Successful intravenous thrombolysis for acute ischemic stroke caused by aortic dissection with severe hypofibrinogenemia: a case report and literature review

Abstract

Background

Intravenous thrombolysis (IVT) for acute brain infarctions caused by aortic dissection (AD) may lead to fatal outcomes; thus, it should be ruled out, especially if hypofibrinogenemia occurs after IVT. Successful management of AD-related acute brain infarction with hypofibrinogenemia after IVT has not been reported previously.

Case report

An 84-year-old woman developed sudden left limb weakness and aphasia for almost 4 h. Alteplase was administered intravenously immediately after cerebral hemorrhage was ruled out by emergent head computed tomography (CT). An anomaly suspected to be AD was detected during subsequent routine chest CT, which was confirmed by CT angiography to be a thoracoabdominal aortic dissecting aneurysm (DeBakey type I). Severe hypofibrinogenemia was also noted. After effective blood pressure control, intramuscular injection of vitamin K, and rehydration therapy, her brain cell metabolism improved, hemiplegia improved slightly, and hypofibrinogenemia recovered gradually. The patient’s cerebral hemorrhage did not progress, there was no chest pain or no aggravation of hemiplegia, and the fibrinogen level gradually returned to normal. The condition was stable during hospitalization. At 1.5 months after discharge, the patient showed minimal change in condition.

Conclusion

The symptoms of AD may be nonspecific and latent. IVT may be allowed to perform for some patients with AD related ischemical stroke, And IVT can improve the neural symptoms of AD-related ischemic stroke, but close monitoring is needed to avoid aneurysm rupture. Fibrinogen levels should also be monitored periodically after IVT for early detection of hypofibrinogenemia.

Keywords:

• Intravenous thrombolysis
• acute ischemic stroke
• aortic dissection
• hypofibrinogenemia
• infarction

Introduction

Intravenous thrombolysis (IVT) is the first-line treatment for acute ischemic stroke (AIS) within the thrombolytic time window [1]. Although aortic dissection (AD) rarely causes cerebral infarction [2], IVT is contraindicated in AD, owing to its high risk of AD rupture [3, 4]. Hypofibrinogenemia, a rare and severe complication of IVT, can increase the risk of symptomatic intracerebral hemorrhage [5]. We report a rare case of successful IVT in a patient with AD-related AIS with severe hypofibrinogenemia.

Case presentation

An 84-year-old woman was admitted to our hospital due to sudden left limb weakness and aphasia for almost 4 h, without abdominal pain or chest pain. According to the information supplied by her family, she had no hereditary diseases, hypertension, or other chronic diseases, and she had no history of surgery. On admission, her blood pressure (BP) was 132/69 mmHg and her heart rate was 77 beats per minute; she was emaciated, had muscle strength of 2/5 in the left upper and lower extremities, had clear consciousness, and had motor aphasia, but there were no other obvious positive neurological signs. The National Institutes of Health Stroke Scale (NIHSS) score was 7. Emergency head computed tomography (CT) showed old lacunar infarctions bilaterally in the area under the cortex of the head (Figure 1(a)). Red blood cell count, platelet counts, random blood glucose, blood electrolytes, and blood coagulation test (Table 1) showed no apparent abnormality. A total of 36 mg of recombinant tissue plasminogen activator (rt-PA; alteplase) was administered, initially with a 0.9 mg/kg intravenous bolus injection of 10% of the total amount, and the rest was administered intravenously within 1 h. The fibrinogen level sharply decreased, and fibrinogen could not be detected anymore (Table 1) after IVT. Intramuscular injection of vitamin K was administered, but no antiplatelet treatment was administered. Her coagulation indicators gradually returned to normal within 48 h. The serum creatinine, glycated hemoglobin, troponin I, and creatine kinase-MB were normal; the hemoglobin concentration (85 g/L) decreased; the percentage of neutrophils (86.9%) increased; the B-type natriuretic peptide (BNP, 3091 pg/mL), plasma D-dimers (1.85 mg/L), C-reactive protein (92 mg/L), lactate dehydrogenase (272 U/L), and serum homocysteine levels (19 µmol/L) increased; BNP decreased to 1734 pg/mL within 3 days after diuretic therapy. The fecal occult blood test was weakly positive. One day after IVT, the muscle strength of the left limb was 3/5 (NIHSS score, 6), and repeat head CT showed a minor hematoma within the focus of the AIS (Figure 1(b)). On the third day after IVT, conventional chest CT showed an anomaly suspected to be AD (Figure 1(c)), and prompt thoracoabdominal CT angiography confirmed a thoracoabdominal AD (DeBakey type I) (Figure 1(d–f)). The patient’s guardians refused endovascular intervention for the AD, and she received medications to control the BP and improve the metabolism of brain cells as well as rehydration therapy. The patient was confined in the hospital for 3 days and then transferred to another hospital for treatment. At discharge, the changes in her condition were not significant, and she had no headache or chest/abdominal pain.

