Immune-mediated platelet refractoriness (PR) remains a significant problem in the setting of platelet transfusion and is predominantly caused by the presence of alloantibodies directed against... Show moreImmune-mediated platelet refractoriness (PR) remains a significant problem in the setting of platelet transfusion and is predominantly caused by the presence of alloantibodies directed against class I human leukocyte antigens (HLA). Opsonization of donor platelets with these alloantibodies can result in rapid clearance after transfusion via multiple mechanisms, including antibody dependent cellular phagocytosis (ADCP). Interestingly, not all alloimmunized patients develop PR to unmatched platelet transfusions, suggesting variation in HLA-specific IgG responses between patients. Previously, we observed that the glycosylation profile of anti-HLA antibodies was highly variable between PR patients, especially with respect to Fc galactosylation, sialylation and fucosylation. In the current study, we investigated the effect of different Fc glycosylation patterns, with known effects on complement deposition and FcγR binding, on phagocytosis of opsonized platelets by monocyte-derived human macrophages. We found that the phagocytosis of antibody- and complement-opsonized platelets, by monocyte derived M1 macrophages, was unaffected by these qualitative IgG-glycan differences. Show less
Diemen, J.J.K. van; Madsen, M.C.; Vrancken, P.; Bie, K. de; Bom, J.G. van der; Veen, G.; ... ; Thijs, A. 2020
Cardiovascular events occur most frequently in the early morning. Similarly, the release of reticulated platelets (RP) by megakaryocytes has a peak in the late night and early morning. Which... Show moreCardiovascular events occur most frequently in the early morning. Similarly, the release of reticulated platelets (RP) by megakaryocytes has a peak in the late night and early morning. Which aspirin regimen most effectively inhibits platelets during these critical hours is unknown. Hence, the primary objective of this trial was to assess platelet function and RP levels at 8.00 AM, in stable cardiovascular (CVD) patients, during three different aspirin regimens. In this open-label randomized cross-over study subjects were allocated to three sequential aspirin regimens: once-daily (OD) 80 mg morning; OD-evening, and twice-daily (BID) 40 mg. Platelet function was measured at 8.00 AM & 8.00 PM by serum Thromboxane B-2(sTxB(2)) levels, the Platelet Function Analyzer (PFA)-200 (R) Closure Time (CT), Aspirin Reaction Units (ARU, VerifyNow (R)), and RP levels. In total, 22 patients were included. At 8.00 AM, sTxB(2)levels were the lowest after OD-evening in comparison with OD-morning (p= <0.01), but not in comparison with BID. Furthermore, RP levels were similar at 8.00 AM, but statistically significantly reduced at 8.00 PM after OD-evening (p= .01) and BID (p= .02) in comparison with OD-morning. OD-evening aspirin intake results in higher levels of platelet inhibition during early morning hours and results in a reduction of RP levels in the evening. These findings may, if confirmed by larger studies, be relevant to large groups of patients taking aspirin to reduce cardiovascular risk. Show less
Porcelijn, L.; Huiskes, E.; Hoogen, L.O. van den; Folman, C.C.; Zwaginga, J.J.; Haas, M. de 2020
Plasma thrombopoietin (Tpo) levels distinguish thrombocytopenia resulting from increased platelet destruction or decreased platelet production. We investigated whether measuring plasma Tpo levels... Show morePlasma thrombopoietin (Tpo) levels distinguish thrombocytopenia resulting from increased platelet destruction or decreased platelet production. We investigated whether measuring plasma Tpo levels in thrombocytopenic newborns is of diagnostic value to establish the underlying mechanism of thrombocytopenia. Tpo levels were measured with in-house developed ELISA in samples referred to our center because of thrombocytopenia noticed in the first 10 days of life. Clinical data were collected. Plasma Tpo levels <128 AU/ml were found in the majority (92%) of 121 newborns with immune-mediated thrombocytopenia (n = 104) and thrombocytopenia due to bacterial infections (n = 7); increased plasma Tpo levels (>= 128 AU/ml) were found in thrombocytopenic newborns with severe asphyxia (n = 24). Highly increased plasma Tpo levels (>200 AU/ml) were found in thrombocytopenic neonates with congenital viral infections (n = 22) or amegakaryocytosis (n = 6). A plasma Tpo level <128 AU/ml excludes (negative predictive value 96%, 95% CI 90-99) severe asphyxia, congenital viral infections and amegakaryocytosis as the cause for thrombocytopenia in newborns. Increased plasma Tpo levels indicate that thrombocytopenia in newborns, as a result of various nonimmune disorders, is often caused by (temporary) bone marrow suppression/failure. Measurement of plasma Tpo levels provides the clinician with an additional tool to decide on the differential diagnosis, the necessity for subsequent diagnostics and treatment in neonates with thrombocytopenia. Show less
