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Anaemia
1
Hidden Anemia
Anaemia
2
• Anemia is defined as a reduction in the
number of circulating red blood cells, the
hemoglobin concentration, or the volume
of packed red cells (hematocrit) in the
blood.
Anemia
3
• Anemia is frequently under diagnosed and under
treated as its signs and symptoms may be vague.
• Frequently, anemia remains undetected because it
is masked by symptoms of the diseases with which
it is associated including:
– Chronic kidney disease
– Cardiovascular diseases
– Diabetes mellitus
– Cancer
– HIV/AIDS
– Rheumatoid arthritis
– Inflammatory bowel disease
– Hepatitis C
– Surgery
Anaemia
4
• Because anemia affects the delivery of
oxygen to all of the body’s organs, its
signs and symptoms are varied.
• It is generally accepted that symptoms
of anemia adversely affect quality of
life, even when anemia is mild.
Anaemia
5
Central nervous system
•Debilitating fatigue
•Depression
•Impaired cognitive function
Gastrointestinal system
•Anorexia
•Nausea
Vascular system
•Low skin temperature
•Pallor of skin, mucous membranes,
and conjunctivae
Immune system
•Impaired T-cell and macrophage function
Cardiorespiratory system
•Exertional dyspnea
•Tachycardia, palpitations
•Cardiac enlargement, hypertrophy
•Increased pulse pressure, systolic ejection
murmur
•Risk of life-threatening cardiac failure
Genital tract
•Menstrual problems
•Loss of libido
Anaemia
6
Reticulocyte Count
• The reticulocyte count estimates the rate of red
cell production
• An elevated reticulocyte count generally indicates
that the marrow is responding to endogenous
erythropoietin stimulation
• The reticulocyte count must be corrected for the
degree of anemia in order to have a valid estimate
of the rate of red cell production
Anaemia
7
Reticulocyte Count
• A normal reticulocyte count in the presence of
anemia suggests impaired erythropoietin
production or an impaired response to
erythropoietin by the erythroid marrow
• An elevated reticulocyte count and slightly
increased MCV suggest a hemolytic process.
• An elevated MCV can reflect a very high
reticulocyte production or a nuclear maturation
defect (eg, vitamin B12 or folic acid deficiency).
Anaemia
8
Assessing Blood Status
Reference Range
Laboratory Test
Hb
14.0 g/dl - 17.4 g/dl
–Males
12.3 g/dl - 15.3 g/dl
–Females
Hct
41.5% - 50.4%
–Males
36.0% - 45.0%
–Females
80 fL – 69 fL
MCV
27.5 pg/cell – 33.2 pg/cell
MCH
33.4 g/dl – 35.5 g/dl
MCHC
0.5% - 2.5%
Reticulocytes
Anaemia
9
Erythropoiesis
• The physiologic regulator of red cell (erythrocyte)
production is the glycoprotein hormone erythropoietin, of
which >90% is made in the kidney.
• The erythropoietin molecule interacts and binds to
specific receptors on the surface of marrow erythroid
progenitor cells, inducing them to proliferate and mature.
• The fundamental stimulus for erythropoietin production
is oxygen availability to the kidney.
Anaemia
10
Chronic Kidney Diseases
Anaemia
11
• Anemia is a common complication of
CKD, mainly due to the inability of the
kidneys to secrete enough
erythropoietin to stimulate adequate
hematopoiesis.
Anaemia
12
• One of the most common and chronic
hypoproliferative anemias of CKD.
• This is a hormone deficiency state, in which the
diseased kidney is incapable of meeting the
endogenous erythropoietin needs of the patient.
• As a result of erythropoietin deficiency, the
moderately shortened lifespan of the circulating red
cells, and the obligatory blood loss that accompanies
dialysis, CKD patients can experience profound,
debilitating anemia. Anaemia
13
Cardiovascular Disease
Anaemia
14
• Anemia is a common condition that may promote or
exacerbate cardiovascular disease (CVD).
• Low Hb and Hct values are associated with increased
CVD morbidity and mortality in patients with end-
stage renal disease and congestive heart failure
(CHF).
• Regression of left ventricular hypertrophy is possible
with correction of anemia.
Anaemia
15
• Anemia provokes a series of cardiovascular alterations
that may result in a compensatory increase in cardiac
output and blood flow in the short term. These initially
favorable adaptations, however, may lead to cardiac
structural changes, which could predispose to CVD over
time.
