• Anaemia

    by  • 15/10/2013 • Haematology

    Definition:  is decreased RBCs, or decreased quantity Hb.

     

    Also, reduced quality of Hb can also be classed as anaemia (with reduced 02 binding properties).

     

    The three main classes of anemia include excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss), excessive blood cell destruction (hemolysis) or deficient red blood cell production (ineffective hematopoiesis).

     

    Classification / type of disease:

    • Aplastic and hypoplastic anaemias0

    • Nutritional anaemias = Iron deficiency and B12/folate deficiency

    • Common haemolytic anaemias (especially sickle cell and thalassaemias)

    • Autoimmune haemolytic anaemias

    • Anaemias of chronic disease (chronic renal failure).

     

    Epidemiology:Anemia is the most common disorder of the blood

    Presenting symptoms / signs:

    Anemia 300x286 Anaemia

     

     

    • There may be signs of specific causes of anemia, e.g., koilonychia (in iron deficiency), jaundice (hemolytic anemia), bone deformities (thalassaemia major) or leg ulcers (sickle cell disease).

     

    • Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants

     

    • Iron deficient anaemics = more likely to have restless leg syndrome.

     

    Diagnostic investigations: In modern FBC counters, four parameters (RBC count, hemoglobin concentration, Mean Corpuscular Volume and Red Blood Cell Distribution Width) are measured, allowing others (hematocrit,  Mean Corpuscular Hb and Mean Corpuscular Hb Concentration) to be calculated, and compared to values adjusted for age and sex.

     

    WHO’s Hemoglobin thresholds used to define anemia

    Age or gender group & Hb threshold (g/dl) =

    • Children (0.5–5.0 yrs) =11.0
    • Children (5–12 yrs) =11.5
    • Teens (12–15 yrs) =12.0
    • Women, non-pregnant (>15yrs) =12.0
    • Women, pregnant =11.0
    • Men (>15yrs) =13.0

     

    I.e. 11-13g/dl

     

    Diagnostic approaches:

    • A reticulocyte count, or a ‘kinetic’ measure, is a quantitative measure of the bone marrow‘s production of new red blood cells.

     

    • The reticulocyte production index is a calculation of the ratio between the level of anemia and the extent to which the reticulocyte count has risen in response.

     

    • If the degree of anemia is significant, even a “normal” reticulocyte count actually may reflect an inadequate response.

     

    • Reticulocytes = are usually slightly larger than older RBCs and show polychromasia.

     

     

    Classifying the cause of anaemia = “kinetic approach”.

    This classification depends on evaluation of several hematological parameters, particularly the blood reticulocyte count.

    Clinical signs of increased loss or destruction = abnormal peripheral blood smear with signs of hemolysis; elevated LDH suggesting cell destruction; or clinical signs of bleeding, such as guiaic-positive stool, radiographic findings, or frank bleeding. As shown below:

     

    Anemia

    Reticulocyte production index shows inadequate production response to anemia.

    Reticulocyte production index shows appropriate response to anemia = ongoing hemolysis or blood loss without RBC production problem.

       

     

       

       

    No clinical findings consistent with hemolysis or blood loss: pure disorder of production.

    Clinical findings and abnormal MCV: hemolysis or loss and chronic disorder of production

    Clinical findings and normal MCV= acute hemolysis or loss without adequate time for bone marrow production to compensate

                       

                     

    Macrocytic anemia (MCV>100)

    Normocytic anemia (80<MCV<100)

    Microcytic anemia (MCV<80)

       

     

     

     

    Morphological approach”, = classified by the size of red blood cells; this is either done automatically or on microscopic examination of a peripheral blood smear.

    The size is reflected in the mean corpuscular volume (MCV). If the cells are < 80 fl = microcytic; normal size = 80–100 fl = normocytic; >100 fl = macrocytic.

    Here is a schematic representation of how to consider anemia with MCV as the starting point:

     

     

    Anemia

    Macrocytic anemia (MCV>100)

    Normocytic anemia (MCV 80–100)

    Microcytic anemia (MCV<80)

       

     

    High reticulocyte count

    Low reticulocyte count

       

     

     

     

    Aetiology:

    Microcytic (primarily a result of hemoglobin synthesis failure/insufficiency) = 

    • heme synthesis defect (iron deficiency*)
    • globin synthesis defect (thalassemia, HbC & HbE syndromes)
    • sideroblastic defect (hereditary, acquired, reversible).
    • *Iron deficiency: most common type of anemia overall and it has many causes. RBCs often appear hypochromic and microcytic when viewed with a microscope. Causes = reduced iron intake (vegan), increased phsiological losses (menstruation/menopause), increased pathological losses (GI malignancy). Seen in LEDCs = parasitic infestation (hookworm, amebiasis, schistosomiasis and whipworm)

    Normocytic = Normocytic anemia occurs when the overall hemoglobin levels are always decreased, but the red blood cell size (MVC) remains normal. Causes include:

    Macrocytic = Megaloblastic anemia, the most common cause of macrocytic anemia, is due to a deficiency of either vitamin B12, folic acid (or both). Deficiency due to inadequate intake or insufficient absorption. B12 deficiency = neuro symptoms.

