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115-549: ATR may refer to: Medicine [ edit ] Acute transfusion reaction Ataxia telangiectasia and Rad3 related , a protein involved in DNA damage repair Science and mathematics [ edit ] Advanced Test Reactor , nuclear research reactor at the Idaho National Laboratory, US Attenuated total reflectance in infrared spectroscopy Advanced tongue root ,

230-538: A chromoprotein , and globulin . In mammals , hemoglobin makes up about 96% of a red blood cell's dry weight (excluding water), and around 35% of the total weight (including water). Hemoglobin has an oxygen-binding capacity of 1.34   mL of O 2 per gram, which increases the total blood oxygen capacity seventy-fold compared to dissolved oxygen in blood plasma alone. The mammalian hemoglobin molecule can bind and transport up to four oxygen molecules. Hemoglobin also transports other gases. It carries off some of

345-441: A coordinate covalent bond , completing the octahedral group of six ligands. This reversible bonding with oxygen is why hemoglobin is so useful for transporting oxygen around the body. Oxygen binds in an "end-on bent" geometry where one oxygen atom binds to Fe and the other protrudes at an angle. When oxygen is not bound, a very weakly bonded water molecule fills the site, forming a distorted octahedron . Even though carbon dioxide

460-520: A German techno band performing "digital hardcore" music ATR (song) , a song by ATR Organisations [ edit ] Absent Teacher Reserve , of teachers in New York City Americans for Tax Reform Anglican Theological Review Other [ edit ] African Traditional Religion A US Navy hull classification symbol: Rescue tug (ATR) ATR: All Terrain Racing ,

575-461: A blood transfusion nearly doubled from 1997, from a rate of 40 stays to 95 stays per 10,000 population. It was the most common procedure performed for patients 45 years of age and older in 2011, and among the top five most common for patients between the ages of 1 and 44 years. According to the New York Times : "Changes in medicine have eliminated the need for millions of blood transfusions, which

690-403: A clinically significant antibody it is vital that the patient receive antigen-negative red blood cells to prevent future transfusion reactions. If there is no antibody present, an immediate spin crossmatch may be performed where the recipient serum and donor rbc are incubated. In the immediate spin method, two drops of patient serum are tested against a drop of 3–5% suspension of donor cells in

805-459: A conformational change in the protein and facilitates the release of oxygen. Protons bind at various places on the protein, while carbon dioxide binds at the α-amino group. Carbon dioxide binds to hemoglobin and forms carbaminohemoglobin . This decrease in hemoglobin's affinity for oxygen by the binding of carbon dioxide and acid is known as the Bohr effect . The Bohr effect favors the T state rather than

920-420: A decrease in blood pH. Ventilation , or breathing, may reverse this condition by removal of carbon dioxide , thus causing a shift up in pH. Hemoglobin exists in two forms, a taut (tense) form (T) and a relaxed form (R). Various factors such as low pH, high CO 2 and high 2,3 BPG at the level of the tissues favor the taut form, which has low oxygen affinity and releases oxygen in the tissues. Conversely,

1035-469: A dimer made up of identical globin subunits, which then evolved to assemble into a tetrameric architecture after the duplication. The development of α and β genes created the potential for hemoglobin to be composed of multiple distinct subunits, a physical composition central to hemoglobin's ability to transport oxygen. Having multiple subunits contributes to hemoglobin's ability to bind oxygen cooperatively as well as be regulated allosterically. Subsequently,

1150-557: A donor, and extracted four ounces of blood from his arm to transfuse into his wife. During the years 1825 and 1830, Blundell performed 10 transfusions, five of which were beneficial, and published his results. He also invented a number of instruments for the transfusion of blood. He made a substantial amount of money from this endeavour, roughly $ 2 million ($ 50 million real dollars ). In 1840, at St George's Hospital Medical School in London, Samuel Armstrong Lane , aided by Blundell, performed

1265-415: 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

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1380-453: 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

1495-580: A heated controversy in Britain and France. Finally, in 1668, the Royal Society and the French government both banned the procedure. The Vatican condemned these experiments in 1670. Blood transfusions fell into obscurity for the next 150 years. The science of blood transfusion dates to the first decade of the 20th century, with the discovery of distinct blood types leading to the practice of mixing some blood from

1610-407: A high pH, low CO 2 , or low 2,3 BPG favors the relaxed form, which can better bind oxygen. The partial pressure of the system also affects O 2 affinity where, at high partial pressures of oxygen (such as those present in the alveoli), the relaxed (high affinity, R) state is favoured. Inversely, at low partial pressures (such as those present in respiring tissues), the (low affinity, T) tense state

1725-400: A life-threatening infection known as transfusion-transmitted bacterial infection. The risk of severe bacterial infection is estimated, as of 2020 , at about 1 in 2,500 platelet transfusions, and 1 in 2,000,000 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

1840-492: A more complex process called apheresis . Before a recipient receives a transfusion, compatibility testing between donor and recipient blood must be done. The first step before a transfusion is given is to type and screen the recipient's blood. Typing of recipient's blood determines the ABO and Rh status. The sample is then screened for any alloantibodies that may react with donor blood. It takes about 45 minutes to complete (depending on

