Anemia is defined based only on the hemoglobin. In his absence, hematocrit could replace but hemoglobin is the best criterion.
There anemia if hemoglobin is:
– <13 g / dL in men;
– <12 g / dL in women and children;
– <10.5 g / dL in pregnant women over 3 months.
We must focus initially on the mean corpuscular volume (MCV) and reticulocyte count, should be asked immediately if there are no microcytosis.
Types of anemia:
We can distinguish four immediately anemia groups that each have their own causes.
Regenerative anemias (reticulocytes 150,000 / mm3):
They may be due to a peripheral hyperdestruction red blood cells (hyperhemolysis), acute hemorrhage, or repair of a previous deficit of erythrocyte production because the high reticulocyte count shows that the marrow is working.
Microcytic anemia (MCV ≤ 80 μ3)
They are due to hemoglobin synthesis failure for whatever cause. Indeed, microcytic character shows that there has been too much in the erythroid mitosis (and each small cell size) because the concentration of hemoglobin had not reached the threshold that stops them. Most of the time these are aregenerative anemia (low levels of reticulocytes) because the spinal cord production decreased.
Note that a microcytic anemia is sometimes Regenerative: This case is rare.
Macrocytic anemia aregenerative (MCV ≥ 98 μ3, reticulocytes 100,000 / mm3):
They always have a central origin, showing low reticulocyte production failure.
The high MCV also reflects a slowdown in mitosis erythroblasts, corresponding to particular causes.
Normocytic anemia aregenerative (reticulocytes <100,000 / mm3 and VGM between 80 and 98 μ3)
They are also of central origin and due to disorders of the production related to other causes than the two previous groups.
However hemodilution creates pseudoanémie which has identical characteristics.
Before undertaking the etiological investigation must remember a few rules (Box 1).
Box 1. What to do initial
Before embarking on the exploration of anemia, it must be ensured that the other lines are normal because the behavior would be different if there was bicytopenia, pancytopenia or anemia with leukocytosis made of lymphocytes, a myelemia or with the presence of abnormal cells in the blood.
Hospital without delay:
– Poorly tolerated anemia
– Anemia Quick Installation
Never treat anemia without diagnosis!
In case of emergency transfusion, do blood tests prior to transfusion.
It is anemia accompanied by a high number of reticulocytes: more than 150 000 cells / mm3.
Technical problem: check the reticulocyte count in uncertain forms (110 000 à 150 000 / mm3).
If it really is regenerative, anemia can have theorized that two causes acute hemorrhage and hyperhemolysis. But there is a misleading situation: recovery phase of anemia was non-regenerative (Box 2).
Constitutes an emergency, it should be considered first. Except in very recent accidental externalized haemorrhage, massive epistaxis or menorrhagia abundant, it is mainly gynecological or gastrointestinal bleeding.
These are sometimes not externalized only during the first examination. Therefore systematic search melena (stool examination, interrogation, DRE), abdominal symptoms (interrogation and examination, vaginal examination in doubt), suspicious history (ulcer, anti-inflammatory drugs, weight loss, etc.) and any sign of bleeding (thirst, tachycardia).
It can sometimes be suspected the existence of jaundice and / or splenomegaly as well as personal or family history of similar episodes, but these signs are inconstant and nonspecific. The diagnosis must absolutely be confirmed by:
– Unconjugated bilirubin high;
– A collapsed haptoglobinémie;
– Possibly some morphological abnormalities of red blood cells in the smears (microspherocytes, shizocytes …).
If evidence of hemolysis is made, the search for the cause almost always require use of the specialist.
Central anemia Repair:
A central cause of anemia in the process of correcting for a few days is regenerative (when the hyperréticulocytose compensates anemia). We must consider this diagnosis if the previous two were formally eliminated.
The most frequent cases of observation in this table are:
– Stopping a toxic erythropoiesis: cancer chemotherapy (2 to 4 weeks after treatment), recent judgment from alcohol poisoning;
– The recent administration of iron, folate or vitamin B12 in subjects who were deficient (anemia then as microcytic or macrocytic cases);
– The recent end of an inflammatory disease which caused anemia.
Box 2. Procedure in the presence of a regenerative anemia
Any regenerative anemia with hemoglobin less than 8 g / 100 mL is a priori an emergency and should be addressed as soon as possible to a specialist because of bleeding or hemolytic, it can quickly become life-threatening.
