Who classification of anemia on the basis of blood hemoglobin level WHO 2011

3.2 Anemia: Morphological and Etiological Classification

Hemoglobin level is highest at birth, ranging from 16 to 20 g/dL, and then declines, with the lowest hemoglobin level observed at 3–6 months, when values of 9–11 g/dL are considered normal. Men have slightly higher levels of hemoglobin, and this is thought to be due to the stimulatory effect of androgens on the bone marrow. The WHO definitions of hemoglobin less than 12 g/dL in nonpregnant women 15 years of age or older, less than 11 g/dL in pregnant woman, and less than 13 g/dL in men 15 years of age or older are widely used for diagnosis of anemia worldwide. Anemia can be classified on the basis of morphology and etiology. Morphological classification of anemia includes the following:

Normocytic normochromic

Microcytic hypochromic

Macrocytic.

Etiologic classification of anemia includes the following:

Anemia due to blood loss

Anemia due to deficiency of hematopoietic factors

Anemia due to bone marrow failure

Anemia due to increased red cell breakdown.

Examples of etiological classification of anemia are listed in Table 3.1.

Table 3.1. Etiological Examples of Anemia

Etiological CauseSpecific ExamplesAnemia due to blood lossGastrointestinal blood loss, menorrhagiaAnemia due to deficiency of hematopoietic factorsIron deficiency, folate deficiency, vitamin B12 deficiency, erythropoietin deficiencyAnemia due to bone marrow failureAplastic anemia, bone marrow infiltration (e.g., metastatic cancer, bone marrow fibrosis), myelodysplasia, bone marrow toxicity (alcohol abuse, chemotherapy)Anemia due to increased red cell breakdownInherited or acquired defects (see Box 3.1)

Treatment of Cancer-Related Anemia

Hemoglobin levels typically decrease early in the course of chemotherapy treatment; with greater than half of patients experience a greater than 1 g/dL drop over the course of the first 9 weeks of therapy. The treatment of anemia related to malignancy depends upon correct identification of the underlying etiology. As noted previously, iron-deficiency anemia is very common in patients with malignancy. Among those patients with cancer who have an absolute iron deficiency (transferrin saturation <20%, ferritin <30 ng/mL), there is evidence that they may benefit from a short course of either oral or low-dose intravenous iron. In this setting, the addition of erythropoiesis stimulating agents (ESAs) is not necessary.

For many patients, transfusion of blood products is an effective therapeutic intervention. Red cell transfusion provides rapid symptomatic relief and is also a source of iron; one unit of packed red blood cells (RBCs) contains roughly 200 mg of iron. Logistic limitations with RBC transfusion, and transfusion-related morbidities have spurred the incorporation of ESAs as alternative agents for treating anemia in cancer patients. The use of ESAs during myelosuppressive treatment increases the hemoglobin level and decreases transfusion requirements by approximately 50%; however, ESA use is associated with an increased rate of cardiovascular and thrombotic events, and may be associated with poorer overall survival and time to cancer progression. This relationship between ESA use and thrombosis may be related to the target hemoglobin concentration as higher hemoglobin targets are associated with increased rates of thrombotic events in cancer patients.

In addition to thrombotic events, a number of concerns have been raised about ESA use and potential worsening of overall survival or time to disease progression. Data regarding ESAs and progression of disease are conflicting; some studies in patients with breast cancer and patients with head and neck cancer suggested worsening progression-free survival or local control of disease with ESA use. The mechanism behind tumor progression is unknown but may relate to decreased chemosensitivity in the setting of ESA use or relate to tumor vascularity and oxygen supply. One study isolated breast cancer stem-like cells, which are thought to promote tumor progression and relapse, and identified expression of the EPO receptor on the cell surface of these chemoresistant cells. Moreover, the concurrent administration of ESAs during chemotherapy had a chemoprotective effect. Other mechanisms that may underlie the association of EPO administration with tumor progression include augmentation of red cell mass and effects on tumor oxygenation.

Because of concerns about thrombotic events, as well as the potential for worsened overall survival and time to disease progression, ESA use is generally restricted to certain indications in patients with cancer. In general, transfusion of blood products and, if indicated, iron therapy, remain the standard of care for anemia associated with malignancy. Future studies considering the safety of ESAs for lower target hemoglobin levels, as well as alternative preparations of iron therapy may provide viable treatment options for cancer patients with anemia. There are some instances where ESAs may be useful adjuncts, specifically among patients with moderate or severe chronic kidney disease, or in palliative settings. In such situations, reversible causes of anemia should be ruled out before ESA use, and the minimal amount of EPO be used to avoid RBC transfusion.

