• Clinical science

Basics of hematology

Summary

Hematology is the study of blood and the disorders related to it. Human blood is composed of ∼45% cellular components and ∼55% plasma. Blood has many functions, including transporting oxygen, regulating body temperature, and supporting the immune system. The cellular component consists of three major cell types, all of which arise from hematopoietic stem cells located primarily in the bone marrow: red blood cells (RBCs), white blood cells (WBCs), and platelets. Red blood cells (RBC, erythrocytes) are hemoglobin-carrying cells that primarily transport oxygen. White blood cells (WBC, leukocytes) take the form of either granulocytes or lymphocytes. Granulocytes are part of the innate immune system and play a key role in the immune response to bacteria, fungi, and parasites. Lymphocytes are highly antigen-specific, meaning they are able to target specific infectious agents, primarily viruses. Platelets are the other major cellular component of blood and are small anucleate cells produced from megakaryocytes in the bone marrow. This learning card provides an overview of the production, morphology, and most important functions of blood cells.

Introduction

  • Function of blood
    • Transports oxygen, nutrients, metabolic waste products
    • Regulation of body temperature, signal transmission, acid-base homeostasis, and immune response
  • Composition of blood
    • 60–80 mL blood/kg body weight ≅ 5 L blood for an adult weighing 70 kg/154 lbs
    • 45% cellular components (→ hematocrit), 55% plasma
  • Production of blood
    • Location: bone marrow; the spleen and liver are the primary sites before birth
    • Hematopoietic stem cells can differentiate into any type of blood cell and give rise to all blood cells through the following two precursor cells:
      1. Lymphoid precursor cells: origin of lymphocytes and natural killer cells
      2. Myeloid precursor cells: origin of erythrocytes, granulocytes, and megakaryocytes
    • Left shift (or blood shift): an increase in immature precursor cells; (e.g., increase in band neutrophils with rod-shaped nuclei in response to acute inflammation) in the blood. In most cases, infection is the cause of a left shift.
    • A reactive increase of a cell line ends in "-cytosis" (e.g., leukocytosis); neoplastic increase is referred to as "-emia" (e.g., leukemia).

References:[1][2][3][4]

Bone marrow

Overview

Bone marrow is the spongy, soft tissue that fills the hollow spaces within cancellous (spongy) bone. It is composed of stromal cells and stem cells, which are the progenitors of all five blood cell lineages. Hematopoiesis is the main function of the bone marrow. It also filters aging RBCs and houses immune cells (e.g., plasma cells).

Red marrow Yellow marrow

Stromal cells of the bone marrow

Stromal cells do not participate in the process of hematopoiesis. However, they play a critical role in maintaining and regulating the process. These cells remove potentially harmful cells or products (e.g., self-reactive cells by clonal deletion).

Cells Characteristics
Adventitial reticular cells
Mesenchymal stem cells
Macrophages
  • Located around sinusoids, in the extravascular surface of the marrow

Growth factors for hematopoiesis

This section focuses on the effect of growth factors and cytokines on bone marrow. For systemic effects, see “The immune system.

Growth factor Characteristics Function
Stem cell factor

Granulocyte-monocyte colony-stimulating factor

(GM-CSF)

  • Produced by endothelial cells and T cells

Granulocyte colony-stimulating factor

(G-CSF)

Monocyte colony-stimulating factor

(M-CSF)

  • Promotes mitosis, differentiation, and activity of monocyte colony-forming units
Erythropoietin
Thrombopoietin
  • Primarily produced in the liver
  • Stimulates thrombopoiesis by promoting megakaryocyte colony-forming units

References:[5][3]

Red cell line - erythrocytes

Erythropoiesis: red blood cell (RBC, erythrocyte) production

Stages of RBC differentiation Causes of erythropoiesis pathology
RBC precursor cells
Proerythroblast
Erythroblast

RBC physiology

Diagnostic parameters

  • Hemoglobin (Hb)
    • Reference range: 13.5–17.5 g/dL; ; 12–16 g/dL
    • Clinical significance: anemia, ↑ polycythemia
    • Hb level is composed of the following components:
      • Heme
      • Globin
        • The globular protein from hemoglobin is a tetramer consisting of 4 individual subunits that bind heme. Between 95–98% of adult hemoglobin (Hb) is HbA1, which consists of two alpha chains and two beta chains.
        • Clinical significance: thalassemia
  • Hematocrit (HCT)
    • Cellular component of blood (erythrocytes account for 99% HCT)
    • Reference range: 41%–53%; 36%–46%
Description Reference value Decrease Increase
Mean corpuscular volume (MCV) Average volume of each RBC 81–100 fL (normocytic)

Microcytic RBCs (e.g., iron deficiency)

Macrocytic RBCs (e.g., in vitamin B12 deficiency)
Mean corpuscular hemoglobin (MCH) Average mass of hemoglobin in each RBC 27–34 pg (normochromic)

Hypochromic RBCs (e.g., iron deficiency)

Hyperchromic RBCs (e.g., in vitamin B12 deficiency)
Mean corpuscular hemoglobin concentration (MCHC) Calculated as hemoglobin/hematocrit: mean hemoglobin concentration of all RBCs 30–36 g/dL Possibly in iron deficiency, thalassemia E.g., in spherocytosis
Absolute Reticulocyte count The percentage of all erythrocytes that are reticulocytes. Represents erythropoietic activity. 0.5–1.5% Insufficient erythropoiesis (e.g., aplastic anemia) Increased erythropoiesis (e.g., secondary to hemolysis or blood loss)
Corrected reticulocyte count (RI) Absolute reticulocyte count × (patient hematocrit/normal hematocrit ) 1-3%
Reticulocyte production index (RPI)

Absolute reticulocyte count/reticulocyte maturation time × (patient hematocrit/normal hematocrit

In anemia: > 3 normal, < 2 inadequate
Red blood cell distribution width (RDW) Measure of the variation in the volume of red blood cells 13%–15% Increased variation in size (called anisocytosis) is a result of conditions that decrease RBC production (e.g. Vitamin B12 deficiency, iron deficiency, sideroblastic anemia).