    • Macrocytic anaemia can be due to pernicious anaemia (=an autoimmune condition targeting the parietal cells [atrophic gastritis] = reduced intrinsic factor production = reduced B12 abs in terminal ileum).
    • Also occurs following gastirc bypass = removal of the functional portion of the stomach.
    • Other causes:
    • methotrexate
    • zidovudine (and other drugs that inhibit DNA replication).
    • “Megaloblastic macrocytic anemia” = failure of DNA synthesis with preserved RNA synthesis, which result in restricted cell division of the progenitor cells.
    • Non-megaloblastic macrocytic anaemia” = various etiologies (i.e. there is unimpaired DNA globin synthesis,)

     

    Dimorphic:When two causes of anemia act simultaneously. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), which suggests a wider-than-normal range of red cell sizes.

     

    Heinz bodies anaemia: HBs form in the cytoplasm of RBCs and appear like small dark dots under the microscope. There are many causes of Heinz body anemia, and some forms can be drug induced

     

    Pathophysiology

     

    *** Impaired production

    • Disturbance of proliferation and differentiation of stem cells = aplastic, renal, endocine…
    • Disturbance of proliferation and maturation of erythroblasts = pernicious anaemia, folate deficiency, iron deficiency, thalassemia, renal failure.

    *** Increased destruction (haemolytic anaemia) = jaundice, elevated LDH,

    Intrinsic (intracorpuscular) abnormalities,where there the red blood cells have defects that cause premature destruction.

    Extrinsic (extracorpuscular) abnormalities

     

    *** Blood loss

    • Anemia of prematurity from frequent blood sampling for laboratory testing, combined with insufficient RBC production.
    • Trauma / surgery
    • Gastrointestinal tract lesions
    • Gynecologic disturbances

    Fluid overload = causes decreased hemoglobin concentration and apparent anemia

     

    Transmission

    Treatment / management:

    • Iron deficiency – find sources of loss such as gastrointestinal bleeding from ulcers or colon cancer. Tx = ferrous sulfate, ferrous fumarate, or ferrous gluconate (s/e’s: stomach upset and/or darkening of the feces). Vitamin C aids in the body’s ability to absorb iron when taken with food – so taking oral iron supplements with orange juice is of benefit.
    • Vitamin supplements given orally (folic acid) or subcutaneously (vitamin B-12) will replace specific deficiencies.
    • In anemia of chronic disease, anemia associated with chemotherapy, or anemia associated with renal disease, some clinicians prescribe recombinant erythropoietin, epoetin alfa, to stimulate red cell production.
    • In severe cases of anemia, or with ongoing blood loss, a blood transfusion may be necessary (but these are generally avoided due to risk of reaction / infection).

     

    Differentials

     

    Prognosis:

     

    Classification / type of disease:

    • Aplastic and hypoplastic anaemias

    • Nutritional anaemias = Iron deficiency and B12/folate deficiency

    • Common haemolytic anaemias (especially sickle cell and thalassaemias)

    • Autoimmune haemolytic anaemias

    • Anaemias of chronic disease (chronic renal failure).

     

    A bit about each…

     

    Aplastic anaemia = aplastic anemia patients have lower counts of all three blood cell types: red blood cells (anaemia), white blood cells (leukopaenia/neutrapenia), and platelets (thrombocytopaenia) = pancytopenia.

    Causes: Often idiopathic, autoimmune, drug induced (chloramphenicol, carbamazepine, felbamate, phenytoin, quinine, andphenylbutazone), benzene exposure, viral hepatitis,

    Diagnosis: Use regular tests to look for anaemia – the diagnosis can only be confirmed on bone marrow examination.

    Treatment: immune-mediated aplastic anemia involves suppression of the immune system, or more severe cases = bone marrow transplant, a potential cure.Medical therapy includes a short course of anti-thymocyte globulin (ATG) or anti-lymphocyte globulin (ALG) and several months of treatment with ciclosporin to modulate the immune system. Mild chemotherapy (cyclophosphamide and vincristine). 

    Prognosis: untreated = fatal in 6-9/12. Well-matched bone marrow transplants from siblings have been successful in young, otherwise healthy people, with a long-term survival rate of 80%-90%

     

    Hypoplastic anaemia: anemia resulting from inadequately functioning bone marrow; can develop into aplastic anemia – A precursor state of aplastic anaemia.

