G-CSF-induced thrombocytopenia in a healthy donor

Minelli, Olivia; Falzetti, Franca; Ianni, Mauro Di; Onorato, Marina; Plebani, S; Silvani, Carlo; Tabilio, Antonio

doi:10.1038/bmt.2008.310

Cited by 18 publications

(11 citation statements)

References 8 publications

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“…McDougall [16] found a slight decrease of red cells count and hematocrit in cows treated at 7 and 21 days after calving [20]. In human hematological studies, side effects of G-CSF therapy include a slight decrease in hemoglobin concentration and in platelet count, although in rare cases, thrombocytopenia has been documented [21,22,23].…”

Section: Introductionmentioning

confidence: 99%

Effect of Pegbovigrastim on Hematological Profile of Simmental Dairy Cows during the Transition Period

Trimboli

Morittu

Loria

et al. 2019

Animals

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Simple SummaryDuring the transition period (TP), the innate and adaptive immune system of dairy cows is impaired, contributing to an increase in susceptibility to infectious disease. Pegbovigrastim is a recombinant form of the granulocyte colony-stimulating factor, that stimulates differentiation of hemopoietic stem cells to granulocyte and shortens maturation time within the bone marrow and their release in circulation. For the first time, this study investigated the effect of pegbovigrastim on the hematologic profile, including red cells and platelets during the TP in dual-purpose Simmental dairy cows. Results confirm the efficacy of pegbovigrastim administration in promoting the numbers of total with cells, mainly neutrophils. Nevertheless, this study highlighted the presence of an anemia condition in treated cows most likely caused by an inflammatory process involving the endothelium. Overall, this study confirms the safety of pegbovigrastim administration, but further studies need to check its ability to reduce infection even in Simmental breed.AbstractPegbovigrastim is a long-acting analog of recombinant bovine granulocyte colony-stimulating factor, that promotes and increases the count and functionality of polymorphonuclear cells in dairy cows. The present study aimed to explore, for the first time in Simmental cows, the clinical and hematological effect of pegbovigrastim during the transition period (TP). Cows were randomly assigned into two groups: treated group (PEG; n = 16) received pegbovigrastim at approximately 7 days before expected parturition and within 6 h after calving, and control group (CTR; n = 16) received saline solution. Blood samples were obtained at −7, 0, 1, 3, 7, 14, 21, and 30 days relative to calving. PEG group showed white blood cells (WBC) count consistently higher compared with CTR group (p < 0.001) until to 3 weeks after calving. Neutrophils remained higher in PEG group (p < 0.001) up to three weeks after calving, compared with CTR group, with slight increment of band cells. Moreover, PEG group displayed a lower index of myeloperoxidase at 1, 3, and 7 days after calving (p < 0.01) compared with CTR. Basophils and lymphocytes showed a similar trend to those observed for neutrophils at 1 day after calving in PEG group. Finally, monocytes remained markedly elevated until 3 days after calving in PEG compared to CTR group (p < 0.001), whereas in PEG group, eosinophils population showed lower percentage values at 1 and 3 days after calving but higher values at 30 days compared with CTR group. PEG group was characterized by lower red blood cells (RBCs) count compared with CTR group (p < 0.05) and higher % of red cell volume distribution width (RDW) from week 2 and mean corpuscular volume (MCV) at 30 days after calving. In addition, the mean platelet volume (MPV) was significantly higher in PEG group at calving, 1, 3, and 7 days after calving compared with CTR group (p < 0.05). For the first time, we described the effect of pegbovigrastim in a breed not specialized exclusively in milk pr...

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Section: Introductionmentioning

confidence: 99%

Effect of Pegbovigrastim on Hematological Profile of Simmental Dairy Cows during the Transition Period

Trimboli

Morittu

Loria

et al. 2019

Animals

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“…Irregular time series are more often observed in the 14 day regimen compared to the 21 day regimen suggesting a possible interaction with G-CSF treatment. Indeed, G-CSF can induce thrombocytopenia in healthy patients [55]. On the other hand, it is well known that G-CSF stimulates stem cells to start differentiation to blast cells [56], which are precursors for both thrombocytes and granulocytes.…”

Section: Discussionmentioning

confidence: 99%

Modeling individual time courses of thrombopoiesis during multi-cyclic chemotherapy

