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straightforward in means or manner or behavior or language or action; "a direct question"; "a direct response"; "a direct approach"
having no intervening persons, agents, conditions; "in direct sunlight"; "in direct contact with the voters"; "direct exposure to the disease"; "a direct link"; "the direct cause of the accident"; "direct vote" (同)unmediated
in precisely the same words used by a writer or speaker; "a direct quotation"; "repeated their dialog verbatim" (同)verbatim
(of a current) flowing in one direction only; "direct current"
be in charge of
being an immediate result or consequence; "a direct result of the accident"
command with authority; "He directed the children to do their homework"
direct in spatial dimensions; proceeding without deviation or interruption; straight and short; "a direct route"; "a direct flight"; "a direct hit"
give directions to; point somebody into a certain direction; "I directed them towards the town hall"
guide the actors in (plays and films)
lacking compromising or mitigating elements; exact; "the direct opposite"
moving from west to east on the celestial sphere; or--for planets--around the sun in the same direction as the Earth
similar in nature or effect or relation to another quantity; "a term is in direct proportion to another term if it increases (or decreases) as the other increases (or decreases)"
undergo a test; "She doesnt test well"
any standardized procedure for measuring sensitivity or memory or intelligence or aptitude or personality etc; "the test was standardized on a large sample of students" (同)mental test, mental testing, psychometric test
the act of undergoing testing; "he survived the great test of battle"; "candidates must compete in a trial of skill" (同)trial
the act of testing something; "in the experimental trials the amount of carbon was measured separately"; "he called each flip of the coin a new trial" (同)trial, run
a hard outer covering as of some amoebas and sea urchins
put to the test, as for its quality, or give experimental use to; "This approach has been tried with good results"; "Test this recipe" (同)prove, try, try out, examine, essay
achieve a certain score or rating on a test; "She tested high on the LSAT and was admitted to all the good law schools"
determine the presence or properties of (a substance)
show a certain characteristic when tested; "He tested positive for HIV"
an examination of the characteristics of something; "there are laboratories for commercial testing"; "it involved testing thousands of children for smallpox"
the act of subjecting to experimental test in order to determine how well something works; "they agreed to end the testing of atomic weapons"
manageable by a supervising agent; "a directed program of study"
(often used in combination) having a specified direction; "a positively directed vector"; "goal-directed"
tested and proved useful or correct; "a tested method" (同)tried, well-tried
tested and proved to be reliable (同)time-tested, tried, tried and true

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『まっすぐな』,一直線の(straight),直進する / (列車などが途中駅に寄らずに)直行 / 直系の / 『直接の』,じかの / 『率直な』,単刀直入の / 全くの,絶対の / 原典どおりの / 『まっすぐに』,直行で / 〈事〉‘を'『指揮する』,監督する / 《文》〈人〉‘に'『命令する』,指図する / 〈人〉‘に'(…への)『道を教える』《+『名』〈人〉+『to』+『名』》 / (…に)〈目・注意・努力など〉‘を'『向ける』《+『名』+『to』(『at, toward』)+『名』(do『ing』)》 / 〈音楽・演劇・映画など〉‘を'『指揮する』,演出する,監督する / (…に)〈手紙など〉‘を'あてる《+『名』+『to』+『名』》
(人の能力などの)『試験』,考査,テスト / (物事の)『試験』,検済,試錬,実験《+of+名》 / 化学分析;試薬 / =test match / …‘を'『試験する』,検査する / …‘を'化学分析する / (…の)試験を受ける,試験をする《+for+名》

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/23 12:02:30」(JST)

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A Coombs test (also known as Coombs' test, antiglobulin test or AGT) is either of two clinical blood tests used in immunohematology and immunology. The two Coombs tests are the direct Coombs test (DCT, also known as direct antiglobulin test or DAT), and the indirect Coombs test (also known as indirect antiglobulin test or IAT).

The Direct Coombs test is used to test for autoimmune hemolytic anemia; i.e., a condition of a low count of red blood cells (aka RBCs) caused by immune system lysis or breaking of RBC membranes causing RBC destruction.

In certain diseases or conditions an individual's blood may contain IgG antibodies that can specifically bind to antigens on the RBC surface membrane, and their circulating RBCs can become coated with IgG alloantibodies and/or IgG autoantibodies. Complement proteins may subsequently bind to the bound antibodies and cause RBC destruction.^[1] The direct Coombs test is used to detect these antibodies or complement proteins that are bound to the surface of red blood cells; a blood sample is taken and the RBCs are washed (removing the patient's own plasma) and then incubated with antihuman globulin (also known as "Coombs reagent"). If this produces agglutination of RBCs, the direct Coombs test is positive, a visual indication that antibodies (and/or complement proteins) are bound to the surface of red blood cells.