1955-440: A national blood policy was in place in 70% of countries and 69% of countries had specific legislation that covers the safety and quality of blood transfusion. The source of blood to be transfused can either be the potential recipient ( autologous transfusion), or someone else ( allogeneic or homologous transfusion). The latter is much more common than the former. Using another's blood must first start with donation of blood. Blood

2070-886: A phonological feature in linguistics Atractyloside , a toxin and inhibitor of "ADP/ATP translocase" ATR 0 , an axiom system in reverse mathematics Technology [ edit ] Answer to reset , a message output by a contact Smart Card Automatic target recognition , recognition ability Autothermal reforming , a natural gas reforming technology Transport [ edit ] ATR (aircraft manufacturer) an Italian-French aircraft manufacturer ATR 42 airliner ATR 72 airliner IATA code for Atar International Airport Andaman Trunk Road Air Transport Rack, standards for plug-in electronic modules in aviation and elsewhere; various suppliers e.g. ARINC Atmore (Amtrak station) , Amtrak station code ATR Music [ edit ] All That Remains (band) , an American heavy metal band Atari Teenage Riot ,

2185-491: A phosphate "pocket" on the fish hemoglobin molecule, which stabilizes the tense state and therefore decreases oxygen affinity. GTP reduces hemoglobin oxygen affinity much more than ATP, which is thought to be due to an extra hydrogen bond formed that further stabilizes the tense state. Under hypoxic conditions, the concentration of both ATP and GTP is reduced in fish red blood cells to increase oxygen affinity. A variant hemoglobin, called fetal hemoglobin (HbF, α 2 γ 2 ),

2300-418: 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 . Transfusion inefficacy or insufficient efficacy of

2415-468: 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

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2530-512: A set of alpha-helix structural segments connected together in a globin fold arrangement. Such a name is given because this arrangement is the same folding motif used in other heme/globin proteins such as myoglobin . This folding pattern contains a pocket that strongly binds the heme group. A heme group consists of an iron (Fe) ion held in a heterocyclic ring, known as a porphyrin . This porphyrin ring consists of four pyrrole molecules cyclically linked together (by methine bridges) with

2645-677: A single unit of blood is the standard for hospitalized people who are not bleeding, with this treatment followed with re-assessment and consideration of symptoms and hemoglobin concentration. Patients with poor oxygen saturation may need more blood. The advisory caution to use blood transfusion only with more severe anemia is in part due to evidence that outcomes are worsened if larger amounts are given. One may consider transfusion for people with symptoms of cardiovascular disease such as chest pain or shortness of breath. In cases where patients have low levels of hemoglobin due to iron deficiency, but are cardiovascularly stable, oral or parenteral iron

2760-528: 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

2875-442: A test tube and spun in a serofuge. Agglutination or hemolysis (i.e., positive Coombs test) in the test tube is a positive reaction. If the crossmatch is positive, then further investigation is needed. Patients with no history of red cell antibodies may qualify for computer-assisted crossmatch, which does not involve combining patient serum with donor cells. If an antibody is suspected, potential donor units must first be screened for

2990-416: 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

3105-563: A video game ATR.1 certificate , in trade between the European Union and Turkey ATR (company) ( Auto-Teile-Ring ), Germany Average True Range , a market volatility indicator ATR (TV channel) , a Crimean Tatar television channel in Ukraine Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title ATR . If an internal link led you here, you may wish to change

3220-506: Is diamagnetic , whereas both oxygen and high-spin iron(II) are paramagnetic . Experimental evidence strongly suggests heme iron is in the iron(III) oxidation state in oxyhemoglobin, with the oxygen existing as superoxide anion (O 2 ) or in a covalent charge-transfer complex. Deoxygenated hemoglobin (deoxyhemoglobin) is the form of hemoglobin without the bound oxygen. The absorption spectra of oxyhemoglobin and deoxyhemoglobin differ. The oxyhemoglobin has significantly lower absorption of

3335-475: Is a colorless, odorless and tasteless gas, and poses a potentially fatal threat, carbon monoxide detectors have become commercially available to warn of dangerous levels in residences. When hemoglobin combines with CO, it forms a very bright red compound called carboxyhemoglobin , which may cause the skin of CO poisoning victims to appear pink in death, instead of white or blue. When inspired air contains CO levels as low as 0.02%, headache and nausea occur; if

3450-450: Is a higher offspring survival rate among Tibetan women with high oxygen saturation genotypes residing at 4,000 m. Natural selection seems to be the main force working on this gene because the mortality rate of offspring is significantly lower for women with higher hemoglobin-oxygen affinity when compared to the mortality rate of offspring from women with low hemoglobin-oxygen affinity. While the exact genotype and mechanism by which this occurs

3565-401: Is a preferred option based on both efficacy and safety. Other blood products are given where appropriate, e.g., fresh frozen plasma to treat clotting deficiencies and platelets to treat or prevent bleeding in thrombocytopenic patients. Before a blood transfusion is given, there are many steps taken to ensure quality of the blood products, compatibility, and safety to the recipient. In 2012,

