Martin Schipperus - Academia.edu (original) (raw)
Uploads
Papers by Martin Schipperus
Transfusion Clinique et Biologique, 2014
Leukemia
In order to obtain more insight into the nature of the abnormal in vitro colony formation in myel... more In order to obtain more insight into the nature of the abnormal in vitro colony formation in myelodysplastic syndromes (MDS), we investigated the kinetics of the colony formation of 23 MDS cases in response to recombinant human interleukin-3 (IL-3), Granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating Factor (G-CSF), and giant cell tumor cell line conditioned medium (GCT-CM). The kinetics of GCT-CM-induced colony formation were comparable to that of G-CSF-induced colony growth, both in MDS and in normal bone marrow cultures. Colony formation was found to be delayed in MDS. The delay in colony formation was most apparent in the GCT-CM (G-CSF) responsive progenitor cell compartment. In MDS cases with clinical features of high risk disease, this delay was more pronounced as compared with low risk cases (7 and 3 days, respectively, in response to GCT-CM). The delay in colony formation was found to be caused by an increase in the time interval before progenitor cells had begun to divide. These results suggest that a prolongation of the time spent in G0 of myeloid progenitor cells in MDS may be the cause of the indolent in vitro colony formation observed in this disease.
Betere registratie moet het mogelijk maken om meer inzicht te krijgen in zowel product als patiën... more Betere registratie moet het mogelijk maken om meer inzicht te krijgen in zowel product als patiënt gerelateerde factoren die invloed hebben op het ontwikkelen van een bacteriemie/sepsis na een bloedtransfusie. Naast door bloedtransfusie overgedragen bacteriële infecties kan er ook sprake zijn van een transfusie gerelateerde bacteriemie/sepsis waarbij bacteriële overdracht door het bloedproduct niet kan worden aangetoond. Tevens zijn er transfusies met bloedproducten waarvan achteraf blijkt dat ze gecontamineerd zijn, maar waarbij na transfusie geen bacteriemie/sepsis bij de ontvanger wordt geconstateerd. Voor het verhogen van de patiëntveiligheid is het nuttig om nader te onderzoeken wat de relatie is tussen transfusie en ontwikkeling van bacteriemie/sepsis bij de ontvanger in gevallen waarbij er geen sprake is van overdracht van bacteriën door het bloedproduct.
Clinical Case Reports, 2015
Prolonged clotting times were observed in a patient with spontaneous hemorrhage. Analysis showed ... more Prolonged clotting times were observed in a patient with spontaneous hemorrhage. Analysis showed severe factor X deficiency due to clearance by a noninhibitory antibody. Lymphadenopathy identified on imaging led to diagnosis of marginal B-cell lymphoma. Treatment of lymphoma with rituximab and chlorambucil resulted in complete disappearance of the bleeding disorder.
Vox sanguinis, Jan 20, 2015
The 2011 Dutch Blood Transfusion Guideline for hospitals incorporates seven internal quality indi... more The 2011 Dutch Blood Transfusion Guideline for hospitals incorporates seven internal quality indicators for evaluation of the hospital transfusion chain. The indicators aim to measure guideline compliance as shown by the instatement of a hospital transfusion committee and transfusion safety officer (structural indicators), observance of transfusion triggers and mandatory traceability of labile blood components (process indicators). Two voluntary online surveys were sent to all Dutch hospitals for operational years 2011 and 2012 to assess compliance with the guideline recommendations. Most hospitals had a hospital transfusion committee and had appointed a transfusion safety officer (TSO). In 2012, only 23% of hospitals complied with the recommended minimum of four annual transfusion committee meetings and 8 h/week for the TSO. Compliance with the recommended pretransfusion haemoglobin threshold for RBC transfusion was achieved by 90% of hospitals in over 80% of transfusions; 58% of h...
