Abstract
In this study, we aimed to compare the treatment outcomes of patients with unruptured aneurysms treated using stent-assisted coil embolization with and without systemic heparinization to examine the intraoperative systemic heparinization efficacy. We included 106 consecutive patients enrolled at Fukuoka Neurosurgical Hospital, Japan, between November 2021 and March 2023. The patients were divided into two groups: the systemic heparinization and nonsystemic heparinization groups. Head magnetic resonance imaging (MRI) performed on postoperative day 1 showed that the number of ischemic foci <2 mm was higher in the nonsystemic heparinization group than in the systemic heparinization group, although the difference was not statistically significant (2 [0–6] vs 1 [0–3], P = .0583). No significant between-group difference was observed concerning the incidence of ischemic and hemorrhagic complications. There was no significant between-group difference regarding the modified Rankin scale (mRS) score; however, the systemic heparinization group had a higher proportion of patients with poor outcomes than did the nonsystemic heparinization group, with one (2.4%) patient with an mRS score of 5 and one (2.4%) patient with an mRS score of 6. In conclusion, intraoperative systemic heparinization during stent-assisted coil embolization of unruptured cerebral aneurysms may suppress diffusion-weighted imaging high-signal spots on head MRI performed on postoperative day 1. Moreover, systemic heparinization may worsen the outcomes of hemorrhagic complications.
Keywords: Intracranial aneurysm, stent-assisted coiling, heparinization, hemorrhagic complication, ischemic complication
Introduction
Intraoperative heparin administration during stent-assisted coil embolization of unruptured cerebral aneurysms is expected to effectively suppress embolic complications. Therefore, local heparinization by continuous irrigation of each catheter with heparinized saline during surgery and systemic heparinization by bolus administration of heparin are routinely performed. Heparin prevents intraoperative embolism by activating antithrombin and suppressing the coagulation system through its anticoagulant properties. Notably, after intravenous administration, heparin exerts its effects rapidly, with a half-life of approximately 40–90 min in the blood, making its use suitable for the duration of neuroendovascular procedures. Furthermore, its effects can be reversed with the addition of protamine. Reportedly, heparin use prevents embolic complications, 1 particularly in endovascular procedures, and it is routinely used during coil embolization. Furthermore, safety studies have shown that intraoperative heparin use does not increase hemorrhagic complications, especially after surgical procedures such as external ventricular drain. 2 On the other hand, a study of coil embolization for ruptured aneurysms using the Neuroform Atlas (Stryker Fremont, California, USA) showed no increase in embolic complications, regardless of whether heparin was administered or not. 3 Moreover, there are reports that heparin administration does not suppress postoperative DWI hyperintensity, 4 and therefore, there is no consensus on the necessity of heparin administration during endovascular procedures.2,5,6 In this study, we aimed to verify the hypothesis that systemic heparinization by heparin bolus administration during stent-assisted coil embolization of unruptured cerebral aneurysms improves postoperative outcomes. We retrospectively assessed the efficacy of systemic heparinization by comparing the perioperative complications between patients who underwent stent-assisted coil embolization for unruptured cerebral aneurysms with systemic heparinization and those who underwent the procedure without systemic heparinization.
Methods
Patient selection
We included 106 consecutive patients who underwent stent-assisted coil embolization of unruptured cerebral aneurysms at Fukuoka Neurosurgical Hospital between November 2021 and March 2023. During this period, the patients were divided into two groups: those who used heparin in the first half and those who did not use heparin in the second half: the systemic heparinization group (n = 42) comprised patients who were administered systemic heparinization, and the nonsystemic heparinization group (n = 64), in which systemic heparinization was not performed.
