Methotrexate Case Study

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A 36-year-old female presents to her physician with a 3-month history of joint pains. The pain is mostly in the joints of her wrists and hands up to the middle interphalangeal joints. The patient says that the pain is worse in the morning, but improves through the day as she uses her hands. On examination, the joints are red, swollen, and tender. Anticyclic citrullinated peptide antibodies are positive. The patient is started on low-dose methotrexate with good results. The patient is followed by her doctor, and complete blood counts between the start of therapy and 1 year later are seen in the image. The best explanation for these changes is:
Complete Blood Count (CBC) Patient at start of methotrexate Patient after 1 year of therapy Reference
…show more content…
Methotrexate, used as the first-choice disease-modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA) and in some cancer chemotherapy regimens, acts by inhibiting dihydrofolate reductase, which results in a relative deficiency of bioavailable folate. Its action as an anti-inflammatory is less clear. The abnormal synthesis of tetrahydrofolate interferes with thymidine metabolism and DNA synthesis. This leads to the nuclear-cytoplasmic maturation dissociation of the megaloblastic anemias, resulting in macrocytic red blood cells. This elevation of MCV in the CBC is seen in all drugs that interfere with DNA synthesis and is common in cancer patients on chemotherapy. Rising MCV can be used in RA as a marker of impending methotrexate toxicity. Folate supplementation can be used to mitigate the effects of methotrexate …show more content…
Anemia of chronic disease is seen in RA and presents as a mild normocytic to microcytic anemia, not as a macrocytic anemia. It is caused by decreased bioavailability of iron due to hepcidin, an acute-phase reactant, and inhibition of marrow erythroblast response to erythropoietin.
Choice "C" is not the best answer. Autoimmune hemolytic anemia is seen in connective tissue diseases like systemic lupus erythematosus (SLE) and RA. It presents as a normocytic anemia with increased reticulocyte count and a positive Coombs test. There is a mild increase in MCV due to the reticulocytosis, since reticulocytes are larger than mature RBCs.
Choice "D" is not the best answer. While vitamin B12 is important in folate metabolism (see Choice “A”), it is not affected by methotrexate.
Choice "E" is not the best answer. Reticulocytosis does raise the MCV, as these young RBCs have an MCV of 110–120 fL. On the CBC, an MCV over 100 fL would not be seen in clinical practice, as it would require reticulocytes to reach 60% of RBCs. Reticulocytosis is seen in hemolytic anemia and after acute

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