Preferably prescribe anything pending hospitalization and transfusion if anemia is almost certainly bleeding.In this case, draw blood prior to transfusion for various subsequent examinations, crucial if it were a hyperhemolysis.
Even outside the urgency of acute hemorrhage, hematologic consultation is warranted for any environment hemolytic anemia because the etiologic diagnosis and treatment are difficult.
This is anemia by increasing the standard rate of destruction of circulating red blood cells.
These are regenerative anemia because bone marrow tends to offset this loss by producing increased numbers of reticulocytes.
The diagnosis is often very complex and involve highly specialized explorations. In addition, the therapeutic consequences are very serious and indications come mostly specialized teams.
Essentially, hemolytic anemia are not the domain of the general.
The diagnosis is based primarily on the concept of regenerative anemia (reticulocytes> 150,000 / mm3) with the need to urgently eliminate anemia Acute hemorrhage.
It also requires proof of hyperhemolysis on anomalous signs of destruction of red blood cells:
– Two clinical signs: jaundice and splenomegaly are neither constant nor specific; two biological signs unconjugated hyperbilirubinemia and the collapse of haptoglobin (theoretical signs of intravascular hemolysis, but always associated with hemolysis in tissue anemia).
Search the existence of similar previous episodes or a family context can evoke a major cause of hemolysis Constitution: Hereditary spherocytosis (Minkowski-Chauffard disease), sickle cell disease, glucose-6-phosphate dehydrogenase etc.
Doing this balance sheet if the anemia is moderate and never delay hospitalization in large-hemolysis:
– Ensure that there is no septic context; Blood culture;
– Ensure that there is no risk of malaria access by geographic, clinical symptoms, thick blood; in doubt, hospital;
– Make a direct Coombs test. If positive, signing an immune hemolytic anemia, autoimmune in most cases, go mid specialized for the etiologic investigation and treatment;
– Ask the lab to check on the blood smear the existence of abnormal red blood cells:
– Large anisopoïkylocytoses,
– Intraglobulaires inclusions
– Sickle cell disease.
In conclusion: these four steps lead immediately or at a later stage to specialist consultation or hospitalization (Box 3).
Box 3. What to do in the presence of hemolytic anemia
Acute hyperhemolysis, that is to say, sudden onset, is still an emergency because of the double risk of anoxia and anuria.
No anti-anemic drug can be helpful.
Corticosteroid may need should not be undertaken without diagnosis. Transfusions may be needed if the anemia is shallow (less than 6 g / Hb / 100 mL). Do them after the samples for the diagnosis retrospectively certain causes that could mask transfusions (Coombs test erythrocyte particular).
She background therapy exclusively by the specialist.
These are anemias with a lower or equal to 80 VGM μ3.
Synonymy: hypochromic anemia (hemoglobin with mean corpuscular concentration of less than 32%) is rare and only reflects a deeper anomaly since microcytosis always precedes hypochromia.
Technical problem: VGM zone limit, 80-82 μ3 requires monitoring of results. In order, when there is anemia, microcytosis is straightforward because it starts before anemia.
Microcytic anemia (hypochromic or not) is always due to an insufficient hemoglobin synthesis in erythroblasts or default in plasma iron, or by abnormal synthesis of globin.
The diagnosis is based initially on the determination of serum iron accompanied by that of the total capacity of transferrin saturation (CTSS) or that of ferritin (Box 4).
Any laboratory is expected to provide reliable determinations of serum iron and CTSS is the measurement of plasma iron binding capacity, but there is still, unfortunately, mistakes.
Microcytic anemia with low serum iron (hyposidérémiques)
They are due in most cases to iron deficiency.
The high rate of CTSS confirmed. Low levels of ferritin have the same meaning. The problem in this case is only to find the cause of the deficiency: chronic bleeding in most cases (≥ 95%).
* In women set:
We must first seek genital bleeding whatever the cause. Before age 40, in the presence of obvious menorrhagia (duration, abundance, clots) it is sufficient gynecological exploration and processing. The correction must be stable provided that the volume of the rules back to normal after treatment of the cause or decrease in the volume of the rules.
