alternatives to whole blood transfusion

Alternatives to Blood Transfusion
Name of the Student
Professor’s Name
Abstract
Blood transfusion has been recognized as a lifesaving intervention. However, there are different risks and adverse reactions that limit the use of whole blood transfusion. There are various complications associated with whole blood transfusion. These complications are either infectious or non-infectious. Transfusion-related infections are less pronounced than non-infectious complications. Indications for RBC transfusion are symptomatic anemia, sickle cell anemia and severe blood loss (representing greater than 30% of total blood volume). Fresh-frozen plasma is implicated for reversing the anticoagulant effects. On the other hand, platelet transfusion is indicated for preventing hemorrhage in patients suffering from thrombocytopenia. One of the major risks of transfusing fresh-frozen plasma is Transfusion Associated lung injury (TRALI). TRALI is featured by acute hypoxia and non-cardiogenic pulmonary edema, which results within 6 hours of fresh-frozen plasma transfusion. Most patients suffering from TRALI recover within three days (with ventilator support, while 5% – 25% patients suffer from fatal outcomes. Hence, use of blood substitutes is mandated for addressing the needs of whole blood transfusion. Growth factors like ESAs (Epoetin-alpha and Darbepoetin-alpha) and CSFs (Filgrastim and Pefilgrastrim) are effective in reducing the need for whole blood transfusion and for managing neutropenia in elder ovarian cancer patients.

Iron –dextran and iron sucrose infusion are effective in alleviating the need for blood transfusion in elective and non-elective orthopedic surgeries. Combined administration of erythropoietin, iron, vitamin B12 and folic acid in individuals (with less than 32 weeks gestational age), significantly reduced the need for whole blood transfusion compared to control subjects
Keywords: “Growth factors” “TRALI” “Iron Folic Acid” “Iron-Sucrose” “Indications” “Blood Transfusion
Alternatives to Blood Transfusion
Growth Factors and Blood Transfusion
The possibilities of hematopoietic growth factors as alternatives to whole blood transfusion have been elucidated in different studies. The role of an erythropoietin-stimulating agent (ESA) and GM-CSF (granulocyte colony stimulating factor) in reducing the need of whole blood transfusion was evaluated in elderly patients suffering from ovarian cancer (Poonawalla et al, 2016). The SEER –Medicare database (Surveillance Epidemiology and End Results-Medicare database) was evaluated for selecting the study participants. The study population comprised of 5572 women (suffering from stage III and stage IV ovarian cancer). Patients were categorized based on the number of infusions of ESA (Epoetin-alpha and Darbepoetin-alpha) and CSF (Filgrastim and Pefilgrastrim). Survival rate was considered as the end point o the study. The survival rates were evaluated in individuals who received either one of the specific therapies (ESA only, CSA only, ESA +CSA based regimes). These growth factors were anticipated to promote erythropoiesis and for increased differentiation of pluripotent stem cells to reticulocytes. Both these mechanisms are effective in addressing blood loss and for alleviating the need of whole blood transfusion. Individuals, who received ESA, had a 48% – 56% reduction in the need for whole-blood transfusion. On the other hand, patients receiving three prophylactic administrations of Filgrastim had 71% – 98% lower risk of neutropenia. The overall survival rate was significantly higher in individuals receiving Pefilgrastim only. However, the risk of mortality was significantly higher in individuals, who received ESA only (p=0.0005). Hence, it was concluded that ESAs effectively reduce the need for whole blood transfusion. On the other hand, GSFs were effective in reducing the prevalence of neutropenia in elder ovarian cancer patients (Poonawalla et al., 2016).
