synthase (eNOS).
**Option C:** Alteplase does not work by stimulating the release of tissue factor pathway inhibitor (TFPI), which is actually a natural anticoagulant that inhibits the tissue factor pathway.
**Clinical Pearl / High-Yield Fact**
A key consideration when using alteplase is the time window for treatment, as the efficacy of the drug decreases significantly after 4.5 hours of symptom onset. Moreover, alteplase can cause bleeding complications, such as intracranial hemorrhage, so careful patient selection and monitoring are essential.
**Correct Answer:** C.