Figure 1. (a) Computed tomography (CT) performed before intravenous thrombolysis (IVT) shows old lacunar infarctions bilaterally in the area under the cortex of the head. (b) Head CT shows low-density foci in the right frontal and temporal lobes with minor hemorrhaging (no space-occupying effect) on the second day after IVT. (c) Chest CT shows inward displacement of the calcified plaques in the thoracic aortic arch (arrow) and suspicious double lumens from the aortic arch to the descending aorta, suggesting aortic dissection (AD). (d) CT angiography of the thoracoabdominal aorta shows a thoracoabdominal AD (DeBakey type I), with the AD extending from the aortic root to the brachiocephalic trunk (e) and then to the right common carotid artery. (f) Intimal slices split the lumen into two cavities in the aortic arch.

Table 1. Coagulation function before and after intravenous thrombolysis.

Coagulation function marker	Date and time				Reference range
	August 11, 2018, 20:41	August 11, 2018, 22:39	August 13, 2018, 09:07	August 14, 2018, 07:47
Thrombin time (s)	28.2	73.6	17.5	18.4	14–20
Prothrombin time (s)	15.8	23.4	13.9	12.5	10.5–14
INR	1.49	2.25	1.24	1.17	0.8–1.2
Fibrinogen (g/L)	1.10	<0.25*	1.72	3.53	2–4
APTT (s)	58.2	105.4	41.7	33.5	21–34
Prothrombin activity (%)	48	27	73	74	88–120

* The fibrinogen level was too low to be measured.

INR, international normalized ratio; APTT, activated partial thromboplastin time.

During the patient’s follow-up at 1.5 months, she appeared to have been treated by the conservative therapy administered in the gerontological hospital, and her condition was the same as that during discharge and was stable.

Discussion and conclusion

Causes and dangers of AD

Hypertension is the most common cause of AD, especially in younger patients with hypertension [2, 6], but patients without hypertension who have AD, like our case, are not rare. Mortality in patients with Stanford type A AD may be as high as 40%–50% if appropriate emergency medical treatment is not obtained promptly [7].

Signs and symptoms of AD

Patients with AD are prone to unstable hemodynamics [8], such as BP difference >20 mmHg between both arms and nonpalpable weak pulse on one side [9]. Typical patients with AD often have chest/back/abdominal pain, but our patient had no chest/back pain during hospitalization. Only 48% (11/23) of patients complained of chest/back pain [10]. The above-mentioned signs and symptoms could deteriorate during IVT [2]. Details of cases involving IVT with rt-PA for AD-related AIS are shown in Table 2. Neurological symptoms such as unconsciousness and dysphrasia can obscure the symptoms of AD, resulting in misdiagnosis of AD [11].

Table 2. Details of cases that underwent IVT with rt-PA for AD-related acute ischemic stroke.

