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Date of last update: 10/12/2017.

Forum Name: Hematology Topics

Question: undiagnosable low hemoglobin+low haematocrit

 misc1234us - Wed Jul 14, 2010 10:25 pm

My dad is on dialysis and he is getting his regular dose for e-poetin injections too. For the past 7 months, his hemaglobin levels have fallen - sometimes as low as 5.5. His most recent tests (CBC. B12, Folate) came up with the following data:

Hemoglobin 6.6
Haematocrit 21 percent
MCV 88 fl
MCH 27.7 pg
MCHC 31.5
RDW 13.7 percent
TLC Count 8.9
Platelet Count 287
Neutrophils 61
Lymphocytes 30
Eosinophils 02
Monocytes 06
Basophils 01
RBC: Normocytic normochromic plus, occasional schistocytes plus, microspherocytes plus, macrocytes plus
WBC: Shift to right
Platelets: Adequate on the smear


The doctor is at a loss about diagnosing why the hemoglobin and haematocrit values are low. He said he "empirically believed" there is a bacterial infection but the infections specialist cannot pinpoint any bacterial infection. Can you please suggest any ideas of what we're missing here or what we should be looking for?
 Dr.M.Aroon kamath - Wed Aug 04, 2010 9:52 am

User avatar Hi,
A majority of patients with chronic renal failure (CRF) are anemic. In most cases, this anemia is normocytic and normochromic and hypoproliferative in nature, with a low reticulocyte count. The main defect responsible for this anemia of CRF is absolute or relative erythropoietin deficiency. Other factors also play a part in the development of anemia such as, malnutrition, acute and chronic blood loss, iron deficiency, hemolysis, acute and chronic inflammatory conditions, severe hyperparathyroidism, folate and vitamin B12 deficiency, aluminum toxicity, inadequate hemodialysis, shortened erythrocyte life span, underlying hemoglobinopathies, hypothyroidism, and multiple myeloma.

The management of this renal anemia consists of effective dialysis, correction of deficiencies (especially iron), and control of renal osteodystrophy, as well as the optimal dosage and duration of treatment with EPO.

Recombinant human erythropoietin (rHuEpo) and its analogues have provided enormous benefit in the prevention and treatment of anaemia in chronic kidney disease (CKD). Unfortunately, in some patients, EPO resistance develops. If anemia is not responding, despite appropriate dosage and duration of therapy, then the reasons for this should be sought.

EPO resistance can be due a variety of causes such as, malnutrition, chronic blood loss, iron deficiency, infections, primary hematological diseases, osteitis fibrosa, aluminum toxicity, folic acid or vitamin B12 deficiency, or multiple myeloma. Angiotensin-converting enzyme inhibitors have been suspected of causing EPO resistance. There have been some isolated reports of bone marrow amyloidosis causing EPO resistance.

Your fathers's lab results (you have omitted the reference ranges) show RBC indices presumably within normal limits, the platelet count is normal and of course a normocytic normochromic anemia.

The folic acid level is difficult to interpret as you have not mentioned whether the values are in ng/ml or nmol/L. The normal range is >3.1–12.4 ng/ml(7–28.1 nmol/L). If it is in ng/ml, then it is HIGH and if it is in nmol/L, it is NORMAL. This why lab results should be correctly mentioned(including the lab reference ranges). Red blood cell folate levels are said to be more reliable than serum folic acid levels(which are commonly performed).The vitamin B12 value is above normal range.

Right shift of the neutrophils can occur in vitamin B12 or folate deficiency, liver disease, chronic uremia etc.

There are a few other relevant findings in the peripheral smear (occasional schistocytes, microspherocytes, and macrocytes).

Schistocytes, microspherocytes and macrocytes are found in certain conditions which include.
- heriditary spherocytosis,
- Autoimmune Haemolytic Anaemia (AIHA).

Microspherocytes (hyperchromic
and significantly smaller sized RBCs)
may be present in
- patients with a spherocytic hemolytic anemia,
- burns and
- microangiopathic hemolytic anemia.

Microangiopathic hemolytic anemia may indicate underlying
disseminated malignany, chronic disseminated
intravascular coagulation(DIC), thrombotic thrombocytopenic
purpura or the hemolytic–uremic syndrome(Thrombotic microangiopathy).

Your father's platelet count is normal. Patients with DIC or hemolytic–uremic syndrome typically have severe thrombocytopenia,they are less likely. If DIC is the cause of thrombocytopenia, one must exclude an underlying infection or a malignancy.

That leaves us with Autoimmune Haemolytic Anaemia (AIHA).
Coombs-negative AIHAs have been reported.

Thus, one likely possibility in your father's case is Autoimmune Haemolytic Anaemia. Drug-induced AIHA also needs to be considered.It is also advisable to check his RBC folate levels. Your father's doctors in all probability, have considered these in the differential diagnosis and there must be a valid reason why infection is being considered. Without actually examining a patient, one can at best, only speculate.
Best wishes!

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