Hemolytic anemia is a pathology of red blood cells, the hallmark of which is the accelerated destruction of red blood cells with the release of an increased amount of indirect bilirubin. For this group of diseases, a combination of anemic syndrome, jaundice and an increase in the size of the spleen is typical. In the process of diagnosis, a general blood test, bilirubin level, stool and urine analysis, ultrasound of the abdominal cavity organs are examined; bone marrow biopsy, immunological studies are performed. Medical, hemotransfusion therapy is used as treatment methods; with hypersplenism, splenectomy is indicated.
Hemolytic anemia (HA) is anemia caused by a violation of the life cycle of erythrocytes, namely, the predominance of the processes of their destruction (erythrocytolysis) over the formation and maturation (erythropoiesis). This group of anemia is very extensive. Their prevalence varies in different geographical latitudes and age cohorts; on average, pathology occurs in 1% of the population. Among other types of anemia, hemolytic anemia accounts for 11%. Pathology is characterized by shortening of the life cycle of erythrocytes and their decay (hemolysis) ahead of time (after 14-21 days instead of 100-120 days in normal). In this case, the destruction of red blood cells can occur directly in the vascular bed (intravascular hemolysis) or in the spleen, liver, bone marrow (extravascular hemolysis).
Hemolytic anemia causes
The etiopathogenetic basis of hereditary hemolytic syndromes is genetic defects of erythrocyte membranes, their enzyme systems or the structure of hemoglobin. These prerequisites cause morphofunctional inferiority of erythrocytes and their increased destruction. Hemolysis of erythrocytes in acquired anemia occurs under the influence of internal factors or environmental factors, including:
- Autoimmune processes. The formation of antibodies agglutinating erythrocytes is possible with hemoblastosis (acute leukemia, chronic lymphocytic leukemia, lymphogranulomatosis), autoimmune pathology (SLE, ulcerative colitis), infectious diseases (infectious mononucleosis, toxoplasmosis, syphilis, viral pneumonia). Posttransfusion reactions, preventive vaccination, and fetal hemolytic disease can contribute to the development of immune hemolytic anemia.
- Toxic effect on red blood cells. In some cases, acute intravascular hemolysis is preceded by poisoning with arsenic compounds, heavy metals, acetic acid, mushroom poisons, alcohol, etc. Taking certain medications (antimalarial drugs, sulfonamides, nitrofuran derivatives, analgesics) can cause the destruction of blood cells.
- Mechanical damage to red blood cells. Hemolysis of erythrocytes can be observed with severe physical exertion (prolonged walking, running, skiing), with DIC syndrome, malaria, malignant arterial hypertension, prosthetics of heart valves and blood vessels, hyperbaric oxygenation, sepsis, extensive burns. In these cases, under the influence of certain factors, traumatization and rupture of the membranes of initially full-fledged red blood cells occur.
The central link in the pathogenesis of HA is the increased destruction of erythrocytes in the organs of the reticuloendothelial system (spleen, liver, bone marrow, lymph nodes) or directly in the vascular bed. With the autoimmune mechanism of anemia, the formation of anti-erythrocyte AT (heat, cold) occurs, which cause enzymatic lysis of the erythrocyte membrane. Toxic substances, being the strongest oxidants, destroy the erythrocyte due to the development of metabolic, functional and morphological changes in the shell and stroma of red blood cells. Mechanical factors have a direct effect on the cell membrane. Under the influence of these mechanisms, potassium and phosphorus ions leave the erythrocytes, and sodium ions enter inside. The cell swells, with a critical increase in its volume, hemolysis occurs. The breakdown of red blood cells is accompanied by the development of anemic and jaundice syndromes (the so-called “pale jaundice”). Intensive staining of feces and urine, enlargement of the spleen and liver is possible.
In hematology, hemolytic anemia is divided into two large groups: congenital (hereditary) and acquired. Hereditary HA include the following forms:
- erythrocyte membranopathy (microspherocytosis – Minkowski-Shoffar disease, ovalocytosis, acanthocytosis) – anemia caused by structural abnormalities of erythrocyte membranes
- fermentopenia (enzymopenia) – anemia caused by a deficiency of certain enzymes (glucose-6-phosphate dehydrogenase, pyruvate kinase, etc.)
