Shock Syndromes II

use in the reversal of warfarin-related acute bleeding disorders (further discussed under Reversal of

Oral Anticoagulant Agents) in life-threatening hemorrhage or for urgent surgery or invasive procedures.

Not indicated for the treatment of hemophilia-related bleeding because other PCC products are

approved.

The package insert warns of an increased thromboembolic risk with Kcentra administration.

Kcentra is contraindicated in patients with known heparin-induced thrombocytopenia because the

product contains heparin.

Few data support the off-label use of PCCs as hemostatic agents in patients with bleeding not

previously receiving anticoagulation; however, interest in this use and evidence are growing.

The RETIC trial, which used PCC and concentrated fibrinogen compared with plasma in

trauma patients with bleeding, was terminated early for safety concerns because of the high

need of rescue therapy and massive transfusion in the plasma group.

ii.

In a double-blind, randomized, placebo-controlled superiority trial conducted in 12 French

designated level I trauma centers, a total of 324 patients at risk of massive transfusion were

included (PROCOAG randomized clinical trial). These patients received either intravenous

4F-PCC or a saline solution as treatment. The study’s primary outcome was 24-hour all

blood product consumption, and the secondary outcome was the occurrence of arterial or

venous thromboembolic events. The results showed that there was no statistically or clinically

significant difference in total 24-hour blood product consumption between the two groups.

The 4F-PCC group consumed a median of 12 units of blood products, and the placebo group

consumed a median of 11 units, with an absolute difference of 0.2 units (95% CI, -2.99 to 3.33;

p=0.72). The study also showed that thromboembolic events were more common in the 4F-PCC

group, with 35% of patients in this group experiencing at least one such event, compared with

24% in the placebo group. The absolute difference was 11% (95% CI, 1%–21%), with a relative

risk of 1.48 (95% CI, 1.04–2.10; p=0.03). These findings do not support the routine use of

4F-PCC in such patients.

iii.

Although use of coagulation factor concentrates (CFCs) for hemostatic resuscitation is less

common in the United States, the 2019 European trauma guidelines recommend CFCs as an

alternative to plasma.

Factor II

(IU)

Factor VII

(IU)

Factor IX

(IU)a

Factor X

(IU)

Additivesb

Vial Dose

(estimated

factor IX IU)

3-factor PCCc

Bebulin VH

Profilnine

< 5

Trace heparin

N/A

200–1200

500, 1000, 1500

4F-PCCd

Kcentra

106.9

55.1

141.4

Protein C, S, Z,

antithrombin III,

heparin

500, 1000

aPCCe

FEIBA

91.7–125

68-135

80–93.3

Protein C

500, 1000, 2500

aExpressed as international units (IU) per 100 IU of factor IX; the individual factor contents vary depending on vial size and can be determined by multiplying the

individual factor content of interest by vial dose and dividing by 100 IU of factor IX equivalent.

bAnticoagulant factors in some PCC products are added to attenuate excessive thrombogenicity.

cConsidered a 3-factor PCC because of limited amounts of factor VII.

dConsidered a 4-factor PCC (4F-PCC) because of a significant concentration of factor VII.

eFEIBA is an aPCC that contains mainly nonactivated factors II, IX, and X; factor VII is mainly in the activated form.

FEIBA = factor eight inhibitor bypassing activity; N/A = not applicable.

Information from: Frontera JA, Lewin JJ, Rabinstein AA, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage. Neurocrit Care 2016;24:6-46;

FEIBA NF [prescribing information]. Baxter Healthcare, 2011.