Thromboembolic complications during endovascular treatment of ruptured cerebral aneurysms

Abstract

Background

In cases of subarachnoid hemorrhage due to aneurysm rupture, the administration of an anticoagulant or antiplatelet agent involves the risk of rebleeding from the aneurysm. There is a possibility of inducing thromboembolic events during the endovascular embolization of ruptured cerebral aneurysms.

Patients and methods

From April 2006 to March 2017, we treated a total of 70 patients with ruptured cerebral aneurysms with an endovascular technique. Among them, five patients (7.1%) showed intra-arterial thrombus formation. The aneurysms were located at the anterior communicating artery and basilar artery in two patients each, and on the internal carotid artery at the bifurcation of the anterior choroidal artery (AChoA) in one. In these patients, the clinical course, radiological findings, and management were retrospectively reviewed.

Results

Thrombus formation was observed in the posterior cerebral artery, anterior cerebral artery (A2), AChoA, and middle cerebral artery. The timing of thrombus formation was during coil delivery in four cases, and guiding catheter advancement in one. As for thrombus management, for all patients, administrations of heparin and antiplatelet agents were performed. For four patients, urokinase injection into the affected arteries was added after the completion of embolization. Cerebral infarction was postoperatively identified in two patients, but no hemorrhage was noted.

Conclusion

Administrations of heparin and antiplatelet drugs should be performed appropriately during procedures, and close observation of the arterial condition on angiography is necessary. Once thromboembolism occurs during the endovascular embolization of ruptured cerebral aneurysms, adequate heparinization, and antiplatelet therapy should first be performed.

Introduction

Endovascular embolization of cerebral aneurysms with platinum coils is a definitive treatment just as effective as clipping. In procedures involving the endovascular embolization of unruptured aneurysms, treatment with anticoagulant and antiplatelet agents is essential to prevent thromboembolic events. However, in cases of rupture, the administration of such agents prior to treatment is risky for rebleeding from the aneurysm.¹ In our institute, anticoagulation is started after partial embolization of the aneurysm with one or two platinum coils. Therefore, there is a possibility of thromboembolic events during the endovascular treatment of ruptured cerebral aneurysms.¹ In this study, we present our experience of patients with ruptured aneurysms who suffered from thromboembolic complications during endovascular treatment. We also discuss the clinical course and management of thrombi in cases of ruptured cerebral aneurysms.

Patients and methods

From April 2006 to March 2017, we treated 70 patients presenting with subarachnoid hemorrhage (SAH) from cerebral aneurysms using the endovascular technique. The clinical data of analyzed 70 cases are summarized in Table 1. Fifty-eight patients were treated by simple endovascular techniques. Other patients were treated by endovascular embolization with a balloon-catheter in 11 or stent-assisted technique in one. Among them, five patients (7.1%) showed intra-arterial thrombus formation during the endovascular procedure. Four cases showing thromboembolic complications were treated by simple technique and one case by balloon-assisted embolization. The patients’ characteristics and clinical courses are summarized in Table 2. The age of the patients ranged from 44 to 87 years old. None of them took anticoagulant or antiplatelet agents transorally before the onset of SAH. For endovascular procedures, all solutions and materials were heparinized. The endovascular treatment was performed via femoral artery. Catheter flushing solutions contained 5000 IU of heparin per 500 ml. A guiding catheter with an inner catheter and guidewire was advanced to the parent artery. After angiography, a microcatheter was advanced to the lesion. If necessary, a balloon catheter was advanced prior to advancement of the microcatheter. A stent was advanced to the lesion after a microcatheter was advanced distal to the aneurysm. For a simple technique, heparin was intravenously administered after detachment of the first to third coil. Dosage of heparin was between 3000 and 5000 IU depending on the patients, with 1000 IU given every hour. For the lesions embolized with a balloon or stent, heparin was administered after insertion of the first platinum coil before detachment. After administration of heparin, the activating clotting time (ACT) was kept at between 250 and 300 seconds during the procedures. Regarding five patients with thrombus formations, the aneurysms were located at the anterior communicating artery (AComA) in two patients, basilar artery (BA) in two, and internal carotid artery (ICA) at the bifurcation of the anterior choroidal artery (AChoA) in one. The elevation of D-dimer was observed in one patient (Case 2) at the time of treatment. In the other two patients (Cases 1 and 4), the elevation of D-dimer was observed during the postoperative period. Another two patients (Cases 3 and 5) showed no elevation of D-dimer during the perioperative period. All five patients were treated endovascularly with platinum coils.

