"Thrombocytopenia and an abnormal CXR"

In morning report we discussed the case of a young patient recently immigrated to Canada. As part of immigration they had routine bloodwork and a CXR done. The patient was called while at home with the results and advised to present to the nearest ER.

Referred to GIM for thrombocytopenia (platelet count of 26) and an abnormal CXR lesion NYD.

We discussed the DDx of low platelets, and those that would also tie in a potential abnormal CXR.


DDx of thrombocytopenia
1. Is it real? Look for clumping on blood film
2. Is it dilutional? (post massive transfusion/fluids)

3. Think: Decreased Production, Increased Destruction, Hypersplenism

Decreased Production

"Factory" problem
- congenital (TAR: thrombocytopenia with absent radii)
- bone marrow problem ie heme malignancies, solid tumours, fibrosis
- aplastic anemia
- MDS
- marrow suppression from sepsis
"Building block" problem
- nutrient deficiency (b12, folate)

Increased destruction

Microangiopathy
- TTP, HUS, DIC, HELLP, Malignant HTN, Scleroderma
Macroangiopathy
- valvular abnormality

Immune
Alloimmune
- PTP (posttransfusion purpura)
Autoimmune
- primary: ITP
- secondary: CTD (e.g. SLE), lymhoproliferative disoders, infections (eg HIV, EBV), drugs (e.g. sulfa, quinine)

Thrombocytopenia with an abnormal CXR? 
(before knowing what the CXR abnormality was)

Thoughts included SLE pericardial or pleural disease + thrombocytopenia.
Major thought was malignancy ie hematologic malignancy, with some sort of lymphoid mass (e.g mediastinal mass) + thrombocytopenia.
Infectious considerations included TB with abnormal CXR and marrow suppression from acute infection.

Coming back to the case, this patient had no significant PMH, was on no meds, OTC or prescribed, no illicit drug or alcohol use or smoking. No family history of signficant disease. Her history was signifcant for a 4 month history of easy bruising, skin changes, but significant bleeding issues. She had no symptoms of CTD, infection, no constitutional symptoms otherwise.

Her exam revealed an enlarged spleen as well as evidence of petechiae and ecchymosis on her extremities. She also had a ~1x1cm palpable, raised, blanchable lesion on her knee.

Lab investigations revealed
CBC: WBC of 16.9 ANC of 1.6, remainder counted as blasts. 
Blood film revealed myeloid blasts with evidence of Auer rods
CXR and subsequent CT revealed a spinal lesion first reported as possibly a neurogenic tumour  ....however in the context of the case, the thought was that this was a chloroma, or granulocytic sarcoma.

Her skin lesion on her knee might represent leukemic infiltration as well.

Unfortunately, as she recently came to Canada, she did not have coverage, but was initially managed in hospital and subsequently she returned back home to complete her investigation and management of her newly diagnosed AML.

A word or two on AML

Acute myeloid leukemia (AML) is characterized by an increase in the number of myeloid cells in the marrow with an arrest in their maturation, This often leads to hematopoietic insufficiency with subsequent decrease in other cell lines and the signs and symptoms they carry with it.

The clinical presentation of AML is diverse, but is attributed in large part to the signs and symptoms secondary to cytopenias (anemia symptoms, thromobocytopenia symptoms). 
It also presents with evidence of leukemic infiltration of tissues: ie liver, spleen, lymphadenopathy, and skin (leukemia cutis). It can also lead to a mass of immature cells termed granulocytic sarcoma, or chloroma.

Lastly, AML can present as an acute blast crisis with hyperleukocytosis. These patients require urgent management in an ICU setting, cytoreduction, fluids, as well as prevention/treatment of tumour lysis syndrome.

There are different subtypes of AML, most important to distinguish M3 or APL as the treatment is different.

Click here for a recent review article including treatment considerations for AML. 

Also see this NEJM review article, while from 1999, still nicely describes the clinical presentation.