Kheifetz

Scholz

2019

PLoS Comput Biol

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BackgroundThrombocytopenia is a major side-effect of cytotoxic cancer therapies. The aim of precision medicine is to develop therapy modifications accounting for the individual’s risk.Methodology/Principle findingsTo solve this task, we develop an individualized bio-mechanistic model of the dynamics of bone marrow thrombopoiesis, circulating platelets and therapy effects thereon. Comprehensive biological knowledge regarding cell differentiation, amplification, apoptosis rates, transition times and corresponding regulations are translated into ordinary differential equations. A model of osteoblast/osteoclast interactions was incorporated to mechanistically describe bone marrow support of quiescent cell stages. Thrombopoietin (TPO) as a major regulator is explicitly modelled including pharmacokinetics and–dynamics of TPO injections. Effects of cytotoxic drugs are modelled by transient depletions of proliferating cells.To calibrate the model, we used population data from the literature and close-meshed individual data of N = 135 high-grade non-Hodgkin’s lymphoma patients treated with CHOP-like chemotherapies. To limit the number of free parameters, several parsimony assumptions were derived from biological data and tested via Likelihood methods. Heterogeneity of patients was explained by a few model parameters. The over-fitting issue of individual parameter estimation was successfully dealt with a virtual participation of each patient in population-based experiments.The model qualitatively and quantitatively explains a number of biological observations such as the role of osteoblasts in explaining long-term toxic effects, megakaryocyte-mediated feedback on stem cells, bi-phasic stimulation of thrombopoiesis by TPO, dynamics of megakaryocyte ploidies and non-exponential platelet degradation. Almost all individual time series could be described with high precision. We demonstrated how the model can be used to provide predictions regarding individual therapy adaptations.ConclusionsWe propose a mechanistic thrombopoiesis model of unprecedented comprehensiveness in both, biological mechanisms considered and experimental data sets explained. Our innovative method of parameter estimation allows robust determinations of individual parameter settings facilitating the development of individual treatment adaptations during chemotherapy.

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“…Healthy donors without autoimmune diseases also experienced thrombocytopenia after G-CSF mobilization. In 2009, Minelli et al [9] reported a 51-year-old healthy male donor. The PLT count decreased on day 1 after G-CSF mobilization and was 78 G/L on day 5, decreasing to 30 G/L after collection.…”

Section: Discussionmentioning

confidence: 99%

G-CSF-induced severe thrombocytopenia in a healthy donor

Wang

et al. 2019

Medicine

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Rationale: Granulocyte colony-stimulating factor (G-CSF) is most frequently used in healthy donors to mobilize progenitor cells into the peripheral blood for collection. While mild thrombocytopenia is common in allogeneic peripheral blood stem cell transplant donors after G-CSF mobilization, serious thrombocytopenia is rarely reported. Herein, we report a case of severe thrombocytopenia caused by G-CSF in a 14-year-old healthy donor and review the relevant literature. To our knowledge, this is the first reported case of severe thrombocytopenia caused by G-CSF in a healthy adolescent donor. Patient concerns: A 14-year-old sister of a girl with T lymphocyte leukemia was selected as a matched donor for transplantation. The donor was healthy with normal blood parameters. Diagnoses: The donor received 10 μg/kg/day G-CSF via subcutaneous injection. On day 4 of G-CSF administration, blood tests before stem cell collection indicated that platelets dropped to 51 g/L. Abdominal ultrasound showed that the spleen was mildly enlarged. Interventions: In order to prevent blood loss and other effects caused by a too low platelet count after collection, the donor's peripheral blood hematopoietic stem cells were collected after platelet transfusion. Outcomes: Checkups for 1 year after G-CSF administration showed normal blood parameters. Lessons: Due to the rare risk of severe thrombocytopenia in G-CSF mobilization, it is necessary to routinely monitor blood parameters during mobilization to ensure smooth progress of the transplantation process.

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G-CSF-induced thrombocytopenia in a healthy donor

Cited by 18 publications

References 8 publications

Effect of Pegbovigrastim on Hematological Profile of Simmental Dairy Cows during the Transition Period

Effect of Pegbovigrastim on Hematological Profile of Simmental Dairy Cows during the Transition Period

Modeling individual time courses of thrombopoiesis during multi-cyclic chemotherapy

G-CSF-induced severe thrombocytopenia in a healthy donor

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