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Anterior Communicating Artery Aneurysm: Incidental AcomA Aneurysm, pCONus-assisted Coil Occlusion, Intracerebral Hematoma due to Hyper-response on Aspirin and Clopidogrel

  • Marta Aguilar Pérez
  • Muhammad AlMatter
  • Hansjörg Bäzner
  • Hans HenkesEmail author
Living reference work entry
  • 98 Downloads

Abstract

A small wide-necked incidental aneurysm of the anterior communicating artery (AcomA) was found in a 65-year-old woman, who was healthy apart from a history of mild arterial hypertension. After discussing all potential management options with the patient and her husband, the final decision was taken to treat the aneurysm by coil occlusion, assisted by a pCONus stent (phenox). The patient was prepared for the stent implantation with dual platelet function inhibition through acetylsalicylic acid (ASA) and clopidogrel. The endovascular procedure was carried out as intended. A pCONus_mini was implanted via the left internal carotid artery and the left A1 segment, with its distal end level with the neck of the AcomA aneurysm, followed by the coil occlusion of the aneurysm. The following morning after this procedure, the patient became aphasic and observed a visual field cut to the right. MRI showed a 5.5 × 3.5 × 3.5 cm intracerebral hematoma in the left temporal and occipital lobe, which was managed conservatively. Multiplate tests (Roche Diagnostics) revealed a hyper-response to the ASA and clopidogrel, which required a monitored dosage reduction of both medications. The phenomenon of hyper-response to medical antiaggregation and the management of this condition are the main topics of this chapter.

Keywords

AcomA pCONus Dual antiplatelet therapy (DAPT) ASA Clopidogrel Hyper-response 

Patient

A 65-year-old, female patient, presenting with an episode of transient global amnesia, with a medical history of well-controlled arterial hypertension, hypercholesterolemia, gluten sensitive enteropathy, and lactose intolerance.

Diagnostic Imaging

In December 2014, this female patient presented with an episode of transient global amnesia to the referring hospital. The diagnostic imaging, comprising of CT/CTA, MRI/MRA, and DSA, revealed a small, wide-necked AcomA aneurysm and was otherwise unremarkable (Fig. 1).
Fig. 1

2D CTA (a), 3D CTA (b), TOF MRA (c), contrast-enhanced MRA (d), and DSA with injection of the right ICA (e) and of the left ICA (f), both in posterior-anterior projection, show an AcomA aneurysm with a fundus diameter of 4 mm and a neck width of 3 mm. The right A1 segment is missing and both ACAs are supplied via the left ICA

Treatment Strategy

The significance of the aneurysm was discussed with the patient and her husband. An annual rupture risk of 1% and fatality and handicap rate of 35%, respectively, per subarachnoid hemorrhage (SAH) were quoted. Conservative management with follow-up imaging, microsurgical clipping, and stent-assisted coil occlusion were factually described. The patient decided on endovascular coil occlusion. The goal of the treatment was to prevent an intracranial aneurysm hemorrhage.

Treatment

Procedure, 04. 02. 2015: pCONus-assisted coil occlusion of an unruptured, small, wide-necked AcomA aneurysm

Anesthesia: general anesthesia; 500 mg thiopental (Trapanal, Nycomed) IV, 3000 IU unfractionated heparin (Heparin Natrium, B. Braun) IV, 1 mg glyceroltrinitrate (Nitrolingual infus., Pohl-Boskamp) IA, 10 ml nimodipine IA in the pressurized flush of the guide catheter (Nimotop S, Bayer Vital)

Premedication: 1× 100 mg ASA (Aspirin, Bayer Vital) PO daily for several years, 1× 600 mg clopidogrel PO (Plavix, Sanofi-Aventis) on 3 February 2015; a Multiplate test (Roche Diagnostics) on 4 February 2015 confirmed the dual platelet function inhibition

Access: right femoral artery; 8F sheath (Terumo); guide catheter: 8F Guider Softip (Boston Scientific); microcatheters: RapidTransit (Codman) for the pCONus, Excelsior SL-10 (Stryker) for the coil insertion; microguidewire: Synchro2 0.014″ 200 cm (Stryker)

Implants: Stent: 1× pCONus_mini 3/20/4 mm (i.e., 3 mm shaft diameter, 20 mm length, 4 mm wingspan of the distal petals); coils, 1× Target 360° nano 3/8, 1× Target 360° nano 2/4, 1× Target helical ultra 1.5/4 (removed) (all Stryker).