- hemoglobinopathies are anemia associated with qualitative disorders of the structure of hemoglobin or a change in the ratio of its normal forms (thalassemia, sickle cell anemia).
Acquired HA are divided into:
- acquired membranopathies (paroxysmal nocturnal hemoglobinuria – b-n Markiafava-Mikeli, spur cell anemia)
- immune (auto- and isoimmune) – due to the effects of antibodies
- toxic – anemia caused by exposure to chemicals, biological poisons, bacterial toxins
- mechanical – anemia caused by mechanical damage to the structure of erythrocytes (thrombocytopenic purpura, marching hemoglobinuria)
Hemolytic anemia symptoms
Hereditary membranopathies, fermentopenias and hemoglobinopathies
The most common form of this group of anemia is microspherocytosis, or Minkowski-Shoffar disease. It is inherited by an autosomal dominant type; it is usually traced in several representatives of the family. The defect of erythrocytes is caused by a deficiency of actomyosin-like protein and lipids in the membrane, which leads to a change in the shape and diameter of erythrocytes, their massive and premature hemolysis in the spleen. The manifestation of microspherocytic HA is possible at any age (in infancy, adolescence, old age), but usually manifestations occur in older children and adolescents. The severity of the disease varies from a subclinical course to severe forms characterized by frequently recurring hemolytic crises. At the moment of the crisis, body temperature increases, dizziness, weakness; abdominal pain and vomiting occur.
The main sign of microspherocytic hemolytic anemia is jaundice of varying degrees of intensity. Due to the high content of sterkobilin, the feces become intensely colored dark brown. Patients with Minkowski-Shoffar disease have a tendency to form gallstones, therefore, signs of exacerbation of calculous cholecystitis often develop, biliary colic attacks occur, and obstructive jaundice occurs when the choledochus is blocked by concretion. With microspherocytosis, the spleen is enlarged in all cases, and in half of the patients, the liver is also enlarged. In addition to hereditary microspherocytic anemia, children often have other congenital dysplasia: a tower skull, strabismus, saddle-shaped deformity of the nose, malocclusion, Gothic palate, polydactyly or bradydactyly, etc. Middle-aged and elderly patients suffer from trophic ulcers of the lower leg, which occur as a result of hemolysis of erythrocytes in the capillaries of the extremities and are poorly treatable.
Enzymopenic anemia is associated with a lack of certain erythrocyte enzymes (more often – G-6-PD, glutathione-dependent enzymes, pyruvate kinase, etc.). Hemolytic anemia may first manifest itself after an intercurrent disease or taking medications (salicylates, sulfonamides, nitrofurans). Usually the disease has an even course; “pale jaundice”, moderate hepatosplenomegaly, cardiac murmurs are typical. In severe cases, a pronounced picture of a hemolytic crisis develops (weakness, vomiting, shortness of breath, palpitations, a collaptoid state). Due to intravascular hemolysis of erythrocytes and the release of hemosiderin in the urine, the latter acquires a dark (sometimes black) color. Independent reviews are devoted to the peculiarities of the clinical course of hemoglobinopathies – thalassemia and sickle cell anemia.
Acquired hemolytic anemia
Among the various acquired variants, autoimmune anemia is more common than others. For them, the common trigger factor is the formation of antibodies to the antigens of their own red blood cells. Hemolysis of erythrocytes can be both intravascular and intracellular in nature. Hemolytic crisis in autoimmune anemia develops acutely and suddenly. It occurs with fever, sharp weakness, dizziness, palpitations, shortness of breath, pain in the epigastrium and lower back. Sometimes acute manifestations are preceded by precursors in the form of subfebrility and arthralgia. During the crisis, jaundice increases rapidly, not accompanied by skin itching, the liver and spleen increase. In some forms of autoimmune anemia, patients do not tolerate cold; at low temperatures, they may develop Raynaud’s syndrome, urticaria, hemoglobinuria. Due to insufficient blood circulation in small vessels, complications in the form of gangrene of the toes and hands are possible.
Toxic anemia occurs with progressive weakness, pain in the right hypochondrium and lumbar region, vomiting, hemoglobinuria, high body temperature. From 2-3 days jaundice and bilirubinemia are added; on 3-5 days hepatic and renal insufficiency occurs, signs of which are hepatomegaly, enzymemia, azotemia, anuria. Certain types of acquired hemolytic anemia are considered in the relevant articles: “Hemoglobinuria” and “Thrombocytopenic purpura”, “Hemolytic fetal disease”.