Vox sanguinis, Jan 30, 2014
The TRIP national hemovigilance and biovigilance office receives reports on side-effects and inci... more The TRIP national hemovigilance and biovigilance office receives reports on side-effects and incidents associated with transfusion of labile blood products. Anaphylactic reactions accounted for the largest number of serious transfusion reactions in the period 2008-2012. In most cases, no cause is found for these reactions. TRIP data show that anaphylactic reactions occur relatively frequently with transfusion of plasma or platelet concentrates. Data from blood services show that 10% or more of plasma donors regularly use medication which is permitted under donation guidelines. It is conceivable that medication taken by the donor in plasma for transfusion could cause an anaphylactic transfusion reaction in the recipient. This exploratory study investigated the presence of drugs or drug metabolites in donor plasma. Samples (5 ml) were taken from thawed, quarantine fresh frozen plasma units (FFP) which had to be rejected for transfusion because of leaks or length of time after thawing....
Haematology and blood transfusion, 1990
Haematologica, 2014
ABSTRACT - Copyright © 2014, Ferrata Storti Foundation.
Vox Sanguinis, 2013
European Union member states must have national haemovigilance reporting of serious adverse react... more European Union member states must have national haemovigilance reporting of serious adverse reactions and events. We sent national competent authorities an email questionnaire about data validation. Responses were received from 23/27 countries. Nine previously had no national haemovigilance system. In 13 (57%), the serious adverse reactions and events can be verified. Coverage of blood establishments is documented in 20 systems (87%) and of hospitals in 15 systems (65%). Although all member states have implemented haemovigilance systems, there are currently wide variations in data quality assurance, not allowing comparisons between countries.
Transfusion Medicine, 2012
The fraction of transfusion-related acute lung injury (TRALI) cases preventable by deferral of al... more The fraction of transfusion-related acute lung injury (TRALI) cases preventable by deferral of allo-exposed donors has previously been estimated, under the assumption this indirectly estimated the contribution of leucocyte antibodies to the occurrence of TRALI. Our aim was to estimate the fraction preventable by deferral of leucocyte antibody positive donors and to investigate the validity of allo-exposure as a marker for leucocyte antibodies. Methods: All donors involved in a series of previously published TRALI patients were tested for leucocyte antibodies. The observed number of antibody positive donors was compared to the expected number. From this comparison we estimated the contribution of leucocyte antibodies to the occurrence of TRALI and compared this to the previously reported estimate for allo-exposed donors. Results: Sixty-one TRALI patients were included. Of 288 involved donors 43 were expected and 67 were observed to be leucocyte antibody positive. The observed percentage of positive donors was 8·3% (95% confidence interval (CI): 5·1-11·5%) in excess of the expected. Overall 59% (95% CI: 34-85%) of TRALI cases was estimated to be preventable by the exclusion of all leucocyte antibody positive donors. For plasma-poor products this was 16% (95% CI: −5·0 to 36%). Conclusions: These estimates were similar to those previously published for allo-exposed donors. This suggests allo-exposure status can effectively be used in donor deferral strategies.
Transfusion, 2007
BACKGROUND: Development of new red blood cell (RBC) alloantibodies (alloimmunization) is one of t... more BACKGROUND: Development of new red blood cell (RBC) alloantibodies (alloimmunization) is one of the most frequent adverse reactions after an RBC transfusion. Few studies have investigated clinical risk factors for alloimmunization.
Transfusion, 1990
Bone marrow was harvested for the purpose of autologous bone marrow transplantation (ABMT) in 21 ... more Bone marrow was harvested for the purpose of autologous bone marrow transplantation (ABMT) in 21 patients previously treated with chemotherapy and in complete remission from acute leukemia or non-Hodgkin's lymphoma. The volume required to obtain 2 x 10(8) nucleated cells per kg was less than 15 mL per kg in 13 patients and more than 15 mL per kg in 8 patients. The blood admixture was proportional to the aspirated volume (p less than 0.0001). The number of granulocyte-macrophage colony-forming units (CFU-GM) harvested in the groups was 8.4 +/- 2.2 and 3.4 +/- 1.4 x 10(4) per kg, respectively (p less than 0.0001). Autologous red cells were transfused into 16 of 21 patients, who did not require further homologous transfusions. The mean drop in hemoglobin from the preoperative level was 1.0 +/- 0.2 g per dL. No adverse effects were noted. It is concluded that large single-volume bone marrow harvests are possible and may reduce the need for a second harvest, and that, through the transfusion of autologous red cells obtained during marrow harvest, homologous blood transfusion can be avoided in most patients.
