Thrombopoietin (TPO) deficiency has been proposed as an important etiologic factor for thrombocytopenia in advanced-stage liver disease. To clarify the contributions of platelet production, platelet consumption, coagulation activation, and splenic sequestration to thrombocytopenia in liver disease, we studied TPO serum levels and markers of platelet production, platelet activation, and coagulation activation before and 14 days after orthotopic liver transplantation (OLT) in 18 patients with advanced liver cirrhosis. Thrombocytopenia before transplantation occurred with low-normal serum levels of TPO, normal levels of platelet and coagulation activation markers, and no increase in bone marrow production of platelets. TPO serum levels increased significantly on the first day after OLT, preceding the increase of reticulated platelets by 3 days and peripheral platelets by 5 days. Normalization of the peripheral platelet count occurred in most patients within 14 days of OLT, irrespective of the change in spleen size assessed by computed tomography volumetry. Normalization of platelet counts was not hampered by a certain degree of platelet activation observed during the steepest increase in the peripheral platelet count. Bone marrow production of platelets increased significantly within 2 weeks of transplantation. Low TPO serum levels with low platelet counts and without platelet consumption suggests low TPO production in end-stage liver disease. The rapid increase in TPO serum levels after transplantation induces an increase in the bone marrow production of platelets. Decreased TPO production in the cirrhotic liver is an important etiologic factor for thrombocytopenia in liver disease that is rapidly reversed by transplantation.
This randomized, double-blind comparison demonstrates that biosimilar filgrastim (EP2006) and the US-licensed reference filgrastim are similar with no clinically meaningful differences regarding efficacy and safety in prevention of severe neutropenia. Biosimilar filgrastim could represent an important alternative to the reference product, potentially increasing access to filgrastim treatment.
This trial shows 1) that initial activation of platelets obtained with the MCS 3P is less than that of platelets obtained with the CS 3000 Plus; 2) that the increase in cP-selectin is a more sensitive marker for initial platelet activation than the expression of P-selectin on the surface; and 3) that the relative amount of cP-selectin is higher in women than in men given the same stimulus. Differences in platelet activation by various cell separators and the sex of the donor may contribute to variability of PC quality.
These findings suggest that repeat platelet donation might lead to a relative exhaustion of thrombopoiesis, as evidenced by the low levels of reticulated platelets exhibited by repeat donors. The reticulated platelet count can be used to monitor the thrombopoietic capacity of long-term platelet donors.
Single-donor plateletpheresis results in a temporary increase in serum TPO levels in healthy platelet donors, which may be part of a compensatory response-boosting megakaryocytopoiesis after platelet collection.
Resting CD4 + T cells in the lymphoid tissue (LT) are essential producers of virions at the beginning of HIV infection in vivo. We previously developed a model that allowed in vitro infection of non-prestimulated T lymphocytes in the presence of autologous B lymphocytes and complement. In this study, we try to clarify the mechanism(s) responsible for virus transmission in unstimulated autologous B cell/T cell co-cultures. Ex vivo analyses of patient plasma samples revealed that HIV was opsonized. Flow cytometry showed that opsonized virus preferentially bound to complement receptor (CR)-2 on B lymphocytes in primary B cell/T cell co-cultures. As indicated by cytokine measurements and transwell experiments, soluble factors seemed to play a minor role in enabling infection. Rather, direct interaction between B and T lymphocytes and direct binding of opsonized virus to CR2 on B cells turned out to be essential for productive infection. Antibodies blocking cell-cell adhesion inhibited p24 antigen production. An anti-CR2 antibody blocking C3d-CR2 binding also significantly reduced viral replication. Since the infection of unstimulated T cells by opsonized primary HIV isolates in the presence of B cells was highly efficient independent of the tropism of the virus, this mechanism may be critical in the pathogenesis of HIV.
Plateletpheresis can be regarded as safe with respect to the activation of coagulation or neutrophils. The consequences for the donor's health of the decrease in D-dimer, PPI, and PAI-1 may deserve further investigation.
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