	Choi et al. [8]	Jo et al. [4]	Do et al. [12]	Rodríguez-Luna et al. [9]	Hong et al. [14]	Kazmi et al. [13]
Age (years)/sex	59/male	75/female	80/female	80/female	64/female	72/female
Hypertension	–	Yes	Yes	No	–	Yes
Initial symptom	Dizziness and seizure	Loss of consciousness and left hemiplegia	Consciousness degradation and left hemiplegia	Consciousness disorder, aphasia, hemianopsia, and monoparesis	Unconsciousness and left hemiparesis	Left hemiparesis and dysarthria
BP (mmHg)	77/66	–	110/70	135/85, decreased to 100/60 during IVT	140/90	109/50
HR/PR (bpm)	HR, 40	–	PR, 62	80, PR decreased during IVT	Bilaterally diminished pulses	PR, 100
NIHSS score	–	4	–	16	Decreased from 8 to 4	Decreased from 6 to 3 after IVT
Chest/back/abdomen pain	–	–	No	No	Transient chest discomfort and the pain developed during IVT	–
Main examination	MRI showed multiple cerebral infarctions.	Troponin I and CK-MB results were not meaningful.	ECG and cardiac enzyme were normal.	ECG and cardiac enzymes were normal.	ECG and cardiac enzymes were normal.	ECG showed sinus bradycardia.
	Chest CT revealed an AD.	Chest X-ray did not suggest AD.	TEE showed heart failure; chest X-ray showed widening of the mediastinum.	Carotid ultrasound demonstrated left common carotid artery dissection.	Chest CT revealed AD.	Chest X-ray demonstrated mild prominence of the mediastinum.
		Chest CT showed AD and hemopericardium.	CTA showed AD.	CTA showed AD.		CTA showed AD.
Main treatment	The emergency operation was delayed for 13 hours due to IVT.	rt-PA was administered intravenously.	Sufficient rt-PA was administered.	rt-PA infusion was stopped after 15 mg was perfused.	Intravenous rt-PA infusion was stopped after 60% of the amount was administered.	Sufficient rt-PA was administered and emergency cardiothoracic surgery was performed.
			Underwent surgery for AD 12 hours after IVT.	Surgical repair was refused	Emergent aortic surgery was performed.
Outcomes and follow-up	The patient died of massive bleeding.	The patient had sudden cardiac arrest and soon died.	Symptoms improved after IVT. The patient had left-sided paralysis after 3 months.	The patient died 2 days later.	He completely recovered	NIHSS score of 16 and modified Rankin scale score of 4 at 30 days post-operation
					MRI revealed postoperative recovery of the arteries.

AD, aortic dissection; BP, blood pressure; bpm, beats per minute; CK-MB, creatine kinase-MB; CT, computed tomography; CTA, computed tomography angiography; ECG, electrocardiogram; HR, heart rate; ICU, intensive care unit; IVT, intravenous thrombolysis; NIHSS, National Institutes of Stroke Scale; PR, pulse rate; rt-PA, recombinant tissue plasminogen activator; TEE, transesophageal echocardiography; –, not mentioned. All patients had Stanford type A aortic dissection.

Methods of AD screening

Routine chest CT is the recommended screening, followed by carotid ultrasound and plasma D-dimers. The examining doctor should perform these screenings before IVT. Most chest X-rays obtained on admission do not show AD-specific clues, but follow-up chest X-ray is useful in AD diagnosis [12]. Positive findings indicating acute AD include occlusion or intimal flap of the common carotid artery on carotid ultrasound, elevated serum D-dimer values, left hemiparesis, systolic BP difference >20 mmHg between the arms, and mediastinal widening on chest radiograph [10]. The combination of physical, radiological, ultrasonographic, and laboratory findings in rapid screening of acute AD as a cause of AIS can help improve the diagnostic rate.

IVT for AD-related ischemic stroke

A few case reports showed that IVT can improve the neural symptoms of patients with AD-related AIS [12–14] (Table 2); however, the greatest risk in IVT is aneurysm rupture induced by IVT. This case involving full-dose successful IVT for AD-related AIS that was successfully treated without operation is exceedingly rare.

In previous reports, AD was found opportunely and IVT was discontinued [9, 14] (Table 2) or emergency surgery was performed to ameliorate the effect of full-dose IVT [12, 13] (Table 2). Fortunately, AD rupture did not occur after full-dose IVT in our patient. It should be noted that IVT is absolutely contraindicated for AD-related AIS.

Hypofibrinogenemia after IVT

Severe hypofibrinogenemia is observed during IVT with rt-PA in nearly 5% of stroke cases [15]. Hypofibrinogenemia is a risk factor for major bleeding such as intracerebral hemorrhage during rt-PA infusions [16], and fibrinogen assessment could be a rapid, inexpensive tool to identify patients at high risk of bleeding [17]. An ∼80% decrease in fibrinogen level was observed 2 h after IVT, reaching ∼80% at 24 h and returning to normal by >2 day [15, 18]. The minor non-space-occupying cerebral hemorrhage in this patient may be related to hypofibrinogenemia, but thankfully there was no AD rupture.

In conclusion, symptoms of AD may be non-specific and latent, and rapidly ruling out AD is extremely important for patients with AIS. Routine chest CT should be performed before IVT. IVT may be allowed to perform for some patients with AD related ischemical stroke, and IVT can improve the neural symptoms of patients with AD-related ischemic stroke, but close monitoring is needed to avoid aneurysm rupture. Fibrinogen levels should also be monitored periodically after IVT for early detection of hypofibrinogenemia.

Ethics approval and consent to participate

The study design was approved by the ethics review board of the 3rd Affiliated Hospital of Shenzhen University (no. 2019-SZLH-LW-003).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Funding

The author received no financial support for the research, authorship, and/or publication of this article.