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3680-491: Is also a concern. Globally around 85 million units of red blood cells are transfused in a given year. The global demand is much higher and there is an unmet need for safe blood for transfusion in many low- and middle-income countries. In the United States, blood transfusions were performed nearly 3 million times during hospitalizations in 2011, making it the most common procedure performed. The rate of hospitalizations with

3795-473: Is bound to amino groups of the globin proteins to form carbaminohemoglobin ; this mechanism is thought to account for about 10% of carbon dioxide transport in mammals. Nitric oxide can also be transported by hemoglobin; it is bound to specific thiol groups in the globin protein to form an S-nitrosothiol, which dissociates into free nitric oxide and thiol again, as the hemoglobin releases oxygen from its heme site. This nitric oxide transport to peripheral tissues

3910-420: Is called the root effect . This is seen in bony fish. It is necessary for hemoglobin to release the oxygen that it binds; if not, there is no point in binding it. The sigmoidal curve of hemoglobin makes it efficient in binding (taking up O 2 in lungs), and efficient in unloading (unloading O 2 in tissues). In people acclimated to high altitudes, the concentration of 2,3-Bisphosphoglycerate (2,3-BPG) in

4025-423: Is carried by hemoglobin, it does not compete with oxygen for the iron-binding positions but is bound to the amine groups of the protein chains attached to the heme groups. The iron ion may be either in the ferrous Fe or in the ferric Fe state, but ferrihemoglobin ( methemoglobin ) (Fe ) cannot bind oxygen. In binding, oxygen temporarily and reversibly oxidizes (Fe ) to (Fe ) while oxygen temporarily turns into

4140-446: Is collected, to make it suitable for use in specific patient populations. Collected blood is then separated into blood components by centrifugation: red blood cells , plasma , and platelets . Plasma can be further processed to manufacture albumin protein , clotting factor concentrates, cryoprecipitate , fibrinogen concentrate, and immunoglobulins ( antibodies ). Red cells, plasma and platelets can also be donated individually via

4255-412: Is denoted as α 2 β 2 . The subunits are structurally similar and about the same size. Each subunit has a molecular weight of about 16,000  daltons , for a total molecular weight of the tetramer of about 64,000 daltons (64,458 g/mol). Thus, 1 g/dL=0.1551 mmol/L. Hemoglobin A is the most intensively studied of the hemoglobin molecules. In human infants, the fetal hemoglobin molecule

4370-430: Is favoured. Additionally, the binding of oxygen to the iron(II) heme pulls the iron into the plane of the porphyrin ring, causing a slight conformational shift. The shift encourages oxygen to bind to the three remaining heme units within hemoglobin (thus, oxygen binding is cooperative). Classically, the iron in oxyhemoglobin is seen as existing in the iron(II) oxidation state. However, the complex of oxygen with heme iron

4485-444: Is found in the developing fetus , and binds oxygen with greater affinity than adult hemoglobin. This means that the oxygen binding curve for fetal hemoglobin is left-shifted (i.e., a higher percentage of hemoglobin has oxygen bound to it at lower oxygen tension), in comparison to that of adult hemoglobin. As a result, fetal blood in the placenta is able to take oxygen from maternal blood. Hemoglobin also carries nitric oxide (NO) in

4600-477: Is good news for patients getting procedures like coronary bypasses and other procedures that once required a lot of blood." And, "Blood bank revenue is falling, and the decline may reach $ 1.5 billion a year this year [2014] from a high of $ 5 billion in 2008." In 2014, the Red Cross was predicting job losses as high as 12,000 within the next three to five years, roughly a quarter of the total in the industry. As of 2019,

4715-467: Is hypothesized to assist oxygen transport in tissues, by releasing vasodilatory nitric oxide to tissues in which oxygen levels are low. The binding of oxygen is affected by molecules such as carbon monoxide (for example, from tobacco smoking , exhaust gas , and incomplete combustion in furnaces). CO competes with oxygen at the heme binding site. Hemoglobin's binding affinity for CO is 250 times greater than its affinity for oxygen, Since carbon monoxide

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4830-499: 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

4945-455: Is made up of 2 α chains and 2 γ chains. The γ chains are gradually replaced by β chains as the infant grows. The four polypeptide chains are bound to each other by salt bridges , hydrogen bonds , and the hydrophobic effect . In general, hemoglobin can be saturated with oxygen molecules (oxyhemoglobin), or desaturated with oxygen molecules (deoxyhemoglobin). Oxyhemoglobin is formed during physiological respiration when oxygen binds to

5060-723: Is most commonly donated as whole blood obtained intravenously and mixed with an anticoagulant . In first-world countries, donations are usually anonymous to the recipient, but products in a blood bank are always individually traceable through the whole cycle of donation, testing, separation into components, storage, and administration to the recipient. This enables management and investigation of any suspected transfusion related disease transmission or transfusion reaction . Developing countries rely heavily on replacement and remunerated donors rather than voluntary nonremunerated donors due to concerns regarding donation- and transfusion-transmitted infection as well as local and cultural beliefs. It

5175-426: Is not yet clear, selection is acting on these women's ability to bind oxygen in low partial pressures, which overall allows them to better sustain crucial metabolic processes. Hemoglobin (Hb) is synthesized in a complex series of steps. The heme part is synthesized in a series of steps in the mitochondria and the cytosol of immature red blood cells, while the globin protein parts are synthesized by ribosomes in