The attitude of systematically practice a gastroscopy is not widespread, but is certainly not an error condition to perform a gastric biopsy (looking Helicobacter pylori) and duodenal (looking for a villous atrophy).
* In humans or non ménorragique woman:
The digestive tract must be explored starting with a high fibroscopy rectoscopy and colonoscopy. Gastric any cause (hiatal hernia, ulcers, cancer, benign tumor) or colon (polyps, cancer) should be treated.
Exploring the hail is only useful if other tests are negative. Other bleeding is rarely at issue (hematuria, epistaxis, etc.). By cons, blood donation, or even in some patients catches repeated blood, may be responsible, alone or in combination with other causes.
In exposed subjects, including Caribbean, look for hookworm.
* Iron deficiency due to malabsorption:
It is much more rare and almost always associated with other deficiencies, especially folate. The main cause of celiac disease is usually identified on villous atrophy on duodenal biopsy and the presence of anti-gliadin and / or endomysial antibodies.
* Relative Deficiency:
Deficiencies “relative” (needs insufficiently covered by contributions) are in order the result of repeated pregnancies.
In infants, it is usually a capital deficiency, linked to insufficient iron-rich diet.
Microcytic anemia of inflammatory syndromes:
Inflammatory syndromes, whatever the cause, result from a complex mechanism anemia normochromic and normocytic first, may become microcytic if the syndrome lasts a few weeks This is particularly common during inflammatory rheumatism and certain neoplasms ( Hodgkin, kidney cancer …).
The low serum iron with low or normal CTSS, is characteristic. The ferritin is not discriminating. The association with a biological inflammatory syndrome is necessary for the diagnosis, erythrocyte sedimentation rate (ESR) high, fibrin, C-reactive protein, elevated α2-globulins.
The problem is the cause that the research is the first of the general spring. It is sometimes difficult. Treatment can only be that of the cause.
Microcytic anemia with normal or high serum iron (normo or hypersidérémiques):
In a young child carrying a homozygous thalassemia splenomegaly of diagnosis should be considered (hemoglobin electrophoresis).
In an adult, the β-thalassemia heterozygous must be considered if the anemia is moderate (hemoglobin 10 and 12 g / 100 mL). The diagnosis is confirmed by electrophoresis of hemoglobin (Hb A2 greater than 3.5% if β-thalassemia, the most common; hemoglobin F only increased when δβ thalassemia much more rare). Genetic counseling in specialized areas (hematology consultation) is highly recommended.
The sideroblastic anemia, very rare, are the exploration in a specialized environment.
Box 4. What to do in the presence of microcytic anemia
It is in good standing with chronic anemia installed very gradually, often asthéniantes but not urgent, except for acute bleeding in chronic bleeding.
Most cases can be fully adjusted by the general provided it be certain of the quality of the laboratory (microcytosis and hyposideremia). Hematologic consultation within five situations:
– Infants (pediatric)
– Any microcytic anemia controlled normal or high serum iron if hemoglobin electrophoresis was normal
– Recurrence of an ordinary iron deficiency anemia when the bleeding has disappeared and iron treatment was okay
– Rare microcytic anemia iron deficiency for which we do not find abnormal bleeding
– Doubt on the bleeding-infl ammation Association
Iron deficiency anemia still required iron therapy.
The hypersidérémiques or normosidérémiques anemias fall specialties.
Aplastic anemia macrocytic:
It is a non-regenerative anemia (reticulocytes <100,000 / mm3) with VGM ≥ 98 μ3. These anemias necessarily a central origin (production disorder). In addition to their macrocytic character oriented towards particular causes which simplifies the investigation.
The procedure to be based initially on some guidance.
Moderate and moderately macrocytic anemia (<105 μ 3):
Think of myxedema and measure TSH.
If there is an alcoholic patient, let alone a cirrhotic, it is not useful for further research in most cases.
Usually the macrocytosis is moderate (<110 μ3), and there are often signs of hypersplenism associated with portal hypertension neutropenia and thrombocytopenia.
Critical examination: myelogram:
Myelogram not a nice gesture, it is always tempting to delay and start practicing dosages of folic acid and vitamin B12 that require a venous sample. This attitude is not recommended because vitamin assays require much more time (over a week) than reading a myelogram (24 hours).
