Cell transfusion therapy

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. 

F. Role in therapy Epoetin alfa represents a major advance in the treatment of anemia associated with chronic renal failure. The hormone is an alternative to androgen and red blood cell transfusion therapy, which had been the mainstay of treatment. It may also provide an alternative for those patients who previously could not be treated with blood transfusions because of religious reasons. 

Harmatz P, Butensky E, Quirolo K, et al. Severity of iron overload in patients with sickle cell disease receiving chronic red blood cell transfusion therapy. Blood 2000 96 76-79. 

The first child S.Y. was initially treated with a calf thymic hormone extract (tP1 Serono Laboratories) but this produced no response. Red cell transfusion therapy initially given weekly and then every fortnight was accompanied by improvement in lymphocyte numbers,... 

Whole blood is seldom used ia modem blood transfusion. Blood is separated into its components. Transfusion therapy optimizes the use of the blood components, using each for a specific need. Red cell concentrates are used for patients needing oxygen transport, platelets are used for hemostasis, and plasma is used as a volume expander or a source of proteins needed for clotting of the blood. 

Cellular cytokines (interferons, G-CSF) and immune response modifiers originally produced from human cells, most often leukocytes, have now been replaced with recombinant products with well-defined structure/function. Futuristic advances in experimental hematology portend development of human blood cells produced from the hemopoetic stem cells. Yet for the foreseeable future, homologous blood donated by healthy, altruistic voluntary blood donors remains the principal source of safe and adequate supply of blood and blood products for transfusion therapy. 

Recommendations in this section may change based on the results from the recent EPO-3 trial (epoetin alfa versus placebo). A difference in red blood cell transfusion rates was not observed between groups. Epoetin alpha therapy improved survival in trauma patients. Epoetin alfa did not have a measurable clinical benefit in medical/surgical non-trauma patients. Epoetin alpha therapy was associated with an increased thrombotic event rate, particularly in patients not receiving pharmacological deep vein thrombosis prophylaxis. 

Chronic transfusion therapy programs have been shown to be beneficial in decreasing the occurrence of stroke in children with sickle cell disease. 

An important overall approach for treatment of sepsis is goal-directed therapy. Mortality can be reduced by early placement and use of a central venous catheter, increased fluid volume administration, dobutamine therapy if needed, and red blood cell transfusion, to achieve specific physiologic goals in the first 6 hours. Evidence-based treatment recommendations for sepsis and septic shock from the Surviving Sepsis campaign are presented in Table 45-3. 

Although research into stem cells is new, the use of stem cells for therapy has been with us for some time. Most of us are familiar with bone marrow transplant for patients with leukemia. This procedure involves finding a matching donor to harvest bone marrow stem cells and transfuse them into the patient with leukemia (see Exhibit 4.16 for details). 

F. Role in therapy According to Micromedex, the goal of therapy with Adagen is to correct immune function by reversal of the biochemical abnormalities caused by adenosine deaminase deficiency. Adagen s role in therapy at this time would appear to be as an alternative when bone marrow transplantation is not feasible or has been unsuccessful. It may also be considered in lieu of transplantation in milder cases of adenosine deaminase deficiency. Adagen is preferable to red cell transfusions in these patients. While regular administration of Adagen can improve immune function and reduce the incidence of opportunistic infections in patients with ADA-deficient SCID, it is of no value in patients with immunodeficiency due to other causes. 

Over the next several years, she had recurrent episodes of reactive airway disease. At the age of 4 years, she had a life-threatening episode of acute chest syndrome requiring admission to the intensive care unit and exchange transfusion. She was subsequently transfused with red blood cells monthly for 6 months to prevent recurrence. Two years later, she was again admitted to the intensive care unit with acute chest syndrome. During this admission, she was found to have Streptococcus pneumoniae sepsis and pneumonia. She again received RBC transfusions monthly for 6 months. Following this course of transfusion therapy, she was offered therapy with hydroxyurea, but this therapy was never instituted. 

