Acute radiation syndrome: lymphocyte triage

A 41-year-old man works as the operator of an industrial cobalt-60 irradiator that sterilizes medical supplies. On a maintenance morning, the system that returns the source to the shielding pool fails, and he enters the irradiation room for about two minutes before the alarm is noticed. An hour later, he starts vomiting. He arrives at the emergency department three hours after exposure, with nausea, fatigue, slightly reddened skin on his face and hands, and a temperature of 37.8 °C. Blood pressure is 128/78 mmHg and heart rate is 104 per minute. The first complete blood count shows leukocytes of 13.1 × 10⁹/L, neutrophils of 11.2 × 10⁹/L and lymphocytes of 1.4 × 10⁹/L. His personal dosimeter was left in the locker in the changing room. The scene is fictional and was written for teaching.

This text uses the case as a setting for clinical reasoning for students and health professionals. The topic is screening for acute radiation syndrome in the first hours and days, when the dose is not yet known. There are three clues: the time to vomiting, the fall in lymphocytes on serial complete blood counts, and biodosimetry tests. The text also covers initial management and the regulatory status of the cytokines approved for the hematopoietic subsyndrome. It does not replace your department's protocol or contact with the reference center for radiological emergencies in your country. If you play the case of the day on NEXO, you will recognize the challenge: deciding with clues that arrive in sequence.

Key points

• Early vomiting suggests a high dose, but it is not specific and must be read together with other data.
• The fall in lymphocytes on serial complete blood counts is one of the first objective clues to the dose received.
• Complete blood count every 9 to 12 hours in the first days, if a dose of 5 Gy or more is suspected.
• The dicentric assay remains the reference for biodosimetry, but it takes days.
• In the United States, four cytokines have an approved indication for the hematopoietic subsyndrome, all under the Animal Rule.
• In Europe, none of these cytokines has an approved indication for radiation exposure.

Why this is a reasoning setting

Acute radiation syndrome is rare, and almost no emergency physician sees a patient like this in their career. That is why the reasoning must be trained beforehand. The illness follows four phases: prodrome, latency, manifest illness and recovery or death (DiCarlo et al., 2011). With doses above about 6 Gy, latency may be short or absent (DiCarlo et al., 2011). The problem is that, in the first hours, the most important information, which is the dose, is almost always missing. The physician must estimate it from clinical signs and from simple tests repeated over time.

The man in the scene brings together clues that point to a significant exposure: vomiting within an hour, early erythema, low-grade fever and leukocytosis with neutrophilia. But each of these clues has limits. The post on signs, symptoms and history helps build the timeline of exposure, and the post on clinical decision-making reminds us that each test must change a decision.

What the scene teaches

The scene trains five habits. The first is recording the exact time of exposure, because all dose estimation tools count time from it. The second is noting the time of the first vomiting. The third is collecting serial complete blood counts at set times. The fourth is requesting the sample for cytogenetic biodosimetry early. The fifth is starting management without waiting for the confirmed dose, when the data already point to high risk.

What is not at stake

The text deals with external exposure, without radioactive contamination of the body. A sealed cobalt-60 source irradiates the worker but does not make him radioactive, and he poses no risk to the team treating him. Internal contamination by cesium-137 and treatment with Prussian blue are the topic of the second text in this series. The post on diagnostic uncertainty helps deal with the missing dose in the first hours.

Published cases that resemble the scene

In China, in 2008, a worker was exposed to a cobalt-60 source and received an estimated dose of 14.5 Gy (Guo et al., 2014). He had frequent vomiting, facial flushing and a fever of 38.9 °C 30 minutes after exposure, and his lymphocytes fell to zero within 45 hours (Guo et al., 2014). He received a peripheral blood stem cell transplant with HLA mismatch and mesenchymal cells, but died of multiple organ failure (Guo et al., 2014). In South Korea, a non-destructive testing worker developed pancytopenia after using unshielded sources (Ahn et al., 2018). His dosimeter read 120 mSv for the month, but the chromosome aberration test estimated 1191 mSv (Ahn et al., 2018). The difference shows that the dosimeter only measures what passes through it, not the real body dose when it is not worn or is outside the beam.

The prodrome: what vomiting says and what it does not say

What the vomiting curve shows

After an exposure, the amount, the severity and the time to vomiting relate to the dose, the dose rate and the part of the body irradiated (REMM, time to vomiting). In general, the higher the absorbed dose, the more severe the picture and the sooner vomiting begins (REMM, time to vomiting). The REMM tool, maintained by the United States Department of Health, uses an algorithm from the radiobiology institute of the American armed forces to estimate the dose from the time to vomiting (REMM, time to vomiting).

