FROSTED

Background

Plasma transfusions are indicated in cases of massive bleeding, Thrombotic Thrombocytopenia Purpura (TTP), Hemolytic-Uremic Syndrome (HUS), liver disease, deficiencies in clotting factors for which concentrates do not exist (e.g. Factor V), and a few other disease states. The two most commonly used forms of plasma for transfusion are Quarantine Fresh Frozen Plasma (Q-FFP) and Solvent/Detergent treated Plasma (SDP). Q-FFP is a one-donor to one-recipient product in which the donor is first tested (for HIV I/II, HVB, HVC, syphilis and, in the case of first-time donors, HTLV I/II) before the plasma is frozen in quarantine. Following this quarantine period, the donor is retested (given the window period of the concerned pathogens) before the product is released for use. SDP, on the other hand, is a pooled product made from around a thousand units of FFP also first tested for viral markers but for which the donors do not undergo secondary testing. Thus it must endure a robust pathogen reduction process to ensure its safety.

As of 2013, a form of Solvent/Detergent treated Plasma (SDP) known as Omniplasma™ is available for use in the Netherlands. It is a pooled, detergent treated product, prion filtered and made exclusively from Dutch donor plasma 1) and has replaced Q-FFP as the standard plasma used for plasma transfusions in the Netherlands. The rationale behind this switch is the expected reduction in risk of transfusion reactions 1-8) and prion infections, and the increase in efficacy 7-8) as compared to Quarantined Fresh Frozen Plasma (Q-FFP). These improvements have been seen in other countries switching from Q-FFP to SDP. However some studies suggest SDP also carries a higher risk of Deep Venous Thrombosis (DVT) 9-10) and hyperfibrinolysis 11-12) than Q-FFP.

Objective

To compare Omniplasma™ and Quarantine Fresh Frozen Plasma (Q-FFP) with regard to cost effectiveness and safety, specifically transfusion reactions, in patients receiving plasma transfusions in the Netherlands during the course of the study.

Study design

FROSTED is a non-experimental study organized by the Sanquin Blood Foundation, the Dutch haemovigilance organization TRIP (Transfusion and transplantation Reactions In Patients), and the Leiden University Medical Centre department of Clinical Epidemiology, in collaboration with both academic and peripheral hospitals throughout the Netherlands. Data will be collected from hospital records and the existing national databases designed to record transfusion reactions and incidents in the transfusion chain, and used to evaluate the safety, efficacy, and cost effectiveness of the two products.

Study population

All patients receiving a plasma transfusion (either Omniplasma™ or Q-FFP) in the Netherlands during the period of the study. 

Main study endpoints

The main study endpoints are the types and number of transfusion reactions, along with type and number of units of plasma and erythrocytes used and details regarding the patient population receiving the products.

Expected result

We will compare incidences of transfusion reactions, effectiveness, and price of treatment for each of the two products. Given similar research performed in other countries, we expect the switch to Omniplasma™ to decrease both adverse events and the total volume of plasma transfused nationally.

References

1. Omniplasma. (2013). Retrieved November 8, 2013, from http://www.sanquin.nl/producten-diensten/plasmaproducten/producten/omniplasma/
2. Baudoux E, Margraff U, Coenen A, Jacobs X, Strivay M, Lungu C, Sondag-Thull D. Hemovigilance: clinical tolerance of solvent-detergent treated plasma. Vox Sanguinis 1998; 74(Suppl. 1):237-9.
3. Flesland O, Seghatchian J, Solheim BG. The Norwegian Plasma Fractionation Project--a 12 year clinical and economic success story. Transfusion and apheresis science: official journal of the World Apheresis Association: official journal of the European Society for Haemapheresis 2003; 28(1):93-100.
4. Solheim BG. Plasma-induced TRALI is avoided with Solvent/Detergent-treated plasma. Trans Alternat Transfus Med 2005; 7(Suppl. 1):57.
5. McCarthy LJ. The experience of treating patients with thrombotic thrombocytopenic purpura with solvent detergent plasma. Br J Haematol 2006; 133(1):107.
6. Flesland O. A comparison of complication rates based on published haemovigilance data. Intensive Care Med 2007; 33 (Suppl 1):S17–21.
7. Krusius T, Auvinen M-K, Nikkinen L. Introduction of octaplas- in clinical use decreased the rate of severe adverse reactions. Vox Sanguinis 2009; 96 (Suppl 1):33.
8. Krusius T, Auvinen M-K, Tuimala J. Introduction of Octaplas in clinical use decreased the rate of serious adverse reactions. Vox Sanguinis 2010; 99(Suppl. 1):461.
9. Flamholz R, Jeon HR, Baron JM, Baron BW. Study of three patients with thrombotic thrombocytopenic purpura exchanged with solvent/detergent-treated plasma: is its decreased protein S activity clinically related to their development of deep venous thromboses? J Clin Apher 2000; 15(3):169-72.
10. Yarranton H, Cohen H, Pavord SR, Benjamin S, Hagger D, Machin SJ. Venous thromboembolism associated with the management of acute thrombotic thrombocytopenic purpura. Br J Haematol 2003; 121(5):778-85.
11. De Jonge J, Groenland TH, Metselaar HJ, IJzermans JN, van Vliet HH, Visser L, Tilanus HW. Fibrinolysis during liver transplantation is enhanced by using solvent/detergent virus-inactivated plasma (ESDEP). Anesth Analg 2002; 94(0003-2999 (Print)): 1127–31, table.
12. Magner JJ, Crowley KJ,  Boylan JF. Fatal fibrinolysis during orthotopic liver transplantation in patients receiving solvent/detergent-treated plasma (Octaplas). J Cardiothorac Vasc Anesth 2007; 21(3):410-3.