Critical Window: Why Early Treatment is Key for Radiation-Exposed Patients
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When exposed to a high enough dose of ionizing radiation, the body’s rapidly dividing cells are damaged. The immediate effect of this damage is termed “acute radiation syndrome.” Your bone marrow is particularly sensitive to radiation and ceases production after significant exposure. Your bone marrow is responsible for generating all of your red blood cells (oxygen-carrying capacity), white blood cells (to fight infection), and platelets (the cells responsible for sticking your blood together when bleeding). You cannot survive without functioning bone marrow.
Radiation medical countermeasures are drugs used after significant ionizing radiation exposure to mitigate the effects of radiation exposure on an individual patient.
One type of medical countermeasures is colony-stimulating factors, which encourage and push the bone marrow to generate cells. If given to a significantly radiation-exposed individual, they can regenerate their bone marrow, limiting the severe anemia and infection risk associated with bone marrow failure.1 These drugs are more commonly used to mitigate bone marrow suppression effects of some chemotherapies in treating cancer.
Countermeasures have been added to the US Strategic National Stockpile for use in the event of a significant radiation exposure.
A granulocyte colony-stimulating factor (G-CSF) specifically supports neutrophils, the white blood cells that prevent bacterial infection. By stimulating the body to make more, decreasing how many existing neutrophils the body destroys, and encouraging young neutrophils to mature, they can help prevent post-radiation infections.1
A myeloid colony-stimulating factor (M-CSF) provides similar bone marrow support as the G-CSF, but initiates it earlier in the hemopoietic cell pathway, even before the body produces granulocytes, resulting in a wider variety of cell lines.2
The sooner after a significant radiation exposure colony-stimulating factors are administered, the more effectively they work. Experts feel optimal treatment should occur within 6 hours of exposure.
Typically, these medications are administered once a day by subcutaneous injection until the white blood cell count has adequately recovered, as evidenced by the casualty’s absolute neutrophil count.3 If not enough of the drug is available for the number of casualties who are significantly radiation exposed, half-dosing recommendations exist to stretch the supply.
More recently, a platelet cytokine (Romiplostim), which maintains hemopoietic stem cells resulting in increased platelet production4, has also been approved and added to the stockpile. It has been shown to increase platelet counts post-radiation exposure, something the other radiation medical countermeasures don’t do. Its greatest survival advantage after lethal radiation exposure seems to be when it is used in combination with colony-stimulating factors. Romiplostim has been studied in various dosing regimens from a single injection, injections three consecutive days, and three consecutive days, followed by weekly injections for 4 weeks.4
Like many medications used to treat CBRN casualties, all of these drugs suffer from little scientific literature showing their effectiveness in CBRN-exposed individuals.
Although robust data shows their safety and effectiveness in treating various non-radiation exposure disease states, their use for treating acute radiation syndrome is limited to various animal and non-human primate models. As it would be unethical to subject human volunteers to significant radiation to test the drugs on human volunteers, the USFDA has approved them as a radiation medical countermeasure based on non-human data.
One tactical downside of these medications is their optimal timeframe for treatment is six hours post-radiation exposure. Experts believe it will take at least 24 hours after a large incident to distribute these drugs, even with the national stockpiles.5
There has even been some limited suggestion colony-stimulating factors may have a role in treating severe sulfur mustard agent exposed casualties. At a high enough exposure, sulfur mustard causes bone marrow suppression. In a solitary Chinese study of 10 dogs injected subcutaneously with sulfur mustard, there was higher survival and improved white blood cell counts in the treated dogs compared to the untreated.6
With no specific treatments for severe radiation exposure, other than supportive care, using these medications in the right clinical setting is certainly reasonable.
References
1 Hofer M, Pospíšil M, Komůrková D, Hoferová Z. Granulocyte colony-stimulating factor in the treatment of acute radiation syndrome: a concise review.2014 Apr 16;19(4):4770-8. doi: 10.3390/molecules19044770.PMID: 24743934; PMCID: PMC6270858.
2https://remm.hhs.gov/cytokines.htm
3 https://remm.hhs.gov/cytokines.htm
4 Singh VK, Seed ™. An update on romiplostim for treatment of acute radiation syndrome.Drugs Today (Barc).2022 Mar;58(3):133-145. doi: 10.1358/dot.2022.58.3.3367994. PMID: 35274632.
5 Rios CI, Garcia EE, Hogdahl TS 2nd, Homer MJ, Iyer NV, Laney JW, Loelius SG, Satyamitra MM, DiCarlo AL. Radiation and Chemical Program Research for Multi-Utility and Repurposed Countermeasures: A US Department of Health and Human Services Agencies Perspective. Disaster Med Public Health Prep.2024 Feb 22;18:e35.doi: 10.1017/dmp.2023.226.PMID: 38384183; PMCID: PMC10948027.
6 Cai Y, Ma Q, Zhang L, Zhao J, Zhu M, Hu W, Jiang P, Yuan W. [Therapeutic effects of rhEPO, rhG-CSF on sulfur mustard induced toxicity in dogs].Wei Sheng Yan Jiu. 2004 Nov;33(6):649-51. Chinese.PMID: 15727166.
