Saturday, 28 March 2015

Differential-icious Pancytopenia March 25th

The differential for pancytopenia is enormous, 100s of case reports on finding everything associated with pancytopenia. Like any cell like that is look, we generally consider decrease production, increase destruction (or sequestration). Blood loss is more specific to red blood cells

A general approach

Pancytopenia
PNH – complement mediated red cell lysis
Aplastic anemia
-       idiopathic
-       - infections (EBV, cmv, heb c, HIV)
-       drug induced (chemo, methotrexate, anti-epileptics)
-       toxins – alcohol

neoplastic – leukemia (AML, CLL), MDS, bone marrow mets
infections – sepsis, TB, histo leishmaniasis
insufficiency – folate, B12, copper
iatrogenic – chemotherapy
consumption – hyperspelnism, immune-mediated (lupus, scleroderma)


Inherited – HLH, (acquired is macrophage activation syndrome)) increase triglycerides, low fibrinogen, high ferritin, liver enzyems

So how do you approach the patient? As always a history and physical may be revealing. B symptoms may suggest malignancy, history of cancer may suggest metastasis to the bone. Neurological findings can suggest b12 deficiency. Consider infectious causes such as hepatitis if risk factors (IVDU), HIV risk factors (male male intercourse). ANY new medications need to be considered as many MANY medications have been associated with pancytopenia.

In terms of investigations, fortunately we can look to reticulocyte count (which after a CBC and peripheral smear... should be our FIRST step) to see if this is a bone marrow production problem.

If the reticu count is high (appropriately responding) we need to consider blood loss + sequestration, destruction etc. **note unfortunately we do not test for a reticulocyte equivalent for platelets and wbcs.

We may look to MCV for some tips (mainly for very high MCV we consider b12/folate deficiency).

Ultimately, bone marrow is the gold standard in helping us make a diagnosis. Specifically it rules out scary things such as leukemia which would need to be treated ASAP.

We briefly discussed how blood malignancies can produce pancytopenia - bone marrow is compact with cells, nothings gets out! Generally we would hope we could some immature (blast) cells to tip us off that it is leukemia.

Aplastic anemia typically shows fat cells, and gives us a dry tap.

b12 deficiency (which we believe is the cause of OUR patients pancytopenia) is needed to make all cell lines, its used to TAKE OFF methyl groups off of tetrahydrofolate (THF) so that other carbon groups can be added on to make DNA molecules. We could assess this with a b12 level, but the assay isn't the greatest and b12 deficient individuals can be found with levels that are normalish. Generally levels 100-300 make us concerned for b12 deficiency, and thus we would send off a methylmalonic acid (and a homocysteine level as well).

Often people would just empirically give vit b12.

What causes b12 deficiency - many things! pernicious anemia, tea and toast diet, pancreatic insufficiency, crohn's disease, gastric bypass. Why is the cause important? If it were a malabsorption issue, we would want to give IM injections every month as opposed to oral pills daily.

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