Hemolytic Anemia Classification

Hemolytic Anemia

• Hemolytic anemia is a group of anemia characterized by the shortening of the life of red blood cells.

Classification of Hemolytic Anemia

• Classification is based on three factors: cause of hemolysis, intra- or extravascular localization of hemolysis, and congenital or acquired character of the disease.

Anemias Caused by Endoerythrocytic Factors

• Hereditary anemia:
  • Defects of the plasmolemma of erythrocytes (membranopathy):
    • Hereditary spherocytosis
    • Elliptocytosis
  • Enzymatic disorders of erythrocytes (fermentopathy):
    • Insufficiency of glucose-6-phosphate dehydrogenase
    • Pyruvate kinase deficiency
  • Disturbance of hemoglobin synthesis (hemoglobinopathy):
    • Disorders of globin chains (hemoglobin variants)
    • Reduction of synthesis of globin chains (thalassemia)
• Acquired anemia:
  • Paroxysmal nocturnal hemoglobinuria

Anemias Caused by Exoerythrocyte Factors

• Acquired anemia:
  • Autoimmune hemolytic anemia:
    • Thermal antibody
    • Cold-blooded
    • Anemia in autoimmune diseases
  • Immune hemolytic anemia:
    • Hemolytic disease of newborns
    • Transfusion hemolytic reaction
    • Medicinal immune hemolytic anemia
    • Hemolysis in response to toxins and chemicals
• Mechanical damage of erythrocytes:
  • Microangiopathic anemia (erythrocyte fragmentation syndrome)
• Anemia in infectious diseases:
  • Malaria
• Hyperplenism
• Mixed species

Classification of Diserythropoietic Anemia

• Classification of diserythropoietic anemia is based on the stage of erythropoiesis affected
• Two main categories: destruction of proliferation and differentiation of stem cells, and destruction of proliferation and differentiation of erythroblasts

Destruction of Proliferation and Differentiation of Stem Cells

• Aplastic anemia: characterized by reduction or absence of hematopoietic stem cells
• Aplasia of the erythroblastic sprout: failure of stem cells to differentiate into erythroblasts
• Anemia in renal insufficiency: impaired erythropoiesis due to chronic kidney disease
• Anemia in endocrine disorders: hormonal imbalances affecting erythropoiesis

Destruction of Proliferation and Differentiation of Erythroblasts

• Disruption of DNA synthesis:
  • Insufficiency or impairment absorption of vitamin B12 and folic acid (megaloblastic anemia)
• Destruction of Hb synthesis:
  • Violation of heme synthesis (Fe deficiency)
  • Violation of globin synthesis (thalassemia)
• Unknown or mixed mechanisms:
  • Anemia due to a violation of Fe metabolism (anemia sideroblast, with chronic diseases, with myelodysplastic syndrome)

Megaloblastic Anemia

• Characterized by violations of hemopoiesis, manifested in the appearance of megaloblasts during the differentiation of the myeloid germ
• Common causes: insufficiency of either vitamin B12 or folic acid
• Rare causes: cytotoxic effect of drugs that inhibit DNA synthesis
• Blood picture:
  • Decrease in the number of erythrocytes, granulocytes, and platelets (pancytopenia)
  • Anisocytosis, macrocytosis, poikilocytosis
  • Nuclei and Howell-Jowley bodies appear in erythrocytes in advanced stages
  • Decrease in reticulocytes, neutropenia, and appearance of large neutrophils with hypersegmented nuclei
  • Fewer platelets, and possibly hemorrhagic syndrome
• Bone marrow picture:
  • Red bone marrow of tubular bones resembling "raspberry jelly"
  • Erythroid hyperplasia, megaloblastic changes, retention of nuclei in differentiating cells, polyploidy, and nuclear fragmentation
  • Giant metamyelocytes, erythrophagia, and hemosiderosis appear
  • Hb synthesis is less disturbed

Bone Marrow Characteristics

• Bone marrow of tubular bones appears as "raspberry jelly" due to red color
• Erythroid hyperplasia, megaloblastic changes, retention of nuclei, polyploidy, and nuclear fragmentation observed
• Giant metamyelocytes, erythrophagia, and hemosiderosis appear

Effects on Oral Mucosa and Gastrointestinal Tract

• Atrophic glossitis (reduction and disappearance of tongue papillae) and ulceration of oral mucosa
• Chronic atrophic gastritis, atrophy of small intestine villi, and infertility due to impaired germ cell maturation