5290-545: Is protected by a reduction system to keep this from happening. Nitric oxide is capable of converting a small fraction of hemoglobin to methemoglobin in red blood cells. The latter reaction is a remnant activity of the more ancient nitric oxide dioxygenase function of globins. Carbon di oxide occupies a different binding site on the hemoglobin. At tissues, where carbon dioxide concentration is higher, carbon dioxide binds to allosteric site of hemoglobin, facilitating unloading of oxygen from hemoglobin and ultimately its removal from

5405-505: Is sometimes said to have been given "the world's first blood transfusion" by his Italian-Jewish physician Giacomo di San Genesio, who had him drink (by mouth) the blood of three 10-year-old boys. The boys consequently died, as did the Pope himself. However, the evidence for this story is unreliable and considered a possible anti-Jewish blood libel . Working at the Royal Society in the 1660s,

5520-579: Is still used in Russia and in states of the former USSR, in which blood types O, A, B, and AB are respectively designated I, II, III, and IV. Dr. William Lorenzo Moss's (1876–1957) Moss-blood typing technique of 1910 was widely used until World War II . Hemoglobin Hemoglobin ( haemoglobin , Hb or Hgb ) is a protein containing iron that facilitates the transportation of oxygen in red blood cells . Almost all vertebrates contain hemoglobin, with

5635-399: Is tasked with oxygen transport. The α- and β-like globin genes encode the individual subunits of the protein. The predecessors of these genes arose through another duplication event also after the gnathosome common ancestor derived from jawless fish, approximately 450–500 million years ago. Ancestral reconstruction studies suggest that the preduplication ancestor of the α and β genes was

5750-472: 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

5865-426: Is unclear whether applying alcohol swab alone or alcohol swab followed by antiseptic is able to reduce contamination of donor's blood. Studies show that the main motivators to blood donation tend to be prosocial (e.g., altruism, selflessness, charity), while the main deterrents include fear, distrust, or perceived racial discrimination in historic contexts. Donated blood is usually subjected to processing after it

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5980-495: Is used, followed by crossmatch as soon as possible. O-negative is also used for children and women of childbearing age. It is preferable for the laboratory to obtain a pre-transfusion sample in these cases so a type and screen can be performed to determine the actual blood group of the patient and to check for alloantibodies. This chart shows possible matches in blood transfusion between donor and receiver using ABO and Rh system. The symbol [REDACTED] indicates compatibility. In

6095-466: Is weakly attracted to magnetic fields . In contrast, oxygenated hemoglobin exhibits diamagnetism , a weak repulsion from a magnetic field. Scientists agree that the event that separated myoglobin from hemoglobin occurred after lampreys diverged from jawed vertebrates . This separation of myoglobin and hemoglobin allowed for the different functions of the two molecules to arise and develop: myoglobin has more to do with oxygen storage while hemoglobin

6210-633: The Edinburgh Royal Infirmary between 1885 and 1892. Edinburgh later became the home of the first blood donation and blood transfusion services. Only in 1901, when the Austrian Karl Landsteiner discovered three human blood groups (O, A, and B), did blood transfusion achieve a scientific basis and become safer. Landsteiner discovered that adverse effects arise from mixing blood from two incompatible individuals. He found that mixing incompatible types triggers an immune response and

6325-517: The Pleistocene . This was also found in hummingbirds that inhabit the Andes. Hummingbirds already expend a lot of energy and thus have high oxygen demands and yet Andean hummingbirds have been found to thrive in high altitudes. Non-synonymous mutations in the hemoglobin gene of multiple species living at high elevations ( Oreotrochilus, A. castelnaudii, C. violifer, P. gigas, and A. viridicuada ) have caused

6440-444: The allergic reaction . Denys's third patient to undergo a blood transfusion was Swedish Baron Gustaf Bonde . He received two transfusions. After the second transfusion Bonde died. In the winter of 1667, Denys performed several transfusions on Antoine Mauroy with calf's blood. On the third account Mauroy died. Six months later in London, Lower performed the first human transfusion of animal blood in Britain, where he "superintended

6555-468: The cells of the body with oxygen . White blood cells are not commonly used during transfusions, but they are part of the immune system and also fight infections. Plasma is the "yellowish" liquid part of blood, which acts as a buffer and contains proteins and other important substances needed for the body's overall health. Platelets are involved in blood clotting, preventing the body from bleeding. Before these components were known, doctors believed that blood

6670-597: The superoxide ion, thus iron must exist in the +2 oxidation state to bind oxygen. If superoxide ion associated to Fe is protonated, the hemoglobin iron will remain oxidized and incapable of binding oxygen. In such cases, the enzyme methemoglobin reductase will be able to eventually reactivate methemoglobin by reducing the iron center. In adult humans, the most common hemoglobin type is a tetramer (which contains four subunit proteins) called hemoglobin A , consisting of two α and two β subunits non-covalently bound, each made of 141 and 146 amino acid residues, respectively. This