Why vomiting alone misleads

REMM itself warns that vomiting is not specific to radiation exposure, especially in infants and children (REMM, time to vomiting). It appears in trauma, psychological stress and chemical and biological threats (REMM, time to vomiting). Used alone, time to vomiting is an imperfect estimate of the dose, but at the start it may be the only clinical information available (REMM, time to vomiting). It should therefore be read together with the other signs and with biodosimetry (REMM, time to vomiting). In an accident with many people, anxiety can make those who received no relevant dose vomit.

Other prodromal signs

The REMM acute radiation syndrome management tool grades the picture by systems, including blood, skin, intestine and nervous system (REMM, acute radiation syndrome management). The consensus on non-hematopoietic organs recalls that skin, intestine, lung and nervous system can also fail at high doses (Dainiak et al., 2011b). In the man from the scene, the combination of vomiting within one hour, erythema and fever points to a high dose, and management begins with that hypothesis. The 2018 consensus suggests prevention of nausea and vomiting with a 5-HT3 antagonist when the suspected dose exceeds 2 Gy, as a weak recommendation (Dainiak, 2018).

Lymphocytes: the curve that helps estimate the dose

Why lymphocytes fall first

Lymphocytes are among the cells most sensitive to radiation, and their absolute count in the blood falls predictably after a whole-body exposure. REMM describes the normal count as between about 1.35 and 3.5 × 10⁹/L (REMM, lymphocyte kinetics). With doses of 2 to 4 Gy, the fall takes about 4 to 6 days; with 4 to 6 Gy, about 2 to 4 days (REMM, lymphocyte kinetics). The detection limit of the method is close to 1 Gy (REMM, lymphocyte kinetics). What matters is the speed of the fall, not an isolated value. REMM gives an example: a count of 1.0 × 10⁹/L on the eighth day corresponds to about 0.8 Gy, while the same count on the first day corresponds to about 10 Gy (REMM, lymphocyte kinetics). This example only serves to show the concept.

When to collect

If the suspected dose is 5 Gy or more, REMM recommends a complete blood count with differential every 9 to 12 hours for 2 to 3 days and then every 24 hours until the ninth day (REMM, lymphocyte kinetics). If it is less than 5 Gy, every 24 hours for 9 days (REMM, lymphocyte kinetics). The tool accepts counts up to 11 days and uses the Guskova and Goans models (REMM, lymphocyte kinetics). In the man in the scene, the first count of 1.4 × 10⁹/L at three hours is still near normal, and on its own it says nothing. The second count, 12 hours later, can already show the slope of the curve.

Limits of the kinetics

The method does not work for partial body exposure or internal contamination, and it has not been validated in children (REMM, lymphocyte kinetics). Burns and trauma alone can also lower lymphocytes (DiCarlo and colleagues, 2011). At the start, neutrophils may rise, and this early granulocytosis can mislead anyone looking only at the total white blood cell count (REMM, management of acute radiation syndrome). That is what happens in the man in the scene: 13.1 × 10⁹/L of white blood cells looks like infection or stress, but the relevant data is in the lymphocyte line.

The table shows how REMM grades the hematopoietic system in the first weeks.

Grade	Lymphocytes (× 10⁹/L)	Neutrophils (× 10⁹/L)	Platelets (× 10⁹/L)	Source
H1	1.5 or more	2 or more	100 or more	(REMM, management of acute radiation syndrome)
H2	1.5 to 1	2 to 1	100 to 50	(REMM, management of acute radiation syndrome)
H3	1 to 0.5	1 to 0.5	50 to 20	(REMM, management of acute radiation syndrome)
H4	Less than 0.5	Less than 0.5 or initial granulocytosis	Less than 20	(REMM, management of acute radiation syndrome)

Differential diagnosis and tests

The differential at the time of arrival

Before confirming the diagnosis of acute radiation syndrome, it is worth ruling out what mimics the picture. Vomiting with fever and leukocytosis can be gastroenteritis, food poisoning or chemical exposure in the same workplace. Erythema can be a thermal or chemical burn. Anxiety after an alarm can cause nausea and vomiting. The history of entering the room with the source exposed changes the weight of these hypotheses, but the physician needs to confirm the exposure with whoever operates the equipment and with the person responsible for radiation protection. The post on differential diagnosis shows how to keep the hypotheses open.

