White blood cells production

Hearn, T., Haurie, C., and Mackey, M., Cyclical neutropenia and the peripheral control of white blood cell production, Journal of Theoretical Biology, Vol. 192, No. 2, 1998, pp. 167-181. 

Synthetic growth factors are being used to stimulate normal white blood cell production following cancer treatments and bone marrow transplants. 

The finite life span of most mature blood cells requires their continuous replacement, a process termed hematopoiesis. New cell production must respond to basal needs and states of increased demand. Red blood cell production can increase >20-fold in response to anemia or hypoxemia, white blood cell production increases dramatically in response to a systemic infection, and platelet production can increase 10-20-fold when platelet consumption results in thrombocytopenia. 

Hematopoietic growth factors also have been produced in mammalian cell cultures by recombinant DNA techniques. Erythropoietin can be used in certain types of anemias to stimulate the production of red blood cells. Colony-stimulating factors (CSFs) and interleukins (ILs) can be used after bone marrow transplants and after chemotherapy to stimulate white blood cell production and decrease the risk of infection. 

This medication stimulates white blood cell production. 

The client receiving a red blood stimulant (Epogen, Procrit, Aranesp) should have the blood pressure monitored because rapid increases in the hematocrit will also increase the blood pressure, but this does not happen with Neulasta, which stimulates white blood cell production. 

High-dose ciclosporin markedly raises etoposide serum levels and increases the suppression of white blood cell production. Severe toxicity has been reported in one patient. 

Primary blood components iaclude plasma, red blood cells (erythrocytes), white blood cells (leukocytes), platelets (thrombocytes), and stem cells. Plasma consists of water dissolved proteias, ie, fibrinogen, albumins, and globulins coagulation factors and nutrients. The principal plasma-derived blood products are siagle-donor plasma (SDP), produced by sedimentation from whole blood donations fresh frozen plasma (FFP), collected both by apheresis and from whole blood collections cryoprecipitate, produced by cryoprecipitation of FFP albumin, collected through apheresis and coagulation factors, produced by fractionation from FFP and by apheresis (see Fractionation, blood-plasma fractionation). 

Packed red cells are prepared from whole blood. These are collected ia blood coUectioa units having integrally attached transfer packs. The red cells are sedimented by centrifugation, and the plasma and huffy coat are expressed from the bag. Further processiag of the packed red cells may be needed for a number of clinical indications. To reduce the white blood cell (WBC) contamination in a red cell product, two separation techniques are used. 

Filtration Filtration (qv) is appHed in blood cell separation to remove leukocytes from ted blood cell (RBC) and platelet concentrates. Centtifugational blood cell separators do not reduce white blood cells (WBC) in red cell and platelet products sufficiently to avoid clinical complications such as GvHD and alloimmunization. A post-apheresis filtration step is needed to further reduce the WBC load. Modem filters are capable of a 3-log reduction in white cell contamination of the blood product, eg, apheresis single-donor platelet units having a typical white cell contamination of 5 x 10 white cells in 4 x 10 platelets can be reduced to a 5 x 10 white cell contamination, a sufficiently low number to avoid severe transfusion reactions. 

There are undifferentiated stem cells of the blood elements in the bone marrow that differentiate and mature into erythrocytes, (red blood cells), thrombocytes (platelets), and white blood cells (leukocytes and lymphocytes). The production of erythrocytes is regulated by a hormone, erythropoietin (see the section on kidney toxicity), that is synthetized and excreted by the kidney. An increase in the number of premature erythrocytes is an indication of stimulation of erythropoiesis, i.e., increased production of erythrocytes in anemia due to continuous bleeding. 

MANAGING HONE MARROW SUPPRESSION. Bone marrow suppression is a potentially dangerous adverse reaction resulting in decreased production of blood cells. Bone marrow suppression is manifested by abnormal laboratory test results and clinical evidence of leukopenia, thrombocytopenia, or anemia For example, there is a decrease in the white blood cells or leukocytes (leukopenia), a decrease in the thrombocytes (thrombocytopenia), and a decrease in the red blood cells, resulting in anemia Fhtients with leukopenia have a decreased resistance to infection, and the nurse must monitor them closely for any signs of infection. 

MANY GROWTH FACTORS REGULATE PRODUCTION OF WHITE BLOOD CELLS... 

Serum concentrations of D-dimer, a by-product of thrombin generation, is usually elevated. The patient may have an elevated erythrocyte sedimentation rate (ESR) and white blood cell (WBC) count. 

Leukopenia A reduction in the circulating white blood cell count also a condition in which the number of circulating white blood cells is abnormally low due to decreased production of new cells, possibly in conjunction with medication toxicities. 

Most cytokines act upon, or are produced by, leukocytes (white blood cells), which constitute the immune and inflammatory systems (Box 8.1). They thus play a central role in regulating both immune and inflammatory function and in related processes such as haematopoiesis (the production of blood cells from haematopoietic stem cells in the adult bone marrow), as well as in wound healing. Indeed, several immunosuppressive and anti-inflammatory drugs are now known to induce their biological effects by regulating production of several cytokines. 

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.)... 

Mylotarg (like most other drugs) does induce some side effects, the most significant of which is immunosuppression. This is induced because certain additional (non-cancerous) white blood cell precursors also display the CD33 antigen on their surface. The immunosuppressive effect is reversed upon termination of treatment, as pluripotent haematopoietic stem cells (Chapter 10) are unaffected by the product. 

Cyclosporine reduces production of cytokines involved in T-cell activation and has direct effects on B cells, macrophages, bone, and cartilage cells. Its onset appears to be 1 to 3 months. Important toxicities at doses of 1 to 10 mg/kg/day include hypertension, hyperglycemia, nephrotoxicity, tremor, GI intolerance, hirsutism, and gingival hyperplasia. Cyclosporine should be reserved for patients refractory to or intolerant of other DMARDs. It should be avoided in patients with current or past malignancy, uncontrolled hypertension, renal dysfunction, immunodeficiency, low white blood cell or platelet counts, or elevated Ever function tests. 

Acridinium ester—labeled chemiluminescent probes have been utilized to detect the specific protein-coding transcripts and to distinguish between transcripts that code for the 190-kDa protein and the two closely related 210-kDa proteins. The assay is called the hybridization protection assay (D3). In this assay, RNA isolated from the patient s white blood cells is first amplified by PCR. The amplified product is incubated with the chemiluminescent probe. The unhybridized probe is removed by selective hydrolysis in sodium tetraborate buffer, containing surfactant Triton X-100 at pH 8.5, in an incubation step at 60°C for 6 min. After the sample is cooled to room temperature, the chemiluminescence of the hybridized probe is measured in a luminometer. The procedure is reported to detect one leukemic cell in a population of a million or more normal cells. It is also rapid, requiring less than 30 min. Its reliability has been attested to by correlation with results obtained on karyotypic and Southern blot analysis (D3). 

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