Thanks to Ling Wu for presenting an excellent firm report today: a 51 year old Sudanese man with subacute fatigue and weight loss, found to have pancytopenia and Coombs-negative hemolysis and ultimately found to have severe B12 deficiency.
Broadly speaking, pancytopenia results from:
- Bone marrow infiltration/replacement: malignancies, infection (TB, fungi), myelofibrosis
- Bone marrow aplasia: nutritional deficiencies, infection (HIV, Parvo B19), immune destruction, medications
- Cell destruction or sequestration: DIC, TTP, MDS, hypersplenism
Pancytopenia has a huge differential which can be looked up on UpToDate, so I won’t put it here.
How to work up new pancytopenia? Things to consider:
- CBC w/ differential, BMP, LFTs (look for hemolysis/jaundice)
- Peripheral blood smear
- PT/PTT/INR, fibrinogen
- B12/folate/iron studies
- Infectious w/u: HIV, HBV/HCV, EBV or CMV as the history dictates, Parvo B19
- Thorough medical review, consider autoimmune workup
Things like flow cytometry and bone marrow biopsy may need to be considered if the initial workup is unrevealing.
This patient was ultimately diagnosed with B12 deficiency.
See the NEJM article below for more comprehensive information on causes of B12 deficiency.
- The B12 assay is imperfect: although an extremely low level (<100) is usually associated with clinical deficiency, such low levels are rare
- Up to 50% of tests have either false positive or false negative values
- Moral of the story: don’t use the lab’s lower limit of normal to reassure yourself that there’s no B12 deficiency. If they have compatible signs/sx despite a value above the LLN, they may still require supplementation.
- The body’s daily requirement of B12 is 2.4 μg
- Severe deficiency may require injected B12, sometimes lifelong if it is for treatment of pernicious anemia
- Neither injection nor oral therapy are very efficiently absorbed
- An increase in the reticulocyte count should be seen in 1 week and correction of megaloblastic anemia in 6-8 weeks
- Stabler S. Vitamin B12 deficiency. NEJM 2013.