Procedure methods
Oral administration of aspirin (100 mg or 81 mg) and clopidogrel (75 mg) or prasugrel (3.75 mg) was initiated at least 5 days before surgery. In cases of emergency surgery, aspirin (200 mg or 162 mg) and clopidogrel (300 mg) or prasugrel (20 mg) were administered as boluses. The efficacy of the antiplatelet drugs was evaluated using VerifyNow (Accumetrics, San Diego, CA, USA). Cases with P2Y12 reaction units (PRUs) > 230 or aspirin reaction units (ARUs) > 550 were considered to be refractory to the respective antiplatelet drugs; accordingly, a boost of aspirin, clopidogrel, or prasugrel was administered based on the values of ARUs or PRUs.
All procedures were performed under general anesthesia using the femoral artery approach. In the systemic heparinization group, after confirming that there was no contrast medium leakage after sheath placement, unfractionated heparin was intravenously administered at 3000–5000 units, as necessary, for systemic heparinization. Each catheter used in the surgery was continuously irrigated with heparinized saline (3000 units of unfractionated heparin mixed with 500 mL of saline) to achieve local heparinization. Regarding stents, Neuroform Atlas was used for aneurysms with severely tortuous blood vessels or bifurcation-type aneurysms, and low-profile visualized intraluminal support (Terumo, Tokyo, Japan) was used for aneurysms with relatively straight blood vessels or sidewall-type aneurysms. In principle, stents were used according to the abovementioned criteria; however, the final choice of stent was made by the attending surgeon. In one patient, the aneurysm was located in the cervical segment of the internal carotid artery (ICA), and coil embolization was performed with the support of Carotid WALLSTENT (Boston Scientific, Santa Rosa, California, USA).
Assessment method
Patient characteristics
Data such as patient age, sex, medical history, and smoking history were extracted from electronic medical records. The medical history included the presence or absence of hypertension, dyslipidemia, and diabetes mellitus. Smoking history was categorized as current, past, or never. Data on the ARU and PRU were also extracted from the VerifyNow results on the day before surgery.
Lesion assessment
Radiological imaging was used to evaluate the lesions. The height, width, and neck diameter of the cerebral aneurysm; aneurysm location; and the presence or absence of branch vessels were evaluated. The diameter of the parent vessel of the aneurysm was also measured. Location was classified into four types: anterior cerebral artery, ICA, middle cerebral artery (MCA), and posterior circulation. Data on the type of stent used during surgery and the operation time were also extracted.
Postoperative assessment
Head magnetic resonance imaging (MRI) was performed on the morning after surgery in all patients, and ischemic lesions were evaluated using MRI-diffusion-weighted imaging (DWI). Spot lesions with high DWI signals were classified as < 2 mm, 2–5 mm, and ≥5 mm, and the number of such spots was counted.
Data on postoperative ischemic and hemorrhagic complications were also collected. Ischemic complications were defined as cases with DWI positivity on head MRI performed the morning after surgery, with the presence of neurological symptoms at the same site. Hemorrhagic complications were defined as cases in which extravasation was observed during the operation and subarachnoid or intracerebral hemorrhage was observed on postoperative head MRI or computed tomography (CT).
Data were also extracted for cases in which the National Institutes of Health Stroke Scale (NIHSS) score worsened by ≥ 4 points after surgery. Data on the length of hospital stay and modified Rankin scale (mRS) scores at discharge were also extracted.
Statistical analyses
Dichotomous variables were expressed as numbers and percentages. Continuous variables were expressed as medians and first-to third-quartiles. Differences between the two groups for dichotomous variables were determined using Fisher’s exact test. Differences in continuous variables between the two groups were determined using the Mann–Whitney U test. P-values <0.05 were considered statistically significant. The statistical software used for the analysis was GraphPad Prism 9 (San Diego, CA, USA) or EZR version 2.13.0 (Saitama Medical Center, Jichi Medical University, Omiya, Saitama, Japan).