     

    Nutritional anaemias = Iron deficiency and B12/folate deficiency:

    Microcytic anaemia: Iron deficiency: most common type of anemia overall.

    Cytology = RBCs often appear hypochromic and microcytic when viewed with a microscope.

    Causes = reduced iron intake (vegan), increased phsiological losses (menstruation/menopause), increased pathological losses (GI malignancy). Seen in LEDCs = parasitic infestation (hookworm, amebiasis, schistosomiasis and whipworm)

    Macrocytic anaemia can be due to pernicious anaemia (=an autoimmune condition targeting the parietal cells [atrophic gastritis] = reduced intrinsic factor production = reduced B12 abs in terminal ileum).

    Tx: ferrous sulphate, EPO, transfusion if indicated.

     

    SCA: a genetic disease causing sickle shape changes to RBCs – which leads to crisis and acute admission.

    Epidemiology:In the UK =~10,000. More common in African, African-Caribbean, Asian or Mediterranean people. On average, 1 in 2,400 babies born in England have SCA.

    Aetiology: mutation of hydrophillic glutamic acidhydrophobic valine in position 6 on C11. This is an autosomal recessive mutation.

    Pathophysiology: The sickle cells are harder and less flexible than normal red blood cells. So, they can get stuck in small blood vessels and block them. This can happen quite suddenly, and causes various symptoms which are known as a ‘sickle cell crisis’ = acute chest syndrome, acute episodes of pain, infections, anaemia episodes, plus symptoms of anaemia (tired, faint, SOB, pallor, palpitations, HSM, generally unwell).

    Also will have a persistent anaemia as reduced functional RBCs (whcih are destroyed in spleen due to their mis-shape).

    Diagnosis: RBC electrophoresis

    p/c: Symptoms usually begin at around age 3-6 months

    Tx: cure = BM transplant. Tx options: access to specialist care, stay healthy with prophylaxic Abs, avoid factors which cause sickling episodes, use painkillers, hydrate, fight infection, blood transfusions, hydroxyurea…

    Prognosis: Life expectancy is shortened, with studies reporting an average life expectancy of 42 in males and 48 in females. Will increase as tx improves.

    Complications: growth, development, stroke or brain injury, spleen problems, parvovirus infection, lungs, heart, kidneys, eyes, priaprism, gallstones, leg ulcers.

     

    Thalassemia: autosomal recessiveblood disease which cause a reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin = anaemia

    NB: SCA = qualative problem, thalassemia = quantative problem. The thalassemia trait may confer a degree of protection against malaria (due to the RBCs easy degradation)

    Classification: The thalassemias are classified according to which chain of the hemoglobin molecule is affected. In α thalassemias, production of the α globin chain is affected, while in β thalassemia production of the β globin chain is affected. β globin chains are encoded by a single gene on chromosome 11; α globin chains are encoded by two closely linked genes on chromosome 16.

    Types of disease: alpha, beta, delta.

    Tx: chronic blood transfusion therapy, iron chelation with deferoxamine, splenectomy, and allogeneic hematopoietic transplantation. Possible cure = stem cell transplant.

     

    Autoimmune haemolytic anaemias (AIHA): where the persons immune system attacks their own RBCs

    Types of AIHA:Warm autoimmune hemolytic anemia, Cold agglutinin disease, and Paroxysmal cold hemoglobinuria.

    Classified:Intravascular haemolysis: Red blood cell lysis occurs in the circulation as a result of activation of the complement system cascade. Extravascular haemolysis: Red blood cells that are coated with antibodies are specifically recognized in the reticuloendothelial system and destroyed by macrophages.

    Pathophysiology:Antibodies and associated complement system components become fixed onto the RBC surface. These antibodies can be detected with the direct antiglobulin test (=direct Coombs test). AIHA can also be induced by several drugs including methyldopa and fludarabine, and also by some disease conditions including Mycoplasma pneumoniae and infectious mononucleosis.

     

    Anaemia linked to chronic renal disease: normochromic normocytic anaemia mainly develops from decreased renal synthesis of erythropoietin. The anaemia becomes more severe as the GFR (glomerular filtration rate) progressively decreases. No reticulocyte response occurs, red blood cell survival is decreased, and there is an associated increased bleeding tendency due to uraemia-induced platelet dysfunction.

    Iron deficiency is also common in patients with chronic renal disease = hypochromic microcytic anaemia

    Investigations: assessment of the degree and cause of anaemia, assessment of renal function, assessment of any cardiovascular complications of anaemia and chronic renal disease, and identifying any other co-existent complications of chronic renal disease.

    Treatment with recombinant human erythropoietin in pre-dialysis patients corrects anaemia, avoids the requirement for blood transfusions and also improves quality of life and exercise capacity

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