Hematology is the study of blood and the disorders related to it. Human blood consists of blood cells and plasma. Blood has many functions, including transporting oxygen and nutrients to tissues, removing waste materials (e.g., carbon dioxide, urea), regulating body temperature, and carrying cells responsible for coagulation and immune response. There are three main types of blood cells, all of which originate from , which are located primarily in the bone marrow: red blood cells (RBCs; erythrocytes), white blood cells (WBCs; leukocytes), and platelets (thrombocytes). RBCs are hemoglobin-carrying cells that primarily transport oxygen. There are two types of WBCs: granulocytes and lymphocytes. Granulocytes are part of the innate immune system and play a key role in the immune response to bacteria, fungi, and parasites. Lymphocytes include cells that are responsible for both the innate (natural killers) and adaptive (T and B cells) immune system. T and B cells, in contrast to the cells involved in innate immunity, can target specific antigens presented to them by . Platelets, small anucleate cells produced by megakaryocytes, are required for hemostasis.
Functions of blood 
- Transport of:
- Protection from pathogens
- Regulation of body temperature, signal transmission, and acid-base homeostasis
- On average, blood constitutes ∼ 7% of the total body weight of adults (∼ 70 mL/kg). 
- The actual circulating blood volume varies and depends on age, weight, and height.
- For children ≥ 35 kg, adolescents, and adults, the total blood volume can be estimated using the Nadler equation: 
- Men: BV = (0.3669 × H3) + (0.03219 × W) + 0.6041
- Women: BV = (0.3561 × H3) + (0.03308 × W) + 0.1833
- BV: blood volume in liters
- H: height in meters
- W: weight in kilograms
- For neonates, infants, and children up to 14 years, the following estimates can be used: 
|Blood volume in individuals of different age|
|Age||Estimated blood volume (mL/kg)|
Blood constituents 
- Plasma: ∼ 55%
- Blood cells: ∼ 45%
|Overview of blood cell types|
|Blood cells in peripheral tissue|
Never Let Monkeys Eat Bananas: Neutrophils > Lymphocytes > Monocytes > Eosinophils > Basophils.
Bone marrow and hematopoiesis
Bone marrow 
|Types of bone marrow|
|Characteristic||Red marrow||Yellow marrow|
|Composition|| || |
Stromal cells of the bone marrow 
Cells of the stromal compartment of bone marrow are not hematopoietic themselves, but they play a critical role in maintaining and regulating hematopoiesis (e.g., by removing potentially harmful cells and substances).
- Adventitial reticular cells
- Mesenchymal stem cells
- Macrophages: : located around sinusoids, in the extravascular surface of the marrow
Hematopoiesis (blood cell production) 
Definition: Hematopoiesis is the process by which multipotent hematopoietic stem cells differentiate into either myeloid or lymphoid precursor cells and, eventually, into mature blood cells. ; 
- Myeloid precursor cells develop into erythrocytes, granulocytes, or megakaryocytes.
- Lymphoid precursor cells develop into lymphocytes or natural killer cells
- Hematopoietic stem and progenitor cells express the transmembrane protein CD34 (used as a marker to identify and enrich hematopoietic stem cells in bone marrow transplantation). 
- Dendritic cells may derive from myeloid or lymphoid precursors. 
- Hematopoietic growth factors influence the differentiation and maturation of blood cells in all stages of their development.
- Some interleukins (e.g, , ) also act as hematopoietic growth factors. See “ ” for more information.
|Overview of hematopoietic growth factors|
|Growth factor||Produced by||Function|
|Stem cell factor (SCF)|| |
|Erythropoietin (EPO)|| |
|Thrombopoietin (TPO)|| |
RomiPLoSTIM STIMulates PLatelets. SarGRaMoSTIM STIMulates GRanulocytes and Monocytes.
Erythropoiesis (RBC production) 
- During embryogenesis/fetal development
- After birth: red bone marrow
- Duration: approx. 1 week (production and maturation)
- Regulation: primarily EPO, along with other hematopoietic growth factors, including GM-CSF, stem cell factor, and IL-3
In bone marrow
- Hematopoietic stem cell (erythroid progenitor cell)
- Proerythroblast: large cells with basophilic cytoplasm and a large nucleus
- Erythroblast: smaller nucleus than proerythroblasts; no nucleoli
- Normoblast: increasingly acidophilic cytoplasm with a compact nucleus
- Reticulocyte: acidophilic cytoplasm with granules composed of cytoplasmic ribosomal RNA (enabling reticulocytes to be stained with methylene blue)
- Reticulocytes are released into the blood.
- After 1–2 days, reticulocytes mature into erythrocytes.
- In bone marrow
To recall the sequence of prenatal erythropoiesis sites, think Young Livers Synthesize Blood: Yolk sac, Liver, Spleen, Bone marrow.