There are problems of interpretation because levels of vitamin B12 or folic acid lowered serum are found not exceptional in the absence of megaloblastic anemia.
For example, the association refractory anemia and folic acid base is fairly common.
Therefore, in practice, consider the results of vitamin dosages are only really useful if megaloblastic anemia is demonstrated. So myelogram is necessary first.
Three groups of pathologies:
The distinction is cytological and requires a competent hematologist to affirm the presence or absence of megaloblasts.
* Refractory anemia (primitive dyserythropoiesis):
It is the most common:
– He may be suspected on a relatively moderate macrocytosis (MCV <110 μ3) sometimes neutropenia and / or thrombocytopenia with no sign;
– Myelogram shows no megaloblasts but other morphological abnormalities.
* Megaloblastic anemias by vitamin deficiencies:
The dosages of vitamins are then very important for diagnosis.
Among the vitamin B12 deficiency, the most common is the pernicious anemia. Suspected to neurological signs (rare), vitiligo (common) or gastric symptoms (frequent), it usually involves neutropenia and thrombocytopenia and mild macrocytosis is large (> 115 μ3). B12 collapsed and normal or elevated folate.
However evidence of gastric intrinsic factor deficiency and possibly self-immunization should be done in a specialized environment. It is therefore essential that the patient is seen by a specialist service.
Deficiencies of folate, a wide variety of causes, associate a collapsed folate and B12 vitaminémie normal (with rare exceptions). Are suspected:
– In the great malnourished;
– Subjects with chronic diarrhea or gastrointestinal resections.
Specialized consultation is highly desirable (Box 5).
Certain malignant hematological diseases can also be a macrocytic anemia: acute myelogenous leukemia or even disease Kahler. Bone marrow is all the more essential.
Box 5. Procedure in the presence of a non-regenerative macrocytic anemia
The problem is always important but the urgency is only a function of the degree of anemia. Do not prescribe anything and especially not to transfuse before exploration, even with significant anemia.
Deficiencies jurisdiction over specific vitaminothérapies exclusively.
Refractory anemia essentially within the transfusion therapy.
Haematological malignancies within specific treatment in a specialized environment. Specialized consultation
It is desirable for all megaloblastic anemias and necessary for refractory anemia afi n to evaluate the prognosis.
Aplastic anemia normocytic:
It is a non-regenerative anemia (reticulocytes <100,000 / mm3) with normal MCV. It is always of central origin anemia (red blood cell production disorder) that are in principle due:
– Nor vitamin deficiency B12 or folate, as would be macrocytic anemia;
– Or to insufficient hemoglobin synthesis, including iron deficiency, as would microcytic anemia.
Some common causes of anemia can be easily recognized by a simple exploration of the field of general practitioner.
The diagnosis is then often so complex and require specialized explorations.
The first element to be worrying about is the state of the other lines. If there are neutropenia and / or thrombocytopenia associated, the most likely diagnosis was overall myelosuppression regardless of the cause (aplasia, fibrosis, or dysmyelopoiesis marrow involvement). Bone marrow and marrow biopsy are essential elements of the diagnosis, but the importance of these tests and the need in all cases of haematological support warrant referral to a specialized environment.
It must be first made to ensure that anemia is real excluding the suspicion of pseudoanémie hemodilution. It is usual:
– During pregnancy in the second half;
– If significant splenomegaly;
– If hyperviscosity (Waldenstrom’s disease);
– In some fluid retention syndrome.
Aplastic anemia before a normocytic isolated and without hemodilution, look second to eliminate some common causes and highlight simple:
– Anemia of inflammation is by far the most common. It occurs in any febrile illness (infectious, inflammatory,
tumor) with VS high as long as this state lasts more than 2 to 3 weeks.
Its diagnosis is based on the association: elevated ESR, other signs of inflammation (hyperalpha-2-globulin, elevated C-reactive protein, hyperfibrinémie, etc.) and low serum iron saturation capacity with normal or low transferrin. It will correct that with the disappearance of inflammation;
– Anemia of renal failure is commonplace patients with renal impairment with creatinine greater than 200 mmol / L, but may be considered when creatinine exceeds 150 mmol / L;
– Endocrine anemia accompanying myxedema (and more rarely pan-hypopituitarism) can reveal the disease. Think therefore if there is a clinical presentation to the exploration of thyroid function (T3, T4, TSH), or sex hormones and the HPA axis (basic cortisol test synacthen, ACTH).