Transfusion, 2011
BACKGROUND: Transfusion-related acute lung injury (TRALI) is one of the most serious complication... more BACKGROUND: Transfusion-related acute lung injury (TRALI) is one of the most serious complications of blood transfusion. It can be caused by incompatible white blood cell antibodies in transfused plasma. The objective of this study was to quantify the reduction of TRALI after introduction of male-only plasma for transfusion as a preventive measure, which took effect in 2007.
Leukemia Research, 1990
The decreased or absent in vitro colony formation in response to single recombinant haematopoieti... more The decreased or absent in vitro colony formation in response to single recombinant haematopoietic growth factors has been reported previously. Here we report on the effects of the combination of interleukin 3 (I1-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF) and the effect of the conditioned medium of the giant tumour cell line (GCT-CM) on the proliferation of myelodysplastic (MDS) marrow myeloid progenitor cells and normal bone marrow (NBM) controls. Colony growth was most effectively sustained by GCT-CM and G-CSF in normal bone marrow (NBM) cultures. GM-CSF and I1-3 were less effective in inducing myeloid granulocytic colony growth, whereas the effects of 11-3 and GM-CSF were found to be approximately additive. The number of NBM granulocytic colonies induced by G-CSF and GCT-CM stimulation were comparable, whereas this granulocyte colony stimulating activity could be neutralized by anti-G-CSF antibodies. In addition GCT-CM was found to contain burst promoting activity, which could be neutralized by anti-I1-3 antibodies. 11-3 did not enhance the G-CSF activity in NBM cultures. No additive effect of stimulation with the combination of II-3 and GM-CSF was observed in MDS marrow cultures, suggesting that these growth factors act on an identical progenitor cell population in MDS. G-CSF stimulated the growth of significantly lower colony numbers than GCT-CM, in contrast to NBM cultures. The decreased granulocytic colony formation of MDS marrow cells could clearly be enhanced by co-stimulation with I1-3. These results suggest that MDS myeloid progenitor cells require the exposure to both a pluripotent colony stimulating factor, like 11-3, and a lineage specific factor, like G-CSF, for optimal proliferation.
Journal of Burn Care & Research, 2006
Current Medical Research and Opinion, 2012
In clinical studies of patients with severe thrombocytopenia, rescue treatments are used to preve... more In clinical studies of patients with severe thrombocytopenia, rescue treatments are used to prevent or stop bleeding. Estimating risk reductions of bleeding for clinical study medications can be challenging. This study evaluated a new and possibly more accurate way of assessing the effects of a treatment intervention on bleeding-related outcomes. We developed a composite endpoint, termed bleeding-related episodes (BRE). BREs were assessed in a post-hoc analysis of patients with chronic immune thrombocytopenia (ITP) who participated in two romiplostim, phase 3, placebo-controlled studies. Patients received romiplostim or placebo once weekly for 24 weeks. A BRE was defined as an actual bleeding event and/or the use of rescue medication. In total, 125 patients (41 placebo, 84 romiplostim) with platelet counts <30 K were enrolled. NCT00102323/NCT00102336. The rate of all BREs across all studies was reduced by 56% in patients receiving romiplostim compared with placebo. The rate of BREs using immunoglobulin (IVIg or anti-D Ig) was reduced by 89% in patients receiving romiplostim compared with placebo. BREs were more frequent in both groups at platelet counts <50 × 10(9)/L. Results were similar between splenectomized and nonsplenectomized patients. We believe that prior to the development of this tool, bleeding events were underdiagnosed. The BRE tool allowed the identification of multiple interventions within bleeding episodes, which may have required separate interventions and were therefore considered to be additional BREs. In this study, the composite endpoint of a bleeding event and the use of rescue medication within close proximity of the bleeding event appears to be feasible and informative. The BRE tool allows for more precise understanding of the effect of rescue therapies in ITP and has broader applications to future clinical trials where assessment of bleeding risk can be complicated or masked by rescue interventions. This was a post hoc analysis. The assignment of platelet counts to a BRE was based on the platelet count on the first day of a BRE, which may not reflect the platelet count during the entire episode, and the assignment of platelet counts was based on the estimation required for events that occurred between weekly measurements.