Each type of HA has its own specific complications: for example, GI – with microspherocytosis, liver failure – with toxic forms, etc. Common complications include hemolytic crises, which can be provoked by infections, stress, childbirth in women. With acute massive hemolysis, it is possible to develop a hemolytic coma characterized by collapse, confused consciousness, oliguria, increased jaundice. The threat to the patient’s life is caused by DIC syndrome, spleen infarction or spontaneous organ rupture. Acute cardiovascular and renal insufficiency require urgent medical care.
Determining the form of HA based on the analysis of causes, symptoms and objective data is the competence of a hematologist. During the initial conversation, the family history, frequency and severity of the course of hemolytic crises are clarified. During the examination, the color of the skin, sclera and visible mucous membranes is evaluated, palpation of the abdomen is performed to assess the size of the liver and spleen. Splenic and hepatomegaly are confirmed by ultrasound of the liver and spleen. The laboratory diagnostic complex includes:
- Blood test. Changes in the hemogram are characterized by normal or hypochromic anemia, leukopenia, thrombocytopenia, reticulocytosis, acceleration of ESR. In biochemical blood samples, hyperbilirubinemia is determined (an increase in the fraction of indirect bilirubin), an increase in the activity of lactate dehydrogenase. In autoimmune anemia, a positive Coombs test is of great diagnostic importance.
- Urine and stool test. Urine examination reveals proteinuria, urobilinuria, hemosiderinuria, hemoglobinuria. The content of sterkobilin is increased in the coprogram.
- Myelogram. For cytological confirmation, a sternal puncture is performed. Examination of the bone marrow punctate reveals hyperplasia of the erythroid germ.
In the process of differential diagnosis, hepatitis, cirrhosis of the liver, portal hypertension, hepatolienal syndrome, porphyria, hemoblastosis are excluded. The patient is consulted by a gastroenterologist, a clinical pharmacologist, an infectious disease specialist and other specialists.
Hemolytic anemia treatment
Various forms of HA have their own characteristics and approaches to treatment. With all variants of acquired hemolytic anemia, care must be taken to eliminate the influence of hemolytic factors. During hemolytic crises, patients need infusions of solutions, blood plasma; vitamin therapy, if necessary, hormone and antibiotic therapy. In microspherocytosis, splenectomy is the only effective method leading to 100% cessation of hemolysis.
In autoimmune anemia, therapy with glucocorticoid hormones (prednisone) is indicated, reducing or stopping hemolysis. In some cases, the desired effect is achieved by the appointment of immunosuppressants (azathioprine, 6-mercaptopurine, chlorambucil), antimalarial drugs (chloroquine). Splenectomy is performed in drug-resistant forms of autoimmune anemia. Treatment of hemoglobinuria involves transfusion of washed erythrocytes, plasma substitutes, the appointment of anticoagulants and antiplatelet agents. The development of toxic hemolytic anemia dictates the need for intensive therapy: detoxification, forced diuresis, hemodialysis, according to indications – the introduction of antidotes.
Prognosis and prevention
The course and outcome depend on the type of anemia, severity of crises, completeness of pathogenetic therapy. With many acquired options, the elimination of the causes and full treatment leads to a complete recovery. The cure of congenital anemia cannot be achieved, but it is possible to achieve long-term remission. With the development of renal failure and other fatal complications, the prognosis is unfavorable. Prevention of acute infectious diseases, intoxication, poisoning allows to prevent the development of HA. Uncontrolled independent use of medicines is prohibited. It is necessary to thoroughly prepare patients for blood transfusions, vaccination with the entire complex of necessary examinations.
- Assessment of anemia / Evan M. Braunstein // MSD Manual Professional.
- Markova V., Norgaard A., Jørgensen K.J., Langhoff-Roos J. Treatment for women with postpartum iron deficiency anaemia // Cochrane Database Syst Rev. — 2015: 13; (8).link
- Low MSY, Speedy J., Styles C.E., De-Regil L.M., Pasricha S.R. Daily iron supplementation for improving anaemia, iron status and health in menstruating women // Cochrane Database of Systematic Reviews. — 2016; 4. ссылка
- Iron with or without folic acid supplementation in women: Full set of recommendations // World Health Organization. — Geneva, 2016.