Results
Patient characteristics
The patient characteristics are summarized in Table 1. There were no significant differences regarding age (P = .301), sex (P = .0906), medical history (hypertension, hyperlipidemia, and diabetes mellitus; P = 1, .828, .76, respectively), or smoking history (P = .743) between the systemic and nonsystemic heparinization groups. The width (4.1 mm vs 5.5 mm, P = .000627), height (3.5 mm vs 4.9 mm, P = .0304), and neck (3.20 mm vs 4.12 mm, P = .00565) of the aneurysms were larger in the systemic heparinization group than in the nonsystemic heparinization group. No significant differences were observed regarding the parent vessel diameter (P = .708), aneurysmal branch (P = .217), or aneurysm location (P = .237) between the two groups. There were no significant differences regarding the VerifyNow results (ARU, PRU; P = .458, P = .754, respectively).
Table 1.
Comparison of characteristic data between cases of aneurysm treated with stent-assisted coiling with and without systemic heparinization.
| Variables | Nonsystemic heparinization (n = 64) | Systemic heparinization (n = 42) | P |
|---|---|---|---|
| Age, years (IQR) | 67 (53.75–76) | 69.5 (58.75–78) | 0.301 |
| Men (n (%)) | 24 (37.5) | 9 (21.4) | 0.0906 |
| Medical history (n (%)) | |||
| Hypertension | 29 (45.3) | 19 (45.2) | 1 |
| Hyperlipidemia | 18 (28.1) | 13 (31.0) | 0.828 |
| Diabetes mellitus | 8 (12.5) | 4 (9.5) | 0.76 |
| Smoking history (n (%)) | 0.743 | ||
| Never-smoker | 42 (65.6) | 30 (71.4) | |
| Past smoker | 8 (12.5) | 3 (7.1) | |
| Current smoker | 14 (21.9) | 9 (21.4) | |
| Aneurysmal characteristics | |||
| Width (IQR) | 4.1 (3.25–5.5) | 5.5 (4.10–7.6) | 0.000627 |
| Height (IQR) | 3.5 (2.8–4.7) | 4.9 (3.0–6.2) | 0.0304 |
| Neck (IQR) | 3.20 (2.495–4.1) | 4.12 (3.2–4.6) | 0.00565 |
| Parent artery diameter (IQR) | 2.20 (1.89–3.25) | 2.55 (1.8125–3.25) | 0.708 |
| Aneurysmal branch (n (%)) | 54 (84.4) | 31 (73.8) | 0.217 |
| Aneurysmal location (n (%)) | 0.237 | ||
| ACA | 4 (6.25) | 0 (0.0) | |
| ICA | 45 (70.3) | 27 (64.3) | |
| MCA | 10 (15.6) | 11 (26.2) | |
| Posterior circulation | 5 (7.8) | 4 (9.5) | |
| VerifyNow | |||
| ARU (IQR) | 396 (387.5–415) | 400 (390.25–468.25) | 0.458 |
| PRU (IQR) | 138 (93–187.5) | 147 (99.75–182) | 0.754 |
IQR: interquartile range; ACA: anterior cerebral artery; ARU: aspirin reaction unit; PRU: P2Y12 reaction unit.
Outcomes
The outcome results are summarized in Table 2. There was no significant between-group difference regarding the type of stent used (P = .521) or operation time (P = .436). Although there was no statistically significant difference in head MRI results on the first postoperative day, patients in the nonsystemic heparinization group showed a higher number of ischemic foci than those in the systemic heparinization group, especially for foci <2 mm (2 [0–6] vs 1 [0–3], P = .0583). No significant differences were observed in the incidence of ischemic or hemorrhagic complications (P = 1.0). One (1.6%) patient in the nonsystemic heparinization group had an NIHSS score that worsened by ≥ 4 points, compared with three (7.1%) patients in the systemic heparinization group. There was no significant between-group difference in terms of the mRS score at discharge (P = .469); however, the systemic heparinization group tended to have a higher proportion of cases with poor outcomes than the nonsystemic heparinization group, with one (2.4%) patient with an mRS score of 5 and one (2.4%) with an mRS score of 6. These patients presented with hemorrhagic complications. The data of patients with complications are summarized in Table 3.
