Clinical guidelines for cryosupernatant transfusions

Introduction. Cryosupernatant is blood component. Cryosupernatant is the supernatant plasma removed during the preparation of cryoprecipitate.

Aim. To provide information on the composition and methods of production, storage, transportation and clinical use of Cryosupernatant.

General findings. In comparison with fresh frozen plasma (FFP) and cryoprecipitate, Cryosupernatant plasma is depleted in factor VIII, fibrinogen factor von Willebrand (VWF). Cryosupernatant is deficient in high molecular weight multimers of VWF, but contains VWF metalloproteinase. The concentrations of factor V, antithrombin III, albumin and immunoglobulins are the same as in FFP and cryoprecipitate. The indications for Cryosupernatant transfusions are massive blood loss in patients with factor VIII inhibitor, plasma exchange in patients with thrombotic thrombocytopenic purpura. For children the doses of Cryosupernatant should be 10-15 mL/kg.

1. Freedman M., Rock G. Analysis of the products of cryoprecipitation: RiCoF is defi cient in cryosupernatant plasma. Transfusion and Apheresis Science. 2010; 43(2): 179–82. DOI: 10.1016/j.transci.2010.07.004.

2. Hori Y., Hayakawa M., Isonishi A. et al. ADAMTS13 unbound to larger von Willebrand factor multimers in cryosupernatant: Implications for selection of plasma preparations for thrombotic thrombocytopenic purpura treatment. Transfusion. 2013; 53(12): 3192–202. DOI: 10.1111/trf.12182.

3. Raife T.J., Friedman K.D., Dwyre D.M. The pathogenicity of von Willebrand factor in thrombotic thrombocytopenic purpura: reconsideration of treatment with cryopoor plasma Thomas. Transfusion. 2006; 46: 74–9. DOI: 10.1111/j.1537- 2995.2006.00674.x.

4. RАТ. Donor blood and its components: characteristics and quality control. XIV. Cryosupernatant plasma. 2005 (In Russian).

5. Canadian Blood Service. Circular of information. For the use of human blood components. 2018.

6. Bhakta V., Jenkins C., Ramirez-Arcos S. et al. Stability of relevant plasma protein activities in cryosupernatant plasma units during refrigerated storage for up to 5 days postthaw. Transfusion. 2014; 54(2): 418–25. DOI: 10.1111/trf.12254.

7. Yarranton H., Lawrie A.S., MacKie I.J. et al. Coagulation factor levels in cryosupernatant prepared from plasma treated with amotosalen hydrochloride (S-59) and ultraviolet a light. Transfusion. 2005; 45(9): 1453–8. DOI: 10.1111/j.1537- 2995.2005.00551.x.

8. O’Shaughnessy D., Atterbury C., Bolton Maggs P. et al. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Hematol. 2004; 126(1): 11–28. DOI: 10.1111/j.1365-2141.2004.04972.x.

9. Palaniappan P., Lionel A.P., Agarwal I. et al. Cryosupernatant and Immunosuppression as Effective Alternative Therapies for TTP in Three Pediatric SLE Patients. Indian J Hematol Blood Transfus. 2014; 30(Suppl 1): S232–6. DOI: 10.1007/ s12288-014-0338-8.

10. von Baeyer H. Plasmapheresis in thrombotic microangiopathy-associated syndromes: review of outcome data derived from clinical trials and open studies. Vol. 6, Ther apher. 2002. p. 320–8. DOI: 10.1046/j.1526-0968.2002.00390.x.

11. Rock G., Shumak K.H., Sutton D.M.C. et al. Cryosupernatant as replacement fl uid for plasma exchange in thrombotic thrombocytopenic purpura. Brit J Haematol. 1996; 94(2): 383–6. DOI: 10.1046/j.1365-2141.1996.d01-1800.x.

12. Mazepa M.A., Raval J.S., Brecher M.E. et al. Treatment of acquired Thrombotic Thrombocytopenic Purpura in the U.S. remains heterogeneous: Current and future points of clinical equipoise. J Clin Apher. 2018; 33(3): 291–6. DOI: 10.1002/jca.21600.

13. Altuntas F., Aydogdu I., Kabukcu S. et al. Therapeutic plasma exchange for the treatment of thrombotic thrombocytopenic purpura: A retrospective multicenter study. Transf Apher Sci. 2007; 36(1): 57–67. DOI: 10.1016/j.transci.2006.05.014.

14. Zeigler Z.R., Shadduck R.K., Gryn J.F. et al. Cryoprecipitate poor plasma does not improve early response in primary adult thrombotic thrombocytopenic purpura (TTP). J Clin Apher. 2001; 16(1): 19–22. DOI: 10.1002/jca.1003.

15. Lin Q., Fan L., Huang H. et al. Combination of Fresh Frozen Plasma and Cryosupernatant Plasma for Therapeutic Plasma Exchange in Thrombotic Thrombocytopenic Purpura: A Single Institution Experience. BioMed Res Int. 2019; 2019. DOI: 10.1155/2019/1756109.

16. Moake J.L., Byrnes J.J., Troll J.H. et al. Effects of fresh-frozen plasma and its cryosupernatant fraction on von Willebrand factor multimeric forms in chronic relapsing thrombotic thrombocytopenic purpura. Blood. 1985; 65(5): 1232–6.

17. Stefanello B., De Paula E.V., Orsi F.A. et al. Safety and effi cacy of cryoprecipitate-poor plasma as a replacement fl uid for therapeutic plasma exchange in thrombotic thrombocytopenic purpura: A single center retrospective evaluation. J Clin Apher. 2014; 29(6): 311–5. DOI: 10.1002/jca.21336.

18. Rock G., Ahluwalia N., Anderson D. Metalloprotease levels are variably altered in thrombotic thrombocytopenic patients at presentation and after plasma exchange with either cryosupernatant plasma or fresh frozen plasma. Blood. 2001; 102: 539а.