6785-434: The vasculature (this hemoglobin-synthetic RNA in fact gives the reticulocyte its reticulated appearance and name). Hemoglobin has a quaternary structure characteristic of many multi-subunit globular proteins. Most of the amino acids in hemoglobin form alpha helices , and these helices are connected by short non-helical segments. Hydrogen bonds stabilize the helical sections inside this protein, causing attractions within

6900-420: The 660 nm wavelength than deoxyhemoglobin, while at 940 nm its absorption is slightly higher. This difference is used for the measurement of the amount of oxygen in a patient's blood by an instrument called a pulse oximeter . This difference also accounts for the presentation of cyanosis , the blue to purplish color that tissues develop during hypoxia . Deoxygenated hemoglobin is paramagnetic ; it

7015-530: The CO concentration is increased to 0.1%, unconsciousness will follow. In heavy smokers, up to 20% of the oxygen-active sites can be blocked by CO. In similar fashion, hemoglobin also has competitive binding affinity for cyanide (CN ), sulfur monoxide (SO), and sulfide (S ), including hydrogen sulfide (H 2 S). All of these bind to iron in heme without changing its oxidation state, but they nevertheless inhibit oxygen-binding, causing grave toxicity. The iron atom in

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7130-619: The Nobel Prize in Physiology and Medicine in 1930; many other blood groups have been discovered since. George Washington Crile is credited with performing the first surgery using a direct blood transfusion in 1906 at St. Alexis Hospital in Cleveland while a professor of surgery at Case Western Reserve University . Jan Janský also discovered the human blood groups; in 1907 he classified blood into four groups: I, II, III, IV. His nomenclature

7245-405: The R state. (shifts the O 2 -saturation curve to the right ). Conversely, when the carbon dioxide levels in the blood decrease (i.e., in the lung capillaries), carbon dioxide and protons are released from hemoglobin, increasing the oxygen affinity of the protein. A reduction in the total binding capacity of hemoglobin to oxygen (i.e. shifting the curve down, not just to the right) due to reduced pH

7360-435: The Royal Society. According to Lower's account, "...towards the end of February 1665 [I] selected one dog of medium size, opened its jugular vein, and drew off blood, until its strength was nearly gone. Then, to make up for the great loss of this dog by the blood of a second, I introduced blood from the cervical artery of a fairly large mastiff, which had been fastened alongside the first, until this latter animal showed ... it

7475-542: The beta subunit is coded by gene HBB on chromosome 11. The amino acid sequences of the globin subunits usually differ between species, with the difference growing with evolutionary distance. For example, the most common hemoglobin sequences in humans, bonobos and chimpanzees are completely identical, with exactly the same alpha and beta globin protein chains. Human and gorilla hemoglobin differ in one amino acid in both alpha and beta chains, and these differences grow larger between less closely related species. Mutations in

7590-420: The binding of oxygen to the remaining three monomers' heme groups, thus saturating the hemoglobin molecule with oxygen. In the tetrameric form of normal adult hemoglobin, the binding of oxygen is, thus, a cooperative process . The binding affinity of hemoglobin for oxygen is increased by the oxygen saturation of the molecule, with the first molecules of oxygen bound influencing the shape of the binding sites for

7705-402: The blood is increased, which allows these individuals to deliver a larger amount of oxygen to tissues under conditions of lower oxygen tension . This phenomenon, where molecule Y affects the binding of molecule X to a transport molecule Z, is called a heterotropic allosteric effect. Hemoglobin in organisms at high altitudes has also adapted such that it has less of an affinity for 2,3-BPG and so

7820-468: The body after the oxygen has been released to tissues undergoing metabolism. This increased affinity for carbon dioxide by the venous blood is known as the Bohr effect . Through the enzyme carbonic anhydrase , carbon dioxide reacts with water to give carbonic acid , which decomposes into bicarbonate and protons : Hence, blood with high carbon dioxide levels is also lower in pH (more acidic ). Hemoglobin can bind protons and carbon dioxide, which causes

7935-564: The body's respiratory carbon dioxide (about 20–25% of the total) as carbaminohemoglobin , in which CO 2 binds to the heme protein . The molecule also carries the important regulatory molecule nitric oxide bound to a thiol group in the globin protein, releasing it at the same time as oxygen. Hemoglobin is also found in other cells, including in the A9 dopaminergic neurons of the substantia nigra , macrophages , alveolar cells , lungs, retinal pigment epithelium, hepatocytes, mesangial cells of

8050-410: The corresponding antigen by phenotyping them. Antigen negative units are then tested against the patient plasma using an antiglobulin/indirect crossmatch technique at 37 degrees Celsius to enhance reactivity and make the test easier to read. In urgent cases where crossmatching cannot be completed, and the risk of dropping hemoglobin outweighs the risk of transfusing uncrossmatched blood, O-negative blood

8165-426: The cytosol. Production of Hb continues in the cell throughout its early development from the proerythroblast to the reticulocyte in the bone marrow . At this point, the nucleus is lost in mammalian red blood cells, but not in birds and many other species. Even after the loss of the nucleus in mammals, residual ribosomal RNA allows further synthesis of Hb until the reticulocyte loses its RNA soon after entering