Table 1.

Summary of analyzed cases.

Number of cases (male/female)	70 (22/48)
Age (years)	43–91 (mean: 69.4)
SAH grade (H&K) (1: 2: 3: 4: 5)	10: 17: 26: 14: 3
Technique (with thromboembolic event)
Simple	58 (4)
Balloon-assisted	11 (1)
Stent-assisted	1 (0)
Location of aneurysm
ACA (A3)	3
AComA	13
BA tip	13
BA-SCA	8
IC-AChoA	3
IC-PComA	22
ICA (proximal to PComA)	1
MCA (M1)	2
VA-PICA	5
mRS at discharge (1: 2: 3: 4: 5: 6)	12: 17: 24: 8: 5: 4

ACA: anterior cerebral artery; AChoA: anterior choroidal artery; AComA: anterior communicating artery; BA: basilar artery; H&K: Hunt and Kosnic; ICA: internal carotid artery; MCA: middle cerebral artery; mRS: modified Rankin scale; PComA: posterior communicating artery; PICA: posterior inferior cerebellar artery; SCA: superior cerebellar artery; VA: vertebral artery.

Table 2.

Summary of five cases presenting with thromboembolism during endovascular treatment.

Case	Age (years)	Sex	Symptom	SAH grade (H&K)	Location of aneurysm	Period to coiling (days)	Size of aneurysm (mm)	Technique	Numbers and length of coils
1	87	F	Headache nausea	2	BA tip	One	7 × 4 × 4	Simple	9 (38 cm)
2	66	F	Headache nausea	2	AComA	Five hours	5.5 × 5 × 4	Simple	7 (40 cm)
3	48	M	Headache	2	IC-AChoA	Two	6 × 3 × 3	Simple	3 (12 cm)
4	78	F	Vomiting	2	AComA	11	7 × 5 × 3	Simple	5 (32 cm)
5	44	M	Headache vomiting	2	BA tip	Five hours	8 × 10 × 12	Balloon- assisted	10 (128 cm)
	d-dimer	Heparinization (timing and dose)	ACT (seconds)	Thrombus (location and timing)	Additional treatment	Results infarction	mRS	Follow-up
1	2.13 (Day 13)	After second coil 5000 IU	172 →282	Left PCA (distal) occluded after first coil	Heparin 3000 IU aspirin 200 mg clopidogrel 75 mg ↓ UK: 240 K IU	Recanalized CI (+)	4	Four months
2	2.04 (Day 0)	After third coil 3000 IU	124→180 →294 →331	Right A2 occluded after the last coil	Heparin 3000 IU aspirin 100 mg clopidogrel 75 mg ↓ UK: 240 K IU	Recanalized	3	One year, five months
3	0.64 (Day 0)	After first coil 5000 IU	108→301	Left AChoA not occluded after the last coil	Heparin 3000 IU aspirin 100 mg clopidogrel 75 mg	No occlusion CI (+)	1	Four months
4	2.04 (Day 6) 6.64 (Day 10)	After first coil 3000 IU	188→269 →219	Left M2 not occluded pre-coiling (GC advancement) thrombus from GC	Heparin 3000 IU aspirin 200 mg ↓ UK: 300 K IU	No occlusion	3	Two months
5	0.54 (Day 0)	After first coil 5000 IU	149→303	Bilateral PCA right occluded after the last coil	Heparin 5000 IU coil cast remodeling ↓ UK: 360 K IU	Recanalized	1	Three years, one month

AChoA: anterior choroidal artery; AComA: anterior communicating artery; ACT: activating clotting time; CI: cerebral infarction; F: female; GC: guiding catheter; H&K: Hunt and Kosnic; mRS: modified Rankin scale; IC: internal carotid artery; IU: international unit; PCA: posterior cerebral artery; UK: urokinase.

Results

Thrombus formation was observed in the posterior cerebral artery (PCA) in cases of BA tip aneurysms, A2 of the anterior cerebral artery (ACA) in an AComA aneurysm, AChoA in an IC-AChoA aneurysm, and middle cerebral artery (MCA) in an AComA aneurysm. The timing of thrombus formation was during coil delivery in four patients (Cases 1–3 and 5) and guiding catheter advancement in one (Case 4). In detail, after the completion of embolization, thrombus formation was detected in three cases (Cases 2, 3, and 5). Heparin was administered intravenously after the first coil placement in three cases, after the second coil placement in one, and after the third coil placement in one. In two patients, arteries were occluded by a thrombus (Cases 1 and 2). In the other two patients with IC-AChoA and AComA aneurysms (Cases 3 and 4), the thrombus was found in the AChoA originating from the aneurysm neck and M2 of the left MCA, respectively. The affected arteries were partially obstructed, and blood flow was observed on angiography. In a case of BA tip aneurysm treated by balloon-assisted embolization, the thrombi were found at the origin of bilateral PCA where a loop of coil protruded.