Erythrocyte morphology and hemoglobin variants

References:[6][7][8][9][9][10][11][12][13][14]

White cell line - leukocytes

Definition Causes
Leukopenia
  • White cell count < 4,500/μL
Leukocytosis
  • White cell count > 10,000/μL
Leukemoid reaction
  • leukocyte alkaline phosphatase (LAP) score
  • Typically secondary to infections or drugs (e.g., steroids)
  • Associated with certain solid tumors (e.g., lung cancer, kidney cancer). Mimics a hematopoietic malignancy.

References:[15][16][17][18][19]

White myeloid cell line - granulocytes, mast cells, and monocytes

White myeloid blood cell (leukocyte) production

Granulocytes

Myeloid cell Characteristics Function Increase Decrease
Neutrophil granulocyte (neutrophil)
  • 50–65% of all leukocytes in the blood
  • Diameter: around 12 μm
  • Maturation: Band (immature) neutrophils develop into segmented (mature) neutrophils over the course of 4–5 days.
  • Migration to sites of inflammation (chemotaxis) → identification, destruction, and phagocytosis of extracellular infectious agents (bacteria, fungi)
  • Neutropenia (mild: 1000–1500 cells/μL; moderate: 500–1000 cells/μL; severe: < 500 cells/μL see “”Agranulocytosis”):

Eosinophil granulocyte (eosinophil)

  • 1–4% of all leukocytes
  • Eosinophilic (= acidophile) granules → stained pink/red on H&E stain
  • Diameter: around 12 μm
  • Histamine attracts eosinophils to the site of inflammation.
  • Immune response against parasites
  • Migration to the site of inflammation (chemotaxis) → release of immunoglobulins (IgE)
  • Limited phagocytic abilities

Basophil granulocyte

(basophil)

  • Around 1% of all leukocytes
  • Diameter: around 10 μm
  • Basophilic granules containing histamine and heparin often obscure the nucleus.
  • Surface receptors for IgE
  • Remain in the bloodstream for minutes before migrating into tissue
  • Basopenia

Monocyte

  • Around 3–7% of all leukocytes
  • Diameter: around 5–20 μm
  • Remain in the bloodstream for only around 8 hours before migrating to tissue
  • Monocytosis (> 500/μL or > 7%)

Mast cell

References:[20][21][9][22][23][24][25][26][27][28][29]

Lymphocytes

Lymphopoiesis (lymphocyte production)

Lymphocyte physiology

  • Concentration: 1000–4000/μL
    • Abnormal lymphocyte concentration: See table below.
Definition Causes
Lymphocytosis Increase in number of lymphocytes in the blood to > 4000/μL (absolute) or > 50% of all leukocytes (relative)
Lymphocytopenia (lymphopenia) Decrease in number of lymphocytes in the blood to <1000/μL (absolute) or < 20% of all leukocytes (relative)

Lymphocytes are constantly looking for "their" antigen. They account for 20–45% of all leukocytes in the blood!

Natural killer cells (NK cells)

  • NK cells arise from lymphoid precursor cells, but receptors can be activated with or without binding antibodies or a major histocompatibility complex.
    • Detection and destruction of cells that do not express MHC-I receptors
      • Cells infected with viruses (especially herpes viruses)
      • Tumor cells
    • Kill via
      • Induction of apoptosis (granzymes, perforin)
      • Antibody-dependent cell-mediated cytotoxicity (activated by binding of CD16)
    • Cytokine production: INF-γ and TNF-α
    • Function enhanced by IFN-α and IFN‑β, IL-2, IL-12

T-lymphocytes (T cells)

Subpopulations Important surface markers Function

Cytotoxic T cells (T-killer cells)

CD8 positive Recognize foreign (mostly viral) antigens presented via MHC-I and, depending on the scenario, trigger apoptosis or cell lysis of the presenting cell
T-helper cells They require antigen presenting cells equipped with MHC-II receptors → recognize presented antigens → cytokine release TH1 cells CD4 positive Initiate the cellular immune responsemacrophage stimulation
TH2 cells Initiate humoral immune response in cooperation with B lymphocytesimmunoglobulin production
TH17 cells Tissue inflammation, both pro- and anti-inflammatory
Regulatory T cells (Tregs, suppressor T cells) Limit and protect against excessive immune response
Memory T cells CD4 & CD8 positive Conservation/memory of a specific acquired immune response

Natural killer T cells (NKT cells)

B lymphocytes (B cells)

References:[31][19][32][33][34][35][36][37][37][38]

Agranulocytosis

References:[39][40]

Platelets

Platelet Production

Platelet physiology

  • Function: : forms plug in bleeding vessel (primary hemostasis)
  • Lifespan: circulation for 8–9 days
  • Concentration: 150,000 to 450,000/μLcells
    • Abnormal platelet production: See table below.
Definition Causes
Thrombocytosis Increase in number of platelets to > 400,000/μL (absolute)
Thrombocytopenia Decrease in number of platelets to < 150,000/μL (absolute)
  • See “Thrombocytopenia

References:[41]

Clinical significance