A Novel Use of Romiplostim for SARS-CoV-2–induced Thrombocytopenia

Schneider, Coursen; Penney, Scott W.; Helfrich, Alison M; Hartman, Kip R.; Lieuw, Kenneth

doi:10.1097/mph.0000000000001961

Cited by 4 publications

(6 citation statements)

References 19 publications

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“…Also, approaches combining JAK1/2 inhibitors with blockade of C5a with eculizumab are being considered as a treatment of severe pulmonary damage in COVID-19 patients [67]. Moreover, drugs such as romiplostim acting as an agonist for the thrombopoietin receptor are also predicted to be useful to treat COVID-19-associated thrombocytopenia, in agreement with a recent case study documenting platelet recovery following treatment with this drug of a COVID-19 pediatric patient [54].…”

Section: Discussionsupporting

confidence: 53%

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Network-based repurposing identifies anti-alarmins as drug candidates to control severe lung inflammation in COVID-19

et al. 2021

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While establishing worldwide collective immunity with anti SARS-CoV-2 vaccines, COVID-19 remains a major health issue with dramatic ensuing economic consequences. In the transition, repurposing existing drugs remains the fastest cost-effective approach to alleviate the burden on health services, most particularly by reducing the incidence of the acute respiratory distress syndrome associated with severe COVID-19. We undertook a computational repurposing approach to identify candidate therapeutic drugs to control progression towards severe airways inflammation during COVID-19. Molecular profiling data were obtained from public sources regarding SARS-CoV-2 infected epithelial or endothelial cells, immune dysregulations associated with severe COVID-19 and lung inflammation induced by other respiratory viruses. From these data, we generated a protein-protein interactome modeling the evolution of lung inflammation during COVID-19 from inception to an established cytokine release syndrome. This predictive model assembling severe COVID-19-related proteins supports a role for known contributors to the cytokine storm such as IL1β, IL6, TNFα, JAK2, but also less prominent actors such as IL17, IL23 and C5a. Importantly our analysis points out to alarmins such as TSLP, IL33, members of the S100 family and their receptors (ST2, RAGE) as targets of major therapeutic interest. By evaluating the network-based distances between severe COVID-19-related proteins and known drug targets, network computing identified drugs which could be repurposed to prevent or slow down progression towards severe airways inflammation. This analysis confirmed the interest of dexamethasone, JAK2 inhibitors, estrogens and further identified various drugs either available or in development interacting with the aforementioned targets. We most particularly recommend considering various inhibitors of alarmins or their receptors, currently receiving little attention in this indication, as candidate treatments for severe COVID-19.

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Section: Discussionsupporting

confidence: 53%

“…The thrombopoietin receptor appears as well to be a valid therapeutic target for agonists in light of the high incidence of thrombocytopenia associated with COVID-19 infection [54]. Rather unexpectedly, Topoisomerase 1 inhibitors, currently used as cytotoxic drugs in…”

Section: Plos Onementioning

confidence: 99%

Network-based repurposing identifies anti-alarmins as drug candidates to control severe lung inflammation in COVID-19

et al. 2021

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“…After screening by title and abstract, 246 articles proceeded to full-text review. Following full-text review, 126 articles, which reported on a total of 48,332 patients, were included for data extraction and analysis 25–148. The PRIMSA flow diagram is provided in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

Coagulation Abnormalities and Clinical Complications in Children With SARS-CoV-2: A Systematic Review of 48,322 Patients

McDaniel

Commander²,

DeLaura

et al. 2021

Journal of Pediatric Hematology/Oncology

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Given the limited information on the coagulation abnormalities of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in pediatric patients, we designed a systematic review to evaluate this topic. A comprehensive literature search was conducted for “SARS-CoV-2,” “coagulopathy,” and “pediatrics.” Two authors independently screened the articles that the search returned for bleeding, thrombosis, anticoagulant and/or antiplatelet usage, and abnormal laboratory markers in pediatric patients with SARS-CoV-2, and the authors then extracted the relevant data. One hundred twenty-six publications were included. Thirty-four (27%) studies reported thrombotic complications in 504 patients. Thirty-one (25%) studies reported bleeding complications in 410 patients. Ninety-eight (78%) studies reported abnormal laboratory values in 6580 patients. Finally, 56 (44%) studies reported anticoagulant and/or antiplatelet usage in 3124 patients. The variety of laboratory abnormalities and coagulation complications associated with SARS-CoV-2 presented in this review highlights the complexity and variability of the disease presentation in infants and children.

