H.B. Feys PhD

O06 OPEN ADAMTS13 CONFORMATION IN IMMUNE-MEDIATED THROMBOTIC THROMBOCYTOPENIC PURPURA IS INDUCED BY ANTI-ADAMTS13 AUTOANTIBODIES

P28 THE MECHANISM OF THE LOSS OF HMW VWF MULTIMERS AFTER LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION IS DIFFERENT BETWEEN HUMANS AND SHEEP

A-132 CRYOPRESERVATION IMPAIRS PLATELET FUNCTION BUT GENERATES PROCOAGULANT PLATELETS

A-145 PLASMA OF HEALTHY DONORS CONTAINS SPECIFIC ANTI-IDIOTYPIC ANTIBODIES THAT RECOGNIZE TWO CLONED HUMAN ANTI-ADAMTS13 AUTOANTIBODIES

Massive clotting in red cell concentrates during transfusion is caused by backflow of patient blood

SUMMARY

We report three cases of massive ex vivo coagulation in a leukocyte depleted red cell concentrate during transfusion. Molecular blood typing indicated that patient blood was present in the filter housing of the infusion set and/or in the blood bag itself. Together with the history of events, this suggested that the observed clotting was caused by backflow of patient blood. Therefore, we recommend maintaining the blood bag above heart level during the entire transfusion procedure, until the infusion set is removed.

(BELG J HEMATOL 2017;8(5):195–7)

Pathogen inactivation of blood components, impact on plasma and platelet function

Summary

Pathogen inactivation technologies are photochemical treatments developed to decrease transfusion transmitted infections. However, the impact of pathogen inactivation technologies on the blood components themselves is not entirely clear. Therefore, we investigated the quality of blood components following pathogen inactivation. First, the impact of three different pathogen inactivation technologies on plasma was compared. The different methods all negatively affected ADAMTS13 activity and antigen level, but to different degrees. The pathogen inactivation technology using riboflavin as a photosensitizer had the largest effect. This effect was caused by reactive oxygen because removal of dissolved molecular oxygen prevented protein damage to occur. Next, we investigated the influence of three different pathogen inactivation technologies on platelet concentrates. For this, platelet function was assessed in microfluidic flow chamber experiments. These indicated a decreased platelet function compared to untreated controls for all pathogen inactivation technologies. Additional experiments showed that the underlying mechanisms of platelet damage were different for every pathogen inactivation technology, but all three resulted in similar thrombus formation deficiencies in flow chambers. We focused on one particular pathogen inactivation technology which combines the photosensitizer amotosalen (a psoralen) and UVA light (PUVA). The data showed a specific inhibition of the phosphatidylinositol 3-kinase signal transduction pathway caused by covalent binding of amotosalen to phospholipids during photoactivation. As the combination of a psoralen with UVA light is clinically used off-label for graft-versus-host disease treatment, phosphatidylinositol 3-kinase signal transduction in T lymphocytes of patient samples was studied and also here inhibition of phosphatidylinositol 3-kinase signal transduction was found. To conclude, research that initiated from the observation that platelet and plasma function is decreased following pathogen inactivation technologies has revealed an overall effect of PUVA on cellular phosphatidylinositol 3-kinase signal transduction by covalent modification of phospholipids.

(BELG J HEMATOL 2016;7(6):240–3)

ADAMTS13-induced destabilization of the von Willebrand factor A2 domain