• Anemia has adverse effects on myocardial oxygenation
that result in the provocation or acceleration of angina,
and anemia may worsen congestive heart failure (CHF).
Anaemia
16
Diabetes
Anaemia
17
• Both diabetic nephropathy and neuropathy likely
contribute to the development of anemia in patients with
diabetes.
• Anemia often develops early in the course of chronic
kidney disease in patients with diabetes.
• It likely contributes to the high incidence of
cardiovascular disease observed in patients with diabetes.
• It is associated with an increased incidence of retinopathy
and macular edema.
Anaemia
18
• As diabetes progresses, the basement
membrane of the glomeruli thickens as a
result of glycosylation, leading to increased
intrarenal pressure.
• This damage ultimately results in chronic
kidney disease (CKD), decreased production
of erythropoietin, and anemia.
Diabetic Nephropathy and anemia
Anaemia
19
Cancer
Anaemia
20
• Because anemia is a common complication of cancer
and its treatment, all cancer patients should be
assessed for anemia.
• It causes debilitating symptoms, with fatigue being
the most prevalent.
• It may have an adverse effect on cancer outcomes.
• Erythropoietin therapy has been shown to decrease
transfusion requirements, improve quality of life, and
improve cancer treatment outcomes.
Anaemia
21
• Anemia related to the progression of cancer can
result from activation of the immune and
inflammatory systems, leading to an increased
release of cytokines, including tumor necrosis factor,
interferon-gamma, and interleukin-1.
• At least three mechanisms participate in the
cytokine-mediated failure of erythropoiesis:
1. Imparied iron utilization.
2. Suppression of erythroid progenitor cell differentiation.
3. Inadequate erythropoietin production.
• In addition:
4. The life span of red blood cells is shortened in cancer-related
anemia, and production of new cells cannot compensate for the
shortened survival time.
5. Bleeding due to systemic coagulopathy may also contribute to
anemia in these patients.
Anaemia
22
• Neoplastic process: chronic anemia of cancer
• Chemotherapy and radiation therapy
• Intercurrent infections
• Clonal disorders of hematopoiesis
• Gastrointestinal blood loss
• Autoimmune hemolysis
• Microangiopathy
• Excessive marrow fibrosis and displacement
• Iron, folate, vitamin B12 deficiency
• Renal impairment
Causes of Cancer-Related Anemia
Anaemia
23
• Approximately 75% of all cancer patients report symptoms
of fatigue, which can present as weakness, listlessness, low
energy, trouble starting and finishing tasks, and the need to
sleep during the day.
• While fatigue is the primary symptom of anemia in cancer
patients, anemia can also cause a range of other symptoms,
including palpitations, impaired cognitive function, nausea,
reduced skin temperature, impaired immune function,
dizziness, headache, chest pain, shortness of breath, and
depression.
Symptoms of Cancer-Related Anemia
Anaemia
24
• One of the ways anemia increases mortality is by
influencing treatment efficacy.
• It reduces response to radiation therapy because it
limits the oxygen-transporting capacity of the
blood and consequently tissue oxygenation.
• Thus anemia can contribute to tumor hypoxia,
which makes solid tumors resistant to sparsely
ionizing radiation and some forms of
chemotherapy.
Cancer-Related Anemia and
Decreased Treatment Efficacy
Anaemia
25
HIV/AIDS
Anaemia
26
• The disease can cause anemia by:
1. Influencing cytokine production and
suppressing hematopoiesis
2. Decreasing erythropoietin concentrations
3. Increasing the risk of opportunistic infection
with agents, such as Mycobacterium avium
complex and parvovirus B-19.
4. Immunosuppression.
Anaemia
27
• Less common mechanisms for HIV-
associated anemia include vitamin B12
deficiency and the autoimmune
destruction of red blood cells.
• Anemia has been associated with
progression to AIDS and shorter
survival times for HIV +ve patients.
Anaemia
28
Rheumatoid Arthritis
Anaemia
29
• Anemia is the most common extraarticular
manifestation of RA (30% to 60% of patients).
• The two primary types of anemia in RA:
1. Iron deficiency anemia.
2. Anemia of chronic disease.
• The most common causes of iron deficiency
anemia in RA are blood loss through menstrual
bleeding and/or gastrointestinal bleeding
secondary to nonsteroidal anti-inflammatory
drugs.
Anaemia
30
Inflammatory Bowel Disease
Anaemia
31
• Anemia affects many patients with
inflammatory bowel disease (IBD) as
ulcerative colitis and Chronis disease.