The above cases excluded, the diagnosis falls specialized exploration.
It begins with myelogram it is better to immediately to a specialist. The diagnoses involved and the necessary additional etiological investigations are not within the standard practice whether in fact:
– Of dyserythropoiesis;
– Marrow fibrosis;
– Hematological malignancies;
– Of metastatic invasion.
Do not rush to treat these anemias (Box 6).
Box 6. Procedure in the presence of a non-regenerative normocytic anemia
It only depends on the depth of anemia because there is always a gradual onset anemia.
Abstention until the diagnosis is not said. In particular, do not prescribe “anti-anemic” and not transfused unless absolutely necessary.
Anaemia in pregnancy:
We must distinguish anemias associated with pregnancy, few and simple diagnosis, and anemia from other causes occurring in a pregnant woman (Box 7).
The first step is to differentiate the true anemia and pseudoanémie hemodilution due to physiological elevation of plasma volume in the second half of gestation. Therefore, it should not be viewed as pathological:
– A still moderate anemia: hemoglobin equal to or greater than 10.5 g / 100 ml;
– Which is normocytic (98 μ3> MCV> 80 μ3) and non-regenerative (reticulocytes ≤ 120,000 / mm3);
– From 4 months basically.
If MCV reveals microcytosis (MCV <82 μ 3):
Think of the extremely common iron deficiency, especially during late pregnancy and more in multiparous. Dose the serum iron and total capacity of saturation and treated.
If MCV reveals macrocytosis (MCV 98 μ ≥ 3):
Think of folate deficiency which occurs mostly in late pregnancy, even if it is twins and in multiparous. It may be associated with thrombocytopenia. Doser folate and address.
Other (rare) cases:
It must be considered that it is anemia occurring during pregnancy but different origin. Whether or not a regenerative anemia, normocytic or not, insulated or not, the patient should preferably be addressed in hematology for exploration.
From the 4th month of pregnancy, hemoglobin 10.5 g / 100 mL is generally not pathological if it is not accompanied by other abnormalities.
Box 7. What to do in front of anemia during pregnancy
The profound anemia (hemoglobin ≤ 8 g) is a risk to the child and must be investigated immediately.
No action is to be taken before hematologic exploration, except in the case of iron deficiency or folate that do not require further investigation. In specialized areas, it may be necessary to transfuse the mother, if the anemia is severe enough (<8 g / dL or more) to sound on the fetus.
Deficiency anemia indispensable factor erythropoiesis:
Treatment with oral iron is well codified and consensual.
Using any iron salt providing at least 25 mg of elemental iron per dosage unit (see dictionary specialties) at a total daily dose of 100 to 200 mg of elemental iron (the amount absorbed is proportional to the dose, the correction Therefore more rapid that the daily dose is higher, but tolerance is even worse than the doses are higher).
Treatment duration was 4 months.
Monitoring of treatment is as follows: blood count monitoring and iron status (iron + total capacity or ferritin) to 4 months. Discontinuation of treatment if reserves are adequate (normal total capacity, normal ferritin).
Side effects noted are:
– Black stools (constant, prevent patients);
– Digestive disorders (diarrhea or constipation or both), rare in humans, rare among women. The intensity of the disorders can be alleged not to continue treatment.
Injectable iron is no longer available in France intravenously and should be administered in hospitals. This form is reserved for rare situations (malabsorption or difficult resection) or exceptional (absolute intolerance to oral iron).
Vitamin B12 deficiency:
It is almost always due to malabsorption.
Treatment should be administered parenterally (intramuscular) cyanocobalamin 1000 mcg / day, 2 to 3 injections per week x 10 for repletion of reserves.
Maintenance treatment: 1 injection per month of 1000 micrograms intramuscular (or every three months if good compliance is assured).
Treatment almost always lasts for life.
Tolerance is generally excellent, allergies are exceptional.
B12 orally is only indicated:
– If you are allergic to vitamin parenteral B12: it is then necessary to very high doses to allow passive absorption of a few micrograms;
– If the capital deficiency that occurs in strict vegans watching their diet for several years. Very low doses (1 mg / d) are then sufficient.