RBC morphology and physiology
- Definition: the process by which granulocytes, monocytes, and mast cells develop from myeloid precursor cells
- Location: bone marrow
- Duration: 6 days 
Stages of development
- Granulocytes (granulopoiesis) : pluripotent hemopoietic stem cell → common myeloid precursor cell → myeloblast → promyelocyte → eosinophilic, neutrophilic, or basophilic myelocyte → metamyelocyte → band cell → granulocyte (eosinophil/neutrophil/basophil)
- Monocytes: pluripotent hemopoietic stem cell → common myeloid precursor cell → myeloblast → monoblast → promonocyte → monocyte
- Mast cells: pluripotent hemopoietic stem cell → common myeloid precursor cell → mast cell
- Granulocytes make up the largest portion of WBCs: 1,500–8,500/mm3. 
- An increase (granulocytosis) or decrease (granulocytopenia) usually contributes the most to changes in the total WBC count (see “ ” and “ ”).
- See also “Hematological parameters” in “ .”
|Types of granulocytes|
|Cell||Characteristics||Function||Causes of increase||Causes of decrease|
|Neutrophil granulocyte|| || || |
| || || |
| || |
- Definition: absence of granulocytes or severe neutropenia (usually defined as absolute neutrophil count of < 500/mm3)
Etiology and pathophysiology 
Drug-induced agranulocytosis (∼ 70% of cases) 
- Immune-mediated mechanism (type II hypersensitivity reaction): Drugs or drug-protein complexes stimulate the development of antibodies against granulocytes.
- Drug toxicity mechanism: direct damage to myeloid precursors
- Drug-independent agranulocytosis (∼ 30% of cases) 
- Drug-induced agranulocytosis (∼ 70% of cases) 
- Clinical features: triad of aphthous stomatitis, sore throat ( ), and fever
- Prevention: monitoring of WBC and differential after starting drugs that can cause agranulocytosis
Monocytes, macrophages, and mast cells ]
|Characteristics of tissue-residing immune cells|
|Cell type||Characteristics||Function||Causes of increase||Causes of decrease|
|Monocyte|| || || |
|Mast cell || || |
Lymphopoiesis (lymphocyte production) 
- Stages of development: pluripotent hematopoietic stem cell → lymphoid progenitor cell → T cell, B cell, or NK cell
- Location of lymphopoiesis: initially in the bone marrow
During the lymphocyte lifecycle, several mechanisms ensure that T and B cells respond to a large variety of foreign antigens, while not reacting to self-antigens.
- Somatic recombination: Random recombination of gene segments coding for lymphocyte receptors enables a cell to specialize in responding to a specific antigen.
- Central tolerance: apoptosis induced in autoreactive cells (respond to self-antigens)
- Mature lymphocytes circulate through the bloodstream, migrate into tissue, and return to the blood via lymphatic vessels.
- Peripheral tolerance: Mature cells that respond to self-antigens become anergic (lose their function) or undergo apoptosis.
- For more detailed information about T- and B-cell maturation and selection, see “ .”
- During the lymphocyte lifecycle, several mechanisms ensure that T and B cells respond to a large variety of foreign antigens, while not reacting to self-antigens.
- Concentration (blood)
- Function: part of the acquired immune system; see “ ”
- All mature T cells express specific surface proteins that distinguish them from other lymphocytes and allow them to recognize antigens presented by MHC molecules of .
- General T cell markers: CD3, CD28,
- The difference in surface protein expression (e.g., CD4 vs. CD8) determines the specific function of .
- Subtypes: T cells can be largely divided into CD8+ T cells (cytotoxic T cells) and CD4+ T cells (T helper cell subpopulations). See “.”
- Definition: CD4+ T cell levels divided by CD8+ T cell levels
Natural killer T cells (NKT cells) 
- Function: part of the antibody production); s (esp. ee “ ”
Surface markers include:
- BCR) (
Natural killer cells (NK cells) 
- Can arise from both lymphoid and myeloid precursor cells 
- Surface markers
- Produce IFN-γ and TNF-α (proinflammatory cytokines that recruit macrophages and promote phagocytosis)
- Stimulated by IFN-α, IFN‑β, IL-2, and IL-12
Mechanism of action
- NK cells are activated under the following conditions:
Mechanisms for pathogen elimination
- Induction of apoptosis, e.g., via the following enzymes:
- Antibody-dependent cell-mediated cytotoxicity (activated by CD16-binding Fc region of bound IgG)
Thrombopoiesis (platelet production) 
- Location: bone marrow
- Duration: ∼ 1 week for production and maturation
- Stages of thrombopoiesis: myeloid precursor cell → megakaryoblasts → megakaryocytes → platelets
- Lifespan: 8–10 days
- Function: primary hemostasis 
- Platelet granules