Acute Myeloid Leukemia / Pancytopenia

Today's case centred around a classic internal medicine differential diagnosis for multilineage cytopenias.  The patient is an elderly man with cirrhosis who presented with fatigue and lethargy.  He was found to have a profound anemia, thrombocytopenia and leukopenia.  He was admitted to the internal medicine service wherein a bone marrow aspiration and biopsy was performed revealing acute myelogenous leukemia.

The approach to the differential diagnosis in this case is very important, as there are multiple diagnostic entities that can produce this syndrome:

·      Malignant processes (think of bone marrow replacement with hematologic malignancies like leukemias, scar as in myelofibrosis, or non-hematologic malignancies with a significant degree of bone marrow infiltration).

·      Cellular destruction (it is unusual for this to cause trilineage cytopenias, but certainly anemia/thrombocycopenia combinations are possible in diagnoses like HUS or TTP)

·      Inflammatory/Autoimmune diseases like SLE can lead to pancytopenia.

·      Drug effects can be categorized into drugs that are intentionally halting cellular maturation and production like chemotherapeutic agents, and drugs that exhibit this as an idiosyncratic side effect like phenytoin or Septra.

·      Substrate deficiency – the example used during morning report was B12 deficiency which can lead to megaloblastic anemia, hypersegmented neutrophils on the blood film, and neurologic complications like dorsal column dysfunction and peripheral neuropathies.

·      Sequestration – Sequestration can happen in tissues like the spleen and liver in conditions that produce portal hypertension, such as cirrhosis.  We usually attribute thrombocytopenia to this condition, but it can certainly be seen in other cell lines.

·      Infections – viral infections like hepatitis B can lead to aplastic anemia.  HIV can certainly lead to cytopenias. In immunocompromised hosts such as those with advanced HIV, disseminated Mycobacterium avium infections can replace bone marrow leading to pancytopenias.

The physical examination of a patient with these clinical entities can be very revealing:

·      On vital signs – findings such as hypotension or tachycardia can be revealing of a hyperdynamic cardiac output secondary to anemia.  Orthostatic changes would suggest hypovolemia.  Fever may suggest an underlying malignant or infectious process.

·      On general appearance – pallor or jaundice may suggest anemia and/or hemolysis.  It’s also important to characterize the degree of distress the patient may have.  Rashes like patecheiae or purpura may relate to the degree of thrombocytopenia.  Inside the mouth, gingival hyperplasia may occur with some variants of leukemia.

·      On cardiovascular examination, a flow murmur over the tricuspid valve due to ramped up cardiac output from anemia may be audible.  In someone with cirrhosis, signs of pulmonary hypertension (TR murmur, high JVP or CV waves, RV heave, loud and/or palpable P2) may be related to portopulmonary hypertension.

·      On abdominal examination, the liver size is important, but splenomegaly is also very important.  Generally, percussion of Traube’s space, followed by Castell’s sign, followed by percussion using Nixon’s method increase in specificity for splenomegaly.  Importantly, your physical examination is only around 80% sensitive for splenomegaly meaning that you cannot rule out splenomegaly on exam alone.  Abdominal ultrasound would be the mainstay of diagnostic tests for splenomegaly.

Management of this condition involves treatment of the underlying process (the leukemia).  This typically involves chemotherapy, the type and duration of which is a highly subspecialized field. It is unusual but possible for leukemia to be present without circulating blasts, but they are otherwise the hallmark of diagnosis.

In addition to treating the leukemia, it is important to recognize the complications of leukemia including bleeding from thrombocytopenia, disseminated intravascular coagulation from some forms of leukemia, and infections as a result of inadequate numbers and function of leukocytes.  Aside from some of these complications, the pathophysiologic process leading to death from acute leukemias is the cytopenias themselves.

Image Credit: de.academic.ru

Further Reading:

Döhner, H., Weisdorf, D. J., & Bloomfield, C. D. (2015). Acute myeloid leukemia. New England Journal of Medicine, 373(12), 1136-1152.

Grover, S. A., Barkun, A. N., & Sackett, D. L. (1993). Does this patient have splenomegaly?. Jama, 270(18), 2218-2221.