Transfusion Clinique et Biologique, 2014
Leukemia
In order to obtain more insight into the nature of the abnormal in vitro colony formation in myel... more In order to obtain more insight into the nature of the abnormal in vitro colony formation in myelodysplastic syndromes (MDS), we investigated the kinetics of the colony formation of 23 MDS cases in response to recombinant human interleukin-3 (IL-3), Granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating Factor (G-CSF), and giant cell tumor cell line conditioned medium (GCT-CM). The kinetics of GCT-CM-induced colony formation were comparable to that of G-CSF-induced colony growth, both in MDS and in normal bone marrow cultures. Colony formation was found to be delayed in MDS. The delay in colony formation was most apparent in the GCT-CM (G-CSF) responsive progenitor cell compartment. In MDS cases with clinical features of high risk disease, this delay was more pronounced as compared with low risk cases (7 and 3 days, respectively, in response to GCT-CM). The delay in colony formation was found to be caused by an increase in the time interval before progenitor cells had begun to divide. These results suggest that a prolongation of the time spent in G0 of myeloid progenitor cells in MDS may be the cause of the indolent in vitro colony formation observed in this disease.
Betere registratie moet het mogelijk maken om meer inzicht te krijgen in zowel product als patiën... more Betere registratie moet het mogelijk maken om meer inzicht te krijgen in zowel product als patiënt gerelateerde factoren die invloed hebben op het ontwikkelen van een bacteriemie/sepsis na een bloedtransfusie. Naast door bloedtransfusie overgedragen bacteriële infecties kan er ook sprake zijn van een transfusie gerelateerde bacteriemie/sepsis waarbij bacteriële overdracht door het bloedproduct niet kan worden aangetoond. Tevens zijn er transfusies met bloedproducten waarvan achteraf blijkt dat ze gecontamineerd zijn, maar waarbij na transfusie geen bacteriemie/sepsis bij de ontvanger wordt geconstateerd. Voor het verhogen van de patiëntveiligheid is het nuttig om nader te onderzoeken wat de relatie is tussen transfusie en ontwikkeling van bacteriemie/sepsis bij de ontvanger in gevallen waarbij er geen sprake is van overdracht van bacteriën door het bloedproduct.
Clinical Case Reports, 2015
Prolonged clotting times were observed in a patient with spontaneous hemorrhage. Analysis showed ... more Prolonged clotting times were observed in a patient with spontaneous hemorrhage. Analysis showed severe factor X deficiency due to clearance by a noninhibitory antibody. Lymphadenopathy identified on imaging led to diagnosis of marginal B-cell lymphoma. Treatment of lymphoma with rituximab and chlorambucil resulted in complete disappearance of the bleeding disorder.
Vox sanguinis, Jan 20, 2015
The 2011 Dutch Blood Transfusion Guideline for hospitals incorporates seven internal quality indi... more The 2011 Dutch Blood Transfusion Guideline for hospitals incorporates seven internal quality indicators for evaluation of the hospital transfusion chain. The indicators aim to measure guideline compliance as shown by the instatement of a hospital transfusion committee and transfusion safety officer (structural indicators), observance of transfusion triggers and mandatory traceability of labile blood components (process indicators). Two voluntary online surveys were sent to all Dutch hospitals for operational years 2011 and 2012 to assess compliance with the guideline recommendations. Most hospitals had a hospital transfusion committee and had appointed a transfusion safety officer (TSO). In 2012, only 23% of hospitals complied with the recommended minimum of four annual transfusion committee meetings and 8 h/week for the TSO. Compliance with the recommended pretransfusion haemoglobin threshold for RBC transfusion was achieved by 90% of hospitals in over 80% of transfusions; 58% of h...