Table 2.
Comparison of outcome between cases of aneurysm treated with stent-assisted coiling with and without systemic heparinization.
| Variables | Nonsystemic heparinization (n = 64) | Systemic heparin (n = 42) | P |
|---|---|---|---|
| Stent type | 0.521 | ||
| Neuroform Atlas | 39 (60.9) | 24 (57.1) | |
| LVIS | 25 (39.1) | 17 (40.5) | |
| Carotid WALLSTENT | 0 (0.0) | 1 (2.4) | |
| Operation time | 56 (47–79.25) | 63.5 (49.75–80.75) | 0.436 |
| MRI-DWI spot postoperative day 1 | |||
| <2 mm (IQR) | 2 (0–6) | 1 (0–3) | 0.0583 |
| 2–5 mm (IQR) | 0 (0–1.25) | 0 (0–1) | 0.498 |
| >5 mm (IQR) | 0 (0–1) | 0 (0–0) | 0.462 |
| Ischemic complication (n (%)) | 3 (4.7) | 2 (4.8) | 1 |
| Hemorrhagic complication (n (%)) | 3 (4.7) | 2 (4.8) | 1 |
| Cases of NIHSS >4 (n (%)) | 1 (1.6) | 3 (7.1) | 0.298 |
| Hospitalization duration (IQR) | 6 (5–11.00) | 6 (4–10.75) | 0.946 |
| mRS score at discharge | 0.469 | ||
| 0 | 46 (71.9) | 28 (66.7) | |
| 1 | 5 (7.8) | 2 (4.8) | |
| 2 | 9 (14.1) | 4 (9.5) | |
| 3 | 1 (1.6) | 3 (7.1) | |
| 4 | 1 (1.6) | 2 (4.8) | |
| 5 | 1 (1.6) | 1 (2.4) | |
| 6 | 0 (0.0) | 1 (2.4) |
DWI: diffusion-weighted imaging; IQR: interquartile range; MRI: magnetic resonance imaging; LVIS: low-profile visualized intraluminal support; NIHSS: National Institutes of Health Stroke Scale.
Table 3.
Summary of complication cases after stent-assisted coiling of aneurysms.
| Variable | With or without heparinization | Age (year) | Sex | Aneurysmal size (width, height, and neck, mm) | Location | Heparin dose (unit/BW) | Stent type | Pre-mRS | mRS score at discharge |
|---|---|---|---|---|---|---|---|---|---|
| Ischemic complication | Without heparinization | 81 (32068) | M | 11.0, 8.1, 6.3 | ICA | Neuroform Atlas | 0 | 0 | |
| 78 (32135) | F | 3.5, 4.9, 3.3 | ICA | LVIS | 0 | 0 | |||
| 39 (32203) | M | 3.8, 2.7, 3.5 | ICA | LVIS | 2 | 2 | |||
| With heparinization | 69 (29934) | M | 8.3, 13.2, 5.3 | ICA | 50.8 | Neuroform Atlas | 0 | 4 | |
| 70 (31466) | F | 9.9, 6.5, 6.3 | MCA | 93.0 | Neuroform Atlas | 3 | 0 | ||
| Hemorrhagic complication | Without heparinization | 62 (32273) | M | 3.0, 5.5, 2.8 | ICA | LVIS | 2 | 2 | |
| 63 (32900) | F | 5.0, 3.8, 1.4 | ICA | LVIS | 0 | 0 | |||
| 63 (33868) | F | 4.8, 2.8, 2 | ICA | Neuroform Atlas | 0 | 5 | |||
| With heparinization | 58 (33379) | F | 8.0, 6.2, 4.6 | Posterior | 55.2 | Neuroform Atlas | 0 | 5 | |
| 72 (33541) | F | 10.7, 7.8, 10.7 | MCA | 53.4 | Neuroform Atlas | 0 | 6 |
BW: body weight; M: male; F: female; LVIS: low-profile visualized intraluminal support; ICA: inferior cerebral artery; MCA: middle cerebral artery; Posterior: posterior circulation; mRS: modified Rankin scale.