Iron Deficiency Anemia

• Main cause is chronic hemorrhage, particularly severe menstrual bleeding and latent hemorrhages
• Ancylostoma invasion causes significant gastrointestinal bleeding and is a major cause of iron deficiency anemia
• Deficiency can also be caused by malabsorption in gluten enteropathy, achlorhydria, and after gastrectomy

Blood Changes

• Anemia is hypochromic, microcytic, and regenerative
• Erythrocytes are pale, reduced in size, and have nuclear remains
• Polychromatophilic erythrocytes and reticulocytes present
• Irregular erythrocytes, including ringshaped, oval, and rod-shaped red blood cells

Bone Marrow Puncture

• No iron-containing material in bone marrow punctate, giving a negative Berlin azure reaction
• Erythroid hyperplasia, hypochromic and microcytic red blood cells

Other Organ and Tissue Changes

• Iron deficiency leads to depletion of iron-containing enzymes and chronic hypoxia
• Nail changes: furrowed, striped, brittle, and eventually spoon-shaped (coilonichia)
• Atrophic glossitis, cracks in mouth corners, and dysphagia (swallowing disorders) due to mucous membrane folding in the cervical esophagus
• Atrophic gastritis leads to achlorhydria, intensifying iron deficiency

Aplastic and Hypoplastic Anemia

• Aplastic anemia is characterized by a small or absent number of cells in the bone marrow.
• Hypoplastic anemia is characterized by a reduced number of cells in the bone marrow.
• Congenital aplastic anemia is also known as Fanconi anemia and is often accompanied by other anomalies such as bone defects or congenital heart diseases.
• Acquired aplastic anemia can be caused by:
  • Idiopathic anemia (50%)
  • Irradiation
  • Treatment with massive doses of cytotoxic drugs
  • Use of certain drugs (e.g. levomycetin, sulfonamides) or idiosyncrasy to medicines
  • Viral infections (e.g. cytomegalovirus or Epstein-Barr virus)
  • Autoreactive T lymphocytes may also play a role in the pathogenesis of bone marrow aplasia
• The main manifestation of aplastic anemia is the inadequacy of proliferation and differentiation of hematopoietic stem cells, leading to pancytopenia, immunodeficiency, and a tendency to bleeding.

Classification of Tumors of the Blood System

• Primary systemic leukemia: tumor cells grow in the bone marrow and often enter the blood.
• Primary-local lymphomas: tumor cells grow in extraosternal lymphoid tissue.
• Leukemia classification:
  • By degree of increase in blood:
    • Leukemic (tens to hundreds of thousands of leukocytes per 1 mm3 of blood)
    • Subleukemic (no more than 15,000-25,000 in 1 mm3 of blood)
    • Leukopenic (the number of leukocytes is reduced, but leukemic cells are detected)
    • Aleukemic (leukemia cells in the blood are absent)
  • By degree of maturity of tumor cells and nature of the course:
    • Acute leukemia: proliferation of blast cells and malignant flow
    • Chronic leukemia: proliferation of differentiated leukemia cells and relative goodness of the course
  • Histogenetic forms of acute leukemia:
    • Undifferentiated
    • Myeloblast
    • Lymphoblastic
    • Monoblast (myelomonoblast)
    • Erythromyeloblast
    • Megakaryoblast
  • Histogenetic forms of chronic leukemia:
    • Chronic leukemia of myelocytic origin:
      • Chronic myeloid leukemia
      • Chronic erythromyelosis
      • Erythremia
      • True polycythemia
    • Chronic leukemias of the lymphocytic series:
      • Chronic lymphocytic leukemia
      • Skin lymphoma (Cesari's disease)
      • Paraproteinemic leukemia (myeloma, or plasmacytoma, Waldenstrom's primary macroglobulinemia, Franklin heavy chain disease)
    • Chronic leukemias of monocytic origin:
      • Monocytic (myelomonocytic) leukemia
      • Histiocytosis (histiocytosis X)

Hemoblastoses

• Hemoblastoses are tumors of the hematopoietic and lymphatic tissue.
• Leukemia is a systemic tumor lesion of the hematopoietic tissue, while malignant lymphomas are regional tumor lesions of lymphoid tissue with possible generalization.

Acute Leukemia

• Characterized by acute onset (high fever, severe intoxication) and rapid progression of the disease.
• The most frequent forms of acute leukemia are acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML).

Acute Lymphoblastic Leukemia (ALL)

• Mainly found in early childhood (3-4 years).
• Bone marrow becomes juicy, crimson-red, and resembles a crimson jelly.