• Multiple factors contribute to anemia in
patients with IBD, including blood loss,
inadequate nutrient intake/absorption, and
the underlying inflammatory disease
process. Anaemia
32
Hepatitis C
Anaemia
33
• Hemolytic anemia is a major side effect
of ribavirin therapy in patients with
hepatitis C.
• Pernicious anemia may be induced in
patients with hepatitis C by long-term
interferon therapy.
Anaemia
34
Surgery
Anaemia
35
• One-third to one-half of surgical patients may be
anemic preoperatively because of conditions for
which they require surgery.
• Postoperative anemia may occur in up to 90% of
patients, probably due to a blunted erythropoietic
response.
• In surgical patients, anemia has been linked to
increased postoperative morbidity and mortality,
and decreased quality of life.
Anaemia
36
• Surgery patients may develop preoperative anemia
from acute or chronic blood loss (e.g., trauma or
peptic ulcer oozing), iron deficiency caused by poor
nutrition or menstrual bleeding, renal
insufficiency, malignancy, or chronic disease (e.g.,
rheumatoid arthritis or inflammatory bowel
disease).
• After surgery, the erythropoietic response may be
severely blunted in anemic patients because of
diminished iron availability and the inhibitory
actions of inflammatory cytokines.
• Reduced red cell life span and occult
gastrointestinal bleeding may also contribute to
anemia in surgical patients.
Anaemia
37
Treatment
Anaemia
38
A. Such patients have benefited greatly from the
availability of epoetin-alfa, (a recombinant human
erythropoietin).
• Epoetin has become widely accepted as an effective and
well-tolerated therapy administered two to three times per
week.
• It has been used successfully to manage the anemia of
patients with CKD or cancer-related anemia.
• 4 months of epoetin treatment increased the mean Hct and
decreased the left ventricular mass index in CKD patients
prior to ESRD. Anaemia
39
B. Recently, darbepoetin-alfa (noval
erythropoiesis stimulating protein, NESP), a
longer-acting erythropoietic agent than
epoetin, has been approved for the treatment
of patients with the anemia of CKD whether
on dialysis or not. Due to longer serum half-
life (25 hours vs. 8.5 hours), darbepoetin-alfa
should be administered less frequently than
epoetin-alfa.
Anaemia
40
C. Replacement therapy, whether it is iron or
epoetin, takes time to correct the anemia. Thus,
if the anemia is severe and the patient is
symptomatic, transfusion therapy with packed
red blood cells is an option.
• Correction of anemia to Hb levels of 11 g/dL to
12 g/dL may decrease morbidity and reduce
hospitalization and mortality.
Anaemia
41
Anaemia
42

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hidden anaemia.pdf

  • 3. • Anemia is defined as a reduction in the number of circulating red blood cells, the hemoglobin concentration, or the volume of packed red cells (hematocrit) in the blood. Anemia 3
  • 4. • Anemia is frequently under diagnosed and under treated as its signs and symptoms may be vague. • Frequently, anemia remains undetected because it is masked by symptoms of the diseases with which it is associated including: – Chronic kidney disease – Cardiovascular diseases – Diabetes mellitus – Cancer – HIV/AIDS – Rheumatoid arthritis – Inflammatory bowel disease – Hepatitis C – Surgery Anaemia 4
  • 5. • Because anemia affects the delivery of oxygen to all of the body’s organs, its signs and symptoms are varied. • It is generally accepted that symptoms of anemia adversely affect quality of life, even when anemia is mild. Anaemia 5
  • 6. Central nervous system •Debilitating fatigue •Depression •Impaired cognitive function Gastrointestinal system •Anorexia •Nausea Vascular system •Low skin temperature •Pallor of skin, mucous membranes, and conjunctivae Immune system •Impaired T-cell and macrophage function Cardiorespiratory system •Exertional dyspnea •Tachycardia, palpitations •Cardiac enlargement, hypertrophy •Increased pulse pressure, systolic ejection murmur •Risk of life-threatening cardiac failure Genital tract •Menstrual problems •Loss of libido Anaemia 6
  • 7. Reticulocyte Count • The reticulocyte count estimates the rate of red cell production • An elevated reticulocyte count generally indicates that the marrow is responding to endogenous erythropoietin stimulation • The reticulocyte count must be corrected for the degree of anemia in order to have a valid estimate of the rate of red cell production Anaemia 7