Blood transfusion and risk of TRALI
Transfusion of fresh frozen plasma has been associated with various risks. One of the major risks of transfusing fresh-frozen plasma is Transfusion Associated lung injury (TRALI). TRALI is featured by acute hypoxia and non-cardiogenic pulmonary edema that occurs within 6 hours of blood transfusion. Most patients suffering from TRALI recover within 3 days (with respiratory support, while 5% – 25% patients suffer from fatal outcomes. TRALI is caused due to accumulation and activation of neutrophils in the pulmonary endothelium. The development of TRALI has been explained by the “Two-Hit” hypothesis. The first hit implicates the role of a recipient factor (within the host) that primes neutrophils, which are present in the pulmonary epithelium. The second hit implicates the role of a mediator (which is present in the transfused fraction) that activates the primed neutrophils. As a result, the increased exudation of neutrophils leads to permeability edema. The different mediators for TRALI include antibodies towards transfused WBCs (Pandey & Vyas, 2012). These antibodies react with the antigens present within the transfused WBCs and generate inappropriate immune responses. The authors reported that donor-derived HLA (Human Leukocyte Antigen) and donor-derived (Human Neutrophil Antigen) had been implicated in the genesis of TRALI. Transfusion of WBC antibodies (along with cognate antigens) leads to agglutination of neutrophils. Agglutination of neutrophils leads to the generation of reactive oxygen species, the release of different enzymes and release of inflammatory mediators. All such mechanisms damage the pulmonary endothelium and lead to permeability edema. HLA Class II antibodies have been implicated in the genesis of TRALI. These antibodies indirectly activate primed neutrophils by activating monocytes and by stimulating the release of different cytokines (like TNF-alpha and IL-1 beta). These cytokines increase the activation and accumulation of neutrophils in the pulmonary endothelium (Pandey & Vyas 2012).
Iron and Folic Acid Supplementation in Preventing Blood Transfusion

Different studies have implicated the role of iron and folic acid supplementation in reducing the need for whole blood transfusion. The role of iron and folic acid in alleviating the need for blood transfusion was evaluated in elective and non-elective orthopedic surgeries (Munoz et al., 2012). The requirement of postoperative blood transfusion was significantly reduced in patients undergoing hip fracture surgeries after they were administered with an intravenous solution of iron-dextran and erythropoietin. Iron-sucrose infusions were safer compared to iron dextran infusions. Infusions of Iron-sucrose have been evaluated in patients undergoing per trochanteric and sub-capital hip surgeries. The studies indicated that pre-operative supplementation of iron-sucrose significantly reduced the need for allogeneic blood transfusion compared to controls (15% versus 36.8%, p= 0.059). Moreover, supplementation of iron infusions was significantly associated with reduced prevalence of post-operative infections and increased 30-day survival rates. Administration of iron infusion also reduced the length of hospital stay, especially when iron sucrose infusions were coupled with recombinant erythropoietin (Munoz et al., 2012).
Combined administration of erythropoietin, iron, vitamin B12 and folic acid in individuals (with less than 32 weeks gestational age), significantly reduced the need for whole blood transfusion compared to control subjects (38% versus 5%, p <0.001). Supplementation of erythropoietin, iron, vitamin B12 and folic acid was strongly associated with the increase and upregulation of transferrin and ferritin receptors (Haiden et al, 2006).

Indications for Blood transfusion
Blood transfusion has been recognized as a life-saving intervention. However, there are different risks and adverse reactions that limit the use of whole blood transfusion. Blood transfusion is mandated for various indications. There are different complications associated with whole blood transfusion. These complications are either infectious or non-infectious. Transfusion-related infections are less pronounced than non-infectious complications. Non-infectious complications are associated with serious hazards. The complications of transfusion occur within 24 hours. However, delayed complications of blood transfusion are equally evident. Hence, there has been a debate in the medical literature on the appropriate use o blood and blood substitutes. Transfusions of RBCs are indicated for managing hemorrhage and for improving perfusion within the tissues. The RBCs should be transfused based on the condition of a patient. Indications for RBC transfusion include symptomatic anemia, sickle cell anemia and acute blood loss (representing greater than 30% of total blood volume). Fresh-frozen plasma is implicated for reversal of anticoagulant effects. On the other hand, platelet transfusion is indicated for preventing hemorrhage in patients suffering from thrombocytopenia. Cryoprecipitate is recommended for managing hypofibrinogenemia, which is witnessed after massive hemorrhage and consumption coagulopathy. Whole blood transfusions are usually recommended when hemoglobin concentrations are lower than 7-8 mg/dl (Sharma, Sharma & Tyler 2011).