As for thrombus management, for three patients with a thrombus, additional heparinization and the administration of antiplatelet agents were conducted immediately after identification of the thrombus. Angiography showed no resolution of the thrombi; therefore, urokinase (UK) was injected into the affected arteries after confirmation of the aneurysm obstruction. For a case of BA tip aneurysm showing thrombi of bilateral PCA origin, an attempt was made to move the protruded coil loop by guidewire. However, recanalization was transient. Therefore, UK was injected subsequently. For another patient with a thrombus in the AChoA without complete occlusion, only heparin and two kinds of antiplatelet agents were administered.

Cerebral infarction was postoperatively noted in two patients. In one patient with a BA tip aneurysm (Case 1), cerebral infarction in the territory of the left PCA developed. In another patient with an ICA aneurysm (Case 3), a small infarction was found on diffusion-weighted images (DWI) of magnetic resonance images (MRI), although the AChoA was not completely occluded. Postoperative hemorrhage was not observed in any case.

The modified Rankin Scale (mRS) at discharge was grade 4 in one patient with cerebral infarction in the PCA territory, grade 3 in two patients, and grade 1 in two.

Case reports

Case 1

An 87-year-old woman with hypertension suddenly developed headache and nausea. Computed tomography (CT) on admission revealed SAH (Figure 1(a)). Angiography demonstrated an aneurysm at the BA tip (Figure 1(b)). Endovascular embolization of the aneurysm was conducted. Advancement of a guiding catheter to the left vertebral artery (VA) was very difficult. A catheter-exchanging technique using a long, stiff guidewire was necessary. It took time to advance the guiding catheter to the VA. After detachment of the second coil, 5000 IU of heparin was intravenously administered and ACT elongation from 172 to 282 seconds was achieved. After the completion of coiling, occlusion of the left PCA was observed on angiography (Figure 1(c)). Retrospective observation revealed that the thrombus had already formed after the first coil insertion. The occluded point was a distal site of the left PCA. Antiplatelet agents, such as 200 mg of aspirin and 75 mg of clopidogrel, were administered through a nasogastric tube. After that, repeated angiography showed no recanalization of the left PCA. Therefore, UK was injected into the left PCA. In the procedures, the microcatheter was inserted deeply into the left PCA just proximal to the occluded point (Figure 1(d)). Care was taken to avoid retrograde UK reflux into the proximal PCA. After the injection of 240,000 IU of UK, the PCA was recanalized (Figure 1(e)). Postoperative CT demonstrated cerebral infarction in the territory of the left PCA, but no hemorrhage (Figure 1(f)). Postoperatively, the patient developed pneumonia and heart failure. She was transferred to another hospital for rehabilitation with disuse syndrome on the 126th day.

Figure 1.

(a) CT on admission showing SAH. (b) Angiography demonstrating an aneurysm at the BA tip. (c) Post-embolization angiography showing occlusion of the aneurysm and occlusion of the left PCA (arrow). (d) A microcatheter is inserted deeply into the left PCA. (e) After treatment with UK, angiography showed recanalization of the left PCA. (f) Postoperative CT demonstrating a cerebral infarction in the left PCA territory, but no hemorrhage. CT: computed tomography; SAH: subarachnoid hemorrhage; BA: basilar artery; PCA: posterior cerebral artery; UK: urokinase.

Case 2

A 66-year-old woman suddenly developed headache and nausea. CT on admission demonstrated SAH (Figure 2(a)). Angiography showed an aneurysm at the AComA, and endovascular embolization was performed (Figure 2(b)). A guiding catheter was advanced to the left ICA. Insertion of the microcatheter to the AComA aneurysm was not difficult. After detachment of the third coil, 3000 IU of heparin was intravenously administered. Immediately after embolization with seven coils, the absence of artery occlusion was confirmed (Figure 2(c)). However, repeated angiography demonstrated occlusion of the right A2 of the ACA (Figure 2(d)). An additional 3000 IU of heparin was administered. Then, 100 mg of aspirin and 75 mg of clopidogrel were administered through a nasogastric tube. At this time, no recanalization was achieved (Figure 2(e)). A microcatheter was inserted into the orifice of the affected right ACA and a total of 240,000 IU of UK was injected. Recanalization of the ACA was achieved (Figure 2(f)). Postoperatively, neither cerebral infarction nor intracerebral hemorrhage was detected on MRI or CT (Figure 2(g)). Her postoperative course was uneventful. She was transferred to another hospital for rehabilitation on the 39th day.