  • 8. Reticulocyte Count • A normal reticulocyte count in the presence of anemia suggests impaired erythropoietin production or an impaired response to erythropoietin by the erythroid marrow • An elevated reticulocyte count and slightly increased MCV suggest a hemolytic process. • An elevated MCV can reflect a very high reticulocyte production or a nuclear maturation defect (eg, vitamin B12 or folic acid deficiency). Anaemia 8
  • 9. Assessing Blood Status Reference Range Laboratory Test Hb 14.0 g/dl - 17.4 g/dl –Males 12.3 g/dl - 15.3 g/dl –Females Hct 41.5% - 50.4% –Males 36.0% - 45.0% –Females 80 fL – 69 fL MCV 27.5 pg/cell – 33.2 pg/cell MCH 33.4 g/dl – 35.5 g/dl MCHC 0.5% - 2.5% Reticulocytes Anaemia 9
  • 10. Erythropoiesis • The physiologic regulator of red cell (erythrocyte) production is the glycoprotein hormone erythropoietin, of which >90% is made in the kidney. • The erythropoietin molecule interacts and binds to specific receptors on the surface of marrow erythroid progenitor cells, inducing them to proliferate and mature. • The fundamental stimulus for erythropoietin production is oxygen availability to the kidney. Anaemia 10
  • 12. • Anemia is a common complication of CKD, mainly due to the inability of the kidneys to secrete enough erythropoietin to stimulate adequate hematopoiesis. Anaemia 12
  • 13. • One of the most common and chronic hypoproliferative anemias of CKD. • This is a hormone deficiency state, in which the diseased kidney is incapable of meeting the endogenous erythropoietin needs of the patient. • As a result of erythropoietin deficiency, the moderately shortened lifespan of the circulating red cells, and the obligatory blood loss that accompanies dialysis, CKD patients can experience profound, debilitating anemia. Anaemia 13
  • 15. • Anemia is a common condition that may promote or exacerbate cardiovascular disease (CVD). • Low Hb and Hct values are associated with increased CVD morbidity and mortality in patients with end- stage renal disease and congestive heart failure (CHF). • Regression of left ventricular hypertrophy is possible with correction of anemia. Anaemia 15
  • 16. • Anemia provokes a series of cardiovascular alterations that may result in a compensatory increase in cardiac output and blood flow in the short term. These initially favorable adaptations, however, may lead to cardiac structural changes, which could predispose to CVD over time. • Anemia has adverse effects on myocardial oxygenation that result in the provocation or acceleration of angina, and anemia may worsen congestive heart failure (CHF). Anaemia 16
  • 18. • Both diabetic nephropathy and neuropathy likely contribute to the development of anemia in patients with diabetes. • Anemia often develops early in the course of chronic kidney disease in patients with diabetes. • It likely contributes to the high incidence of cardiovascular disease observed in patients with diabetes. • It is associated with an increased incidence of retinopathy and macular edema. Anaemia 18
  • 19. • As diabetes progresses, the basement membrane of the glomeruli thickens as a result of glycosylation, leading to increased intrarenal pressure. • This damage ultimately results in chronic kidney disease (CKD), decreased production of erythropoietin, and anemia. Diabetic Nephropathy and anemia Anaemia 19
  • 21. • Because anemia is a common complication of cancer and its treatment, all cancer patients should be assessed for anemia. • It causes debilitating symptoms, with fatigue being the most prevalent. • It may have an adverse effect on cancer outcomes. • Erythropoietin therapy has been shown to decrease transfusion requirements, improve quality of life, and improve cancer treatment outcomes. Anaemia 21
  • 22. • Anemia related to the progression of cancer can result from activation of the immune and inflammatory systems, leading to an increased release of cytokines, including tumor necrosis factor, interferon-gamma, and interleukin-1. • At least three mechanisms participate in the cytokine-mediated failure of erythropoiesis: 1. Imparied iron utilization. 2. Suppression of erythroid progenitor cell differentiation. 3. Inadequate erythropoietin production. • In addition: 4. The life span of red blood cells is shortened in cancer-related anemia, and production of new cells cannot compensate for the shortened survival time. 5. Bleeding due to systemic coagulopathy may also contribute to anemia in these patients. Anaemia 22
  • 23. • Neoplastic process: chronic anemia of cancer • Chemotherapy and radiation therapy • Intercurrent infections • Clonal disorders of hematopoiesis • Gastrointestinal blood loss • Autoimmune hemolysis • Microangiopathy • Excessive marrow fibrosis and displacement • Iron, folate, vitamin B12 deficiency • Renal impairment Causes of Cancer-Related Anemia Anaemia 23
