Anemia

Diagnosed when hematocrit or hemoglobin decreased 2 SD below the mean.

Anemia of any causes present in approximately 6% of the US population.

The most common hematologic disorder seen in general medical practice.

Affects approximately one third of the world’ population.

Anemia increases with age and incidence is increased in racial minority populations.

Half the cases of worldwide anemia are due to iron deficiency.

Classification system is based on the mean corpuscular volume (MCV).

Microcytic (MCV <80 fL).

Normocytic (MCV 80-100 fL)

Macrocytic (MCV >100 fL)

Additionally subclassified according to the reticulocyte count as: Hyperproliferative (reticulocyte count >2%), and hypoproliferative (reticulocyte count <2%).

Morphological subcategories includes:

Megaloblastic: a deficiency of DNA production or maturation resulting in the appearance of large immature RBCs (megaloblasts) and hypersegmented neutrophils in the circulation.

Nonmegaloblastic: encompasses all other causes of macrocytic anemia in which DNA synthesis is normal.

Defined as a hemoglobin of less than 13.0 g/dL in males and 12.0 g/dL in women.

Characterized by reduction in hemoglobin concentration, red blood cell count, or packed volume, and subsequent impairment of meeting oxygen demand of tissues.

Risk factors include extremes of age, female gender, lactation, and pregnancy.

Age, sex, and pregnancy status, environmental factors such as smoking and altitude affect hemoglobin concentration.

Classification scales: NCI, WHO

 

1-mild                Hgb 10-normal                9.5-10.9
2-moderate                 8-10                    8-9.4
3-severe                   6.5-7.9                 6.5-7.9
4-life-threatening         <6.5                     <6.5

Prevalence higher in elderly African-American men and women compared to Caucasian men and women.

Affects 1.6 2 billion people globally (WHO).

Prevalence estimated at 9% in countries with high development and 43% in countries with low development (WHO).

Children and women of reproductive age are most at risk, with global anemia prevalence estimated to be 47% in children younger than five years, 42% in pregnant women, and 30% in non-pregnant women aged 15-49 years (WHO).

Contributes to more than 115,000 maternal deaths and 591,000 perinatal deaths globally each year (WHO).

Contributes to loss of productivity, cognitive impairment, and increased risk to infection.

Rate at which anemia develops is often as important as its severity, as a rapid decline can overwhelm the compensatory mechanisms.

Causes full into three major categories-blood loss, impaired of red blood cell production, and accelerated raid cell destruction.

It may be a sign of an underlying disorder.

Can negatively affect physical performance, particularly work productivity as a result of reduced oxygen transport and reduced celluliular oxidative capacity.

There is a positive association in older people between anemia iand cognitive decline and incidence of dementia.

Dilutional anemia may be associated with normal or increased total red cell mass in pregnancy, macroglobulinemia and splenomegaly.

In the elderly associated with significant morbidity including falls, decreased physical performance, impaired cognitive status, increased hospitalizations and increased mortality.

Leads to tissue hypoxia, including CNS hypoxia and or cardiac remodeling that may contribute to physical and cognitive impairments.

Hemoglobin the pref2242ed marker of anemia since is correlates directly with the oxygen-carrying capacity of blood.

Cancer patients with anemia have a median survival that is reduced by 20-43% compared to non-anemic cancer patients.

Up to 75% of cancer patients have cancer associated anemia.

Cancer associated anemia resembles anemia of chronic disease, which may blunted erythropoietin response and an adequate erythropoietin production.

Approximately 24% of people over 65 years of age have anemia.

Associated with increased deficits in cognition in the elderly.

77% of patients admitted to the ICU develop anemia during their stay.

Common complication of malignancies, infections, inflammatory states and traumatic injuries.

Iron deficiency is the most common cause.

A risk factor for cardiovascular disease.

Anemia is an independent predictor of adverse outcomes in acute coronary syndromes.

Low hemoglobin levels and anemia independently predict higher mortality after percutaneous coronary intervention or coronary artery bypass graft surgery.

Hemolytic anemias are associated with increased destruction of RBCs with a resultant increase in circulating indirect bilirubin.