Course of treatment: A continuously flushed 8F guide catheter with dual rotating hemostatic valves was inserted into the left ICA. Despite the significant elongation of the cervical left ICA, the catheterization of the neck level of the AcomA aneurysm with the RapidTransit catheter was well controlled. Under road map conditions, a pCONus_mini with a distal wingspan of 4 mm was deployed inside the aneurysm. On a side note, it should be mentioned that in such small aneurysms the petals of the pCONus_mini tend to be deployed in the center of the aneurysm fundus than at neck level. After the pCONus_mini was fully anchored in the left A1 segment, the stent remained undetached. The aneurysm fundus was now catheterized with an Excelsior SL-10 microcatheter without any difficulty. The nitinol shaft of the pCONus is hardly visible on fluoroscopy but can be visualized using flat panel CT techniques (e.g., DynaCT, Siemens; XperCT, Philips). We do not use this as a matter of routine; however, if the catheterization of the aneurysm with the coiling catheter is not straightforward, a potential underlying collapse or ovalization of the pCONus shaft can be identified and corrected. The aneurysm fundus was then occluded with coils. In order to achieve an interaction between the coil loops and the four petals of the pCONus, coils with 3D features were chosen. With the aim of avoiding loose coil packing and subsequent coil compaction with aneurysm reperfusion, we usually continue with the coil insertion to the point at which the last coil can no longer be deployed, as in this case. Finally, the pCONus_mini was detached after the coiling catheter had been withdrawn. The key images of this procedure can be found in Fig. 2.
Fig. 2

pCONus-assisted coil occlusion of a small, unruptured, wide-necked AcomA aneurysm (a). The pCONus_mini petals were deployed in the middle of the aneurysm sac (b), followed by catheterizing the aneurysm sac with a second microcatheter (c). Two 3D coils were used to fill the aneurysm sac (d–i). The final DSA run confirmed the patency of the dependent vessels on the left ICA (j)

Duration: 1st–10th DSA run: 67 min; fluoroscopy time: 26 min

Complications: In the morning of the day following the procedure (5 February 2015), the patient presented with sensory aphasia and a fluctuating hemianopia to the right. MRI 27 h after the end of the endovascular procedure showed a left temporo-occipital intracerebral hematoma (5.5 × 3.5 × 3.5 cm). At this time, the patient was being continuously monitored, and both uncontrolled hypertension and head trauma can be ruled out.

Postmedication: The intended postmedication would have been 1× 100 mg ASA PO daily lifelong and 1× 75 mg clopidogrel PO daily for 3 months. Since the most likely cause of the intracerebral hematoma was a hyper-response to the dual antiplatelet “therapy” (DAPT), a gradual reduction of the dosages of ASA and clopidogrel was initiated. At this time, we used the Multiplate analyzer (Roche Diagnostics) as the single point-of-care test. The following table summarizes the results of the Multiplate tests and the respective dosage adaptations (Table 1).
Table 1

Dosage adaptation for ASA and clopidogrel in a patient with severe hyper-response

Date

Time

ADP AUC

ASPI AUC

Medication dosage

Remarks

04 February 2015

 

3

1

1× 100 mg ASA had been administered daily for years

1× 600 mg clopidogrel on 3 February 2015

Loading dose

05 February 2015

    

intracerebral hematoma

06 February 2015

2.06 pm

1

0

No ASA, no clopidogrel

 

07 February 2015

9.54 am

0

0

No ASA, no clopidogrel

 

08 February 2015

7.08 am

7

1

No ASA, no clopidogrel

 

10 February 2015

11.43 am

8

2

No ASA, no clopidogrel

 

12 February 2015

 

11

21

→ 1× 50 mg ASA daily

KollADP 73, KollEpi >300

13 February 2015

   

1× 50 mg ASS and 1× 37.5 mg clopidogrel

 

14 February 2015

1.56 pm

0

0

No ASA, no clopidogrel

 

15 February 2015

9.09 am

3

1

No ASA, no clopidogrel

 

16 February 2015

12.01 am

19

62

→ 1 × 100 mg ASA, no clopidogrel

 

