Guidelines for Peri- and Intra-Procedural
Anticoagulation and Antiaggregation

A Research Project of World Federation of Interventional and Therapeutic Neuroradiology (WFITN)

BACKGROUND AND PURPOSE: It is a matter of particular concern for interventional and therapeutic neuroradiologists in endovascular therapy to avert embolic complications with infarction and, at the same time, to minimize the bleeding risk. The purpose of this study was to evaluate the optimal management structure for the anticoagulation and antiaggregation therapy in various interventional procedures and to develop guidelines which could be used by all neurointerventional departments for application in endovascular therapy.

METHODS: We designed a questionnaire consisting of 20 questions on 4 topics

• general questions,
• pre- and post-procedural coagulation status,
• intra-procedural anticoagulation / antiaggregation,
• pre- and post-procedural anticoagulation / antiaggregation,

which has been sent to all email addresses of members in the mailing list of WFITN in Milan in June 2007. The accrued data were summarized and analyzed to determine the most common therapies, as well as details pertaining to experiences and complications. On the other hand, we drew conclusions based on the results of the current neuroradiological, radiological, cardiological literature review. Several interviews with cardiologists took place about the guidelines of cardiological interventional anticoagulation and antiaggregation therapy. The results from the questionnaire, literature review and interviews were subsumed to determine the recommended protocol for anticoagulation and antiaggregation management in neurointerventional procedures.

RESULTS: The questionnaire has been sent to all email addresses of members in the mailing list of WFITN in Milan (N=493), not considering good standing in June 2007. We received 38 replies of questionnaire filled out from 14th June to 15th August 2007. When we act on the assumption, that there are approximately 200 to 250 active interventional neuroradiologists / departments worldwide, the rate of return is equivalent to approx. 15-20 %. The most frequent neurovascular procedures are (in parentheses each with the average of number of endovascular interventions per year): Aneurysm coiling (79.6), extracranial stenting (40.3), AVM/DAVF embolization (33.8), balloon-remodeling of aneurysm (20), tumor embolization (15.7), aneurysm coiling with stenting (10.1), mechanical thrombectomy combined with local fibrinolysis (9.9), intracranial stenting (9.0) and aneurysm stenting without coiling (8.7), in order of frequency. Medical history and present medication, international normalized ratio (INR), activated partial thromboplastin time (aPTT) and blood count (BC) were parameters routinely determined before the interventions. The activated clotting time (ACT) was determined pre-, intra- and post-procedural. During the procedure, heparin was administered continuously in 69%. In small neck aneurysm coiling, 68% administer no platelet inhibitors (PI) pre- and post-procedural. In wide neck coiling, 42% without PI face 41% giving only aspirin. In aneurysm stenting without additional coiling, 58% treat the patients with dual-therapy of aspirin and clopidogrel, whereas 79% do so in stenting with additional coiling. Slightly more than half of the answers do not administer PI after aneurysm balloon-remodeling. In case of intra- and extracranial stenting 97% administer aspirin and clopidogrel, the majority begins with the dual-therapy three days before the intervention, for three months in case of bare metal stent (BMS) and, for one year in case of drug eluting stent (DES) implantation. In embolization of AVM/DAVF and tumor, the anticoagulation therapy was administered only during the procedure without further antiaggregation postprocedurally. Because of heterogeneity of answers about anticoagulation and antiaggregation therapy in mechanical thrombectomy in acute stroke situation, there is no significant result to be presented.

RECOMMANDATION: On the basis of the results from the questionnaire, literature review and interviews we recommend the following protocol for anticoagulation and antiaggregation management in neurointerventional procedures.

1. Parameters routinely determined before and after the interventions
   • Medical history and present medication
   • INR pre-procedural
   • aPTT pre-procedural
   • Blood count pre-procedural
   • ACT pre-/intra-/post-procedural


2. Small Neck Aneurysm Coiling
   • Only during the procedure
   • Heparin bolus of 5000 U, than 1000 U/l continously during the procedure, with control of ACT (~200)
   • No antiaggregation therapy


3. Wide Neck Aneurysm Coiling
   • No pretreatment:
   • Intraprocedural: Heparin bolus 5000 U, than 1000 U/l continously, with control of ACT ~200
   • Posttreatment: Aspirin 100 mg to be continued indefinitely thereafter


4. Aneurysm Stenting without Additional Coiling
   • Pretreatment: 3 days before procedure, aspirin 100 mg and clopidogrel 75 mg
   • Intraprocedural: Heparin bolus 5000 U, than 1000 U/l continously, with control of ACT ~200
   • Posttreatment: dual-therapy depending on stent-model, with aspirin to be continued indefinitely thereafter


5. Aneurysm Stenting + Coiling
   • Pretreatment: 3 days before procedure, aspirin 100 mg and clopidogrel 75 mg
   • Intraprocedural: Heparin bolus 5000 U, than 1000 U/l continously, with control of ACT ~200
   • Posttreatment: dual-therapy depending on stent-model, with aspirin to be continued indefinitely thereafter


6. Aneurysm Balloon-Remodeling
   • Only during the procedure
   • Heparin bolus of 5000 U, than 1000 U/l continously during the procedure, with control of ACT (~200)
   • No antiaggregation therapy


7. Bare Metal Stent (BMS)
   • Pretreatment: 3 days before procedure, aspirin 100 mg and clopidogrel 75 mg
   • Intraprocedural: Heparin bolus 5000 U, than 1000 U/l continously, with control of ACT ~200
   • Posttreatment: dual-therapy for three months, with aspirin to be continued indefinitely thereafter


8. Drug-Eluting-Stent (DES)
   • Pretreatment: 3 days before procedure, aspirin 100 mg and clopidogrel 75 mg
   • Intraprocedural: Heparin bolus 5000 U, than 1000 U/l continously, with control of ACT ~200
   • Posttreatment: dual-therapy for one year, with aspirin to be continued indefinitely thereafter


9. Acute Stroke Intervention
   • Because of heterogeneity of the answers on duration and dosage no general recommendation
   • The combination of IIb/IIIa inhibitors with rtPA significantly reduced infarct size and improved neurologic outcome in a rat model of embolic stroke evaluation


10. Embolization of AVM/DAVF and Tumor
    • Only during the procedure
    • Heparin bolus of 5000 U, than 1000 U/l continously during the procedure, with control of ACT (~200)

CONCLUSION: Our questionnaire aimed to sum up the clinical reality, not to calculate an official statistic. There is no widely accepted anticoagulation and antiplatelet regimens in neurovascular interventions. Selected agents and doses reported vary widely, frequently based on individual operator experience and practice patterns rather than on an extrapolation of the existing data. Our recommendation is thought to be an initiation for official guidelines, further discussion on this important clinical matter is required