Journal Reading

How to approach chronic anemia

Mark J. Koury1,2 and Mellisa Rhodes3,4
1Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville,TN;
2Veterans Affairs Tennesse Valley Healthcare System, Nashville, TN; 3Department of Pediatrics, The Ohio State University

College of Medicine, Columbus, OH and 4Department of Hematology/Oncology, Nationwide Children’s Hospital,

Columbus, OH.

*Dr. Mohamad Ananto C

**Dr. Laksmi Wijayati SpPD

*Resident of Internal Medicine, Medical Faculty of Brawijaya University

**Supervisor Internal Medicine, Dr Iskak General Hospital, Tulung Agung 1
 Introduction
!   Understanding the pathophysiology of decreased numbers of
circulating erythrocytes can help in the diagnosis and
treatment anemia

!   Chronic anemia à when the life span circulating erythrocytes

is decreased to less than 110 days without compensatory in
increase reticulocytes production, fewer of produced than the
number senescent erythrocytes phagocytosed

!   CBC shows a persistently decreased hematocrit and

hemoglobin concentration (Hct/Hgb)
 Introduction (2)
!   Four spesific patterns of chronic anemia are
emphasized in terms of the underlying erythropoietic
defects that give rise to the abnormal CBC :
1.  Abnormal platelet and/or leukocyte counts

2.  Increased reticulocyte count

3.  Life long persistence of an abnormal CBC

4.  Abnormal erythrocyte size (ie, macrocytosis or

microcytosis) when reticulocyte count is decreased
 Staging of erythropoietic differentiation
Separated into 4 sequential :
1.  Before EPO dependence
2.  EPO dependent
3.  Terminal differentiation when cell size decreases and Hgb
accumulates
4.  Reticulocyte maturation in the blood

!   In clinical practice some patients will have a combination

of these effects on erythroid cells.
Erythropoietic stages and the development of
chronic anemia
 Chronic anemia associated with abnormal
platelets and or leukocytes

!   Any disorder that disrupts the BM space à affect all blood cell
lineages.

!   Hematopoietic Stem Cell (HSC) and multilineage progenitors

between the HSC and BFU-E stages give rise to all blood cell
types, disease affecting these early stage hematopoietic
progenitor à effect platelet, leukocyte as well as erythrocytes.

!   In chronic liver disease, portal hypertension from cirrhosis

enlarges the spleen and traps erythrocytes, platelets, and
neutrophils, but the chronic anemia is multifactorial, with
upper GI bleeding due to varices combined with
trombocitopeny and/or coagulopathy
 Chronic anemia associated with abnormal
platelets and or leukocytes (2)

!   Chronic alcohol consumption can have direct Bone Marrow

(BM) toxicity and can be associated with poor intake of folate

!   Antiviral treatments for Hepatitis C à suppress erythropoiesis

!   Hepatitis B, C or autoimmune hepatitis à can be complicated

aplastic anemia

!   The absence of splenomegaly with multilineage citopenias

usually indicates a primary BM disease, including aplastic
anemia, MDS, Acute leukemia or BM invasion by metastatic
solid tumor
 Chronic anemia associated with abnormal
platelets and or leukocytes (3)

!   Frequently, chronic anemia due to iron deficiencies is

accompanied by increased platelets à resolves with iron
repletion

!   In severe iron deficiencies anemia, pts may have

trombocytopenia which also resolves with iron therapy

!   Chronic anemia can be accompanied by increased leucocytes

in pts with chronic inflammation/infection, and the
leucocytosis may help distinguish iron deficiency from anemia
of chronic inflammation.
Algorithm for evaluation of chronic anemia
based on the CBC (1)
Algorithm for evaluation of chronic anemia
based on the CBC (2)
 Chronic anemia with increased reticulocyes

!   Absolute reticulocyte counts and reticulocyte index (RI) indicate

whether BM erythrocyte production is appropriately increased

!   In chronic anemia, an increased absolute reticulocytes or RI

indicates low grade hemolysis or blood loss

!   Increased indirect serum bilirubin, LDH, decreased haptoglobulin

à hemolysis

!   Without evidence of hemolysis, chronic anemia with increased

reticulocytes can result from bleeding

! Spherocytes on the smear suggest hereditary spherocytosis or

immune hemolysis
Life-long history of abnormal CBC ( no previously
normal CBC)
!   The most common cause of congenital anemia is thalassemia, the
most frequent caused of undiagnosed chronic anemia

!   Chronic anemia due to α-thalassemia is caused by deletions or

abnormalities 2,3 or 4 α- globin genes on chromosome 16 and result
ineffective erythropoiesis from early fetal life

!   If not diagnosed by newborn screening , patients will have microcytic

anemia that can be differentiated from iron deficiency anemia by
normal or elevated RBC and RBC distribution width.

!   Chronic normocytic anemia present from birth are usually due to

nonthalassemic hemoglobinopathies, RBC enzyme deficiences, or
RBC membrane defects.
 Chronic anemia with inappropriately low
numbers of reticulocytes
!   One the most common chronic anemia with low numbers of
reticulocytes , indicating a dysfunctional Bone Marrow
!   Even in adults , the patient who has never had previously
normal Hct/Hb à may well have a congenital anemia ;
hemoglobinopathy, sideroblastic anemia, or diamond-blackfan
anemia whereas the history of previously normal CBC to an
acquired BM dysfunction such as MDS, fibrosis, or aplastic
anemia.
!   For both congenital and acquired anemia, determining
whether the chronic anemia is macrocytic, microcytic or
normocytic can be helpful in diagnosing its cause
Acquired normocytic chronic anemia with normal
platelets and leukocytes

!   Represent one of the largest groups of patients encountered

during the evaluation of chronic anemia.

!   Anemia of renal failure à the most common EPO deficiency,

also contribution of iron deficiency and inflammation

!   The majority patient with normocytic anemia have the anemia

of chronic inflammation à Anemia of chronic disease (ACD),
ec rheumatology disorder (PMR, SLE , IBD), unrecognized
bacterial abscess, endocarditis, HIV, or fungal infection
 Conclusion
!   This review emphasizes the pathophysiology and
diagnosis chronic anemia based on patient history and
complete blood count (CBC)

!   Understanding the pathophysiology of decreased

numbers of circulating erythrocytes can help in the
diagnosis and treatment anemia
THANK YOU
Iron Deficient anemia
Anemia of chronic disease
 Chronic anemia associated with abnormal
platelets and or leukocytes (3)
!   Frequently, chronic anemia due to iron deficiencies is accompanied
by increased platelets, and this trombocytosis resolves with iron
repletion
!   In severe iron deficiencies anemia, pts may have trombocytopenia
which also resolves with iron therapy
!   Chronic anemia can be accompanied by increased leucocytes in pts
with chronic inflammation/infection, and the leucocytosis may help
distinguish iron deficiency from anemia of chronic inflammation.

!   Conversely, chronic anemia is a negative prognostic sign when

associated with increased platelet due to essential thrombosithemia
(ET) or with increased leukocytes due to myelofibrosis.