1. Presence of medication taken by blood donors in plasma for transfusion A.van Tilborgh, J. Wiersum, M. Schipperus D. Touw F. Hudig 3-6-2013 ISBT Regional Congress Amsterdam

2. 70-year-old female patient, von Willebrand disease type II, with known allergies (plasters, barium contrast, fruit, penicillin?) Fractured collar bone 21/114.00 hrsstart platelet transfusion, BP 160/71 21/114.10 hrsbronchospasm, glottis edema, urticaria, hypotension Tavegil and hydrocortisone:quick recovery (BP 180/90) No IgA deficiency TRIP report:Anaphylactic reaction, imputability probable, severity grade 2 3-6-2013 ISBT Regional Congress Amsterdam Case historie

3. 3-6-2013 ISBT Regional Congress Amsterdam Every year TRIP receives several reports like this one. The category of anaphylactic reaction, defined as allergic reactions with systemic features such as airway obstruction, fall in blood pressure, vomiting or diarrhoea, accounts for the largest number of serious transfusion reactions. In most cases no cause is found for these reactions.

4. Distributed blood components 3-6-2013 ISBT Regional Congress Amsterdam TRIP data show that anaphylactic reactions occur relatively frequently during or after transfusion of plasma or platelet concentrates. Most platelet units are also rich in plasma. Data from blood services show that approximately 10% or more of plasma donors use medication which is permitted under donation guidelines.

5. 3-6-2013 ISBT Regional Congress Amsterdam Thawed FFP  rejected for transfusion  sample 5 ml This exploratory study investigated the presence of drugs or drug metabolites in donor plasma after quarantine, storage and thawing. Only samples for which the blood supply organisation confirmed that the donor had consented to research use were included.

6. 3-6-2013 ISBT Regional Congress Amsterdam I-Tox screening The samples were analysed for approximately 800 drugs or drug metabolites

7. 3-6-2013 ISBT Regional Congress Amsterdam 87 samples have been processed All detectable substances that were recognised as drug or drugmetabolite were considered a positive screening result

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10. The most prescribed drugs in The Netherlands in 2009/2010 Metoprolol Omeprazol (also OTC) Acetylsalicylic acid (also OTC) We expected that frequently prescribed drugs or over the counter drugs were most likely to be found in some of the donor plasma units. 3-6-2013 ISBT Regional Congress Amsterdam

11. Type of drugNameFreqPublication / FTK # Lareb $ Antidepressant (SSRI) Paroxetine Citalopram 1 1 (C1*) Antipsychotic Pipamperon Quetiapine 1 (C1*) Antihypertensive (ARB) Valsartan Telmisartan 2 3 (C2*) Ca channel blocker Amlodipine1 (C2*) ß-blocker Metoprolol1 (C2*) Antidiabetic Glicazide1 # Publication Yes – No / mentioned in FTK = Farmacotherapeutisch Kompas $ Lareb = Netherlands Pharmacovigilance center, number of reports in database * C. = combination of medication 3-6-2013 ISBT Regional Congress Amsterdam

12. Type of drugNameFreqPublication / FTK # Lareb $ Antidepressant (SSRI) Paroxetine Citalopram 1 1 (C1) N /very rare (<0.01%) Y / ? 9696 Antipsychotic Pipamperon Quetiapine 1 (C1) N / ? N /sometimes (<1%) -2-2 Antihypertensive (ARB) Valsartan Telmisartan 2 3 (C2) N / ? N /rare (<0,1%) 3131 Ca channel blocker Amlodipine1 (C2) N /very rare (<0.01%) 3 ß-blocker Metoprolol1 (C2) N / -9 Antidiabetic Glicazide1N / -- * C. = combination of medication # Publication Yes – No / mentioned in FTK = Farmacotherapeutisch Kompas $ Lareb = Netherlands Pharmacovigilance center, number of reports in database 3-6-2013 ISBT Regional Congress Amsterdam

13. Type of drugNameFreqPublication/FTKLareb Antidepressant (SSRI) Paroxetine Citalopram 1 1 (C1) - / very rare (<0.01%) Y / ? 9696 Antipsychotic Pipamperon Quetiapine 1 (C1) - / ? - / sometimes (<1%) -2-2 Antihypertensive (ARB) Valsartan Telmisartan 2 3 (C2) - / - / rare (<0,1%) 3131 Ca channel blocker Amlodipine1 (C2) - / very rare (<0.01%) 3 ß-blocker Metoprolol1 (C2) - / -9 Antidiabetic Glicazide1- / -- PPI (OTC) Omeprazol1Y / rare (<0,1%) 16 NSAID (OTC) Naproxen4Y / rare (<0,1%) 50 3-6-2013 ISBT Regional Congress Amsterdam

14. Type of drugNameFreqPublication/FTKLareb Antidepressant (SSRI) Paroxetine Citalopram 1 1 (C1) - / very rare (<0.01%) Y / ? 9696 Antipsychotic Pipamperon Quetiapine 1 (C1) - / ? - / sometimes (<1%) -2-2 Antihypertensive (ARB) Valsartan Telmisartan 2 3 (C2) - / - / rare (<0,1%) 3131 Ca channel blocker Amlodipine1 (C2) - / very rare (<0.01%) 3 ß-blocker Metoprolol1 (C2) - / -9 Antidiabetic Glicazide1- / -- PPI (OTC) Omeprazol1Y / rare (<0,1%) 16 NSAID (OTC) Naproxen4 (C3) Y / rare (<0,1%) 50 Anabolic steroid Metenolon1 (C3) -- Preservative Methylparaben1Y- http://www.lareb.nl/LarebCorporateWebsite/media/publicaties/Anafylactische-reacties-op-NSAID-s.pdf 3-6-2013 ISBT Regional Congress Amsterdam

15. 3-6-2013 ISBT Regional Congress Amsterdam Conclusions It is possible to detect medication in donor plasma after freezing, quarantine, storage and thawing It cannot be excluded that medication taken by the donor in plasma for transfusion could cause an anaphylactic reaction in the recipient

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