Vox sanguinis, Jan 30, 2014
The TRIP national hemovigilance and biovigilance office receives reports on side-effects and inci... more The TRIP national hemovigilance and biovigilance office receives reports on side-effects and incidents associated with transfusion of labile blood products. Anaphylactic reactions accounted for the largest number of serious transfusion reactions in the period 2008-2012. In most cases, no cause is found for these reactions. TRIP data show that anaphylactic reactions occur relatively frequently with transfusion of plasma or platelet concentrates. Data from blood services show that 10% or more of plasma donors regularly use medication which is permitted under donation guidelines. It is conceivable that medication taken by the donor in plasma for transfusion could cause an anaphylactic transfusion reaction in the recipient. This exploratory study investigated the presence of drugs or drug metabolites in donor plasma. Samples (5 ml) were taken from thawed, quarantine fresh frozen plasma units (FFP) which had to be rejected for transfusion because of leaks or length of time after thawing....
Haematology and blood transfusion, 1990
Haematologica, 2014
ABSTRACT - Copyright © 2014, Ferrata Storti Foundation.
Vox Sanguinis, 2013
European Union member states must have national haemovigilance reporting of serious adverse react... more European Union member states must have national haemovigilance reporting of serious adverse reactions and events. We sent national competent authorities an email questionnaire about data validation. Responses were received from 23/27 countries. Nine previously had no national haemovigilance system. In 13 (57%), the serious adverse reactions and events can be verified. Coverage of blood establishments is documented in 20 systems (87%) and of hospitals in 15 systems (65%). Although all member states have implemented haemovigilance systems, there are currently wide variations in data quality assurance, not allowing comparisons between countries.
Transfusion Medicine, 2012
The fraction of transfusion-related acute lung injury (TRALI) cases preventable by deferral of al... more The fraction of transfusion-related acute lung injury (TRALI) cases preventable by deferral of allo-exposed donors has previously been estimated, under the assumption this indirectly estimated the contribution of leucocyte antibodies to the occurrence of TRALI. Our aim was to estimate the fraction preventable by deferral of leucocyte antibody positive donors and to investigate the validity of allo-exposure as a marker for leucocyte antibodies. Methods: All donors involved in a series of previously published TRALI patients were tested for leucocyte antibodies. The observed number of antibody positive donors was compared to the expected number. From this comparison we estimated the contribution of leucocyte antibodies to the occurrence of TRALI and compared this to the previously reported estimate for allo-exposed donors. Results: Sixty-one TRALI patients were included. Of 288 involved donors 43 were expected and 67 were observed to be leucocyte antibody positive. The observed percentage of positive donors was 8·3% (95% confidence interval (CI): 5·1-11·5%) in excess of the expected. Overall 59% (95% CI: 34-85%) of TRALI cases was estimated to be preventable by the exclusion of all leucocyte antibody positive donors. For plasma-poor products this was 16% (95% CI: −5·0 to 36%). Conclusions: These estimates were similar to those previously published for allo-exposed donors. This suggests allo-exposure status can effectively be used in donor deferral strategies.
Transfusion, 2007
BACKGROUND: Development of new red blood cell (RBC) alloantibodies (alloimmunization) is one of t... more BACKGROUND: Development of new red blood cell (RBC) alloantibodies (alloimmunization) is one of the most frequent adverse reactions after an RBC transfusion. Few studies have investigated clinical risk factors for alloimmunization.
Transfusion, 1990
Bone marrow was harvested for the purpose of autologous bone marrow transplantation (ABMT) in 21 ... more Bone marrow was harvested for the purpose of autologous bone marrow transplantation (ABMT) in 21 patients previously treated with chemotherapy and in complete remission from acute leukemia or non-Hodgkin's lymphoma. The volume required to obtain 2 x 10(8) nucleated cells per kg was less than 15 mL per kg in 13 patients and more than 15 mL per kg in 8 patients. The blood admixture was proportional to the aspirated volume (p less than 0.0001). The number of granulocyte-macrophage colony-forming units (CFU-GM) harvested in the groups was 8.4 +/- 2.2 and 3.4 +/- 1.4 x 10(4) per kg, respectively (p less than 0.0001). Autologous red cells were transfused into 16 of 21 patients, who did not require further homologous transfusions. The mean drop in hemoglobin from the preoperative level was 1.0 +/- 0.2 g per dL. No adverse effects were noted. It is concluded that large single-volume bone marrow harvests are possible and may reduce the need for a second harvest, and that, through the transfusion of autologous red cells obtained during marrow harvest, homologous blood transfusion can be avoided in most patients.
