Safety and efficacy of transfusions of autologous cryopreserved platelets derived from recombinant human thrombopoietin to support chemotherapy-associated severe thrombocytopenia: a randomised cross-over study

Vadhan‐Raj, Saroj; Kavanagh, John J.; Freedman, Ralph S.; Folloder, Jody; Currie, Laura; Bueso-Ramos, Carlos; Verschraegen, Claire F.; Narvios, Aida; Connor, Jerome; Hoots, W. Keith; Broemeling, Lyle D.; Lichtiger, Benjamin

doi:10.1016/s0140-6736(02)09090-6

Cited by 68 publications

(37 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These platelets were functional and, when transfused to a thrombocytopenic patients undergoing myeloablative therapy, produced a dose-dependent rise in platelet count [57][58][59]. Similar results were seen in studies with rhTPO [60].…”

Section: Lessons Learned From Clinical Studies With Recombinant Thrommentioning

confidence: 61%

The biology of thrombopoietin and thrombopoietin receptor agonists

2013

View full text Add to dashboard Cite

Thrombopoietin (TPO) is the major physiological regulator of platelet production. TPO binds the TPO receptor, activates JAK and STAT pathways, thus stimulating megakaryocyte growth and platelet production. There is no ''sensor'' of the platelet count; rather TPO is produced in the liver at a constant rate and cleared by TPO receptors on platelets. TPO levels are inversely proportional to the rate of platelet production. Early recombinant TPO molecules were potent stimulators of platelet production and increased platelets in patients with immune thrombocytopenia, chemotherapy-induced thrombocytopenia, myelodysplastic syndromes and platelet apheresis donors. Neutralizing antibodies formed against one recombinant protein and ended their development. A second generation of TPO receptor agonists, romiplostim and eltrombopag, has been developed. Romiplostim is an IgG heavy chain into which four TPO agonist peptides have been inserted. Eltrombopag is an oral small molecule. These activate the TPO receptor by different mechanisms to increase megakaryocyte growth and platelet production. After administration of either to healthy volunteers, there is a delay of 5 days before the platelet count rises and subsequently reaches a peak after 12-14 days. Both have been highly effective in treating ITP and hepatitis C thrombocytopenia. Studies in a wide variety of other thrombocytopenic conditions are underway.

show abstract

Section: Lessons Learned From Clinical Studies With Recombinant Thrommentioning

confidence: 61%

The biology of thrombopoietin and thrombopoietin receptor agonists

2013

View full text Add to dashboard Cite

show abstract

“…Various clinical trials on cancer patients have demonstrated beneficial effects of TPO for treating chemotherapy-induced severe thrombocytopenia. [37][38][39][40] Vadhan-Raj et al 39 (2003) suggested that the timing of TPO administration (1 dose before and 1 after chemotherapy) was important for optimal effects on platelet recovery in cohorts of sarcoma patients. The application of TPO for reduction of cardiotoxicity might therefore provide additional beneficial outcomes by ameliorating neutropenia and thrombocytopenia in patients receiving chemotherapy and dexrazoxane.…”

Section: Discussionmentioning

confidence: 99%

Thrombopoietin Protects Against In Vitro and In Vivo Cardiotoxicity Induced by Doxorubicin

et al. 2006

View full text Add to dashboard Cite

Background-Doxorubicin (DOX) is an important antineoplastic agent. However, the associated cardiotoxicity, possibly mediated by the production of reactive oxygen species, has remained a significant and dose-limiting clinical problem. Our hypothesis is that the hematopoietic/megakaryocytopoietic growth factor thrombopoietin (TPO) protects against DOX-induced cardiotoxicity and might involve antiapoptotic mechanism exerted on cardiomyocytes. Methods and Results-In vitro investigations on H9C2 cell line and spontaneously beating cells of primary, neonatal rat ventricle, as well as an in vivo study in a mouse model of DOX-induced acute cardiomyopathy, were performed. Our results showed that pretreatment with TPO significantly increased viability of DOX-injured H9C2 cells and beating rates of neonatal myocytes, with effects similar to those of dexrazoxane, a clinically approved cardiac protective agent. TPO ameliorated DOX-induced apoptosis of H9C2 cells as demonstrated by assays of annexin V, active caspase-3, and mitochondrial membrane potential. In the mouse model, administration of TPO (12.5 g/kg IP for 3 alternate days) significantly reduced DOX-induced (20 mg/kg) cardiotoxicity, including low blood cell count, cardiomyocyte lesions (apoptosis, vacuolization, and myofibrillar loss), and animal mortality. Using Doppler echocardiography, we observed increased heart rate, fractional shortening, and cardiac output in animals pretreated with TPO compared with those receiving DOX alone. Conclusions-These data have provided the first evidence that TPO is a protective agent against DOX-induced cardiac injury. We propose to further explore an integrated program, incorporating TPO with other protocols, for treatment of DOX-induced cardiotoxicity and other forms of cardiomyopathy.

show abstract

“…It has been observed that alloimmunized patients have difficulty managing their thrombocytopenia after platelet transfusion, and are refractory to fresh allogeneic platelets [42,60]. Additionally, some studies have found decreased CCI values using platelet additive solution (PAS), and further, it has been observed that all patients who were refractory to fresh allogeneic platelet transfusion had successful CCI results to autologous cryopreserved platelets [16,29,60]. Table 3 presents the transfusion efficacy of apheresis platelets according to different approaches to apheresis, which showed that the successful platelet transfusion in all apheresis instruments.…”

Section: And Pprmentioning

confidence: 99%

Plateletpheresis: the Process, Devices, and Indicators of Product Quality

Jang¹,

Kim²,

Kim³

et al. 2014

Journal of Life Science

View full text Add to dashboard Cite

Platelet products are used to treat hemorrhagic or platelet dysfunction diseases. Plateletpheresis involves collecting the platelet components of blood using an apheresis blood-collection system. Various indicators are available for evaluating the qualities of the apheresis platelets. The productivity of platelet collection is evaluated through both the collection efficiency and collection rates. Platelet storage quality can be evaluated in vitro using several indicators, including visual appearance, metabolic activities, volume, platelet count, white blood cell count, microparticles, and various platelet activation markers. Platelet activation markers have been used as indicators of storage quality in various studies. Post-transfusion platelet quality can be evaluated based on the corrected count increment and the percentage of platelet recovery. Although various studies have investigated the aspects of plateletpheresis, no article has systemically presented assessments of the platelet products obtained from different plateletpheresis devices. The present study provides a review of plateletpheresis, including the specifics of the process, the types of devices employed, the platelet quality, the overall efficacy, and the evaluation indicator qualities. Furthermore, the differences in functionality among the different apheresis devices are discussed. Although adverse reactions to the citrate anti-coagulant have been reported, apheresis processing may provide a safer option for donors who are at a high risk for presyncopal or syncopal reactions related to whole blood collection.

show abstract

Safety and efficacy of transfusions of autologous cryopreserved platelets derived from recombinant human thrombopoietin to support chemotherapy-associated severe thrombocytopenia: a randomised cross-over study

Cited by 68 publications

References 28 publications

The biology of thrombopoietin and thrombopoietin receptor agonists

The biology of thrombopoietin and thrombopoietin receptor agonists

Thrombopoietin Protects Against In Vitro and In Vivo Cardiotoxicity Induced by Doxorubicin

Plateletpheresis: the Process, Devices, and Indicators of Product Quality

Contact Info

Product

Resources

About