Indications for a protective function of beta2-glycoprotein I in thrombotic thrombocytopenic purpura.

It has been shown that ß(2) -glycoprotein I (ß(2) GPI) interacts with von Willebrand factor (VWF) in a glycoprotein (GP)Ib binding state. Given the presence of active VWF multimers in thrombotic thrombocytopenic purpura (TTP), we speculated that ß(2) GPI might play a role in TTP. We found that ß(2) GPI plasma levels were significantly lower in acute and remission TTP patients than in normal controls, showing a direct correlation with ADAMTS 13 levels and an inverse correlation with the extent of VWF activation. In vitro flow experiments demonstrated that ß(2) GPI can block platelet adhesion to endothelial cell-derived VWF strings. We confirmed the direct binding of ß(2) GPI to VWF by surface plasmon resonance, and determined that domain I of ß(2) GPI is the binding site of VWF A1 domain. Adhesion of ß(2) GPI to erythrocytes and platelets was increased in the presence of active VWF, indicating that ß(2) GPI may be cleared from the circulation during TTP episodes together with blood cells. Our findings suggest that ß(2) GPI may protect from the effects of hyper-functional VWF by inhibiting its interaction with platelets.

Transfusion-related acute lung injury reports in the Netherlands: an observational study.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious, sometimes fatal complication of transfusion, attributed to white blood cell (WBC)-reactive antibodies present in the blood product. This study investigated incidence and etiology in the Netherlands. STUDY DESIGN AND METHODS: From January 2005 through July 2007, all TRALI cases reported to the Sanquin Blood Banks were evaluated. Only cases meeting the Canadian Consensus Conference criteria for TRALI were included and investigated for patient, donor, and product characteristics. Patients and donors were screened for HLA Class I, HLA Class II, and granulocyte antibodies. RESULTS: A total of 56 TRALI cases were reported of which 49 were completely evaluated. Seventy-eight percent of the patients needed monitoring or mechanical ventilation on the intensive care unit, 10 patients died. In 61% of cases large-volume plasma products were involved. WBC-reactive antibodies in donors were found in 73% of cases, with proven incompatibility in 21 of 44 (48%) investigated cases. Possible TRALI cases, as defined by the Canadian Consensus Conference, had significantly lower incompatibility rates compared to TRALI cases, 18% versus 58% (p = 0.036). In the 21 alloimmune cases, a total of 31 implicated donors were found, of which 26 were female, including 12 fresh-frozen plasma (FFP) products. CONCLUSION: TRALI is the most serious transfusion complication in the Netherlands, causing severe morbidity and mortality. Antibodies were found in the majority of the cases, but causality with proven incompatibility could be established in 21 cases (48%). Female FFP products were involved in 57% of proven alloimmune cases and would theoretically be prevented using male FFP only.

Donor selection criteria to maximize double platelet products (DPP) by platelet apheresis.

Variant Creutzfeldt-Jakob disease brought us to perform a study to diminish donor exposure from transfusion of platelet concentrates. The current study aimed to develop donor selection criteria that maximize the likelihood of deriving single donor platelets and producing double platelet products (DPP). Donors were recruited among plasmapheresis donors and among other donors when the selected donors did not show up. Donor precount and body weight and haematocrit were examined as determinants of higher split-rates combined with procedure time. When the criterion was set on 225; 82% of the procedures (n=717) with a precount of >225 yielded DPP compared to 54% of the procedures with a precount <225 (p<.01). Body weight >65 kg gave good results in split-rate. Procedure time showed an inverse correlation with the highest correlating precount (r=-.14; p<.001). Eighty one percent of the donors reported a willingness to donate at least seven times a year and 75% accepted the mean procedure time. This confirmed logistical feasibility of the conversion to AP-PC although profits would be reduce 13% compared to platelets from pooled buffy coats.