Several weeks ago Dr. Doherty presented an excellent case of anemia at Delight. The patient was a 69 year old man who presented with symptoms of fatigue, shortness of breath on exertion, and lightheadedness and was found to have a Hb of 5.
His only past medical history was marginal zone lymphoma with recent signs of progression (new renal and lung masses noted on most recent PET scan). He was taking ibrutinib for this per the last oncology note as he had declined IV chemotherapy options. His social history was significant for the fact that he did not have stable housing and was living in a storage unit. He had no surgical history, and there was no family history of anemias.
We used the approach outlined in https://tulaneimchiefs.com/approach-to-anemia/ to think through the differential for the case. The patient’s history of cancer narrowed our differential initially to include toxic effect of chemotherapy (ibrutinib) on marrow precursors, anemia of chronic inflammation from progressive cancer, nutritional deficiencies given his history of housing insecurity, direct bone marrow infiltration by his cancer (given history of recent PET scan with new lung and renal masses), and hemolysis.
On exam, he was noted to have normal vitals. He was thin and chronically ill appearing with a relatively normal exam. He had no obvious lymphadenopathy or splenomegaly. On labs, his MCV was 120, RDW 30 (elevated). Platelets were within normal limits. Tbili was elevated. On further testing, reticulocyte index was calculated and found to be low, suggestive of a hypoproliferative disorder. Peripheral smear revealed the presence of numerous immature types of RBCs as well as large platelets. There were no schistocytes detected. LDH was elevated while haptoglobin was undetectably low. Coagulation factors, fibrinogen, and D-dimer were within normal limits. A diagnostic test was performed.
Given the patient’s low reticulocyte index, we knew that there was a hypoproliferative disorder occurring (which could have been due to his chemo, inflammation from his cancer, direct infiltration of his bone marrow by his lymphoma, or nutritional from B12 deficiency). However a haptoglobin <25 has a positive LR of 21 for hemolysis, and this patient had other signs of a hemolytic process (elevated LDH and Tbili, enlarged platelets, elevated MCV and RDW possibly suggestive of reticulocyte production). Patients with cancer are at risk for multiple hemolytic anemias with the most common including DIC, TTP, and autoimmune hemolytic anemia. Given our patient’s normal coagulation factors, lack of schistocytes on smear, normal D-dimer, normal fibrinogen, and normal number of platelets, DIC and TTP were both considered less likely. A direct antiglobulin test or Coomb’s test was performed and was positive. The patient was diagnosed with warm autoimmune hemolytic anemia and was treated with high dose steroids, IVIG, and blood transfusion with improvement and stabilization of his Hb.
Pearls:
- Autoimmune hemolytic anemia has an association with hematologic malignancies such as CLL, multiple myeloma, and lymphoma.
- Patients with cancer can have multiple underlying etiologies of their anemia, and it is crucial to rule out more life threatening causes like hemolysis.
- Large platelets on smear can be associated with multiple congenital etiologies but also have been associated with ITP and hemolytic processes.
Excellent review article of workup of anemia in patients with cancer: https://pubmed.ncbi.nlm.nih.gov/33201870/
An approach to hemolytic anemia from the clinical problem solvers:
Large platelets: