3F-PCC in paediatric cardiac surgery

A Retrospective Analysis of the Use of 3-Factor Prothrombin Complex Concentrates for Refractory Bleeding After Cardiopulmonary Bypass in Children Undergoing Heart Surgery: A Matched Case-Control Study

Harris AD, Hubbard RM, Sam RM, Zhang X, Salazar J, Gautam NK. Semin Cardiothorac Vasc Anesth. 2020 Sep;24(3):227-231. doi: 10.1177/1089253219899255.

• 3F-PCC was not associated with an increased risk of thromboembolic events, mortality or need for post-operative oxygen support compared to propensity-matched controls
• Results suggest that 3F-PCC is safe for treatment of refractory bleeding after cardiopulmonary bypass in children undergoing cardiac surgery

Excessive bleeding following a cardiopulmonary bypass (CPB) is a well-known complication of congenital heart surgery. While post-bypass coagulopathy and bleeding can be treated with high-volume allogeneic blood transfusions, in the post-bypass period these can lead to pulmonary oedema, poor cardiac function, delayed sternal closure, anasarca, and end-organ damage (Faraoni et al., 2017; Bockeria et al., 2012; Winch et al., 2013; Cholette et al., 2012; Cholette et al., 2018).

Alternative haemostatic agents, such as factor concentrates, may offer a treatment pathway for patients with bleeding after bypass that remains refractory to standard therapy.

3-factor prothrombin complex concentrates (3FPCC) have previously been suggested as a possible treatment for refractory bleeding after CPB in congenital heart surgery (Harper et al. 2018), however there is currently little data that evaluates the use of this agent in paediatric cardiac surgery (Guzzetta et al., 2017).

There are also safety concerns, such as the creation of an in situ, overcompensated procoagulant state that could place patients at risk for thrombotic events (Guzzetta et al., 2017).

To examine the rate of clinical complications following the use of a 3FPCC (Factor IX Complex) in paediatric cardiac surgery patients (N=59) Harris et al. conducted a single-institution retrospective database analysis of outcomes in patients <18 years of age who received 3FPCC to treat refractory post-CPB bleeding.

The primary outcome was to assess thrombotic and thromboembolic complications. Secondary outcomes included in-hospital mortality and the need for post-operative extracorporeal membrane oxygenation (ECMO).

The impact of 3FPCC on thrombotic and thromboembolic events

Of the 964 surgeries carried out during the study period, Harris et al. reviewed 65 patients (89% < 1 year of age) exposed to 3FPCC and 181 controls. Of the 65 patients, 59 were matched to controls based on demographics and surgical characteristics.

Figure 1: Comparison of outcomes between 3FPCC group and matched controls.
3FPCC, 3-factor prothrombin complex concentrate; ECMO, extracorporeal membrane oxygenation. ^aMcNemar’s test was used for proportion comparisons.

The retrospective analysis showed and insignificantly higher number of radiographically confirmed thrombotic and thromboembolic events in the 3FPCC group compared to the control group. All patients with documented thrombosis received systemic anticoagulation.

These events were:

• Deep venous thromboses (N=6)
• Systemic-pulmonary artery shunt thrombus (N=1)
• Arterial thrombus (N=1)
• Sagittal vein thrombus (N=1)
• Left pulmonary artery thrombus (N=1)

Mortality was similar in both groups (11.9% vs 17%) and the length of hospital stay for the 3FPCC group was 26 days compared with 19 days for the control group (P = .013). The need for extracorporeal membrane oxygenation (ECMO) resuscitation was also similar in both groups.

Outcomes of the retrospective analysis

The common reasons contraindicating the use of PCCs in paediatric cardiac surgery include:

• An imbalance of pro- and anticoagulant properties among the available PCCs
• An increased risk of thrombosis due to an elevated thrombin generation potential
• Few objective laboratory tests that quantify factor levels to reliably guide their usage

As this study found no significant difference in thromboembolic episodes or mortality with the use of 3FPCC, these findings together with the decreased transfusion requirements of 3FPCC support the use of this agent for the treatment post-cardiotomy haemorrhage.

While these findings support previous studies examining thrombotic complication rates with the utilisation of other factor concentrates (Karsies et al., 2010), this study had limitations. The study was retrospective, had potential confounding factors contributing to clinical complications, an insufficient power for any measured outcome, and had a narrow timeframe at a single institution.

Research into the use of PCCs for treatment of post-CPB haemorrhage in children will remain limited without further multicentre, prospective, powered, and randomised investigations.

References

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Karsies TJ, Nicol KK, Galantowicz ME, Stephens JA, Kerlin BA. Thrombotic Risk of Recombinant Factor Seven in Pediatric Cardiac Surgery: A Single Institution Experience. Ann Thorac Surg. 2010;89(2):570–576.

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