Laboratory studies

Serum bicarbonate and hemoglobin can be helpful and diurnal arterial blood gas (ABG) can be diagnostic of hypoventilation, but diurnal hypercapnia is a late finding. Serum bicarbonate level rises in response to hypoventilation and elevated levels may indicate sleep hypoventilation even if the awake partial pressure of carbon dioxide (PaCO2) is within normal range (Böing and Randerath, 2015). Although there is no bicarbonate level that is diagnostic of hypoventilation in RTD, a level of 27 mEq/L has a sensitivity of 92% and specificity of 50% in obesity hypoventilation syndrome (another syndrome defined by daytime hypercapnia) (Mokhlesi and Tulaimat, 2007). ABG is the gold standard to establish a diagnosis of daytime hypoventilation, but it is not enough to screen for sleep-related hypoventilation as sleep-related hypoventilation precedes daytime hypercapnia (Ragette et al., 2002; Hillman et al., 2014; Ward et al., 2005; Paiva et al., 2009). In patients with uncomplicated myopathy, hypercapnia was found to be most likely when vital capacity was less than 55% of the predicted value and when respiratory muscle strength was less than 30% of normal value (Braun et al., 1983). One study found that daytime PaCO2 > 40 mmHg and inspiratory vital capacity <40% in progressive RTD was predictive of nocturnal hypoventilation while another showed that PaCO2 ≥ 45 mmHg (particularly with base excess ≥4 mmol/L) was predictive of nocturnal hypoventilation requiring noninvasive positive pressure ventilation (NIPPV) (Hukins and Hillman, 2000; Mellies et al., 2003). During sleep, an average increase in PaCO2 of 20 mmHg (compared to wake) may be seen in RTD (Aboussouan, 2015). Polycythemia, may indicate significant hypoxemia and is a late finding (Mellies et al., 2003).

HemoCue blood haemoglobin system

HemoCue Blood Haemoglobin System (see Chapter 3) is a battery- or mains-operated portable, direct read-out machine that uses disposable dry chemistry cuvettes. Measurements are precise and accurate but only if specified cuvettes are used, the reading surfaces are kept clean and the cuvettes are properly filled with blood. Unlike most other systems, measurement does not require predilution of the sample. Although the use of unique disposable cuvettes makes this method relatively expensive, the cuvettes for the new Hb 301 version are generally cheaper than those for the Hb 201 and are designed for adverse climatic conditions. HemoCue is fast and simple to use so some costs may be offset by savings on training and supervision time. Disadvantages also include need for an effective supply chain to ensure availability of cuvettes and waste management of used cuvettes. In addition, Hb 310 is not suitable for EQA using haemoglobin lysate.

Iron Deficiency Anemia

When hemoglobin levels and the hematocrit begin to decrease, iron deficiency anemia is present. There are a number of conditions that mimic iron deficiency anemia, such as anemia of chronic disease, lead poisoning, thalassemia minor, or other mild hereditary anemias. These other conditions need to be considered and excluded. The WHO recently recommended using hemoglobin, ferritin, and transferrin receptor levels to identify iron deficiency anemia, and hemoglobin, ferritin, and C-reactive protein to monitor anemia.123

Comparison of the NHANES III and the present NHANES data suggests that the prevalence of iron deficiency and iron deficiency anemia have decreased. National data place the prevalence of iron deficiency at 9% and iron deficiency anemia at 3% of toddlers.124 Looking at disadvantaged areas, the prevalence is reported to be as high as 24% for iron deficiency and 11% for iron deficiency anemia.125 Presently, two types of screening programs are recommended: universal and selective screening. Universal screening at 9 to 12 and 15 to 18 months of age is used in communities with a high incidence of iron deficiency. In communities where iron deficiency is not common, selective screening uses the same schedule, but screens only children thought to be at risk. At-risk children include preterm babies, those with a low birth weight, those not receiving iron-fortified formula, and breast-fed children over the age of 6 months not consuming a diet with adequate iron. Confirmation of a positive screen with a second test will eliminate most false positives.126

There are a number of possible approaches to dealing with the problem of iron deficiency in the toddler years: selective treatment, universal supplementation, and food fortification. At present, selective treatment based on the screening programs outlined above is recommended. Oral supplementation (3 to 6 mg/kg daily of elemental iron) is given for 4 weeks, and hemoglobin and hematocrit are then remeasured. An appropriate rise in the hemoglobin concentration (1 g/dL) confirms iron deficiency anemia. An insufficient rise should trigger further investigations, including adherence, blood loss, hemoglobinopathy, and lead poisoning. This selective treatment approach is certain to miss a proportion of children with iron deficiency and iron deficiency anemia. In view of the long-term sequelae associated with iron deficiency, including behavioral and developmental changes, we may want to consider another approach.

WHO anemia classification based on hemoglobin?

What are the 3 major classifications of anemia?

WHO criteria for anemia severity?

WHO anaemia definitions?