Representative cases
Case 1
A 72-year-old female.
The patient had undergone wrapping for an unruptured right MCA aneurysm at another hospital 7 years prior. She had a medical history of hypertension, dyslipidemia, and cerebral infarction. Owing to the history of cerebral infarction, the patient had residual right hemiparesis. Before surgery, the patient was able to walk using a cane, and her mRS score was 2. The aneurysm was located at the bifurcation of the right MCA and was 10.7 mm wide, 7.8 mm high, and had a 10.7-mm neck (Figure 1(a)). Under general anesthesia, a 6-F sheath was inserted into the right femoral artery, and a 5-F sheath was inserted into the left femoral artery. After sheath insertion, no contrast leakage was observed, and 3000 units of heparin (53.4 units/kg body weight) were administered. A 6-F guiding catheter was placed in the right ICA, and a 5-F guiding catheter was inserted into the right ICA. A SHORYU2 HR (Kaneka, Tokyo, Japan) balloon catheter was inserted through the 5-F guiding catheter to prepare for hemostasis in case of rupture. A microcatheter was inserted into the M2 superior trunk for stent placement. However, the proximal part of the microcatheter fell into the aneurysm. The microcatheter was then anchored to the M2 superior trunk using a stent retriever, pulled, and straightened. A microcatheter was then inserted into the M2 inferior trunk, and a Neuroform Atlas 4.5-mm × 30-mm stent was deployed. A microcatheter and flaming coil were inserted into the aneurysm. A confirmatory scan showed contrast leakage from the M2 superior trunk (Figure 1(b)). Heparin reversal was performed by administering 100 mg of protamine, and blood flow was blocked using an SHORYU balloon to achieve hemostasis (Figure 1(c)). A coil was inserted simultaneously with the hemostasis procedure, and hemostasis was confirmed (Figure 1(d)). The patient’s level of consciousness worsened postoperatively, and head CT revealed intracerebral hemorrhage and subarachnoid hemorrhage, primarily in the right temporal lobe (Figure 1(e)). Although an emergency craniotomy was performed on the same day to remove the hematoma, the patient died 6 days after the operation.
Figure 1.
Right internal carotid artery imaging reveals an irregular cerebral aneurysm at the bifurcation of the M1/2 of the right middle cerebral artery (a). Right internal carotid artery imaging during coil insertion reveals contrast agent extravasation from the M2 superior trunk of the right middle cerebral artery (white arrow) (b). Hemostasis was performed using an SHORYU2 HR balloon catheter (c). Right internal carotid artery imaging at the end of surgery reveals no contrast agent extravasation (d). Postoperative head computed tomography plain imaging reveals intracerebral hemorrhage and subarachnoid hemorrhage in the right temporal lobe.
Case 2
A 63-year-old male.
