Background and Objectives Alloantibodies against red-blood-cell (RBC) antigens often coincide with alloantibodies against leucocytes and platelets and sometimes with autoantibodies towards various... Show moreBackground and Objectives Alloantibodies against red-blood-cell (RBC) antigens often coincide with alloantibodies against leucocytes and platelets and sometimes with autoantibodies towards various antigens. Chimerism may be one of the factors responsible for the combination of allo- and autoantibodies. Women with alloantibodies against RBC antigens causing haemolytic disease of the fetus and neonate may need to receive intrauterine transfusions. These transfusions increase not only maternal antibody formation but also fetomaternal bleeding and may enhance fetal chimerism. We determined the prevalence of and risk factors for autoantibodies against some common clinical target antigens, in alloimmunized women after IUT.Materials and Methods We tested for autoantibodies against RBC, anti-thyroid peroxidase, anti-extractable nuclear antigens, anti-cyclic citrullinated proteins and anti-tissue transglutaminase. Women with and without autoantibodies were compared for age; number of RBC alloantibodies, pregnancies and IUTs, and other factors that may play a role in immunization.Results Non-RBC-targeted autoantibodies were present in 40 of 258 tested women (15 center dot 5%, with 90% anti-TPO specificity), comparable to the prevalence reported in healthy Dutch women of these ages. Surprisingly, compared with women who had a single RBC alloantibody, a significantly higher proportion of women with multiple RBC alloantibodies had autoantibodies (5 center dot 3% and 18 center dot 4%, respectively; odds ratio 4 center dot 06, 95% CI: 1 center dot 20-13 center dot 7). Other characteristics of women with and without autoantibodies were not different.Conclusion Multiple RBC alloantibodies after extensive allogeneic exposure during pregnancy and presumed increased fetomaternal chimerism are not associated with (selected) autoantibodies. Lack of allo-RBC multi-responsiveness seems associated with decreased auto(-TPO) antibody formation. Show less
Ypma, P.F.; Geloven, N. van; Kerkhoffs, J.L.H.; Boekhorst, P. te; Zwaginga, J.J.; Beckers, E.A.M.; ... ; Eikenboom, J.C.J. 2019
In daily haematological practice, predicting bleeding in thrombocytopenic patients is difficult, and clinicians adhere to transfusion triggers to guide patients through the aplastic phase of... Show moreIn daily haematological practice, predicting bleeding in thrombocytopenic patients is difficult, and clinicians adhere to transfusion triggers to guide patients through the aplastic phase of chemotherapy. Platelet count is not the only determinant of bleeding and additional mechanisms for impending haemostasis are likely. Beside clot formation, platelets are essential for the maintenance of integrity of vascular beds. We therefore prospectively investigated associations between biomarkers for endothelial damage (urine albumin excretion) and inflammation (C-reactive protein) and bleeding (WHO grading) in 88 patients with 116 on-protocol episodes. We found an increase in grade 2 bleeding with a higher urine albumin/creatinine ratio one day after the measurement [odds ratio (OR) 1·24 for every doubling of the ratio, 95% CI 1·05-1·46, P-value 0·01] and a 29% increase in the odds of grade 2 bleeding for every doubling of serum C-reactive protein (CRP) (95% CI 1·04-1·60, P-value 0·02) after correction for morning platelet count. The 24 h post-transfusion corrected count increment (CCI24 ) showed a significant association with these biomarkers: increasing urine albumin/creatinine ratio and CRP were associated with lower CCI24. We report two inexpensive and easy-to-apply biomarkers that could be useful in designing a prediction model for bleeding risk in thrombocytopenic patients Show less
Ypma, P.F.; Geloven, N. van; Kerkhoffs, J.L.H.; Boekhorst, P. te; Zwaginga, J.J.; Beckers, E.A.M.; ... ; Eikenboom, J.C.J. 2019
Patients refractory to platelet transfusions because of alloimmunization require HLA-matched platelets, which is only possible if a large HLA-typed donor pool is available. However, even then,... Show morePatients refractory to platelet transfusions because of alloimmunization require HLA-matched platelets, which is only possible if a large HLA-typed donor pool is available. However, even then, patients with broad immunization or rare haplotypes may not have suitable donors. In these patients, transfusions with platelets showing low HLA class I expression may be an alternative to fully HLA-matched transfusions. In this study, we quantified the proportion of donors with consistently low HLA-B8, -B12, and -B35 expression on platelets using human monoclonal antibodies specific for these antigens. Furthermore, as model for in vivo clearance, antibody-mediated internalization of these platelets by macrophages was investigated. The expression of HLA-B8, -B12, or -B35 on platelets was extremely variable between individuals (coefficients of variation, 41.4% to 73.6%). For HLA-B8, but not for HLA-B12 or -B35, this variation was in part explained by zygosity. The variation was most pronounced in, but not exclusive to, platelets. Expression within one donor was consistent over time. Remarkably, 32% of 113 HLA-B8, 34% of 98 HLA-B12, and 9% of 66 HLA-B35 donors showed platelet antigen expression that was not or only minimally above background. Antibody-mediated internalization of platelets by macrophages correlated with antibody opsonization and antigen expression and was absent in platelets with low or minimal HLA expression. In conclusion, our findings indicate that a substantial proportion of donors have platelets with consistently low expression of specific HLA class I antigens. These platelets may be used to treat refractory patients with antibodies directed against these particular antigens, despite HLA mismatches. Show less
Saris, A.; Tomson, B.; Brand, A.; Mulder, A.; Claas, F.H.; Lorinser, J.; ... ; Meer, P.F. van der 2018
