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Detailed thrombogenicity phenotyping and 1 year outcomes in patients undergoing WATCHMAN implantation: (TARGET-WATCHMAN) a case–control study

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Abstract

The relation of device related thrombosis (DRT) and major bleeding after left atrial appendage closure (LAAC) to laboratory thrombosis and hemostasis markers has not been studied. We performed a prospective case control study to identify clinical characteristics and laboratory markers in patients who developed DRT and major bleeding following WATCHMAN LAAC. Thromboelastography, platelet aggregation (PA), urinary 11-dehydrothromboxane B2 (UTX), fibrinogen, d-dimer, thrombin time and von Willebrand factor activity were determined at baseline, immediately following, and at 45 and 180 days post-LAAC (n = 32) and outcomes were followed for 1 year. Baseline characteristics and thrombogenic profiles of patients with and without DRT and/or BARC bleeding were compared. Mean age was 76 ± 8 years and CHADS2 VASc score was 4.4 ± 1.4. There were 3 DRTs (2 within 6 months, and 1 at 12 months), 4 Type 3A BARC bleeds, and 2 non-cardiac deaths. Patients with DRT had higher baseline thrombin-induced platelet–fibrin clot strength (68.0 ± 1.8 vs. 62.7 ± 4.7 mm, p = 0.06); FCS (35.6 ± 6.0 vs. 24.4 ± 6.6 mm, p = 0.009); and d-dimer (1712 ± 2330 vs. 283 ± 213 ng/mL, p = 0.001). At baseline, 5 patients had all 3 factors associated with high thrombotic risk and 2 experienced a DRT within 6 months. Patients with Type 3A BARC bleeding had lower baseline collagen-induced and 45-day ADP-induced PA (p < 0.01 for both). DRT following LAAC was associated with a baseline prothrombogenic profile whereas bleeding was associated with low platelet reactivity. These preliminary findings warrant further validation and have future implications on patient selection and adjunctive antithrombotic therapy following LAAC.

Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03040622.

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Abbreviations

ADP:

Adenosine diphosphate

AF:

Atrial fibrillation

BARC:

Major bleeding using the Academic Research Consortium

DRT:

Device related thrombosis

FCS:

Fibrin clot strength

HPR:

High platelet reactivity

INR:

International normalized ratio

LAAC:

Left atrial appendage closure

NOAC:

Novel oral anticoagulant

PA:

Platelet aggregation

TEE:

Transesophageal echocardiography

TEG:

Thrombelastography

TT:

Thrombin time

TIP-FCS:

Thrombin induced platelet–fibrin clot strength

TRAP:

Thrombin receptor-activating peptide

UTX:

Urinary 11-dehydrothromboxane B2

ULN:

Upper limits normal

vWF:

Von Willebrand factor

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Acknowledgements

We wish to acknowledge Andrea Fitzgerald BSN-RN, MA for her contributions to this study

Funding

This study was funded by Boston Scientific Corporation (300 Boston Scientific Way Marlborough, MA).

Author information

Authors and Affiliations

  1. Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, VA, USA

    Matthew Sherwood, Leonard Ilkhanoff, Adam Strickberger, Sharam Yazdani, Robert McSwain, Haroon Rashid, Tracy Plummer & Wayne Batchelor

  2. Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, USA

    Kevin P. Bliden, Rahul Chaudhary, Udaya S. Tantry & Paul A. Gurbel

  3. Colorado Heart & Vascular, Lakewood, CO, USA

    Ganesh Venkataraman

  4. Cardiovascular Institute, Mater Dei Hospital, Bari BA, Italy

    Eliano P. Navarese

  5. Division of Hospital Internal Medicine, Mayo Clinic, Rochester, MN, USA

    Rahul Chaudhary

Authors
  1. Matthew Sherwood
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Contributions

MS: Conceptualization, Methodology, Roles/Writing—original draft; KPB: Conceptualization, Data curation, Formal analysis, Roles/Writing—original draft; LI: Methodology, Project administration, Resources; GV: Supervision, Validation, Visualization; AS: Funding acquisition, Investigation, Methodology, Project administration; SY: Formal analysis, Methodology, Software; RM: Conceptualization, Methodology; HR: Project administration, Resources; EPN: Formal analysis, Writing—review & editing; TP: Data curation, Formal analysis; WB: Software, Investigation, Methodology, Project administration; RC: Validation; Visualization, Writing—review & editing; UST: Conceptualization, Data curation, Writing—review & editing, PAG: Conceptualization, Funding acquisition, Investigation, Writing—review & editing.

Corresponding author

Correspondence to Paul A. Gurbel.

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Conflict of interest

Dr. Gurbel receives honoraria for lectures, consultations, including service on speakers’ bureaus from Bayer, Merck, Janssen, Medicure, and World Medical; receiving grants from the National Institutes of Health, Janssen, Merck, Bayer, Haemonetics, Instrumentation Labs, and Amgen. Dr. Gurbel is holding stock or stock options in Merck, Medtronic, and Pfizer; and holding patents in the area of personalized antiplatelet therapy and interventional cardiology. Dr. Sherwood receives honoraria from Medtronic. Dr. Navarese reports honoraria and payment for lectures from Astra Zeneca, Daiichi Sankyo/Lilly, Sanofi-Regeneron and Amgen; and receipt of grants from Amgen. Dr. Batchelor reports honoraria from Boston Scientific Corporation. Other authors report no disclosures.

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Sherwood, M., Bliden, K.P., Ilkhanoff, L. et al. Detailed thrombogenicity phenotyping and 1 year outcomes in patients undergoing WATCHMAN implantation: (TARGET-WATCHMAN) a case–control study. J Thromb Thrombolysis 50, 484–498 (2020). https://doi.org/10.1007/s11239-020-02205-5

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