Newly Published
Perioperative Medicine  |   June 2019
Prothrombin Complex Concentrate-induced Disseminated Intravascular Coagulation Can Be Prevented by Coadministering Antithrombin in a Porcine Trauma Model
Author Notes
  • From the Departments of Anesthesiology (O.G., M.H., A.R., R.R.) and Pathology (T.B.), RWTH Aachen University Hospital, Aachen, Germany; and the Department of Anesthesiology and Intensive Care, AUVA Trauma Centre, Salzburg, Austria (H.S.).
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • Submitted for publication November 30, 2018. Accepted for publication April 4, 2019.
    Submitted for publication November 30, 2018. Accepted for publication April 4, 2019.×
  • Correspondence: Address correspondence to Dr. Grottke: RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany. ogrottke@ukaachen.de. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Coagulation and Transfusion / Hematologic System / Respiratory System / Trauma / Burn Care
Perioperative Medicine   |   June 2019
Prothrombin Complex Concentrate-induced Disseminated Intravascular Coagulation Can Be Prevented by Coadministering Antithrombin in a Porcine Trauma Model
Anesthesiology Newly Published on June 6, 2019. doi:10.1097/ALN.0000000000002797
Anesthesiology Newly Published on June 6, 2019. doi:10.1097/ALN.0000000000002797
Abstract

Editor’s Perspective:

What We Already Know about This Topic:

  • Prothrombin complex concentrates are increasingly used as part of bleeding management algorithms in surgery and trauma

  • There are potential risks of thromboembolic complications and disseminated intravascular coagulopathy with prothrombin complex concentrate in this setting, despite the low risks in warfarin reversal

What this Article Tells Us That Is New:

  • In this animal polytrauma model, 50 IU/kg prothrombin complex concentrate is associated with a risk of disseminated intravascular coagulopathy and thromboembolism

  • The addition of antithrombin appears to balance the procoagulant effects of prothrombin complex concentrate, consequently reducing the risk of complications without impairing efficacy

Background: The risk of thromboembolic complications with prothrombin complex concentrates (PCCs) appears low when used for reversal of vitamin K antagonists but might be different in other indications (e.g., trauma). A difference in risk could arise from the plasma ratio of pro- versus anticoagulant proteins. This study used a porcine trauma model to investigate combined treatment with PCC and antithrombin. The hypothesis was that antithrombin can modulate prothrombotic effects and prevent adverse events of PCC.

Methods: Nine treatment groups (n = 7 per group) were included: control (placebo), PCC (50 IU/kg), PCC plus antithrombin (three groups, with antithrombin doses of 12.5, 25, or 50 IU/kg), fibrinogen concentrate (100 mg/kg) plus PCC, fibrinogen concentrate plus PCC plus antithrombin dose of 50 IU/kg, tranexamic acid (15 mg/kg) plus fibrinogen concentrate plus PCC, and tranexamic acid plus fibrinogen concentrate plus PCC plus antithrombin dose of 50 IU/kg. In each group, bilateral femur fractures and thorax contusion were followed 60 min later by blunt liver injury. Study treatment was then administered, and animals were subsequently observed for 210 min.

Results: Total blood loss (mean ± SD) was statistically significantly lower in all three PCC plus antithrombin groups (PCC plus antithrombin dose of 50 IU/kg, 672 ± 63 ml; PCC plus antithrombin dose of 25 IU/kg, 535 ± 72 ml; and PCC plus antithrombin dose of 12.5 IU/kg, 538 ± 50 ml) than in the PCC group (907 ± 132 ml), which in turn had statistically significantly reduced bleeding versus the control group (1,671 ± 409 ml). Signs of disseminated intravascular coagulation were apparent with PCC monotherapy, and early deaths occurred with fibrinogen concentrate plus PCC, attributable to pulmonary emboli. Antithrombin was protective against both of these effects: signs of disseminated intravascular coagulation were absent from the PCC plus antithrombin groups, and there were no early deaths in the group with fibrinogen concentrate plus PCC plus antithrombin dose of 50 IU/kg.

Conclusions: According to this trauma model, 50 IU/kg PCC increases the risk of disseminated intravascular coagulation and other thromboembolic complications, most notably when coadministered with fibrinogen concentrate. The addition of antithrombin appears to reduce this risk.