Blood cells Neutrophils Platelets

A basic understanding of normal hematopoiesis is needed before one can understand the pathogenesis of leukemia. The reader is referred to Chap. 98 for a detailed discussion of hematopoiesis. Normal hematopoiesis consists of multiple well-orchestrated steps of cellular development. A pool of pluripotent stem cells undergoes differentiation, proliferation, and maturation, to form the mature blood cells seen in the peripheral circulation. These pluripotent stem cells initially differentiate to form two distinct stem cell pools. The myeloid stem cell gives rise to six types of blood cells (erythrocytes, platelets, monocytes, basophils, neutrophils, and eosinophils), while the lymphoid stem cell differentiates to form circulating B and T lymphocytes. Leukemia may develop at any stage and within any cell line. 

Labeling of blood cells has gained importance as routine procedure in nuclear medicine. A variety of different blood cells such as red blood cells (RBC), platelets, and white blood cells ([WBC] neutrophils, lymphocytes and monocytes and recently stem cells) can be radiolabeled and applied for diagnosis and therapeutic monitoring in specific disease states. 

Several cytokines are in clinical use that support immune responses, such as IL-2, DFNs, or colony-stimulating factors. IL-2 supports the proliferation and effector ftmction of T-lymphocytes in immune compromised patients such as after prolonged dialysis or HIV infection. IFNs support antiviral responses or antitumoral activities of phagocytes, NK cells, and cytotoxic T-lymphocytes. Colony-stimulatory factors enforce the formation of mature blood cells from progenitor cells, e.g., after chemo- or radiotherapy (G-CSF to generate neutrophils, TPO to generate platelets, EPO to generate erythrocytes). 

Table 52-11. Examples of integrins that are important in the function of neutrophils, of other white blood cells, and of platelets. ...

Lipoxygenases catalyse the regio-specific and stereoselective oxygenation of unsaturated fatty acids. The mammalian enzymes have been detected in human platelets, lung, kidney, testes and white blood cells. The leukotrienes, derived from the enzymatic action of the enzyme on arachidonic acid, have effects on neutrophil migration and aggregation, release of lysosomal enzymes, capillary permeability, induction of pain and smooth muscle contraction (Salmon, 1986). 

Hematopoiesis is defined as the development and maturation of blood cells and their precursors. In utero, hematopoiesis may occur in the liver, spleen, and bone marrow. However, after birth, it occurs exclusively in the bone marrow. All blood cells are generated from a common hematopoietic precursor, or stem cell. These stem cells are self-renewing and pluripotent and thus are able to commit to any one of the different lines of maturation that give rise to platelet-producing megakaryocytes, lymphoid, erythroid, and myeloid cells. The myeloid cell line produces monocytes, basophils, neutrophils, and eosinophils, whereas the lymphoid stem cell differentiates to form circulating B and T lymphocytes. In contrast to the ordered development of normal cells, the development of leukemia seems to represent an arrest in differentiation at an early phase in the continuum of stem cell to mature cell.1... 

The G-CSF receptor has been well characterized. It is a single transmembrane polypeptide found on the surface of neutrophils, as well as in various haemopoietic precursor cells, platelets, endothelial cells and, notably, various myeloid leukaemias. (Myeloid means derived from bone marrow leukaemia refers to a cancerous condition in which there is uncontrolled overproduction of white blood cells in the bone marrow or other blood-forming organs. The white cells produced are generally immature/abnormal and result in the suppression of production of healthy white blood cells.)... 

Lead exposure Not a substitute for effective abatement of lead exposure. Neutropenia Mild to moderate neutropenia has been observed in some patients receiving succimer. While a causal relationship to succimer has not been definitely established, neutropenia has been reported with other drugs in the same chemical class. Obtain a complete blood count with white blood cell differential and direct platelet counts prior to and weekly during treatment. Withhold or discontinue therapy if the absolute neutrophil count (ANC) is below 1200/mcL and follow the patient closely to document recovery of the ANC to above 1500/mcL or to the patient s baseline neutrophil count. There is limited experience with reexposure in patients who have developed neutropenia. Therefore, rechallenge such patients only if the benefit of succimer therapy clearly outweighs the potential risk of another episode of... 

Figure 5.2 All types of blood cells are formed from uncommitted blood (hematopoietic) stem cells in a process called differentiation. Specific protein factors drive the development of erythrocytes (red blood cells), platelets, and the w/hite blood cells including neutrophils and eosinophils, basophils, all with multi-lobed nuclei, and the mononuclear monocytes and lymphocytes that provide specific protein and cellular defenses to the body.

