Short Summary

74-year-old female evaluated for pancytopenia of unknown etiology, which required blood transfusions. Bone marrow aspirate and biopsy showed a hypocellular bone marrow with trilineage maturation. The treatment include immunosuppressive agents and erythropoietin.

Patient's Questions

1. What is the most likely diagnosis?
2. What further clinical tests or examinations would you suggest?
3. What treatment would you suggest?
4. What is the prognosis?

Medical Background

• Bilateral saphenectomy
• Left meniscectomy
• Approximately 3 years ago, polypectomy during colonoscopy
• Osteoporosis and arthrosis

Admitted to the internal medicine department , diagnosed with “pancytopenia and myelodysplasia" (currently in the process of being assigned a histological definition); arterial hypertensionobesity; and unilateral (left) multicystic kidney”.

Following further tests at the day hospital, without reaching any diagnostic certainty as to the pancytopenia (WT-1 gene analysis repeatedly negative;hypo cellular haemopoietic bone marrow with regular trilinear maturation); regular (every 4 days) need for transfusion support for red blood cells and platelets.

In order to obtain a better clinical assessment of the case, initial values are provided, to allow for comparison with a more recent patient hemochrome:
RESULTS (Interval of reference):
Red blood cells 2.46 x106 cells/mcl (4x106–5.6x10cells/mcl)
Haemoglobin 8.8 gr/dl (12-16 gr/dl)
Hematocrit 26.7% (36-48%)
MCV 108.5 fl (81-98 fl)
MCH 35.7 pg/cell (27-33 pg/cell)
MCHC 32.9 gr/dl (31.5-36 gr/dl)
RDW-SD 63.5 fl (37- 54 fl)
RDW-CV 16.3% (11.88-14.32%)
PLATELETS 25,000 platelets/mcl (140,000-440,000 platelets/mcl)
MPV 11.1 fl (9-14 fl)
PDW 12.3 fl (9-17 fl)
P-LCR 32.7% (13-43%)
LEUKOCYTES 3,370 cells/mcl (4,000-10,000 cells/mcl)
NEUTROPHILS 1,310 cells/mcl (1,600-7,400 cells/mcl)
LYMPHOCYTES 1,779 cells/mcl (760-4,800 cells/mcl)
MONOCYTES 279 cells/mcl (80-1,100 cells/mcl)
EOSINOPHILS 0 cells/mcl (8-700 cells/mcl)
BASOPHILES 0 cells/mcl (0-150 cells/mcl)

7 months later:
Red blood cells 2.63x106 cells/mcl (4x106–5.6x10cells/mcl)
Haemoglobin 7.9 gr/dl (12-16 gr/dl)
Hematocrit 23.8% (36-48%)
MCV 90.4 fl (81-98 fl)
MCH 30.0 pg/cell (27-33 pg/cell)
MCHC 33.1 gr/dl (31.5-36 gr/dl)
RDW-SD 49.8 fl (37- 54 fl)
RDW-CV 16.6% (11.88-14.32%)
PLATELETS 36,000 platelets/mcl (140,000-440,000 platelets/mcl)
MPV 11 fl (9-14 fl)
PDW 13.1 fl (9-17 fl)
P-LCR 33.6% (13-43%)
LEUKOCYTES 2,070 cells/mcl (4,000-10,000 cells/mcl)
NEUTROPHILS 728 cells/mcl (1,600-7,400 cells/mcl)
LYMPHOCYTES 1250 cells/mcl (760-4,800 cells/mcl)
MONOCYTES 80 cells/mcl (80-1,100 cells/mcl)
EOSINOPHILS 10 cells/mcl (8-700 cells/mcl)
BASOPHILES 0 cells/mcl (0-150 cells/mcl)

In addition:
Bone marrow needle aspiration report-
“The lymphocytes and monocytes show no phenotypical abnormalities. Blastic levels are within normal limits. The myeloid population would appear to show a slight maturative unbalance with a reduction of the most differentiated component. The erythroblast levels would appear to basically fall within normal limits”.
Erythropoietin 493 mUI/mL.

Last admitted to the department of internal medicine at the hospital, because following a check-up at the day hospital, severe anaemia and thrombocytopenia was reported, with tarry stools in the ampulla of the rectum.
Diagnosis upon discharge was:
-Pancytopenia of uncertain pathogenesis
-Erythematosus gastritis
-Arterial hypertension
-Unilateral (left) multicystic kidney

During the hospital stay:
-Emergency transfusions of concentrated red blood cells and platelets carried out.
-Esophagogastroduodenoscopy performed, reporting erythematosus gastritis without haemorrhaging.
-Improvement of the patient’s condition, and with no further haemorrhaging; repeated blood transfusions.
-Transfusion of platelet concentrates and GRF 2 units.
-Immunosuppressant treatment started with cyclosporine, in view of a hypothesised autoimmune pathogenesis of pancytopenia.

Advised home treatment:
-Sandimmun 100 mg 1 tablet twice a day
-Pantorc 20 mg 1 tablet to be taken in the morning.


Expert's Opinion

The differential diagnosis of pancytopenia in a 74-year old woman is broad, but I will mention the more common and more likely possibilities:
-Myelodysplastic syndrome (MDS): The age, pancytopenia, the high MCV and some myelodysplasia in the marrow – all consistent with this diagnosis.  However, this should be confirmed by bone marrow analysis by an expert, also with at least cytogenetic analysis.
-Liver disease with cirrhosis – this should be tested by blood tests (liver function tests, serology) ultrasound and sometimes liver biopsy (if indicated).
-Immune pancytopenia, whether primary hematological disease, or secondary to connective tissue disease / vasculitis or secondary to lymphatic disease.
-Other primary bone marrow diseases such as aplastic / hypoplastic anemia, PNH, myeloproliferative disease and others.
 BM analysis and specific tests can help.
-Megaloblastic anemiaB12 and / or folic acid deficiency.
-Drug induced or viral induced (B19, EBV, CMV) BM suppression.

Missing information / Documents:
History – symptoms, clinical picture.
Routine blood tests – especially chemistry.
Anemia work up.
GI work up.
Specific tests – see above.

Once definite diagnosis is established, treatment can be discussed. For instance, if MDS is the problem, than several options can be considered:
Supportive treatment (RBC transfusions); Erythropoietin injections; Immune suppression (Globulins / ATG, cyclosporine); Thalidomide;Lenalidomide; Chemotherapy; Decitabine; 5-aza-cytabine – just to name a few options.
If the problem is immune – immune suppression can be the preferred approach
If the liver is the problem, than another approach should be considerd.

Final recommendation: attempt to establish a definite diagnosis.