Rare severe hypofibrinogenemia induced by tissue plasminogen activator in stroke patients: Case report

Abstract

Rationale: Severe hypofibrinogenemia after intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is rare and easily overlooked, but hypofibrinogenemia increases the risk of major bleeding. However, it is unclear when hypofibrinogenemia reaches the peak and when hypofibrinogenemia is resolved.

Patient concerns: Case 1 was of a 66-year-old man who was hospitalized due to sudden onset of vague speech and right hemiplegia for 4 hours. Case 2 was of an 84-year-old woman who was hospitalized for sudden onset of left hemiplegia and vague speech for 4 hours. In case 1, fibrinogen levels decreased from normal values to <0.25 g/L within 4.5 hours after commencing IVT and returned to normal at 35 hours later. In case 2, fibrinogen levels decreased from 1.1 to <0.25 g/L within 2 hours after commencing IVT and normalized 36.5 hours later.

Diagnoses: Both patients were diagnosed with rt-PA-related hypofibrinogenemia.

Interventions: No antiplatelet or symptomatic treatment was administered during the period of hypofibrinogenemia.

Outcomes: Fibrinogen levels gradually recovered. In case 1, the patient did not experience cerebral hemorrhage during hypofibrinogenemia. His symptoms improved significantly within 1 week. In case 2, repeat computed tomography revealed minor cerebral hemorrhage, but no deterioration in her condition was noted until she was discharged.

Lessons: Rapid, severe, and prolonged hypofibrinogenemia may occur after IVT with rt-PA, which may increase the risk of massive hemorrhage and affect the related therapy. Prompt diagnosis of hypofibrinogenemia is important for preventing complications. We recommend checking the fibrinogen levels routinely after IVT. Fibrinogen replacement therapy and platelet transfusion are the main management routes for rt-PA-related symptomatic intracranial hemorrhage.

Figure 1

Changes in fibrinogen levels and neuroimaging results. (A) Changes in fibrinogen (FBG) levels in patient 1 (blue line) and patient 2 (red line) after intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA). FBG levels sharply decreased immediately after IVT, and the peak status was sustained for hours, followed by a slight increase. Brain magnetic resonance (MR) diffusion-weighted imaging (B) shows multiple abnormal signals in the blood supply area of the left middle cerebral artery (MCA), suggesting acute watershed infarction in patient 1. Brain magnetic resonance angiography (C) shows severe stenosis of the left internal carotid artery (arrow) and signs of recanalization of the left MCA in patient 1. (D) Brain computed tomography (CT) before IVT shows a few old cerebral infarctions in bilateral subcortex areas in patient 2. (E) Brain CT on the second day after IVT shows a minor hemorrhage (arrow) within the focus of the right frontal and temporal lobe cerebral infarctions in patient 2.