Biodosimetry by cytogenetics

The dicentric chromosome assay in lymphocytes is the reference for estimating dose, but it requires lymphocyte culture for 48 hours (Aryankalayil and colleagues, 2023). In partial body exposure, the distribution of dicentrics among cells helps show that the dose was not uniform, and the analysis increases to 50 metaphases when the estimated dose is 2 Gy or more (Prasanna and colleagues, 2010). REMM brings together three dose estimation tools: time to vomiting, lymphocyte kinetics and dicentrics (REMM, three biodosimetry tools). They should be used together.

New markers

RNA and metabolite markers change within hours, before the cytogenetic test is ready (Aryankalayil and colleagues, 2023). The FDXR gene showed increased expression in the blood of radiotherapy patients already after the first fraction, with a dose effect (O'Brien and colleagues, 2018). These are research tools, not yet used routinely in triage. In the armed forces, the need is for rapid methods that can be done near the site, to triage many people (Flood and colleagues, 2016).

Tests on arrival

• Complete blood count with differential, with the collection time noted.
• Repeat the blood count every 9 to 12 hours if a dose of 5 Gy or more is suspected.
• Blood for the dicentric assay, in the tube the reference laboratory requests.
• Biochemistry, electrolytes and kidney function.
• Early HLA typing, in case stem cell transplantation is considered.
• Photograph of the skin with date and time, to track the erythema.

HLA typing needs to come early because lymphocytes can be gone within a few days, and without them the test becomes difficult. The post on diagnostic pause helps to remember this collection before the window closes.

Management in the first 72 hours

Where the patient should stay

REMM uses the response categories of the METREPOL system to choose the site of care (REMM, management of acute radiation syndrome). In category 1, the patient can be followed as an outpatient; in 2, on a ward with blood components; in 3, in a hematology service with reverse isolation, intensive care and cytokines; in 4, in a specialized center with stem cell transplantation (REMM, management of acute radiation syndrome). The man in the scene, with vomiting within one hour and early erythema, should be transferred early to a hematology center with experience in aplasia. In the United States, the radiation injury treatment network exists to provide that surge capacity (DiCarlo and colleagues, 2021).

Cytokines

The 2011 World Health Organization consensus reviewed five accidents with documented use of cytokines, including Goiânia, Tokai-mura, Henan, Istanbul and Gilan (Dainiak and colleagues, 2011). Among those who received more than 5 Gy, 1 of 3 treated patients survived; below 5 Gy, 14 of 15 survived (Dainiak and colleagues, 2011). The group interpreted the finding as a possible benefit when the blood is the only critical organ in failure (Dainiak and colleagues, 2011). The 2018 consensus, with 34 specialists from 12 countries, recommends G-CSF or GM-CSF when neutrophils fall below 0.5 × 10⁹/L, as a strong recommendation (Dainiak, 2018).

REMM advises starting the cytokine when the likely dose is 2 Gy or more, when neutrophils reach 0.5 × 10⁹/L or less, or when there is radiation with trauma or burns (REMM, myeloid cytokines). It also says that the lack of a blood count should not delay the cytokine (REMM, myeloid cytokines). The Neupogen label indicates 10 mcg/kg once a day subcutaneously, as soon as possible after suspected or confirmed exposure to a dose above 2 Gy (Neupogen label of 07/2026). REMM advises continuing filgrastim until neutrophils exceed 1 × 10⁹/L on three consecutive blood counts or 10 × 10⁹/L after the nadir (REMM, myeloid cytokines). The Neulasta label indicates two doses of 6 mg subcutaneously one week apart for adults and children weighing 45 kg or more, and a weight-based dose below that (Neulasta label of 08/2026). The Leukine label indicates 7 mcg/kg per day above 40 kg, 10 mcg/kg between 15 and 40 kg and 12 mcg/kg below 15 kg (Leukine label of 05/2022). The Nplate label indicates a single dose of 10 mcg/kg subcutaneously, as soon as possible after exposure above 2 Gy (Nplate label of 02/2025).

Infection, blood and transplant

The 2018 consensus suggests a fluoroquinolone for prophylaxis starting at 2 to 4 days, as a weak recommendation, and does not recommend routine erythropoiesis-stimulating agents (Dainiak, 2018). It suggests considering stem cell transplantation when the cytokine fails for 2 to 3 weeks and there is no failure of other organs, also as a weak recommendation (Dainiak, 2018). The Chinese case shows the limit of transplantation when the dose is very high and other organs fail (Guo and colleagues, 2014). Blood components follow the routine for patients with aplasia at your service.