The existence of some blood cells, such as erythrocytes and platelets, with long lifespans make cell transfusion therapy practical. Cell transfusion therapy cannot be developed for short-lived cells such as neutrophils with turnover rates of less than 8 hours. Fortunately, for neutrophils, colony stimulating factors can be used to recruit the needed number in blood within 24 hours after administration of these factors. 

Histamine Release. Histamine release is mainly caused by cross-linking of immunoglobulin E on the mast cell surface by antigens. Basophil degranulation is caused mainly by histamine-releasing factors produced by inflammatory cells, such as neutrophils, platelets, and eosinophils. After its release, histamine diffuses rapidly into the blood stream and surrounding tissues. 

While confirming the general normality of the mutant mice and problems with lymphocyte homeostasis, these studies focused on identifying defects in peripheral leukocytes. The Lsc- - mice had a twofold increase in circulating neutrophils and lymphocytes but normal platelet counts and red blood cells. In functional studies, the Lsc-/ neutrophils showed a reduced ability to stimulate formation of Rho-GTP and abnormal pseudopod development in response to fMLP. An increased motility and lower adherence of the neutrophils when stimulated with fMLP (Francis et ah, 2006) are similar to the behavior of B cells from Lsc / mice when stimulated with serum (Girkontaite et ah, 2001). While these studies imply a role for a G12/i3 Lsc-RhoA pathway in the phenotypes of these cells, the molecular details are not yet known. 

Fig. 6.1. Scanning electron micrographs showing the different surface textures of red (Er) and white blood cells. A Cells within a blood vessel. B,C A comparison of scanning electron micrographs with conventional light microscope images of the same field of stained cells. Enlarged pictures at the right emphasize the different surface textures of monocytes (Mo) and platelets (PI) in D, lymphocytes (Ly) in E, and neutrophils (Ne) in F. From Kessel RG and Kardon RH (1979). Tissues and Organs A Text Atlas of Scanning Electron Microscopy, WH Freeman, NY.

Adenosine, in addition to serving as a substrate for the generation of cAMP plays a physiologic role as a platelet inhibitor and a vasodilator and may attenuate neutrophil-mediated damage to endothelial cells, Adenosine diphosphate (ADP)— a potent platelet agonist—is converted to adenosine, which is taken up rapidly by cells, especially erythrocytes and endothelial cells, A small proportion is metabolized to the aforementioned cyclic nucleotides. The remainder is broken down to inosine and subsequently to xanthine. Dipyridamole inhibits the active transport of adenosine into cells, but does not interfere with the passive diffusion. Since the platelet inhibitory effects of adenosine proceed via stimulation of adenylate cyclase, these effects can also be amplified by dipyridamole, In circulating blood, the largest amount of adenosine is found in red blood cells, This may, in part, help explain why dipyridamole is much more effective in whole blood than in plasma. 

Bone marrow Suppression of bone marrow function can lead to significant reduction in white blood cells, platelets, anemia, and neutrophils caused by almost all anticancer drugs. 

Moderate depression Decrease dose by 50%. If condition remains stable, continue reduced dosage. If symptoms improve and are stable for > 4 weeks, continue reduced dosage regimen or return to normal dose Severe depression Discontinue PEG-interferon a-2b permanently White blood cell count neutrophil count <750/mm or platelet count <80,000/mm Decrease dose by 50%... 

Hemoglobin <8.5 g/dL, white blood cell count neutrophil count <500/mm5 or platelet count <50,000/mm Permanently discontinue therapy... 

Such microvesicles have size variable between 50 nm to 1 (xm and differ from other vesicles (like exosomes (30-100 nm)). In general, microparticles are phospholipids vesicles derived from eukaryotic cells as a result of different types of stimulation. Microparticles can also be defined as phospholipids microvesicles containing certain membrane proteins originating from the parental cell. Microparticles circulate in the blood and contribute to numerous physiological processes. MPs have been described in various haematopoietic cells as platelets (Heijnen et al. 1999), T-cells (Blanchard et al. 2002), polynuclear neutrophils (Mesri and Altieri 1999) or dendritic cells. After have been considered as cell dust, MPs are now considered to reflect cell activation. Platelet derived microparticles have been the most extensively studied until now. They are now accepted to play an important role in the procoagulant... 

The circulatory system contains a number of types of cells. Nearly half of the volume of whole blood consists of red blood cells whereas only about / of the blood consists of white blood cells. The function of the red blood cells is to transport ojtygeri to the tissues. White blood cells are part of the immune system. There are several types of white blood ceils neutrophils, macrophages, and lymphocytes. Neutrophils are also called polymorphonuclear leukocytes. The smallest type of ceil in the bloodstream is the platelet. Platelets are used in the clotting of blood, as outlined under Vitamin K. 

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