  • 24. • Approximately 75% of all cancer patients report symptoms of fatigue, which can present as weakness, listlessness, low energy, trouble starting and finishing tasks, and the need to sleep during the day. • While fatigue is the primary symptom of anemia in cancer patients, anemia can also cause a range of other symptoms, including palpitations, impaired cognitive function, nausea, reduced skin temperature, impaired immune function, dizziness, headache, chest pain, shortness of breath, and depression. Symptoms of Cancer-Related Anemia Anaemia 24
  • 25. • One of the ways anemia increases mortality is by influencing treatment efficacy. • It reduces response to radiation therapy because it limits the oxygen-transporting capacity of the blood and consequently tissue oxygenation. • Thus anemia can contribute to tumor hypoxia, which makes solid tumors resistant to sparsely ionizing radiation and some forms of chemotherapy. Cancer-Related Anemia and Decreased Treatment Efficacy Anaemia 25
  • 27. • The disease can cause anemia by: 1. Influencing cytokine production and suppressing hematopoiesis 2. Decreasing erythropoietin concentrations 3. Increasing the risk of opportunistic infection with agents, such as Mycobacterium avium complex and parvovirus B-19. 4. Immunosuppression. Anaemia 27
  • 28. • Less common mechanisms for HIV- associated anemia include vitamin B12 deficiency and the autoimmune destruction of red blood cells. • Anemia has been associated with progression to AIDS and shorter survival times for HIV +ve patients. Anaemia 28
  • 30. • Anemia is the most common extraarticular manifestation of RA (30% to 60% of patients). • The two primary types of anemia in RA: 1. Iron deficiency anemia. 2. Anemia of chronic disease. • The most common causes of iron deficiency anemia in RA are blood loss through menstrual bleeding and/or gastrointestinal bleeding secondary to nonsteroidal anti-inflammatory drugs. Anaemia 30
  • 32. • Anemia affects many patients with inflammatory bowel disease (IBD) as ulcerative colitis and Chronis disease. • Multiple factors contribute to anemia in patients with IBD, including blood loss, inadequate nutrient intake/absorption, and the underlying inflammatory disease process. Anaemia 32
  • 34. • Hemolytic anemia is a major side effect of ribavirin therapy in patients with hepatitis C. • Pernicious anemia may be induced in patients with hepatitis C by long-term interferon therapy. Anaemia 34
  • 36. • One-third to one-half of surgical patients may be anemic preoperatively because of conditions for which they require surgery. • Postoperative anemia may occur in up to 90% of patients, probably due to a blunted erythropoietic response. • In surgical patients, anemia has been linked to increased postoperative morbidity and mortality, and decreased quality of life. Anaemia 36
  • 37. • Surgery patients may develop preoperative anemia from acute or chronic blood loss (e.g., trauma or peptic ulcer oozing), iron deficiency caused by poor nutrition or menstrual bleeding, renal insufficiency, malignancy, or chronic disease (e.g., rheumatoid arthritis or inflammatory bowel disease). • After surgery, the erythropoietic response may be severely blunted in anemic patients because of diminished iron availability and the inhibitory actions of inflammatory cytokines. • Reduced red cell life span and occult gastrointestinal bleeding may also contribute to anemia in surgical patients. Anaemia 37
  • 39. A. Such patients have benefited greatly from the availability of epoetin-alfa, (a recombinant human erythropoietin). • Epoetin has become widely accepted as an effective and well-tolerated therapy administered two to three times per week. • It has been used successfully to manage the anemia of patients with CKD or cancer-related anemia. • 4 months of epoetin treatment increased the mean Hct and decreased the left ventricular mass index in CKD patients prior to ESRD. Anaemia 39
  • 40. B. Recently, darbepoetin-alfa (noval erythropoiesis stimulating protein, NESP), a longer-acting erythropoietic agent than epoetin, has been approved for the treatment of patients with the anemia of CKD whether on dialysis or not. Due to longer serum half- life (25 hours vs. 8.5 hours), darbepoetin-alfa should be administered less frequently than epoetin-alfa. Anaemia 40
  • 41. C. Replacement therapy, whether it is iron or epoetin, takes time to correct the anemia. Thus, if the anemia is severe and the patient is symptomatic, transfusion therapy with packed red blood cells is an option. • Correction of anemia to Hb levels of 11 g/dL to 12 g/dL may decrease morbidity and reduce hospitalization and mortality. Anaemia 41