Figure 2.

(a) CT on admission showing SAH. (b) Angiography demonstrating an aneurysm at the AComA. (c) Post-embolization angiography demonstrating patency of the bilateral ACAs. (d) Repeat angiography showing occlusion of the right A2 of the ACA (arrows). (e) After the administration of heparin and antiplatelet agents, angiography showed no recanalization of the right ACA. (f) After the injection of UK, angiography demonstrated recanalization of the right ACA (arrows). (g) DWI of MRI after treatment showing no infarction or hemorrhage. CT: computed tomography; SAH: subarachnoid hemorrhage; AComA: anterior communicating artery; ACA: anterior cerebral artery; UK: urokinase; DWI: diffusion-weighted imaging; MRI: magnetic resonance imaging.

Case 3

A 48-year-old man with a previously diagnosed left ICA aneurysm developed a severe headache. He visited a local hospital the next day. CT revealed a thin SAH in the left Sylvian fissure (Figure 3(a)), and MRI revealed enlargement of the pre-existing ICA aneurysm. He was referred to our hospital. Emergency angiography demonstrated a snowman-shaped aneurysm on the left ICA at the origin of the AChoA (Figure 3(b)). The AChoA originated from the neck of the aneurysm. Endovascular embolization was performed after angiography. The aneurysm was embolized with three platinum coils. After the first coil placement, 5000 IU of heparin was intravenously administered, and elongation of the ACT was achieved. On post-embolization angiography, thrombus formation was observed at two locations in the AChoA; however, the whole course of the AChoA was opacified (Figure 3(c)). Three thousand IU of heparin was added, and 100 mg of aspirin and 75 mg of clopidogrel were administered through a nasogastric tube. Angiography after 15 minutes revealed patency of the AChoA, despite the persistence of a thrombus (Figure 3(d)). Postoperatively, cerebral infarction in the territory of the AChoA was noted on MRI (Figure 3(e)). Angiography on the 11th day showed favorable patency of the AChoA and a small residual cavity of the aneurysm. His postoperative course was uneventful despite cerebral infarction. He was discharged without deficit on the 14th day.

Figure 3.

(a) CT showing a thin SAH mainly in the left Sylvian fissure. (b) Angiography demonstrating a snowman-shaped aneurysm on the ICA at the bifurcation of the AChoA. (c) Post-embolization angiography showing thrombi in the AChoA (arrows). The AChoA was not completely occluded. (d) Angiography after 15 minutes still showing thrombi in the AChoA and partial canalization of the artery. (E) Post-embolization MRI (DWI) showing a cerebral infarction in the territory of the left AChoA. CT: computed tomography; SAH: subarachnoid hemorrhage; ICA: internal carotid artery; AChoA: anterior choroidal artery; MRI: magnetic resonance imaging; DWI: diffusion-weighted imaging.

Case 4

A 78-year-old woman suddenly vomited. She visited a local hospital six days later. CT revealed SAH mainly in the interhemispheric fissure (Figure 4(a)), and MRI showed an aneurysm with a diameter of 5 mm at the AComA. Three-dimensional-CT angiography and angiography demonstrated that the aneurysm neck was wide and the right A1 was hypoplastic (Figure 4(b)). On day 11, endovascular embolization of the aneurysm was performed. Although one loop of the first coil protruded to the A2 origin, the loop was closely attached to the arterial wall and blood flow was sufficient (Figure 4(c)). After the first coil detachment, 3000 IU of heparin was intravenously administered. The aneurysm was embolized with a total of five coils. After embolization, angiography demonstrated a thrombus in the left M2 branch (Figure 4(d)). Therefore, 3000 IU of heparin and 200 mg of aspirin were additionally administered. However, the occluded artery was not recanalized. Then, 300,000 IU of UK was injected to the occluded M2 through a microcatheter inserted into the M2 branch, and recanalization was achieved (Figure 4(e)). In this patient, D-dimer was 2.04 and 6.64 on Days 6 and 10, respectively. Postoperatively, MRI demonstrated neither cerebral infarction (Figure 4(f)) nor hemorrhage in the left MCA territory. She showed mild right hemiparesis and aphasia immediately after embolization. The symptoms improved significantly on the next day. She was discharged with mild right hemiparesis on the 14th day.

