Coagulation in Acute Aortic Dissection

Summary

Acute aortic dissection (AAD) involving the ascending aorta (Stanford classification type A) remains a life-threatening disease. Excessive perioperative bleeding requiring massive transfusion of allogeneic blood products, and surgical reexploration remain major challenges in these patients. Previous research has indicated that patients with AAD show pronounced haemostatic alterations prior to surgery which are aggravated during major aortic surgery with cardiopulmonary bypass and hypothermia full heparinization.

Intensified anticoagulation management guided by heparin dose response (HDR) calculation, and repeated measurement of heparin concentration may be more effective than standard empiric weight-based heparin and protamine management monitored by activated clotting time (ACT) measurements to suppress thrombin generation during surgery for AAD.

This randomized controlled clinical trial compares the impact of two recommended anticoagulation management strategies during surgery for AAD including deep hypothermia on activation of coagulation: Heparin/protamine-management based on HDR-titration by means of HMS Plus® versus current institutional standard (HDR- versus ACT-approach).

Primary endpoint is thrombin generation as measured by early postoperative prothrombin fragment 1+2 (F1+2). Secondary endpoints are other markers of coagulation and fibrinolysis as well as clinical outcome.

Conditions

• Acute Aortic Dissection
• Coagulation Disorder

Interventions

PROCEDURE

Individualized HDR-approach

Heparin concentration necessary to achieve target ACT \> 480 sec. calculated based on individual HDR-curve. If HDR slope ˂80 s/IU/mL (reduced sensitivity to heparin), 1000 IU of AT concentrate (Antitrombin III "Baxalta"®, Takeda Pharma, Vallensbæk Strand, DK). Whole blood concentration of circulating heparin assessed by heparin assays. Additional heparin given as required. After weaning, protamine necessary to reverse circulating heparin calculated according to heparin-protamine titration measurement. After protamine, heparin reversal evaluated with low-range heparin-protamine titration cartridge and additional protamine given as required.

PROCEDURE

Conventional ACT-approach

Initial Heparin 400 IU/kg (500 IU/kg if treated with heparin prior to surgery). ACT Assessment with Hemochron® Signature Elite (ITC, International Technidyne Corp., Edison, NJ, USA). Additional heparin until ACT \> 480 sec. If ACT \< 480 sec. after despite repeated heparin supplement with 1000 IU of AT III concentrate. Target ACT \> 480 sec. during normothermic CPB, and target ACT \> 700 seconds during hypothermia After weaning, protamine 10mg/mL (0.7 mg of protamine/ 100 IU total heparin administered). Heparin reversal is evaluated with an activated partial thromboplastin (APTT). If APTT \> 40 seconds, additional protamine (25-50 mg i.v.).

Sponsors & Collaborators

• Ivy susanne Modrau, MD

  lead OTHER

Principal Investigators

• Jens Eschen, Stud.med. · Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Denmark

• Ivy Modrau, MD, dr.med. · University of Aarhus

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-11-01

Primary Completion

2024-09-17

Completion

2024-12-15

Countries

• Denmark

Study Locations