Hematopoiesis is de ned as the process whereby pluripo-tent hematopoietic stem cells self-renew and differentiate into all the specialized circulating blood cells, including white blood cells, red blood cells, and platelets (Fig. 3111). Hematopoiesis occurs in a specialized bone marrow micro-environment, composed of cellular and noncellular ele-ments critical to localization and control of blood cell pro-duction. Figure 3112 illustrates the various stages during the evolution of the mature discocytic red cell.

Red cell antigens and autoantibodies: blood group antigens are carbohydrate or protein determinants carried on various red blood cell (RBC) membrane components. Blood group autoantibodies have clinical relevance because they may cause hemolysis of transfused antigen-positive RBCs, and during pregnancy they may result in hemolytic disease of the newborn. Testing to detect antibody in a patients serum

is required before selection of donor blood for transfusion; it is also performed during pregnancy as part of standard prenatal care (Fig. 3113). The mechanisms of immune-mediated hemolysis following transfusion are illustrated in Figure 3114. Table 3111 shows the selection of ABO-compatible donor blood.

Granulocytopoiesis: neutrophils circulate in the peripheral blood for only 3 to 6 hours, requiring a constitutive high level of neutrophil production by the bone marrow. They arise from pluripotent stem cells under the in uence of cy-tokines, notably granulocyte and granulocyte-macrophage colony-stimulating factors, which induce an intricate tran-scriptional program that drives morphologic maturation and neutrophil-speci c gene expression. Figure 3115 illus-trates the differentiation schema of the neutrophil.

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311 Section 13: Blood

Chapter 311 Basic principles of hematology

Stemcell

LINEAGE COMMITMENT PROLIFERATION DIFFERENTIATION

White bloodcells

Progenitor cells Precursor cells

Red bloodcells

Platelets

Fig 3111Hematopoiesis.(From Young NS, Gerson SL, High KA [eds]: Clinical Hematology. St. Louis, Mosby, 2006.)

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Chapter 311: Basic principles of hematology 311 Immunity can be divided into innate and adaptive immune

responses. Major effector cells of the immune response in-clude natural killer (NK) cells, NK T cells, dendritic cells (DCs), macrophages, and granulocytes (Fig. 3116).

Megakaryocyte development: in megakaryocyte develop-ment, lineage commitment begins when a marrow stem cell

gives rise to a bipotent erythromegakaryocytic progenitor cell (see Fig. 3111). This cell can then further commit to development of either erythrocytes or megakaryocytes. Members of the GATA family of transcription factors, along with obligate cofactor FOG, play a major role in transcrip-tional regulation of megakaryocytopoiesis (Fig. 3117).

Enucleation

Immaturereticulocyte

Maturereticulocyte

Mature redblood cell

Fig 3112Transmission (left column) and scanning (right column) electron micrographs showing the various stages during the evolution of the mature disco-cytic red cell. The non-nucleated immature reticulocyte is produced when the normoblast extrudes its nucleus. The immature reticulocyte is multi-lobular and motile and contains mitochondria and ribosomes. These motile reticulocytes evolve rst to deep cup-shaped nonmotile mature reticu-locytes that contain ribosomes and nally to mature, fully hemoglobinized discocytic red blood cells lacking organelles.(From Young NS, Gerson SL, High KA [eds]: Clinical Hematology. St. Louis, Mosby, 2006.)

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311 Section 13: Blood

Anti-Areagent

A

Anti-Breagent

5%patientcells

5%patientcells

5%patientcells

Centrifuge and readfor agglutination

ABO AND RH TYPING SERUM ANTIBODY DETECTION

Centrifuge and readfor agglutination

37C Incubation

Centrifuge and readfor agglutination

B

Anti-Dreagent

D

A B D

Patientserum

A1cellsreagent

Bcellsreagent

A1

Patientserum

Patientserum

Patientserum

B

A1 B

Ab. det.cell Ireagent

Anti-IgGreagent

Ab. det.cell IIreagent

I

Anti-IgGreagent

II

3X wash

I II

I II

I II

Fig 3113Pretransfusion testing of recipient. The protocol includes typing the recipients red blood cells (RBCs) for ABO and Rh, and testing of the recipients serum (or plasma) for clinically signi cant blood group anti-bodies (antibody screen). Because the antibodies involved in ABO and Rh typing are IgM, the method used is direct agglutination. Because clinically signi cant antibodies are IgG, an indirect antiglobulin method is used. The nal step is a match between patient and donor by com-puter or by physically testing the patients serum against the selected donors RBCs. Ab. det., antibody detection.(From Young NS, Gerson SL, High KA [eds]: Clinical Hematology. St. Louis, Mosby, 2006.)

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Chapter 311: Basic principles of hematology 311INTRAVASCULAR HEMOLYSIS

EXTRAVASCULAR HEMOLYSIS

RBC

IgGantibody

IgMantibody

RBC

Fc receptor

Ingestion

Lysis

Spherocyteformation

IgGantibody

C1Complement

recognition unit

Reticuloendothelial cell

C2aC3C4bComplementactivation unit

C5b6789Membrane

attack complex

RBC lysis

Fig 3114Mechanisms of immune-mediated hemolysis following transfusion. RBC, red blood cell.(From Young NS, Gerson SL, High KA [eds]: Clinical Hematology. St. Louis, Mosby, 2006.)

TABLE 3111 Selection of ABO-compatible donor blood*

Recipients type Donor RBC type Donor plasma type

O O O A B AB

A A O A AB

B B O B AB

AB AB A B O AB

*Group O red blood cell (RBC) donors are called universal donors.From Young NS, Gerson SL, High KA (eds): Clinical Hematology. St. Louis, 2006, Mosby, 2006.

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311 Section 13: Blood

Proliferative pool:

Storage pool:

Surface markers:CD34

CD33

CD16

CD11b/CD18

Granules:1

2

3

Myeloblast Promyelocyte Myelocyte Metamyelocyte BandSegmentedneutrophil

Fig 3115Differentiation of the neutrophil. The morphologic stages of neutrophil maturation are correlated with marrow pool distribution, stage-speci c gran-ule production, and characteristic surface marker expression.(From Young NS, Gerson SL, High KA [eds]: Clinical Hematology. St. Louis, Mosby, 2006.)

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Chapter 311: Basic principles of hematology 311

Fig 3116Innate immune cells found in the peripheral blood. Shown are a monocyte, two natural killer (NK) cells, and a T lymphocyte.(From Young NS, Gerson SL, High KA [eds]: Clinical Hematology. St. Louis, Mosby, 2006.)

Erythro-megakaryocyticbipotentialprogenitor cell

Megakaryocyteprogenitor cellcompartment

GATA1+ FOG

Maturing megakaryocytes

NF-E2Fli-1HZf

Red blood cells

Platelets

Fig 3117Transcriptional regulation of megakaryocytopoiesis.(From Young NS, Gerson SL, High KA [eds]: Clinical Hematology. St. Louis, Mosby, 2006.)

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