17 February 2015

   

1 × 25 mg ASA daily and 1 × 37.5 mg clopidogrel daily

 

18 February 2015

9.14 am

0

0

1 × 25 mg ASA daily and 1 × 37.5 mg clopidogrel daily

 

19 February 2015

   

1 × 25 mg ASA daily and 1 × 37.5 mg clopidogrel daily

 

20 February 2015

2.44 pm

0

0

→ 1 × 25 mg ASA and 1 × 37.5 mg clopidogrel on alternating days

 

23 February 2015

4.43 pm

2

1

→ 1 × 25 mg ASA and 1 × 37.5 mg clopidogrel on alternating days

 

27 February 2015

3.36 pm

18

0

dito

 

06 March 2015

6.24 pm

0

0

dito

 

09 March 2015

   

dito

Dedicated hemostaseological evaluation:

No disturbance of plasmatic coagulation

No von Willebrand syndrome

No disturbance of platelet function, no ASA or clopidogrel effect (?)

17 March 2015

3.58 pm

11

1

→ 1 × 50 mg ASA every third day

1 × 37.5 mg clopidogrel everyday

 

24 March 2015

   

dito

Dedicated hemostaseological evaluation:

No clopidogrel effect

Sufficient ASA effect

30 March 2015

1.42 pm

4

3

dito

 

08 April 2015

2.38 pm

5

2

dito

 

20 April 2015

3.22 pm

11

18

dito

 

27 April 2015

11.01 am

14

2

dito

 

05 May 2015

10.57 am

9

0

dito

 

11 May 2015

   

dito

Dedicated hemostaseological evaluation:

Sufficient clopidogrel effect

No ASA effect

01 June 2015

9.41 am

22

11

dito

 

29 June 2015

12.12 am

6

0

→ 1 × 50 mg ASA every third day

1 × 37.5 mg clopidogrel every other day

 

27 July 2015

11.19 am

20

0

1 × 50 mg ASA every third day

1 × 37.5 mg clopidogrel every other day; → 1 × 100 mg ASA daily no clopidogrel

 

10 August 2015

11.22 am

42

0

dito

 

10 September 2015

11.11 am

51

0

→ 1 × 50 mg ASA daily no clopidogrel

 

30 September 2015

11.44 am

99

0

→ 1 × 50 mg ASA every other day, no clopidogrel

 

20 October 2015

9.35 am

66

2

1 × 50 mg ASA every other day, no clopidogrel

 

30 November 2015

12.47 am

93

2

1 × 50 mg ASA every other day, no clopidogrel

 

28 December 2015

12.11 am

38

1

1 × 50 mg ASA every other day, no clopidogrel

 

20 January 2016

11.44 am

49

0

1 × 50 mg ASA every other day, no clopidogrel

 

06 April 2016

11.46 am

39

0

1 × 50 mg ASA every other day, no clopidogrel

 

26 April 2016

1.34 pm

45

0

1 × 50 mg ASA every other day, no clopidogrel

VerifyNow

P2Y12 0% inhibition

ARU 492 (significant platelet inhibition)

05 May 2017

8.17 am

72

12

1 × 50 mg ASA every other day, no clopidogrel

VerifyNow

P2Y12 0% inhibition

ARU 502 (significant platelet inhibition)

Clinical Outcome

The intracerebral hematoma did not increase in size and was therefore managed conservatively. Comprehensive laboratory tests did not show abnormal coagulation parameters, apart from platelet function inhibition. The sensory aphasia completely resolved. In May 2017, there was no neurological deficit remaining which could prevent the patient from carrying out her previous everyday activities (mRS 1).

