Human fibrinogen concentrate Fibryga^® enables rapid reversal of thrombolysis and timely repair of acute Stanford type A aortic dissection: a case report

Abstract

Background

Acute Stanford type A aortic dissection (ATAAD) may mimic acute ischaemic stroke (AIS), occasionally resulting in administration of thrombolytics and potentially leading to life-threatening haemorrhage. Rapid recognition and reversal of thrombolysis-associated coagulopathy are essential to permit timely surgery.

Case summary

A 53-year-old man with history of poorly controlled hypertension presented with acute right-sided hemiparesis, aphasia, and dysarthria. AIS was suspected, and intravenous tenecteplase (TNK) was administered once intracranial haemorrhage was ruled out on non-contrast head computerized tomography (CT) scan. Shortly after thrombolysis, CT angiogram revealed an ATAAD with occlusion of the left common carotid artery, significant compression of true lumen, and involvement of both femoral arteries. TNK was immediately reversed with cryoprecipitate and human fibrinogen concentrate (Fibryga®), raising fibrinogen level within an hour from 102 to 234 mg/dL, thereby enabling timely emergent repair of acute type A dissection. Despite a complicated intra- and post-operative course that included cardiac arrest secondary to rupture and haemopericardium, acute kidney injury, and bowel perforation, the patient was discharged to rehabilitation facility with favourable neurological function.

Discussion

This case illustrates the diagnostic pitfall of ATAAD presenting as stroke and highlights the utility and safety of fibrinogen concentrate (Fibryga®) in rapid reversal of thrombolysis-associated coagulopathy, allowing for safe and timely surgical intervention for ATAAD.

Learning points.

• ATAAD can present as a stroke mimic, and absence of chest or back pain does not exclude aortic dissection.

• Rapid replacement with HFC and cryoprecipitate can normalize fibrinogen and facilitate emergent ATAAD repair after inadvertent thrombolysis

Introduction

Acute ischaemic stroke (AIS) is a leading cause of morbidity globally, and requires rapid diagnosis and treatment. Current guidelines¹ recommend early administration of intravenous thrombolysis (IVT) within a narrow therapeutic window. However, IVT poses significant risks, especially when dealing with AIS mimics, which are conditions that are clinically indistinguishable from stroke but arise from entirely different pathologies.^2,3 One notable high-risk stroke mimic is acute Stanford type A aortic dissection (ATAAD), where administration of IVT has been linked to major life-threatening complications.^2,4 This case report outlines the complex course of a 53-year-old man who presented with symptoms of stroke, and was treated with IVT, and was later diagnosed with ATAAD. We emphasize the diagnostic challenges, the prompt use of Fibryga® and other agents to reverse coagulopathy, and the subsequent emergent surgical repair that led to a favourable outcome.

Summary figure

Case presentation

A 53-year-old man with a history of poorly controlled hypertension presented to the emergency department (ED) after developing acute-onset generalized weakness, mild headache, and dizziness followed by syncope. In the ED, the patient was noted to have significant right-sided weakness, aphasia, and dysarthria, and AIS was suspected. A non-contrast head computerized tomography (CT) revealed no evidence of intracranial haemorrhage. Tenecteplase (TNK) was administered in accordance with established hospital AIS protocol.⁵

Following thrombolysis, CT angiogram (CTA) of the head and neck was performed, and it demonstrated a dissected arch with head vessels. The subsequent chest, abdomen, and pelvis CTA revealed a 5.5-cm ATAAD extending into major head vessels, resulting in the complete occlusion of the left common carotid artery, as well as involvement of both femoral arteries (Figure 1). Cardiac surgery evaluation was requested. Immediate reversal of thrombolytics began with 10 units of cryoprecipitate (CP) and 4 g of human fibrinogen concentrate (HFC; Fibryga®), and an initial fibrinogen level of 102 mg/dL was corrected to 234 mg/dL.

Figure 1.