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“…Several additional prospective trials are ongoing to evaluate romiplostim for the treatment of CIT in patients with non-hematologic cancers (phase 2; NCT02052882), gastrointestinal or colorectal cancer (phase 3; NCT03362177), and NSCLC, ovarian cancer, or breast cancer (phase 3; NCT03937154). Although there is little evidence regarding optimal management strategies for thrombocytopenia in the setting of COVID-19, two recent cases have been reported of patients with acute thrombocytopenia secondary to COVID-19 successfully treated with romiplostim (81,82). A 67-year-old male patient developed severe thrombocytopenia complicated by subdural hematoma and rectal bleed, associated with COVID-19.…”

Section: Romiplostimmentioning

confidence: 99%

“…The second patient was a 6-year-old male with a complex m edical history, including m ild chronic thrombocytopenia. Following a further reduction in platelet count that was associated with SARS-CoV-2 infection, he received romiplostim to stimulate platelet production, which resulted in the resolution of spontaneous bleeding and improvement of platelet counts (82). Based on these (albeit limited) findings, it is feasible that the use of romiplostim may also be of benefit in preventing or treating acute thrombocytopenia in patients receiving myelosuppressive chemotherapy in a COVID-19/post-COVID-19 setting, including those with existing COVID-19 infection.…”

Section: Romiplostimmentioning

confidence: 99%

Improving Outcomes of Chemotherapy: Established and Novel Options for Myeloprotection in the COVID-19 Era

2021

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Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HPSCs) often results in myelosuppression that adversely affects patient health and quality of life. Currently, chemotherapy-induced myelosuppression is managed with chemotherapy dose delays/reductions and lineage-specific supportive care interventions, such as hematopoietic growth factors and blood transfusions. However, the COVID-19 pandemic has created additional challenges for the optimal management of myelosuppression. In this review, we discuss the impact of this side effect on patients treated with myelosuppressive chemotherapy, with a focus on the prevention of myelosuppression in the COVID-19 era. During the COVID-19 pandemic, short-term recommendations on the use of supportive care interventions have been issued with the aim of minimizing the risk of infection, reducing the need for hospitalization, and preserving limited blood supplies. Recently, trilaciclib, an intravenous cyclin-dependent kinase 4 and 6 inhibitor, was approved to decrease the incidence of myelosuppression in adult patients when administered prior to platinum/etoposide-containing or topotecan-containing chemotherapy for extensive-stage small cell lung cancer (ES-SCLC). Approval was based on data from three phase 2 placebo-controlled clinical studies in patients with ES-SCLC, showing that administering trilaciclib prior to chemotherapy significantly reduced multilineage myelosuppression, with patients receiving trilaciclib having fewer chemotherapy dose delays/reductions and myelosuppression/sepsis-related hospitalizations, and less need for supportive care interventions, compared with patients receiving placebo. Several other novel agents are currently in clinical development for the prevention or treatment of multilineage or single-lineage myelosuppression in patients with various tumor types. The availability of treatments that could enable patients to maintain standard-of-care chemotherapy regimens without the need for additional interventions would be valuable to physicians, patients, and health systems.

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A Novel Use of Romiplostim for SARS-CoV-2–induced Thrombocytopenia

Cited by 4 publications

References 19 publications

Network-based repurposing identifies anti-alarmins as drug candidates to control severe lung inflammation in COVID-19

Network-based repurposing identifies anti-alarmins as drug candidates to control severe lung inflammation in COVID-19

Coagulation Abnormalities and Clinical Complications in Children With SARS-CoV-2: A Systematic Review of 48,322 Patients

Improving Outcomes of Chemotherapy: Established and Novel Options for Myeloprotection in the COVID-19 Era

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