Abstract
INTRODUCTION: A clot-in-transit (CIT) is a mobile thrombus within the right heart associated with acute pulmonary embolism (PE) and high mortality. Although systemic thrombolysis remains the standard treatment for massive or high-risk PE, management of thrombolytic failure and associated CIT remains challenging, particularly when surgical embolectomy and catheter-directed thrombectomy are unavailable. Sequential systemic thrombolysis represents a practical therapeutic option in these high-risk scenarios. CASE DESCRIPTION: A 54-year-old woman with hypertension presented with progressive dyspnoea and pleuritic chest pain. Computed tomography pulmonary angiography confirmed massive bilateral PE, and she was treated with intravenous tenecteplase. Despite initial hemodynamic improvement, hypoxemia persisted, and echocardiography revealed a large CIT within the right atrium. In the absence of surgical or catheter-directed options, she received repeat systemic thrombolysis with alteplase, achieving complete thrombus resolution and rapid clinical recovery without bleeding complications. Further evaluation revealed large uterine fibroids compressing the iliac veins as the likely source of extensive deep vein thrombosis. DISCUSSION: This case demonstrates the potential role of sequential systemic thrombolysis in managing thrombolytic failure and CIT when advanced interventions are unavailable. Switching to alteplase after unsuccessful thrombolysis with tenecteplase may enhance thrombus dissolution due to pharmacological differences in fibrin affinity and duration of fibrinolytic activity. Early reassessment following thrombolysis is critical to detect persistent thrombus and guide timely intervention. CONCLUSION: Sequential systemic thrombolysis can serve as a safe, effective, and practical rescue strategy for clot-in-transit complicating massive PE, particularly in low-resource settings where surgical or catheter-based interventions are not available. LEARNING POINTS: Sequential systemic thrombolysis can be a safe and effective rescue option following thrombolytic failure in massive pulmonary embolism.Early echocardiographic reassessment is essential to detect treatment failure and guide further therapy.Large uterine fibroids can cause iliac vein compression and predispose to extensive deep vein thrombosis.