8280-417: The donor and the receiver before the transfusion (an early form of cross-matching ). In the early 19th century, British obstetrician Dr. James Blundell made efforts to treat hemorrhage by transfusion of human blood using a syringe. In 1818, after experiments with animals, he performed the first successful transfusion of human blood to treat postpartum hemorrhage . Blundell used the patient's husband as

8395-413: The donor cells being tested are shown in a chart. The patient's serum is tested against the various donor cells using an indirect Coombs test . Based on the reactions of the patient's serum against the donor cells, a pattern will emerge to confirm the presence of one or more antibodies. Not all antibodies are clinically significant (i.e. cause transfusion reactions, HDN, etc.). Once the patient has developed

8510-511: The first successful whole blood transfusion to treat haemophilia . However, early transfusions were risky and many resulted in the death of the patient. By the late 19th century, blood transfusion was regarded as a risky and dubious procedure, and was largely shunned by the medical establishment. Work to emulate James Blundell continued in Edinburgh. In 1845 the Edinburgh Journal described

8625-403: The genes for hemoglobin can result in variants of hemoglobin within a single species, although one sequence is usually "most common" in each species. Many of these mutations cause no disease, but some cause a group of hereditary diseases called hemoglobinopathies . The best known hemoglobinopathy is sickle-cell disease , which was the first human disease whose mechanism was understood at

8740-409: The globin part of the molecule. This improves oxygen delivery in the periphery and contributes to the control of respiration. NO binds reversibly to a specific cysteine residue in globin; the binding depends on the state (R or T) of the hemoglobin. The resulting S-nitrosylated hemoglobin influences various NO-related activities such as the control of vascular resistance, blood pressure and respiration. NO

8855-399: The heme component of the protein hemoglobin in red blood cells. This process occurs in the pulmonary capillaries adjacent to the alveoli of the lungs. The oxygen then travels through the blood stream to be dropped off at cells where it is utilized as a terminal electron acceptor in the production of ATP by the process of oxidative phosphorylation . It does not, however, help to counteract

8970-401: The heme group must initially be in the ferrous (Fe ) oxidation state to support oxygen and other gases' binding and transport (it temporarily switches to ferric during the time oxygen is bound, as explained above). Initial oxidation to the ferric (Fe ) state without oxygen converts hemoglobin into "hem i globin" or methemoglobin , which cannot bind oxygen. Hemoglobin in normal red blood cells

9085-574: The higher pressures at sea level. Recent studies of deer mice found mutations in four genes that can account for differences between high- and low-elevation populations. It was found that the genes of the two breeds are "virtually identical—except for those that govern the oxygen-carrying capacity of their hemoglobin. . . . The genetic difference enables highland mice to make more efficient use of their oxygen." Mammoth hemoglobin featured mutations that allowed for oxygen delivery at lower temperatures, thus enabling mammoths to migrate to higher latitudes during

9200-452: The introduction in [a patient's] arm at various times of some ounces of sheep's blood at a meeting of the Royal Society, and without any inconvenience to him." The recipient was Arthur Coga, "the subject of a harmless form of insanity." Sheep's blood was used because of speculation about the value of blood exchange between species; it had been suggested that blood from a gentle lamb might quiet the tempestuous spirit of an agitated person and that

9315-400: The iron complex, it causes the iron atom to move back toward the center of the plane of the porphyrin ring (see moving diagram). At the same time, the imidazole side-chain of the histidine residue interacting at the other pole of the iron is pulled toward the porphyrin ring. This interaction forces the plane of the ring sideways toward the outside of the tetramer, and also induces a strain in

9430-425: The iron ion bound in the center. The iron ion, which is the site of oxygen binding, coordinates with the four nitrogen atoms in the center of the ring, which all lie in one plane. The heme is bound strongly (covalently) to the globular protein via the N atoms of the imidazole ring of F8 histidine residue (also known as the proximal histidine) below the porphyrin ring. A sixth position can reversibly bind oxygen by

9545-709: The kidney, endometrial cells, cervical cells, and vaginal epithelial cells. In these tissues, hemoglobin absorbs unneeded oxygen as an antioxidant , and regulates iron metabolism . Excessive glucose in the blood can attach to hemoglobin and raise the level of hemoglobin A1c. Hemoglobin and hemoglobin-like molecules are also found in many invertebrates, fungi, and plants. In these organisms, hemoglobins may carry oxygen, or they may transport and regulate other small molecules and ions such as carbon dioxide, nitric oxide, hydrogen sulfide and sulfide. A variant called leghemoglobin serves to scavenge oxygen away from anaerobic systems such as

9660-425: The link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=ATR&oldid=1237975337 " Category : Disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Acute transfusion reaction Red blood cells (RBC) contain hemoglobin and supply

9775-737: The method used). The blood bank scientist also checks for special requirements of the patient (e.g. need for washed, irradiated or CMV negative blood) and the history of the patient to see if they have previously identified antibodies and any other serological anomalies. A positive screen warrants an antibody panel/investigation to determine if it is clinically significant. An antibody panel consists of commercially prepared group O red cell suspensions from donors that have been phenotyped for antigens that correspond to commonly encountered and clinically significant alloantibodies. Donor cells may have homozygous (e.g. K+k+), heterozygous (K+k-) expression or no expression of various antigens (K−k−). The phenotypes of all