Microangiopathic hemolytic anemias produce a hyperproliferative normocytic anemia, with underlying disease process producing endothelial damage and activation of the coagulation cascade, leading to fibrin deposition on damaged endothelial surfaces.

In small vessels, the endothelial fibrin causes mechanical fragmentation and shearing of RBCs, leading to hemolysis. The irregular-shaped RBC fragments produced by this process are called schistocytes and can be seen on a peripheral blood smear.

Suppresses hepcidin production.

Tissue hypoxia can regulate hepcidin at the cellular level and a similar mechanism regulates the production of EPO.

In CHF a interaction between cardiac performance, activation of neurohormonal and inflammatory effects, renal dysfunction, adverse effects of drugs, and impaired bone marrow response contribute to the development of anemia.

Anemia of congestive heart failure associated with increased erythropoietin level in proportion to the severity of heart failure, but not to the degree of the severity of the anemia, suggesting the erythropoietin response is blunted in CHF.

Three most common causes are nutritional (iron, B12 or folate), anemia of chronic illness and neoplasms.

Symptoms most commonly fatigue, lightheadedness and dyspnea.

When severe can lead the high-output cardiac failure.

Associated with higher rates of cardiovascular disease and renal events.

Signs of anemia include pallor of the conjuntivae, palmar crease and nailbeds

Associated with cancer may cause tissue hypoxia which may facilitate tumor clone growth with a more malignant phenotype, may activate oncogene expression and stimulate the production of angiogenesis.

May foster increasing aggressiveness of a malignancy and reduce sensitivity to radiation and chemotherapy.

Anemia associated with cancer approaches a prevalence of 50% and in certain malignancies and those undergoing chemotherapy or radiation it may be a high as 90%.

Stresses cardiovascular system leading to tachycardia and increased cardiac output to compensate for reduced oxygen carrying capacity and vasodilation induced by vasoactive substances released in response to hypoxia.

Physiologic changes during anemia include increased blood flow, as blood viscosity decreases, and increased oxygen offloading in hypoxic tissues as the concentration of 2,3-diphosphoglycerate increases in the red cells, and overall blood volume is maintained with increased plasma volume.

In long-standing anemia left ventricular dilation and left ventricle hypertrophy occur.

Increased cardiac work load that accompanies anemia causes fatigue and tiredness.

With anemia cardiac output increases to maintain adequate perfusion.

Reduced oxygen delivery to tissues contributes the fatigue that patients with anemia experience.

Circulating levels of proinflammatory cytokines such as tumor necrosis factor alpha, interleukin-1, interleukin-6, and CRP are inversely related to hemoglobin (Anand IS).

IL-6 and TNF-alpha inhibit renal erythropoietin production and also inhibit bone marrow erythroid cells (Anand IS).

Hypoxia effects the CNS leading to depression, dizziness, headache, fatigue, impaired cognition and insomnia.

In severe anemia forceful apical tachycardia, prominent peripheral pulses and systolic murmurs may be heard over the heart and carotid arteries.

May lead to reduced renal circulation with fluid retention and peripheral edema.

In a study involving 4038 patients with diabetes, chronic kidney disease, and anemia were randomly assigned to darbepoetin to achieve a hemoglobin of approximately 13 g per deciliter compared to placebo and darbepoetin rescue when the hemoglobin was less than 9 g per deciliter: the use of darbepoetin for diabetic patients with chronic kidney disease and moderate anemia, who were not undergoing dialysis did not reduce death, or cardiovascular events, or renal events and was associated with an increased risk of stroke(Trial to Reduce Cardiovascular Events with Aranesp Therapy [TREAT}.

In severe anemia congestive heart failure and pulmonary edema may occur.

Preoperative anemia is associated with increased morbidity and mortality in patients undergoing cardiac surgery.

Preoperative anemia, even to a mild degree, is associated with increased 30 day morbidity and mortality in patients undergoing non–cardiac surgery (Mussalam KM et al).

In severe disease retinal hemorrhage can occur as a complication of hyperdynamic retinal circulation and tissue hypoxia.