or attack on donor's white blood cells by recipient's antibodies. this type of reaction occurs in about 7% of transfusions. fever is generally short lived and is treated with antipyretics, and transfusions may be finished as long as an acute hemolytic reaction is excluded. this is a reason for the now-widespread use of leukoreduction – the filtration of donor white cells from red cell product units. allergic transfusion reactions are caused by ige anti-allergen antibodies. when antibodies are bound to its antigens, histamine is released from mast cells and basophils. either ige antibodies from the donor's or recipient's side can cause the allergic reaction. it is more common in patients who have allergic conditions such as hay fever. patient may feel itchy or having hives but the symptoms are usually mild and can be controlled by stopping the transfusion and giving antihistamines. anaphylactic reactions are rare life-threatening allergic conditions caused by iga anti-plasma protein antibodies. for patients who have selective immunoglobulin a deficiency, the reaction is presumed to be caused by iga antibodies in the donor's plasma. the patient may present with symptoms of fever, wheezing, coughing, shortness of breath, and circulatory shock. urgent treatment with epinephrine is needed. post-transfusion purpura is an extremely rare complication that occurs after blood product transfusion and is associated with the presence of antibodies in the patient's blood directed against both the donor's and recipient's platelets hpa (human platelet antigen). recipients who lack this protein develop sensitization to this protein from prior transfusions or previous pregnancies, can develop thrombocytopenia, bleeding into the skin, and can display purplish discolouration of skin which is known as purpura. intravenous immunoglobulin (ivig) is treatment of choice. transfusion-related acute lung injury (trali) is a syndrome that is similar to acute respiratory distress syndrome (ards), which develops during or within 6 hours of transfusion of a plasma-containing blood product. fever, hypotension, shortness of breath, and tachycardia often occurs in this type of reaction. for a definitive diagnosis to be made, symptoms must occur within 6 hours of transfusion, hypoxemia must be present, there must be radiographic evidence of bilateral infiltrates and there must be no evidence of left atrial hypertension (fluid overload). it occurs in 15% of the transfused patient with mortality rate of 5 to 10%. recipient risk factors includes: end-stage liver disease, sepsis, haematological malignancies, sepsis, and ventilated patients. antibodies to human neutrophil antigens (hna) and human leukocyte antigens (hla) have been associated with this type of transfusion reaction. donor's antibodies interacting with antigen positive recipient tissue result in release of inflammatory cytokines, resulting in pulmonary capillary leakage. the treatment is supportive. transfusion associated circulatory overload (taco) is a common, yet underdiagnosed, reaction to blood product transfusion consisting of the new onset or exacerbation of three of the following within 6 hours of cessation of transfusion: acute respiratory distress, elevated brain natriuretic peptide (bnp), elevated central venous pressure (cvp), evidence of left heart failure, evidence of positive fluid balance, and/or radiographic evidence of pulmonary edema. transfusion-associated graft versus host disease frequently occurs in immunodeficient patients where recipient's body failed to eliminate donor's t cells. instead, donor's t cells attack the recipient's cells. it occurs one week after transfusion. fever, rash, diarrhoea are often associated with this type of transfusion reaction. mortality rate is high, with 89.7% of the patients dead after 24 days. immunosuppressive treatment is the most common way of treatment. irradiation and leukoreduction of blood products is necessary for high risk patients to prevent t cells from attacking recipient cells. infection the use of greater amount of red blood cells is associated with a high risk of infections. in those who were given red blood only with significant anemia infection rates were 12% while in those who were given red blood at milder levels of anemia infection rates were 17%. on rare occasions, blood products are contaminated with bacteria. this can result in a life-threatening infection known as transfusion-transmitted bacterial infection. the risk of severe bacterial infection is estimated, as of 2002, at about 1 in 50,000 platelet transfusions, and 1 in 500,000 red blood cell transfusions. blood product contamination, while rare, is still more common than actual infection. the reason platelets are more often contaminated than other blood products is that they are stored at room temperature for short periods of time. contamination is also more common with longer duration of storage, especially if that means more than 5 days. sources of contaminants include the donor's blood, donor's skin, phlebotomist's skin, and containers. contaminating organisms vary greatly, and include skin flora, gut flora, and environmental organisms. there are many strategies in place at blood donation centers and laboratories to reduce the risk of contamination. a definite diagnosis of transfusion-transmitted bacterial infection includes the identification of a positive culture in the recipient (without an alternative diagnosis) as well as the identification of the same organism in the donor blood. since the advent of hiv testing of donor blood in the mid/later 1980s, ex. 1985's elisa, the transmission of hiv during transfusion has dropped dramatically. prior testing of donor blood only included testing for antibodies to hiv. however, because of latent infection (the "window period" in which an individual is infectious, but has not had time to develop antibodies) many cases of hiv seropositive blood were missed. the development of a nucleic acid test for the hiv-1 rna has dramatically lowered the rate of donor blood seropositivity to about 1 in 3 million units. as transmittance of hiv does not necessarily mean hiv infection, the latter could still occur at an even lower rate. the transmission of hepatitis c via transfusion currently stands at a rate of about 1 in 2 million units. as with hiv, this low rate has been attributed to the ability to screen for both antibodies as well as viral rna nucleic acid testing in donor blood. other rare transmissible infections include hepatitis b, syphilis, chagas disease, cytomegalovirus infections (in immunocompromised recipients), htlv, and babesia. comparison table comparison of symptoms of blood transfusion reactions characterized by fever. + =occasionally present ++ =frequently present febrile nonhemolytictraliacute hemolyticbacterial contamination appearance of symptoms during or