(A) CTA chest at the aortic root showing an intimal flap. (B) CTA of the arch demonstrating severe true-lumen compression. (C) CTA at the level of head vessels with dissection flap in innominate artery.

Within an hour after the initiation of reversal, the patient was taken emergently to the operating room. Upon induction of anaesthesia and intubation, the patient had a short period of cardiopulmonary resuscitation (CPR) due to profound hypotension and cardiac arrest. The patient was stabilized prior to initiation of cardiopulmonary bypass. Ascending aorta with inner curvature of the arch was replaced with a 28-mm Dacron graft (Hemiarch technique). Intraoperative findings revealed an extensive dissection with an intimal tear in the ascending aorta with an extension into the arch vessels. Intraoperatively, vascular surgery had to emergently perform reconstruction of the right femoral artery with an interposition graft to restore the flow to the right lower extremity, with four compartment fasciotomy. To achieve hemostasis patient received an additional 4 g of Fibryga®, 5 U of CP, 2 U of fresh frozen plasma (FFP), 2 bags of platelets, and a total of 4 U packed red blood cells. Despite the patient’s complicated presentation and the need for CPR due to intraoperative cardiac arrest, his neurological function was encouraging after completion of surgery with improvement in his motor examination on the right side. Patient’s bleeding resolved within 24 h after surgery. The patient developed rhabdomyolysis with creatinine phosphokinase levels of 22 000 U/L, leading to renal failure despite demonstration of flow on renal ultrasound. Patient was started on haemodialysis (HD) on post-operative day (POD) 3. After fluid removal with HD patient was extubated on POD 4 and mobilized shortly thereafter. Closure of fasciotomy sites with skin grafts was performed on POD 13. Throughout the patient’s stay, he had intermittent abdominal distention with some abdominal pain and even had a bloody bowel movement early on in his post-operative course, and ultimately developed bowel perforation requiring right hemicolectomy with ileostomy, small bowel resection, and omentectomy on POD 19. Patient regained his bowel function and was discharged to a rehabilitation facility with a much improved neurological outcome. The patient at the time of discharge had 3/5 strength in the right lower extremity and 4/5 strength in the right upper extremity, which allowed the patient to walk with a walker. Patient’s aphasia and dysarthria had resolved.

Discussion

ATAAD can present similarly to large-vessel AIS, leading to potential misdiagnosis and inappropriate thrombolysis. Neurological involvement occurs in approximately 17%–40% of ATAAD cases, with stroke being the most frequently observed manifestation.⁶ Notably, up to one-third of these patients may not exhibit the classic tearing chest or back pain, making clinical identification particularly challenging and increasing the risk of inadvertent thrombolysis under stroke protocols.⁶

Distinguishing between ATAAD and AIS is crucial, as the consequences of misdiagnosis can be lethal. In cases where thrombolysis was administered, the fibrinolytic activity of these agents can significantly increase the risk of aortic rupture or severe haemorrhage, including mediastinal haemorrhage and cardiac tamponade secondary to haemopericardium, frequently leading to rapid deterioration and death.^2,4 In early stroke reports where thrombolysis was given before recognizing Stanford type A dissection, mortality was about 75% in the few treated cases, whereas patients in whom thrombolysis was withheld or stopped had lower mortality (about 43%),² highlighting the need for accurate early diagnosis and immediate reversal when thrombolysis has been mistakenly administered. In our case report, the patient received TNK before further imaging revealed extensive aortic dissection, and that may have contributed to haemopericardium and further instability of the patient requiring CPR. A review of the literature describing outcomes in patients that received thrombolysis in the setting of ATAAD (Table 1), despite its small sample size, demonstrates that the vast majority of patients that were thrombolysed prior to surgery for ATAAD survived (7 out of 8), while one patient that did not undergo surgery expired. This emphasizes importance of reversal to enable timely surgery.

Table 1.

