Chiefs’ Inquiry Corner – 5/23/22

 The JAK2V617F mutation is present in the majority of patients with polycythemia vera, essential thrombocythemia, or primary myelofibrosis.You can consider sending the screening test as part of the evaluation of erythrocytosis, thrombocytosis, bone marrow fibrosis, or other symptoms that are somewhat unique to these conditions (such as splanchnic vein thrombosis, aquagenic pruritus, and unexplained splenomegaly or leukocytosis). Note that you do not require an abnormal blood count to consider JAK2V617F mutation screening in patients with splanchnic vein thrombosis.

References: JAK2 and MPL Mutation Screening: What Are the Indications and How to Interpret the Results

 In a patient with suggestive symptoms, physical findings, or family history, a combination of transferrin saturation (TS) and ferritin should be obtained rather than relying on a
single test. If either TS is >45% or ferritin is above the upper limit of normal) then HFE
mutation analysis should be performed. Although a cutoff TS value of 45% is often chosen for its high sensitivity for detecting C282Y homozygotes, it has a lower specificity and positive predictive value compared to higher cutoff values. Using a cutoff TS of 45% will also identify persons with minor secondary iron overload. Serum ferritin has less biological variability than TS, but it has a significant false positive rate because of elevations related to inflammation. Serum ferritin levels may range anywhere from 150-1000 (typically asymptomatic) up to 500-6000+ (usually symptomatic). Testing should also be sent on adult 1st degree relatives of individuals with confirmed hereditary hemochromatosis.

References: Diagnosis and management of hemochromatosis

 According to the Choosing Wisely Campaign, the role of peripheral flow cytometry should be reserved for settings in which you have observed morphologically abnormal cells on a peripheral smear (such as blasts) or there is a high pre-test probability based on other findings (such as neutropenia, absolute lymphocytosis, lymphadenopathy, or splenomegaly). In general, flow cytometry should also be performed for an absolute lymphocyte count (ALC) >30,000 cells/microL without a known diagnosis. You should also consider this workup for a rising ALC or an unexplained ALC >4000 for >1 month.

References: American Society for Clinical Pathology