References
HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/?term=Haiden%20N%5BAuthor%5D&cauthor=true&cauthor_uid=17079573” Haiden N,  HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/?term=Schwindt%20J%5BAuthor%5D&cauthor=true&cauthor_uid=17079573” Schwindt J,  HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/?term=Cardona%20F%5BAuthor%5D&cauthor=true&cauthor_uid=17079573” Cardona F,  HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/?term=Berger%20A%5BAuthor%5D&cauthor=true&cauthor_uid=17079573” Berger A,  HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/?term=Klebermass%20K%5BAuthor%5D&cauthor=true&cauthor_uid=17079573” Klebermass K,  HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/?term=Wald%20M%5BAuthor%5D&cauthor=true&cauthor_uid=17079573” Wald M, 
C HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/?term=Jilma%20B%5BAuthor%5D&cauthor=true&cauthor_uid=17079573” Jilma B,  HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/?term=Pollak%20A%5BAuthor%5D&cauthor=true&cauthor_uid=17079573” Pollak A (2006). Effects of a combined therapy of erythropoietin, iron, folate,
and vitamin B12 on the transfusion requirements of extremely low birth weight infants.
HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/17079573” o “Pediatrics.” Pediatrics. 118(5), 2004-2013.
HYPERLINK “http://europepmc.org/search/?scope=fulltext&page=1&query=AUTH:%22Mu%26%23x000f1%3Boz%20M%22” Muñoz M  HYPERLINK “http://europepmc.org/search/?scope=fulltext&page=1&query=AUTH:%22Garc%26%23x000ed%3Ba-Erce%20JA%22” José Antonio García-Erce,  HYPERLINK “http://europepmc.org/search/?scope=fulltext&page=1&query=AUTH:%22Cuenca%20J%22” Jorge Cuenca,  HYPERLINK “http://europepmc.org/search/?scope=fulltext&page=1&query=AUTH:%22Bisbe%20E%22” Elvira Bisbe,  HYPERLINK “http://europepmc.org/search/?scope=fulltext&page=1&query=AUTH:%22Naveira%20E%22” Enrique Naveira (2012)
On the role of iron therapy for reducing allogeneic blood transfusion in orthopaedic
surgery Blood Transfus.; 10(1), 8–22
HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/?term=Poonawalla%20IB%5BAuthor%5D&cauthor=true&cauthor_uid=26509851” Poonawalla IB,  HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/?term=Piller%20LB%5BAuthor%5D&cauthor=true&cauthor_uid=26509851” Piller LB,  HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/?term=Lairson%20DR%5BAuthor%5D&cauthor=true&cauthor_uid=26509851” Lairson DR,  HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/?term=Chan%20W%5BAuthor%5D&cauthor=true&cauthor_uid=26509851” Chan W,  HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/?term=Du%20XL%5BAuthor%5D&cauthor=true&cauthor_uid=26509851” Du XL.(2016). Impact of Hematopoietic
Growth Factors on Blood Transfusion Needs, Incidence of Neutropenia, and Overall
Survival Among Elderly Advanced Ovarian Cancer Patients Treated With
Chemotherapy. HYPERLINK “https://www.ncbi.nlm.nih.gov/pubmed/26509851” o “International journal of gynecological cancer : official journal of the International Gynecological Cancer Society.” Int J Gynecol Cancer.  26(1), 95-103.
Pandey S & Vyas G (2012) Adverse effects of plasma transfusion Transfusion 1537-2995.
Sharma, S Sharma,P Tyler, L (2011) Transfusion of Blood and Blood Products: Indications
and Complications Am Fam Physician. 83(6), 719-724.