9890-513: The molecular level. A mostly separate set of diseases called thalassemias involves underproduction of normal and sometimes abnormal hemoglobins, through problems and mutations in globin gene regulation . All these diseases produce anemia . Variations in hemoglobin sequences, as with other proteins, may be adaptive. For example, hemoglobin has been found to adapt in different ways to the thin air at high altitudes, where lower partial pressure of oxygen diminishes its binding to hemoglobin compared to

10005-487: The molecular mass of hemoglobin to n × 16000 ( n =number of iron atoms per hemoglobin molecule, now known to be 4), the first determination of a protein's molecular mass. This "hasty conclusion" drew ridicule from colleagues who could not believe that any molecule could be so large. However, Gilbert Smithson Adair confirmed Engelhart's results in 1925 by measuring the osmotic pressure of hemoglobin solutions. Although blood had been known to carry oxygen since at least 1794,

10120-431: The molecule, which then causes each polypeptide chain to fold into a specific shape. Hemoglobin's quaternary structure comes from its four subunits in roughly a tetrahedral arrangement. In most vertebrates, the hemoglobin molecule is an assembly of four globular protein subunits. Each subunit is composed of a protein chain tightly associated with a non-protein prosthetic heme group. Each protein chain arranges into

10235-411: The next ones, in a way favorable for binding. This positive cooperative binding is achieved through steric conformational changes of the hemoglobin protein complex as discussed above; i.e., when one subunit protein in hemoglobin becomes oxygenated, a conformational or structural change in the whole complex is initiated, causing the other subunits to gain an increased affinity for oxygen. As a consequence,

10350-441: The nitrogen-fixing nodules of leguminous plants, preventing oxygen poisoning. The medical condition hemoglobinemia , a form of anemia , is caused by intravascular hemolysis , in which hemoglobin leaks from red blood cells into the blood plasma . In 1825, Johann Friedrich Engelhart discovered that the ratio of iron to protein is identical in the hemoglobins of several species. From the known atomic mass of iron, he calculated

10465-416: The objective of ensuring the safety of blood for transfusion, but their organisational set-up and operating principles can vary. Transfusions of blood products are associated with several complications, many of which can be grouped as immunological or infectious. There is controversy on potential quality degradation during storage. The use of greater amount of red blood cells has been suggested to increase

10580-553: The oxygen binding curve of hemoglobin is sigmoidal , or S -shaped, as opposed to the normal hyperbolic curve associated with noncooperative binding. The dynamic mechanism of the cooperativity in hemoglobin and its relation with low-frequency resonance has been discussed. Besides the oxygen ligand , which binds to hemoglobin in a cooperative manner, hemoglobin ligands also include competitive inhibitors such as carbon monoxide (CO) and allosteric ligands such as carbon dioxide (CO 2 ) and nitric oxide (NO). The carbon dioxide

10695-414: The oxygen-carrying property of hemoglobin was described by Hünefeld in 1840. In 1851, German physiologist Otto Funke published a series of articles in which he described growing hemoglobin crystals by successively diluting red blood cells with a solvent such as pure water, alcohol or ether, followed by slow evaporation of the solvent from the resulting protein solution. Hemoglobin's reversible oxygenation

10810-399: The physician Richard Lower began examining the effects of changes in blood volume on circulatory function and developed methods for cross-circulatory study in animals, obviating clotting by closed arteriovenous connections. The new instruments he was able to devise enabled him to perform the first reliably documented successful transfusion of blood in front of his distinguished colleagues from

10925-544: 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

11040-441: The protein helix containing the histidine as it moves nearer to the iron atom. This strain is transmitted to the remaining three monomers in the tetramer, where it induces a similar conformational change in the other heme sites such that binding of oxygen to these sites becomes easier. As oxygen binds to one monomer of hemoglobin, the tetramer's conformation shifts from the T (tense) state to the R (relaxed) state. This shift promotes

11155-491: The protein to have less of an affinity for inositol hexaphosphate (IHP), a molecule found in birds that has a similar role as 2,3-BPG in humans; this results in the ability to bind oxygen in lower partial pressures. Birds' unique circulatory lungs also promote efficient use of oxygen at low partial pressures of O 2 . These two adaptations reinforce each other and account for birds' remarkable high-altitude performance. Hemoglobin adaptation extends to humans, as well. There

11270-410: The protein will be shifted more towards its R state. In its R state, hemoglobin will bind oxygen more readily, thus allowing organisms to perform the necessary metabolic processes when oxygen is present at low partial pressures. Animals other than humans use different molecules to bind to hemoglobin and change its O 2 affinity under unfavorable conditions. Fish use both ATP and GTP . These bind to

11385-433: The protein's chemical properties and function. The amino acid sequence of any polypeptide is translated from a segment of DNA, the corresponding gene . There is more than one hemoglobin gene. In humans, hemoglobin A (the main form of hemoglobin in adults) is coded by genes HBA1 , HBA2 , and HBB . Alpha 1 and alpha 2 subunits are respectively coded by genes HBA1 and HBA2 close together on chromosome 16, while