Regulatory status: FDA and EMA

How the cytokines were approved

It is not ethical to expose people to radiation to test a drug. That is why the FDA uses the Animal Rule, from 2002, which allows approving products for serious conditions caused by radiation based on animal studies (DiCarlo and colleagues, 2018). The four approvals for the hematopoietic subsyndrome used this pathway, and there are no randomized trials in humans (REMM, myeloid cytokines). The program of the American institute of infectious diseases funds the development of these countermeasures for the strategic national stockpile (Rios and colleagues, 2014).

The table summarizes the dates, checked in the approval letters, the labels and Drugs@FDA on October 24, 2026.

Product	First FDA approval	Indication in acute radiation syndrome	Current label	EMA
Neupogen (filgrastim)	02/20/1991	03/30/2015 (Neupogen approval letter)	07/2026 (Neupogen package insert from 07/2026)	No centralized authorization
Neulasta (pegfilgrastim)	01/31/2002	11/13/2015 (Neulasta approval letter)	08/2026 (Neulasta package insert from 08/2026)	Authorization of 08/22/2002, only chemotherapy-induced neutropenia (Neulasta page on the EMA)
Leukine (sargramostim)	03/05/1991	03/29/2018 (Leukine approval letter)	05/2022 (Leukine package insert from 05/2022)	No centralized authorization
Nplate (romiplostim)	08/22/2008	01/28/2021 (Nplate approval letter)	02/2025 (Nplate package insert from 02/2025)	Authorization of 02/04/2009, only immune thrombocytopenia (Nplate page on the EMA)

Situation in Europe

At the EMA, Nplate received a positive opinion on 11/20/2008 and authorization on 02/04/2009, with indications only for immune thrombocytopenia, on a page updated on 10/15/2025 (Nplate page on the EMA). Neulasta received an opinion on 05/30/2002 and authorization on 08/22/2002, only for chemotherapy-induced neutropenia, on a page updated on 12/08/2025 (Neulasta page on the EMA). Neupogen and Leukine have no centralized authorization. In Europe, use in a radiological emergency would be off-label or would depend on national rules. The post about interprofessional clinical reasoning recalls the role of the pharmacy in this decision.

How NEXO helps train this reasoning

In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues, and you propose the diagnosis by searching for the ICD-10 code. Acute radiation syndrome is a good exercise because the dose is almost never known at the start and each blood count changes the estimate. The post about case-based learning explains why this format fixes knowledge.

Three exercises with cases

Change the timing. Say what changes if the first vomiting came six hours later and the lymphocytes were still normal on the second day.

Change the geometry. Say what changes if only the hand had been near the source, and why lymphocyte kinetics loses value.

Change the patient. Say what the Leukine dose would be for a 30 kg child.

The post about simulation of care helps train the team arrival, and the post about clinical deterioration in the ward helps recognize worsening in the manifest illness phase.

The limits of use of the game are described on the NEXO economy page. If you research teaching of clinical reasoning, the page for researchers explains how to get in touch. Professionals who write or review cases find information in curation and in creators, and institutions can learn about the proposal on the partnerships page.

Frequently asked questions

Is a patient irradiated by a sealed source dangerous to the team?

No. Someone who was only irradiated does not become radioactive. The situation changes when there is contamination by radioactive material.

Does a normal blood count on arrival rule out severe exposure?

No. In the first hours lymphocytes may be normal and neutrophils may rise (REMM, management of acute radiation syndrome). What matters is the curve (REMM, lymphocyte kinetics).

Do I need to wait for the dicentric assay to start the cytokine?

No. REMM says that the lack of a blood count should not delay the cytokine when the probable dose is high (REMM, myeloid cytokines).

Is the personal dosimeter enough to know the dose?

No. In the Korean case, the dosimeter read 120 mSv and cytogenetics estimated 1191 mSv (Ahn et al., 2018).

Are the cytokines indicated in Europe?

Not for radiation. The EMA pages for Nplate and Neulasta only list other indications (Nplate page on the EMA) (Neulasta page on the EMA).

Final checklist

• I noted the time of exposure and the time of the first vomiting.
• I confirmed with radiation protection whether there was only irradiation or also contamination.
• I collected a blood count with differential and marked the next times.
• I sent blood for the dicentric assay.
• I requested HLA typing before the lymphocytes ran out.
• I graded the blood, skin and intestine.
• I considered the cytokine without waiting for the confirmed dose.
• I called the reference center and planned the transfer.

Want to practice reasoning with progressive clues? Play the case of the day.

References

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