Figure 4.

(a) CT showing a thin SAH. (b) Angiography demonstrating an aneurysm with a relatively wide neck at the AComA. (c) Angiography demonstrating the protrusion of a coil loop to A2. (d) Post-embolization angiography showing partial occlusion of the left M2 of the MCA (arrow). (e) Angiography after the injection of UK showing improvement of blood flow in the MCA branch (arrows). (f) MRI after treatment showing no fresh infarction in the territory of the left MCA. CT: computed tomography; SAH: subarachnoid hemorrhage; AComA: anterior communicating artery; MCA: middle cerebral artery; UK: urokinase.

Case 5

A 44-year-old man suddenly experienced headache and vomiting. CT demonstrated SAH (Figure 5(a)). Angiography demonstrated an aneurysm at the BA tip (Figure 5(b)). After angiography, endovascular embolization was performed. A guiding catheter was placed in the left VA. Advancement of the guiding catheter and microcatheter was not difficult. Initially, a balloon catheter was advanced to the left PCA. However, the balloon was unstable and it was not placed at the aneurysm neck and the left PCA orifice. Therefore, the balloon catheter was not inflated, but placed in the left PCA (Figure 5(c)). The first coil was inserted and detached in the aneurysm. A loop of the coil was located at the neck close to the right PCA orifice (Figure 5(c)). An attempt was made to insert a microguidewire or microcatheter into the right PCA, but this failed. After the first coil detachment, 5000 IU of heparin was administered. ACT elongation was achieved. Subsequently, a total of 10 coils were inserted and detached in the aneurysm cavity. Post-embolization angiography demonstrated occlusion of the right PCA (Figure 5(d)). A microcatheter was not able to be inserted into the right PCA. A microguidewire was inserted to the right PCA, and coil cast remodeling was performed by pushing the microguidewire. Transient recanalization of the right PCA was achieved. The thrombus was found at the coil protruding at the bilateral PCA origin (Figure 5(e)). Therefore, after confirmation of no aneurysm opacification with contrast medium, 360,000 IU of UK was injected from a microcatheter located at the top of the BA. The thrombus was reduced in size, but had not completely disappeared (Figure 5(f)). Angiography showed recanalization of the right PCA. The patient’s postoperative course was uneventful. No cerebral infarction was observed (Figure 5(g)). He was discharged without neurological deficit on the 39th day.

Figure 5.

(a) CT demonstrating SAH mainly in the basal cistern. (b) Angiography demonstrating an aneurysm at the BA tip. (c) A balloon catheter is advanced to the left PCA. After insertion of the first coil, a loop of the coil is located at the neck close to the right PCA orifice. (d) Post-embolization angiography demonstrating occlusion of the right PCA, and thrombus in the left PCA. (e) Angiography showing blood flow (arrow) in the left PCA after coil cast remodeling. (f) Angiography after UK injection showing opacification of the right PCA. (G) CT after treatment showing no cerebral infarction. CT: computed tomography; SAH: subarachnoid hemorrhage; BA: basilar artery; PCA: posterior cerebral artery; UK: urokinase.

Discussion

Thromboembolic complications during or immediately after endovascular embolization of cerebral aneurysms have been reported to occur during 3%–28% of procedures.^2,3 Thromboembolic complications induce perioperative morbidity. Therefore, avoiding thrombus formation during endovascular treatment is important. Once thromboembolism occurs, thrombus management by any method should be conducted.

In our five cases, thromboembolism occurred during coil delivery in four cases and guiding catheter advancement in one. In the former four cases, thrombi formed in related arteries distal or close to the aneurysms. In these cases, the anatomical factors of the lesions might have contributed to thrombus formation. On the other hand, in the last case, the thrombus formed in an unrelated artery far from the aneurysm. The thrombus had already formed during guiding catheter advancement. In this case, the treatment was conducted on the 11th day of SAH and an elevation of D-dimer had already been observed preoperatively. There is a report describing that high D-dimer correlates with systemic complications after SAH.⁴ In an acute stage of SAH, elevated D-dimer might relate to coagulopathy. Therefore, for such cases with elevated D-dimer, strict heparinization and antiplatelet therapy should be conducted before and during endovascular treatment.