11500-417: The red blood-cells clump. The immunological reaction occurs when the receiver of a blood transfusion has antibodies against the donor blood-cells. The destruction of red blood cells releases free hemoglobin into the bloodstream, which can have fatal consequences. Landsteiner's work made it possible to determine blood group and allowed blood transfusions to take place much more safely. For his discovery he won

11615-586: 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

11730-551: The risk of infections, not only transfusion-transmitted infections, but also due to a phenomenon known as transfusion-related immunomodulation (TRIM). TRIM may be caused by macrophages and their byproducts. In those who were given red blood cells only with significant anemia ("restrictive" strategy), serious infection rates were 10.6% while in those who were given red blood at milder levels of anemia ("liberal" strategy), serious infection rates were 12.7%. On rare occasions, blood products are contaminated with bacteria. This can result in

11845-486: The same way that the safety of pharmaceutical products is overseen by pharmacovigilance , the safety of blood and blood products is overseen by haemovigilance. This is defined by the World Health Organization (WHO) as a system "...to identify and prevent occurrence or recurrence of transfusion related unwanted events, to increase the safety, efficacy and efficiency of blood transfusion, covering all activities of

11960-503: The shy might be made outgoing by blood from more sociable creatures. Coga received 20 shillings (equivalent to £217 in 2023) to participate in the experiment. Lower went on to pioneer new devices for the precise control of blood flow and the transfusion of blood; his designs were substantially the same as modern syringes and catheters . Shortly after, Lower moved to London, where his growing practice soon led him to abandon research. These early experiments with animal blood provoked

12075-439: 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

12190-412: The sole exception of the fish family, Channichthyidae . Hemoglobin in the blood carries oxygen from the respiratory organs ( lungs or gills ) to the other tissues of the body, where it releases the oxygen to enable aerobic respiration which powers an animal's metabolism . A healthy human has 12   to 20   grams of hemoglobin in every 100   mL of blood. Hemoglobin is a metalloprotein ,

12305-487: The successful transfusion of blood to a woman with severe uterine bleeding. Subsequent transfusions were successful with patients of Professor James Young Simpson , after whom the Simpson Memorial Maternity Pavilion in Edinburgh was named. Various isolated reports of successful transfusions emerged towards the end of the 19th century. The largest series of early successful transfusions took place at

12420-452: The transfusion chain from donor to recipient." The system should include monitoring, identification, reporting, investigation and analysis of adverse events, near-misses, and reactions related to transfusion and manufacturing. In the UK this data is collected by an independent organisation called SHOT (Serious Hazards Of Transfusion). Haemovigilance systems have been established in many countries with

12535-469: The trend of declining transfusions appeared to be stabilizing, with 10,852,000 RBC units transfused in the United States. Beginning with William Harvey 's experiments on the circulation of blood, recorded research into blood transfusion began in the 17th century, with successful experiments in transfusion between animals. However, successive attempts by physicians to transfuse animal blood into humans gave variable, often fatal, results. Pope Innocent VIII

12650-452: The α gene also underwent a duplication event to form the HBA1 and HBA2 genes. These further duplications and divergences have created a diverse range of α- and β-like globin genes that are regulated so that certain forms occur at different stages of development. Most ice fish of the family Channichthyidae have lost their hemoglobin genes as an adaptation to cold water. When oxygen binds to

12765-427: Was administered by Dr. Jean-Baptiste Denys , eminent physician to King Louis XIV of France, on June 15, 1667. He transfused the blood of a sheep into a 15-year-old boy, who survived the transfusion. Denys performed another transfusion into a labourer, who also survived. Both instances were likely due to the small amount of blood that was actually transfused into these people. This allowed them to withstand

12880-455: Was described a few years later by Felix Hoppe-Seyler . With the development of X-ray crystallography , it became possible to sequence protein structures. In 1959, Max Perutz determined the molecular structure of hemoglobin. For this work he shared the 1962 Nobel Prize in Chemistry with John Kendrew , who sequenced the globular protein myoglobin . The role of hemoglobin in the blood

12995-612: Was elucidated by French physiologist Claude Bernard . The name hemoglobin (or haemoglobin ) is derived from the words heme (or haem ) and globin , reflecting the fact that each subunit of hemoglobin is a globular protein with an embedded heme group. Each heme group contains one iron atom, that can bind one oxygen molecule through ion-induced dipole forces. The most common type of hemoglobin in mammals contains four such subunits. Hemoglobin consists of protein subunits ( globin molecules), which are polypeptides , long folded chains of specific amino acids which determine

13110-468: Was homogeneous. Because of this scientific misunderstanding, many patients died because of incompatible blood transferred to them. Historically, red blood cell transfusion was considered when the hemoglobin level fell below 100g/L or hematocrit fell below 30%. Because each unit of blood given carries risks, a trigger level lower than that, at 70 to 80g/L, is now usually used, as it has been shown to have better patient outcomes. The administration of

13225-641: Was overfilled ... by the inflowing blood." After he "sewed up the jugular veins", the animal recovered "with no sign of discomfort or of displeasure". Lower had performed the first blood transfusion between animals. He was then "requested by the Honorable [Robert] Boyle ... to acquaint the Royal Society with the procedure for the whole experiment", which he did in December 1665 in the Society's Philosophical Transactions . The first blood transfusion from animal to human

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