The patient had previously visited the neurosurgery department of another hospital for the treatment of diabetes mellitus and hypertension. An unruptured right ICA-posterior communicating artery bifurcation aneurysm was identified. He visited the same hospital because he developed symptoms of ptosis, and head MRI revealed enlargement of the aneurysm. He was diagnosed with an imminent aneurysmal rupture and referred to our hospital for further treatment. As he was already taking 75 mg of clopidogrel, he was started on 162 mg of oral aspirin. VerifyNow confirmed that his ARU was 505 and PRU was 195, both within the optimal range. Therefore, we decided to perform stent-assisted coil embolization to prevent aneurysmal rupture. The aneurysm was 3.0 mm wide, 5.5 mm high, and had a 2.8-mm neck (Figure 2(a)). A 6-F sheath was placed in the right femoral artery and a 5-F sheath in the left femoral artery. A 5-F guiding catheter was placed in the right ICA from the left femoral artery, and an SHORYU2 HR was placed for hemostasis in the event of a rupture. A 6-F guiding catheter was inserted into the right ICA from the right femoral artery. The microcatheter was guided to the right M2, and a low-profile visualized intraluminal support of 4 × 17 mm was deployed. A microcatheter was inserted into the aneurysm using a guiding catheter, and coil embolization was performed. During the coil insertion, the coil deviated from the aneurysm. Although the coil was continuously inserted, and images were obtained to confirm this, extravasation of the contrast medium was observed (Figure 2(b)). Therefore, balloon hemostasis was performed using the SHORYU catheter, as described previously. Subsequent imaging confirmed hemostasis, and the procedure was terminated (Figure 2(c) and (d)). The patient recovered well after the surgery, and there were no new neurological findings. A slight subarachnoid hemorrhage was observed the day after surgery (Figure 2(e)).
Figure 2.
Right internal carotid artery imaging reveals a cerebral aneurysm at the bifurcation of the right internal carotid artery and posterior communicating artery (a). Right internal carotid artery imaging during coil insertion reveals faint contrast agent extravasation (black circle) (b). Right internal carotid artery imaging at the end of surgery reveals no contrast agent extravasation. The aneurysm was filled with coils, confirming complete occlusion (c), (d). Fluid-attenuated inversion recovery magnetic resonance imaging of the head performed the day after surgery reveals signs of subarachnoid hemorrhage in both Sylvian fissures (e).
Discussion
We compared complication occurrence in patients with unruptured cerebral aneurysms treated using coil embolization with versus without systemic heparinization using heparin bolus administration. In the evaluation of acute ischemic foci using head MRI after coil embolization, there was a tendency for fewer ischemic foci in the systemic heparinization group, although the difference was not statistically significant. However, there was no significant between-group difference in the incidence of ischemic and hemorrhagic complications. Furthermore, when examining the outcomes of hemorrhagic complications in detail, the patients in the nonsystemic heparinization group had a good outcome, except for one patient who developed hemorrhage (mRS score, 5), whereas the patients in the systemic heparinization group had a poor prognosis, with two patients developing hemorrhage: one with an mRS score of 5 and one with an mRS score of 6.
Systemic heparinization via heparin bolus administration during stent-assisted coil embolization for unruptured cerebral aneurysms has been previously reported.2,5,6 Heparin dose significantly reduces the postoperative DWI positivity rate. 2 This study also demonstrated that systemic heparinization is likely to suppress new ischemic lesions. However, the presence or absence of systemic heparinization during coil embolization using the Neuroform Atlas in cases of ruptured aneurysms does not increase the incidence of embolic complications. 7 Furthermore, the administration of heparin during the endovascular treatment of unruptured aneurysms cannot prevent embolic complications. 3 However, the longer the operation time, the higher the DWI positivity rate. 8 Therefore, ischemic complications did not clearly increase even without systemic heparinization in this study because of the development of devices used in endovascular surgery and the associated reduction in operation time. Furthermore, local heparinization of each catheter using heparinization alone may be sufficient to suppress ischemic complications. In addition, when comparing the number of postoperative DWI high signals with and without ischemic complications in this study, a significant difference was observed in the number of ischemic foci ≥5 mm, but no significant difference was observed in the number of ischemic foci <5 mm (Figure 3). Considering that the ischemic foci that can be prevented by systemic heparinization are lesions <2 mm in size, based on the results of this study, systemic heparinization may have little effect on preventing ischemic complications. In our previous study using CAS, ischemic lesions <2 mm in size were not found to be associated with ischemic symptoms. 6 The treatment of unruptured cerebral aneurysms is currently being performed by conventional stent coil embolization instead of treatment using flow diverters.9,10 Although the amount of metal coverage with the flow diverters is greater than that with conventional stents, the operation time is relatively short. This indicates the need for further investigations into whether systemic heparinization is necessary when using flow diverters.