Follow-Up Examinations

MRI follow-up examinations showed the gradual absorption of the intracerebral hematoma (Fig. 3).
Fig. 3

Intracerebral hematoma due to hyper-response to dual antiplatelet medication, which occurred after stent-assisted coil occlusion of an AcomA aneurysm. The sequential T2W MRI shows the gradual absorption of the hematoma and the disappearance of the mass effect. The first MRI examination was carried out about 1.5 h after the clinical onset on 5 February 2015, 1 day after the endovascular procedure (a). The hematoma did not increase during the following 2 days and was therefore not evacuated (b). After 1 month it can be seen that the hematoma is beginning to be absorbed and that the mass effect has already reduced (6 March 2015, c). After 27 months, the absorption of the hematoma is completed, leaving a glial scar but no mass effect (5 May 2017, d)

The AcomA aneurysm remained completely occluded during the 27 months of angiographic follow-up (Fig. 4).
Fig. 4

Follow-up DSA after the pCONus-assisted coil occlusion of a small, unruptured, wide-necked AcomA aneurysm on 4 February 2015. Aneurysm occlusion was confirmed on 4 May 2015 (a), 26 April 2016 (b), and 4 May 2017 (c)

Discussion

Stent-assisted coiling and flow diversion have hugely increased the spectrum of intracranial aneurysms which can be considered for endovascular treatment. Stents and flow diverters have one major drawback in common: their surface is highly thrombogenic and they can only be used under dual platelet function inhibition. The relevant medication, however, and the tests available to evaluate their effect are both unreliable. A significant number of patients do not respond as intended to clopidogrel (Müller et al. 2003; Flechtenmacher et al. 2015), but the same can also be said of aspirin (Clavijo et al. 2017), prasugrel (Xanthopoulou et al. 2013), and ticagrelor (Ghamasaee et al. 2017). In order to address this issue, point-of-care (POC) tests have been developed. In Europe the Multiplate Analyzer (Roche Diagnostics) and VerifyNow (Accriva) are the most frequently used POC tests. The results are certainly useful in daily practice, but significant inconsistencies have been encountered (Cuisset et al. 2010a; Flechtenmacher et al. 2015). The impact of testing the platelet response on the clinical outcome is a matter of controversy, and it might be difficult to prove the benefit in a clinical trial. At the same time, some practitioners are very likely to feel uncomfortable if asked to deploy a stent in patient’s cerebral arteries without proper antiaggregation. Hypo-response, especially on clopidogrel, may be overcome by increasing the dosage. Alternatively, a different P2Y12 inhibitor (e.g., prasugrel or ticagrelor) can be used off-label. Hyper-response to antiaggregants is far less frequent, easily missed, and difficult to confirm and monitor with POC tests, and there is no standard mode to cope with this phenomenon (Goh et al. 2013). As long as no stent has been implanted, withdrawing this medication should be straightforward. As soon as a stent or flow diverter is in place, a sudden withdrawal of the antiplatelet drug is very likely to result in a thrombotic occlusion of the artery in question. Hyper-response should be suspected if patients who receive aspirin and P2Y12 inhibitors at a standard dosage complain of epistaxis, contusions, hypermenorrhea, or other signs of a hemorrhagic diathesis. The spontaneous development of intra- and/or extracranial hemorrhages under dual antiaggregation is the final alarming sign (Cuisset et al. 2010b; Delgado Almandoz et al. 2014). Both Multiplate and VerifyNow may show, but also may fail to show, excessive platelet function inhibition. A hint of hyper-response may be adequate platelet function inhibition in the POC tests under reduced medication dosage. There are several options to deal with hyper-responders:
  • Transfusion of platelet concentrates in the case of acute hemorrhagic complications. This may result in the thrombotic occlusion of the stent or flow diverter.

  • Dosage reduction of the antiaggregants being administered, to be monitored by POC tests with the aim of achieving desired values on low dosage. This may, as demonstrated by the above described case, take a long time, and again, under-dosage may result in stent occlusion.

  • Changing medication. If a platelet-related issue is suspected, replacing one P2Y12 inhibitor with another is of dubious value. Another option might be the combination of a direct anticoagulant (e.g., dabigatran) with an antiaggregant (e.g., prasugrel).

The reader should keep in mind that these concepts are off-label and can only be individual treatment strategies, which may require special precautions according to local regulations and medicolegal restrictions.

The most important step forward, however, will be the availability of stents and flow diverters, which simply do not require dual platelet function inhibition.

Cross-References

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Marta Aguilar Pérez
    • 1
  • Muhammad AlMatter
    • 1
  • Hansjörg Bäzner
    • 2
  • Hans Henkes
    • 1
    Email author
  1. 1.Neuroradiologische KlinikNeurozentrum, Klinikum StuttgartStuttgartGermany
  2. 2.Neurologische KlinikNeurozentrum, Klinikum StuttgartStuttgartGermany

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