Folic acid deficiency:
The Spéciafoldine® 5 mg / tablet, 1 tablet / day, is widely suffi cient (need 20 mcg / day). This is true even if malabsorption (passive absorption).
The folinic acid (tetrahydrofolic acid) is reserved for hospital indications.
Iron, folic acid and vitamin B12 have no indication outside a challenge demonstrated cit.
The simultaneous prescription of several of these drugs is justified only in cases of dual demonstrated deficiency (iron + folic acid being the least exceptional).
Only chronic renal failure is responsible for anemia whose main cause is the lack of production of erythropoietin.
Different specialties are available subcutaneously to patients not on dialysis, intravenous dialysis patients.Subcutaneous injection every 15 days is usually sufficient (eg start with 40 or 50 micrograms of Aranesp® every 15 days).
The indication and the initial prescription are made by the nephrologist.
Recombinant erythropoietin is not a substitute treatment for anemia outside of chronic renal failure.
Autoimmune anemia (hemolysis, PRCA):
Using a greater than 1 mg / kg for 3 weeks corticosteroid, then tapering.
The indication and monitoring are in a specialized environment.
Hemolytic anemia and steroid-steroid or steroid-often benefit from splenectomy.
Congenital anemia (hemolytic almost always):
Splenectomy is indicated in symptomatic forms of hereditary spherocytosis and some major thalassemia. Indication of specialists:
– Sickle cell disease can be treated by Hydrea®: indication of specialists;
– The glucose-6-phosphate dehydrogenase should be especially preventive education (list of proscribed drugs);
– Other congenital anemias are very rare and their treatment in the field of hyperspécialiste.
Erythrocyte transfusion therapy is formally indicated in cases of anemia:
– Acute or deep or at risk of homelessness;
– Chronic but poorly tolerated because of its degree or state of hypoxia-sensitive tissues (heart, brain, muscles).
It is not appropriate when dealing with anemia due to access to drug treatment, including anemia deficiency in hematopoietic factor.
The acute hemorrhagic anemia is a formal indication for RBC transfusions.
Hemolytic anemia can be acute indication, knowing that in case of severe extra-corpuscular hemolysis (autoimmune hemolytic anemia, mechanical hemolytic anemia), the effect of the transfusion will be short, the transfused red cells with only no more resistance than the red blood cells of the patient!
Chronic anemia without etiological treatment:
The main indications are:
– Acute leukemia, either during initial treatment or by treatment failure;
– Various chronic lymphoid or myeloid malignancies at an advanced stage of evolution (chronic lymphocytic leukemia, myelofibrosis …)
– Myelodysplastic syndromes (refractory anemia), which represent a major indication of the long-term transfusion hematology;
– The rebels Aplasia treating or awaiting trial latter; rarely severe forms of inflammatory anemia not accessible treatment of the cause (active inflammatory cancer).
In acquired pathologies, indications depend hemoglobin and tolerance.
For a patient to lead an active life close to normal, it usually maintain hemoglobin levels above 9 g / dL. This threshold varies from patient to patient and determined empirically.
Homozygous thalassemia is an indication almost constant transfusion therapy from an early age.
Some forms of sickle cell disease should also be transfused to repeat (hyper-specialist indication).
In all chronic diseases, where anemia is the only or main pathological symptom, survival and quality of life can be excellent with red cell transfusion therapy well conducted. The main problem is that of iron overload. The iron chelation therapy by Desferal® in slow subcutaneous infusion is effective but often difficult to accept. New orally active molecules entering the market (Exjade 10 to 30 mg / kg / day orally , the essential cons-indication is renal failure).
Treatment with erythropoietin outside chronic renal failure:
With replacement doses, recombinant erythropoietin is effective in chronic renal failure.
At higher doses:
– It can be effective, especially associated with small doses of growth factors (GCSF), in some myelodysplastic syndromes, provided the endogenous erythropoietin level is not too high. This effect is usually transient (months or years). This is an indication currently no authorization for the market, so in principle be reserved for clinical trials;indication specialist; is increasingly used to raise the hemoglobin of patients with cancer receiving chemotherapy, this even if the degree of anemia does not justify transfusion. No studies have shown a positive effect on survival.This treatment is only effective doses. It is extremely expensive for treatment comfort; indication specialist.