Summary of case reports describing outcomes in type A dissection patients who received thrombolysis prior to surgery

Study	Number of patients (n)	Thrombolytic agent	Surgery	Survival
Marian 19937	1	rTPA 60 mg	Yes	Yes
Fessler 20008	1	rTPA 72 mg	No (0)	No
Ibaraki 20029	1	Urokinase 720 000 U	Yes (1)	1
Uchino 200510	1	rTPA started, 10% bolus then stopped	Yes (1)	1
Chua 20054	1	tPA	Yes (1)	1
Hong 20092	1	rtPA	Yes (1)	1
Verma 20233	2	tPA	Yes (2)	1 survived 1 died

There is currently no standardized approach for reversing thrombolysis in stroke mimics such as aortic dissection. European Stroke Organization guidelines emphasize careful patient selection for IVT and rapid recognition of mimics; when thrombolysis has been given in error, reversal aims to restore haemostatic function promptly to permit urgent surgery.¹ Expert recommendations emphasize immediate reversal by rapidly replenishing fibrinogen and clotting factors, typically through CP, FFP, and HFC.⁴ Thrombolysis with recombinant tissue plasminogen activator (rTPA) significantly lowers circulating fibrinogen, sometimes to levels below 150 mg/dL, a critical threshold associated with an increased risk of haematoma expansion after thrombolysis.¹¹ This manuscript reports for the first time the use of Fibryga® (HFC), which allowed for rapid controlled reversal of thrombolysis. In addition, adjunctive anti-fibrinolytics like tranexamic acid or ε-aminocaproic acid may also be employed.

There are two lyophilized HFC products that are currently available to treat low fibrinogen levels: Fibryga® and RiaSTAP®. Both offer several advantages over CP, including rapid bedside preparation, precise dosing, lower risk of transfusion reactions,¹² and effectiveness in normalizing coagulation parameters during urgent surgical intervention. CP must be thawed, delivers variable fibrinogen doses, and carries standard transfusion-related risks. Although fibrinogen concentrates are increasingly used to correct hypofibrinogenemia, most published clinical experience has involved RiaSTAP® rather than Fibryga®.

In Europe, RiaSTAP® is known as Haemocomplettan P, and has been approved for both acquired and congenital fibrinogen deficiencies since 1986, while in the USA, it is only approved for use in congenital cases, making its use in acquired fibrinogen deficiencies off-label. Fibryga® was approved in congenital cases in the USA in 2017 and finally approved in acquired deficiencies in 2024. Fibryga® also includes dosing and monitoring guidance for acquired bleeding in its label, which makes it more practical for hospital use. For urgent situations like surgery after thrombolysis, Fibryga® offers on-label use and fast correction.^13–15

Conclusion

This case highlights the critical importance of recognizing aortic dissection as a potential mimic of AIS, particularly in patients who present with atypical stroke symptoms. Immediate reversal of thrombolytic therapy using HFC and CP was crucial in stabilizing the patient and facilitating emergent surgical intervention, which markedly improves survival and neurological outcomes, converting potential catastrophe into meaningful patient recovery.

Lead author biography

Daniel Murdahayev is a medical student at the CUNY School of Medicine in New York, NY. He is interested in cardiovascular medicine, critical care, and internal medicine. He is currently gaining clinical experience and developing an interest in academic writing through case reports. Daniel plans to pursue residency training in internal medicine and hopes to continue exploring subspecialty training by pursuing a fellowship.

Author contributions

Daniel Murdahayev (Data curation, Writing—original draft, Writing—review & editing), Charles Mack (Investigation, Methodology, Writing—review & editing), Christopher Lau (Conceptualization, Investigation, Methodology, Writing—review & editing), Berhane Worku (Writing—original draft, Writing—review & editing), and Iosif Gulkarov (Conceptualization, Data curation, Writing—original draft, Writing—review & editing)

Consent: Written informed consent for publication of the clinical details and images in this case was obtained from the patient.

Funding

None declared.

Data availability

No new data was generated or analyzed in support of this research.