As a treatment for thromboembolism during endovascular treatment for cerebral aneurysms, mechanical thrombectomy using a retrieval stent,^5,6 forced suction using a reperfusion catheter,⁷ and the intra-arterial administration of antiplatelet agents such as abciximab^2,8 and epitifibatide⁹ have been reported to be effective. Cho et al.³ reported patients who presented with hemorrhage after the intra-arterial infusion of abciximab for a thrombus during endovascular embolization. They used tirofiban instead of abciximab, and reported its usefulness. Feng et al.¹⁰ reported the effectiveness of the combined use of tirofiban and UK for thromboembolic complications during coil embolization. However, the application of UK is restricted during the endovascular coiling of ruptured aneurysm cases because of a significant risk of cerebral hemorrhage.⁹ Hayashi et al.¹¹ reported a case of a ruptured AComA aneurysm presenting with thromboembolism in the ACA during endovascular treatment. The patient was treated with a local infusion of 240,000 IU of UK and recanalization was achieved. However, a small hemorrhage adjacent to the embolized AComA aneurysm developed. Cronqvist et al.¹² reported 19 cases of thromboembolism treated with UK. Among them, two patients showed hemorrhage due to aneurysm rerupture, and one had intracerebral hemorrhage. They concluded that clot fragmentation and superselective drug infusion improved the rate of recanalization. Although there are some reports describing the effectiveness of UK, it is associated with a risk of bleeding and rerupture of the aneurysm. The intra-arterial infusion of UK was conducted for our cases because there were no available drugs to treat thrombi other than UK. In Japan, the above-mentioned antiplatelet agents such as abciximab, epitifibatide, and tirofiban are available only in the field of coronary intervention. However, these antiplatelet agents are also associated with a risk of hemorrhage. Therefore, a new agent applicable for thromboembolism in the central nervous system must be introduced to reduce the risk of intracranial hemorrhage.¹⁰

In our cases, heparin was administered intravenously, and antiplatelet agents were administered transorally prior to the induction of UK fibrynolysis. Even after the embolization of aneurysms, rebleeding from the coiled aneurysm could occur. Kang et al.¹³ reported that an uneven distribution of the coil masses and the spontaneous resolution of a thrombus among the strands of coils could be a possible mechanism of rebleeding. Therefore, even after embolization, the use of thrombolytic agents might still involve a risk of causing rebleeding from the aneurysm. It has been reported that the decision to perform thrombolysis with thrombolytic agents should be based on the involved vascular territory and blood flow pattern including collateral blood supply.¹¹ It has also been reported that mechanical destruction of the thrombus should be performed prior to thrombolysis to avoid rebleeding.¹² Although intracranial hemorrhage did not occur after UK injection in our cases, UK use involves the risk of inducing hemorrhage. Therefore, thrombolysis using UK is not recommended as the first choice for thromboembolic events. For the injection of fibrinolytic agents, the microcatheter should be advanced as far as possible from the aneurysm to prevent the agent from flowing into the embolized aneurysms or other nonaffected arteries.

As for antiplatelet therapy during the endovascular embolization of ruptured cerebral aneurysms, Shimamura et al.¹⁴ reported that preoperative dual-antiplatelet therapy leads to a low rate of thromboembolic events and this strategy has no adverse influence on bleeding complications. Ries et al.¹ reported that the intravenous administration of acetylsalicylic acid after the detachment of the first coil reduced thromboembolic events during the endovascular embolization of ruptured and unruptured aneurysms. Concerning the timing of heparinization, Cronqvist et al.¹² reported that heparinization was started as soon as the introducer sheath was inserted. The timing of heparinization and antiplatelet therapy in our cases was delayed compared with the above-mentioned reports. And thromboembolism occurred before or during the first coil placement in two cases. Even for ruptured aneurysms, adequate heparinization and treatment of antiplatelet agents with proper timing are needed. Regarding the timing of heparinization, Pelz et al. reported that they performed bolus injection of heparin at the beginning of the procedures even for cases of acute SAH. Other reports also described heparinization before guiding-catheter placement.¹⁵ Therefore, systemic heparinization after guiding-catheter placement might be ideal. And the close observation of parent arteries on serial angiography is necessary to promptly identify thromboembolic events.

Conclusion

For the endovascular treatment of cerebral aneurysms, heparinization, and the administration of antiplatelet agents should be conducted appropriately and close observation of the artery condition on angiography is mandatory. Once thromboembolism occurs, anticoagulant or antiplatelet agents should first be used followed by mechanical destruction of the thrombus, if possible.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was partly supported by research funds to promote the hospital functions of Japan Organization of Occupational Health and Safety to M.N.