Acute Myeloblastic Leukemia (AML)

• Occurs at any age, but most often in adolescents (peak at 15-20 years).
• Bone marrow acquires a greenish (pus-like) hue, also known as pioid marrow.

Common Characteristics of Acute Leukemias

• Proliferation of blasts without signs of differentiation.
• Infiltration of all hematopoiesis and parenchymatous organs with undifferentiated homogeneous cells.
• Leukocytosis with the presence of blasts in peripheral blood.
• Characteristic leukemia failure (hiatus leucemicus) - a sharp increase in blast cells and single mature elements in the absence of transient maturing forms.

Clinical Manifestations

• Lymph node enlargement is often observed with ALL and acute monocytic leukemia, but usually absent with AML.
• Enlargement of the spleen is relatively small, reaching 500-600 grams.
• Anemia is severe and rapidly developing, manifested by pallor of the skin and symptoms of hypoxia.
• Thrombocytopenia leads to petechial hemorrhages (hemorrhagic diathesis).
• Neutropenia manifests as frequent infectious diseases and ulceration (necrosis) on the mucous membranes of the oral cavity, tonsils, and gastrointestinal tract.
• Reduction of immunity and general reactivity of the organism is accompanied by activation of infections and development of alterative inflammation.

Chronic Leukemia

• Characterized by a gradual onset, slow progression, and a life expectancy of 10-15 years without treatment.

Chronic Lymphocytic Leukemia (CLL)

• More common in people older than 60 years
• Leukemia cells are represented by lymphoid cells of B-lymphocyte origin
• Unable to differentiate into antibody-producing cells
• Diffuse leukemia infiltration of the bone marrow, spleen, liver, and lymph nodes
• Often accompanied by autoimmune hemolytic anemia
• Average life expectancy of patients is 3 to 7 years, and treatment does not have a significant impact on it
• Spleen increases to 1 kg

Chronic Myelocytic Leukemia (CML)

• Occurs in all age groups, but most often in 40-50 years
• Leukemia cells are represented by myeloid cells - myelocytes, promyelocytes
• Often, the Philadelphia chromosome is identified: deletion of the 22nd chromosome due to reciprocal translocation between the 9th and 22 chromosomes
• Forming a hybrid bcr-abl gene responsible for the tumor transformation in this leukemia
• Bone marrow of flat and tubular bones acquires a pyoid appearance (pus-like)
• Spleen increases to 5-6 kg, with a tense capsule, gray-red in color with a brownish tint on the cut
• Small areas of white necrosis are visible under the capsule

Blast Crisis

• Develops in the terminal stage of chronic leukemia
• Blast forms of cells appear in the blood
• Disease sharply becomes heavier, and the current resembles acute leukemia
• Often ends in a fatal outcome

True Polycythemia

• Characterized by significant erythrocytosis, moderate granulocytosis, and thrombocytosis
• Splenomegaly and decreased erythropoietin level are present
• Tendency to thrombotic and thrombotic hemorrhagic complications
• Blast crisis possible in the terminal stage

Myelofibrosis

• Growth of fibrous tissue in bone marrow cavities
• Megakaryocytosis of bone marrow, leading to thrombocytosis
• Tumor growth factor of thrombocytes and TGF-p may cause fibroblast proliferation
• Anemia, poikilocytosis, and massive splenomegaly are expressed
• Blood precursors of granulocytes and erythrocytes of varying degrees of maturity are found
• Blast crisis possible

Paraproteinemic Leukemia

• Characterized by the ability of leukemia cells to synthesize homogeneous immunoglobulins or their fragments (paraproteins)
• Paraproteins form an M-gradient during plasma protein electrophoresis
• Allocate the following forms: myeloma, Waldenstrom's macroglobulinemia, Franklin heavy chain disease

Myeloma (Rustitsky-Kahler disease)

• Leukemic cells are B-lymphocytes and plasma cells producing Ig of one class (IgG, IgA, or light chains)
• Myeloma cells produce Ig that are filtered into urine and called "Bens-Jones protein"
• Myeloma cells are not detected in peripheral blood (aleukemic leukemia)
• Proliferating myeloma cells in bone marrow produce a factor that activates osteoclasts, leading to:
  • Foci of axillary resorption and osteoporosis
  • Pain in bones and frequent spontaneous fractures
  • Osteolysis leading to hypercalcemia and focal points of metastatic calcification