For many years, blood transfusion has been a therapy for children and adults with sickle cell disease. Prior to the 1980s, due to the lack of availability of blood products and the standard of care at that time, transfusion was used infrequently and generally only for catastrophic complications of this disease. During the 1980s, the risk of infection through transfusion was so high that transfusion continued to be used infrequently. When reliable testing for infectious diseases (e.g., HTV and hepatitis) in blood products became available, the use of red cell transfusion became standard of care for complications of sickle cell disease. 

Iron therapy is indicated only for the prevention or cure of iron deficiency. In general terms, making 25 mg of iron per day available to the bone marrow will allow an iron deficiency anaemia to respond with a rise of 1% of haemoglobin (0.15 g Hb/100 ml) per day a reticulocyte response occurs between 4 and 12 days. An increase in the haemoglobin of at least 2 g/dl after 3 weeks of therapy is a reasonable criterion of an adequate response. Oral preparations are the treatment of choice for almost all patients due to their effectiveness, safety and low cost. Parenteral preparations should be restricted to the few patients unable to absorb or tolerate oral preparations. Red cell transfusion is necessary only in patients with severe symptomatic rmaemia or where chronic blood loss exceeds the possible rate of oral or parenteral replacement. 

Ex vivo therapeutic strategies may take different forms. Chronic lymphocytic leukemias have been treated for long periods of time by using cell separators to reduce the burden of lymphocytosis, and to permit red cell transfusion. Laser-directed cell sorters may be used to select appropriate subpopulations of lymphocytes, which are then transfected with an appropriate gene product ex vivo and returned to the patient, where these cells will hopefully target some diseased tissue such as widespread melanoma. Expense, availability of therapy and the duration and specificity of effect currently limit the widespread application of these approaches. 

Splenic sequestration crisis is a major cause of mortality in young patients with SCD. The sequestration of RBCs in the spleen may result in a rapid drop of hematocrit, leading to hypovolemia, shock, and death. Immediate treatment is red cell transfusion to correct hypovolemia. Broad-spectrum antibiotic therapy, which includes coverage for pneumococci and H. influenzae, may also be beneficial, because infection may precipitate crises. " ... 

Scothorn DJ, Price C, Schawartz D, et al. Risk of recurrent stroke in children with sickle cell disease receiving blood transfusion therapy for at least five years after initial stroke. J Pediatr 2002 140 348-354. 

Russell MO, Goldberg HI, Hudson A, et al. Effect of transfusion therapy on arteriographic abnormahties and on recurrence of stroke in sickle cell disease. Blood 1984 63 162-169. 

Early goal-directed therapy of sepsis consisting of hemodynamic monitoring with a central venous catheter, volume resuscitation, inotropic therapy, and red blood cell transfusions demonstrated a significant clinical outcome benefit with a 16% absolute reduction in 28-day mortality. 

These drugs find clinical utility in settings such as prevention of rebleeding in intracranial hemorrhages, as adjunctive therapy in hemophilia, and of course, in treatment of bleeding associated with fibrinolytic therapy. In most bleeding conditions, however, -aminocaproic acid therapy has not been shown to be of definitive benefit. In recent trials, tranexamic acid was found to reduce red cell transfusion better than -aminocaproic acid or placebo in patients undergoing liver transplantation (136). 

Shander A, Sazama K. Clinical consequences of iron overload from chronic red blood cell transfusions, its diagnosis, and its management by chelation therapy. Transfusion 2010 50(5) 1144—55. 

Severe combined immunodeficiency (SCID) due to adenosine deaminase deficiency (ADA) exhibits autosomal recessive inheritance, and may account for up to 209 of cases (l). Accumulation of intracellular toxic deoxynucleotides and/or S-adenosyl homocysteine particularly in T cells, is considered responsible for the severe lymphoid depletion and dysfunction observed in affected children (2). Unlike other forms of SCID, this variety is amenable to enzyme replacement therapy using regular fresh irradiated red blood cell transfusions as the source of enzyme. Another form of therapy suggested from in vitro studies, is the use of deoxycytidine which theoretically would act as a competitive substrate for deoxycytidine kinase, the enzyme considered responsible for the intracellular accumulation of deoxy-ATP (dATP). This study reports our experience of various treatments in three ADA deficient children. 

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