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5PSQ-008 Resistance to sodium heparin treatment or treatment failure to the equivalent analogue?
  1. A Iezzi1,
  2. I Clerici2,
  3. J Villa2,
  4. E Omodeo Salè2
  1. 1Centro Cardiologico Monzino, Servizio Di Farmacia Ospedaliera, Milano, Italy
  2. 2Centro Cardiologico Monzino, Hospital Pharmacy, Milan, Italy


Background and importance The most frequent cause of heparin resistance is lack of antithrombin (AT). However, there are non-AT mediated heparin resistance cases in the literature but they are less prevalent.

Aim and objectives The aim of the study was to investigate if we had managed the onset of non-AT mediated heparin resistance or a treatment failure to an equivalent analogue during cardiac surgery.

Material and methods A 53-year-old, non-smoker, hypertensive Caucasian man was studied. In December 2013, a heart murmur and mitral regurgitation was found. In July 2014, correction of mitral valve disease by surgery was indicated but surgery was postponed for personal reasons. On 2 May 2019, valvuloplasty was performed and a heparin bolus of 25 000 IU was administrated (Pharepa). Activated clotting time (ACT) was 120 which was not adequate for establishment of extracorporeal circulation.

Antithrombin III and an additional dose of heparin were administered but the ACT value was the same. The procedure was delayed due to further investigation.

On 8 May 2019, haematology counselling was requested. AT levels were within the limits (114%) and factor VIII was at the upper limits (142%). A test dose of heparin Epsoclar was recommended to assess the biological response because of suspected heparin resistance.

Results On 4 June 2019, tests were performed with increasing doses of Epsoclar which showed an appropriate dose–response correlation. On 10 July 2019, after a new Epsoclar dose–response test, valvuloplasty surgery was performed. Systemic heparinisation was carried out with Epsoclar and the anticoagulant action was assessed. Once the correct ACT was obtained, the extracorporeal circulation was implanted with subsequent intervention.

Conclusion and relevance This clinical case showed a lack of therapeutic effect after administration of Pharepa heparin. The results of the dose–response study showed an adequate correlation with exclusion of non-AT mediated heparin resistance. Tests conducted on administered heparin analogues showed that heparinisation failure occurred with Pharepa while verification tests included the use of Epsoclar, also used during the second surgery. Of the 38 adverse drug reaction reports included in the National Pharmacovigilance Network for Pharepa, 16.7% refer to a lack of therapeutic effect of the medicine. All adverse drug reactions were severe and two led to patient death. The case report highlights how differences in response between synthesis analogues can exist and underlines the importance of proceeding with further investigation in cases of diagnostic doubt.

References and/or acknowledgements No conflict of interest.

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