after transfusion usually toward end. 5–10% appear up to 2 hours after.early (after 10–15 ml)early (after 50–100 ml)up to 8 hours after transfusion fever +++++++ chills +++++++++ cold ++-+- discomfort ++--- rigors +--- headache +-+- nausea and/or vomiting +-++- dyspnea +++++- cyanosis -++++- hypotension / circulatory shock -++++++ disseminated intravascular coagulation --++++ hemoglobinuria --+++ renal failure --++++ back pain --++- inefficacy transfusion inefficacy or insufficient efficacy of a given unit(s) of blood product, while not itself a "complication" per se, can nonetheless indirectly lead to complications – in addition to causing a transfusion to fully or partly fail to achieve its clinical purpose. this can be especially significant for certain patient groups such as critical-care or neonatals. for red blood cells (rbc), by far the most commonly transfused product, poor transfusion efficacy can result from units damaged by the so-called storage lesion – a range of biochemical and biomechanical changes that occur during storage. with red cells, this can decrease viability and ability for tissue oxygenation. although some of the biochemical changes are reversible after the blood is transfused, the biomechanical changes are less so, and rejuvenation products are not yet able to adequately reverse this phenomenon. there has been controversy about whether a given product unit's age is a factor in transfusion efficacy, specifically about whether "older" blood directly or indirectly increases risks of complications. studies have not been consistent on answering this question, with some showing that older blood is indeed less effective but with others showing no such difference; these developments are being closely followed by hospital blood bankers – who are the physicians, typically pathologists, who collect and manage inventories of transfusable blood units. certain regulatory measures are in place to minimize rbc storage lesion – including a maximum shelf life (currently 42 days), a maximum auto-hemolysis threshold (currently 1% in the us, 0.8% in europe), and a minimum level of post-transfusion rbc survival in vivo (currently 75% after 24 hours). however, all of these criteria are applied in a universal manner that does not account for differences among units of product. for example, testing for the post-transfusion rbc survival in vivo is done on a sample of healthy volunteers, and then compliance is presumed for all rbc units based on universal (gmp) processing standards (rbc survival by itself does not guarantee efficacy, but it is a necessary prerequisite for cell function, and hence serves as a regulatory proxy). opinions vary as to the "best" way to determine transfusion efficacy in a patient in vivo. in general, there are not yet any in vitro tests to assess quality or predict efficacy for specific units of rbc blood product prior to their transfusion, though there is exploration of potentially relevant tests based on rbc membrane properties such as erythrocyte deformability and erythrocyte fragility (mechanical). physicians have adopted a so-called "restrictive protocol" – whereby transfusion is held to a minimum – in part because of the noted uncertainties surrounding storage lesion, in addition to the very high direct and indirect costs of transfusions. however, the restrictive protocol is not an option with some especially vulnerable patients who may require the best possible efforts to rapidly restore tissue oxygenation. although transfusions of platelets are far less numerous (relative to rbc), platelet storage lesion and resulting efficacy loss is also a concern. other a known relationship between intra-operative blood transfusion and cancer recurrence has been established in colorectal cancer. in lung cancer intra-operative blood transfusion has been associated with earlier recurrence of cancer, worse survival rates and poorer outcomes after lung resection. also studies shown to us, failure of the immune system caused by blood transfusion can be categorized as one of the main factors leading to more than 10 different cancer types that are fully associated with blood transfusion and the innate and adaptive immune system. allogeneic blood transfusion, through five major mechanisms including the lymphocyte-t set, myeloid-derived suppressor cells (mdscs), tumor-associated macrophages (tams), natural killer cells (nkcs), and dendritic cells (dcs) can help the recipient's defense mechanisms. on the other hand, the role for each of the listed items includes activation of the antitumor cd8+ cytotoxic t lymphocytes (cd8+/ctl), temporal inactivation of tregs, inactivation of the stat3 signaling pathway, the use of bacteria to enhance the antitumor immune response and cellular immunotherapy. transfusion-associated volume overload is a common complication simply because blood products have a certain amount of volume. this is especially the case in recipients with underlying cardiac or kidney disease. red cell transfusions can lead to volume overload when they must be repeated because of insufficient efficacy (see above). plasma transfusion is especially prone to causing volume overload because large volumes are usually required to give any therapeutic benefit. it has been proved that blood transfusion produce worse outcomes after cytoreductive surgery and hipec. hypothermia can occur with transfusions with large quantities of blood products which normally are stored at cold temperatures. core body temperature can go down as low as 32 °c and can produce physiologic disturbances. prevention should be done with warming the blood to ambient temperature prior to transfusions. transfusions with large amounts of red blood cells, whether due to severe hemorrhaging and/or transfusion inefficacy (see above), can lead to an inclination for bleeding. the mechanism is thought to be due to disseminated intravascular coagulation, along with dilution of recipient platelets and coagulation factors. close monitoring and transfusions with platelets and plasma is indicated when necessary. metabolic alkalosis can occur with massive blood transfusions because of the breakdown of citrate stored in blood into bicarbonate. hypocalcemia can also occur with massive blood transfusions because of the complex of citrate with serum calcium. calcium levels below 0.9 mmol/l should be treated. blood doping is often used by athletes, drug addicts or military personnel for reasons such as to increase physical stamina, to fake a drug detection test or simply to remain active and alert during the duty-times respectively. however a lack of knowledge and insufficient experience can turn a blood transfusion into a sudden death. for example, when individuals run the frozen blood sample directly in their veins this cold blood rapidly reaches the heart, where it disturbs the heart's original pace leading