Transfusion, 2011
BACKGROUND: Transfusion-related acute lung injury (TRALI) is one of the most serious complication... more BACKGROUND: Transfusion-related acute lung injury (TRALI) is one of the most serious complications of blood transfusion. It can be caused by incompatible white blood cell antibodies in transfused plasma. The objective of this study was to quantify the reduction of TRALI after introduction of male-only plasma for transfusion as a preventive measure, which took effect in 2007.
Leukemia Research, 1990
The decreased or absent in vitro colony formation in response to single recombinant haematopoieti... more The decreased or absent in vitro colony formation in response to single recombinant haematopoietic growth factors has been reported previously. Here we report on the effects of the combination of interleukin 3 (I1-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF) and the effect of the conditioned medium of the giant tumour cell line (GCT-CM) on the proliferation of myelodysplastic (MDS) marrow myeloid progenitor cells and normal bone marrow (NBM) controls. Colony growth was most effectively sustained by GCT-CM and G-CSF in normal bone marrow (NBM) cultures. GM-CSF and I1-3 were less effective in inducing myeloid granulocytic colony growth, whereas the effects of 11-3 and GM-CSF were found to be approximately additive. The number of NBM granulocytic colonies induced by G-CSF and GCT-CM stimulation were comparable, whereas this granulocyte colony stimulating activity could be neutralized by anti-G-CSF antibodies. In addition GCT-CM was found to contain burst promoting activity, which could be neutralized by anti-I1-3 antibodies. 11-3 did not enhance the G-CSF activity in NBM cultures. No additive effect of stimulation with the combination of II-3 and GM-CSF was observed in MDS marrow cultures, suggesting that these growth factors act on an identical progenitor cell population in MDS. G-CSF stimulated the growth of significantly lower colony numbers than GCT-CM, in contrast to NBM cultures. The decreased granulocytic colony formation of MDS marrow cells could clearly be enhanced by co-stimulation with I1-3. These results suggest that MDS myeloid progenitor cells require the exposure to both a pluripotent colony stimulating factor, like 11-3, and a lineage specific factor, like G-CSF, for optimal proliferation.
Journal of Burn Care & Research, 2006
Current Medical Research and Opinion, 2012
In clinical studies of patients with severe thrombocytopenia, rescue treatments are used to preve... more In clinical studies of patients with severe thrombocytopenia, rescue treatments are used to prevent or stop bleeding. Estimating risk reductions of bleeding for clinical study medications can be challenging. This study evaluated a new and possibly more accurate way of assessing the effects of a treatment intervention on bleeding-related outcomes. We developed a composite endpoint, termed bleeding-related episodes (BRE). BREs were assessed in a post-hoc analysis of patients with chronic immune thrombocytopenia (ITP) who participated in two romiplostim, phase 3, placebo-controlled studies. Patients received romiplostim or placebo once weekly for 24 weeks. A BRE was defined as an actual bleeding event and/or the use of rescue medication. In total, 125 patients (41 placebo, 84 romiplostim) with platelet counts <30 K were enrolled. NCT00102323/NCT00102336. The rate of all BREs across all studies was reduced by 56% in patients receiving romiplostim compared with placebo. The rate of BREs using immunoglobulin (IVIg or anti-D Ig) was reduced by 89% in patients receiving romiplostim compared with placebo. BREs were more frequent in both groups at platelet counts <50 × 10(9)/L. Results were similar between splenectomized and nonsplenectomized patients. We believe that prior to the development of this tool, bleeding events were underdiagnosed. The BRE tool allowed the identification of multiple interventions within bleeding episodes, which may have required separate interventions and were therefore considered to be additional BREs. In this study, the composite endpoint of a bleeding event and the use of rescue medication within close proximity of the bleeding event appears to be feasible and informative. The BRE tool allows for more precise understanding of the effect of rescue therapies in ITP and has broader applications to future clinical trials where assessment of bleeding risk can be complicated or masked by rescue interventions. This was a post hoc analysis. The assignment of platelet counts to a BRE was based on the platelet count on the first day of a BRE, which may not reflect the platelet count during the entire episode, and the assignment of platelet counts was based on the estimation required for events that occurred between weekly measurements.