Figure 3.
Number of diffusion-weighted imaging high-signal spots by size in head magnetic resonance imaging performed the day after surgery. Comparison of ischemic complications between the two groups (upper row) and comparison with and without systemic heparinization (lower row).
Hemorrhagic complications during stent-assisted coil embolization should also be considered. In particular, because stent-assisted coil embolization requires insertion of a microcatheter into the aneurysm, it is difficult to eliminate this complication completely. Although several previous studies have reported the safety of heparin use, no studies have compared the use of systemic heparinization with or without it.11,12 The safety of heparin has been emphasized because it can be reversed using protamine. In cases of intraoperative coil embolization of cerebral aneurysms, except for coil dislodging from the aneurysm, intraoperative changes in vital signs are often observed. However, in approximately 40% of cases in which intraoperative rupture occurs, there are no changes in vital signs. 13 To clarify further, even if intraoperative rupture occurs, there are cases wherein bleeding continues unnoticed during surgery and cases wherein increased bleeding due to the effect of heparin at the time of intraoperative rupture cannot be avoided, which may have led to the high number of poor outcomes in the systemic heparinization group in this study.
If this study proves that systemic heparinization is not necessary for coil embolization of unruptured aneurysms, it may expand the treatment options for cerebral aneurysms in cases where heparin cannot be used owing to puncture site problems associated with systemic heparinization or heparin-induced thrombocytopenia,2,4 and further studies are required in the future.
Limitations
This study has some limitations. First, the study had a small sample size. Given that the DWI positivity rate was higher in the nonsystemic heparinization group than in the systemic heparinization group, the incidence of ischemic complications may increase in the nonsystemic heparinization group as the number of cases increase. However, it may be postulated that the number of cases with poor prognosis due to bleeding complications will also increase in the systemic heparinization group. Therefore, to verify whether systemic heparinization is necessary for the stent-assisted coil embolization of unruptured cerebral aneurysms, randomized controlled trials and further studies with larger sample sizes are necessary. Second, there were between-group differences in terms of aneurysm background. This study was not a randomized trial, and based on the study design, the patients treated in the first part of the study period were enrolled in the systemic heparinization group and those treated in second part of the study period were enrolled in the nonsystemic heparinization group, resulting in differences in patient backgrounds. In this study, aneurysms tended to be larger in the systemic heparinization group than in the nonsystemic heparinization group. However, reportedly, bleeding complications are more likely to occur in small aneurysms,1,14 and large aneurysm size may have had little effect on bleeding complications in the systemic heparinization group. Third, the effectiveness of heparin could not be assessed. Heparin effectiveness is usually assessed using activated clotting time (ACT). 11 At our institution, we do not routinely measure ACT to assess heparin effectiveness. Furthermore, the effects of local continuous heparin perfusion could be analyzed in more detail by local blood sampling using ACT. Further studies are warranted to verify this.
Conclusion
Systemic heparinization during stent-assisted coil embolization of unruptured cerebral aneurysms may suppress high-signal spots on MRI-DWI on the day after surgery. However, no difference is observed in the incidence of ischemic and hemorrhagic complications with or without systemic heparinization during surgery. Systemic heparinization may worsen the outcome of hemorrhagic complications.
Footnotes
Author contributions: All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Takashi Fujii. The first draft of the manuscript was written by Takashi Fujii, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical considerations
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Ethics Committee of our hospital.
Consent to participate
Because this study was a retrospective study and all data in this study were anonymized, informed consent from each of the eligible patients was substituted by the opt-out method.
ORCID iD
Takashi Fujii https://orcid.org/0000-0002-2551-1144
Data Availability Statement
All supporting data are available from the corresponding author upon reasonable request.*
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All supporting data are available from the corresponding author upon reasonable request.*