3 ways clinicians misclassify anemia drivers in MF—and why it matters
Industry Buzz
There’s no magic test to say this patient’s anemia is from inflammation or from impaired hematopoiesis; it’s often a multifactorial problem.
—Aaron Gerds, MD, MS
Anemia is common in myelofibrosis (MF), but it remains one of the disease’s most challenging complications to manage. Between 35% and 54% of patients with MF experience it at diagnosis. Within the first year, about 60% will develop anemia, and 46% will require red blood cell transfusion support.[][]
“There’s no magic test to say this patient’s anemia is from inflammation or from impaired hematopoiesis; it’s often a multifactorial problem,” Aaron Gerds, MD, MS, tells MDLinx. Dr. Gerds is a hematologist-oncologist at the Cleveland Clinic Taussig Cancer Center and a media expert with the American Society of Hematology (ASH). In 2025, Gerds co-authored a review in Blood titled “How I treat anemia in myelofibrosis.”
The following are three common pitfalls when diagnosing and treating anemia in MF.
1. Missing noninflammatory drivers
It’s true that inflammation is a chief driver of anemia in MF. However, it’s not the only cause, stresses Dr. Gerds. Other causes include impaired hematopoiesis, splenic sequestration, or as a result of treatment. He also notes that iron loss rarely plays a role.
“Most patients have some degree of inflammation—it just depends on how much, and whether our interventions can actually help them,” Dr. Gerds says. Over-attributing anemia to inflammation and focusing on JAK inhibitors could obscure treatments for anemia targeting other mechanisms, such as the erythroid maturation agent luspatercept or erythropoiesis-stimulating agents (ESAs).
The former, for instance, acts as a ligand trap for select TGF-β superfamily members and improves various deficiencies associated with ineffective erythropoiesis. Additionally, luspatercept supports erythroid maturation and increases erythroid precursors in the bone marrow. []
Importantly, inflammation increases IL-6 and other cytokine levels, which increase hepcidin levels. Hepcidin traps iron, thereby reducing the availability of iron.
Related: IL-6, hepcidin, and the hidden driver of anemia in MF: Are you targeting the right pathway?“The analogy I like to use is the cork,” says Dr. Gerds. “Hepcidin will lock that export of iron out of the iron stores … and hold it in there.”
Typically, a mixed clinical picture of splenomegaly, cytopenias, and exposure to other treatments, as well as a lack of response to inflammation-targeted strategies such as JAK inhibitors, may tip the clinician off that factors other than inflammation are at play.
2. Misinterpreting ferritin concentrations
Ferritin is often used as a standalone marker of anemia. However, ferritin levels can be misleading.
“Ferritin is an acute-phase reactant, so it goes up with inflammation, not just iron stores,” says Dr. Gerds.
Higher levels of ferritin usually represent inflammation rather than iron deficiency because in inflammatory states, ferritin rises independently of iron stores.
“A high ferritin doesn’t necessarily mean iron overload; it may just reflect underlying inflammation,” continues Dr. Gerds.
High ferritin levels, along with a normal or high TSAT, likely indicate an inflammatory block.
“You always have to interpret ferritin in context, alongside transferrin saturation and the clinical picture,” says Dr. Gerds.
Misinterpreting ferritin levels can result in unnecessary iron therapy, delayed prescription of mechanism-specific treatments, and failure to detect functional iron deficiency.
3. Misreading treatment-emergent cytopenias
Determining the cause of—and therefore properly treating—cytopenias that manifest during treatment can be tricky. Timing should be strongly considered, as these cytopenias are often multifactorial, according to Dr. Gerds.
“Both the disease and the treatments can cause cytopenias, so the challenge is figuring out what’s causing what,” he says.
Drug-related causes of cytopenia appear shortly after the start of treatment, while later declines after a period of stability are likely secondary to disease progression, notes Dr. Gerds.
One common mistake is stopping therapy too early when the cytopenia is transient. A second common mistake is teasing the effects of drug toxicity from JAK inhibitors from those of disease progression, as both conditions cause anemia and thrombocytopenia, explains Dr. Gerds.
Anemia in MF rarely points to a single, easy-to-treat cause. For clinicians, the workup should account for inflammation, transferrin saturation, splenomegaly, marrow function, treatment timing, and disease trajectory.
Dr. Gerds frames the approach as individualized rather than algorithmic: “You have to use clinical judgment and work through the management of anemia in myelofibrosis with each individual patient to figure out what’s going to [work] best [for] their anemia.”
Related: Why JAK inhibitors worsen anemia in myelofibrosis—and how one agent changes the equation