The indirect Coombs test is used in prenatal testing of pregnant women, and in testing blood prior to a blood transfusion. It detects antibodies against RBCs that are present unbound in the patient's serum. In this case, serum is extracted from the blood sample taken from the patient. Then, the serum is incubated with RBCs of known antigenicity; that is, RBCs with known reference values from other patient blood samples. If agglutination occurs, the indirect Coombs test is positive.^[2]

1 Mechanism
2 Direct Coombs test
- 2.1 Examples of diseases that give a positive direct Coombs test
  - 2.1.1 Examples of alloimmune hemolysis
  - 2.1.2 Examples of autoimmune hemolysis/immunohemolytic hemolysis
  - 2.1.3 Drug-induced immune-mediated hemolysis
- 2.2 Laboratory method
3 Indirect Coombs test
- 3.1 Examples of clinical uses of the indirect Coombs test
  - 3.1.1 Blood transfusion preparation
  - 3.1.2 Antenatal antibody screening
- 3.2 Laboratory method
  - 3.2.1 First stage
  - 3.2.2 Second stage
  - 3.2.3 Titrations
4 Coombs reagent
5 Enhancement media
6 History of the Coombs test
7 References
8 External links

Mechanism

Schematic showing the direct and indirect Coombs tests.

The two Coombs tests are based on the fact that anti-human antibodies, which are produced by immunizing non-human species with human serum, will bind to human antibodies, commonly IgG or IgM. Animal anti-human antibodies will also bind to human antibodies that may be fixed onto antigens on the surface of red blood cells (also referred to as RBCs), and in the appropriate test tube conditions this can lead to agglutination of RBCs. The phenomenon of agglutination of RBCs is important here, because the resulting clumping of RBCs can be visualised; when clumping is seen the test is positive and when clumping is not seen the test is negative.

Common clinical uses of the Coombs test include the preparation of blood for transfusion in cross-matching, screening for atypical antibodies in the blood plasma of pregnant women as part of antenatal care, and detection of antibodies for the diagnosis of immune-mediated haemolytic anemias.

Coombs tests are done on serum from venous blood samples which are taken from patients by venipuncture. The venous blood is taken to a laboratory (or blood bank), where trained scientific technical staff do the Coombs tests. The clinical significance of the result is assessed by the physician who requested the Coombs test, perhaps with assistance from a laboratory-based hematologist.

Direct Coombs test

The direct Coombs test (also known as the direct antiglobulin test or DAT) is used to detect if antibodies or complement system factors have bound to RBC surface antigens in vivo. The DAT is not currently required for pre-transfusion testing but may be included by some laboratories.

Examples of diseases that give a positive direct Coombs test

The direct Coombs test is used clinically when immune-mediated hemolytic anemia (antibody-mediated destruction of RBCs) is suspected. A positive Coombs test indicates that an immune mechanism is attacking the patient's own RBC's. This mechanism could be autoimmunity, alloimmunity or a drug-induced immune-mediated mechanism.

Examples of alloimmune hemolysis

Hemolytic disease of the newborn (also known as HDN or erythroblastosis fetalis)
- Rh D hemolytic disease of the newborn (also known as Rh disease)
- ABO hemolytic disease of the newborn (the indirect Coombs test may only be weakly positive)
- Anti-Kell hemolytic disease of the newborn
- Rh c hemolytic disease of the newborn
- Rh E hemolytic disease of the newborn
- Other blood group incompatibility (RhC, Rhe, Kidd, Duffy, MN, P and others)
Alloimmune hemolytic transfusion reactions

Examples of autoimmune hemolysis/immunohemolytic hemolysis

Warm antibody autoimmune hemolytic anemia
- Idiopathic
- Systemic lupus erythematosus
- Evans' syndrome (antiplatelet antibodies and hemolytic antibodies)
Cold antibody immunohemolytic anemia
- Idiopathic cold hemagglutinin syndrome
- Waldenström's macroglobulinemia
- Infectious mononucleosis
- Paroxysmal cold hemoglobinuria (rare)

Drug-induced immune-mediated hemolysis

Methyldopa (IgG mediated type II hypersensitivity)
Penicillin (high dose)
Quinidine (IgM mediated activation of classical complement pathway and Membrane attack complex, MAC)

(A memory device to remember that the DAT tests the RBCs and is used to test infants for haemolytic disease of the newborn is: Rh Disease; R = RBCs, D = DAT.)

Laboratory method

The patient's red blood cells (RBCs) are washed (removing the patient's own serum) and then centrifuged with antihuman globulin (also known as Coombs reagent). If immunoglobulin or complement factors have been fixed on to the RBC surface in-vivo, the antihuman globulin will agglutinate the RBCs and the direct Coombs test will be positive. (A visual representation of a positive direct Coombs test is shown in the upper half of the schematic).

Indirect Coombs test

The indirect Coombs test (also known as the indirect antiglobulin test or IAT) is used to detect in-vitro antibody-antigen reactions. It is used to detect very low concentrations of antibodies present in a patient's plasma/serum prior to a blood transfusion. In antenatal care, the IAT is used to screen pregnant women for antibodies that may cause hemolytic disease of the newborn. The IAT can also be used for compatibility testing, antibody identification, RBC phenotyping, and titration studies.

Examples of clinical uses of the indirect Coombs test

Blood transfusion preparation

The indirect Coombs test is used to screen for antibodies in the preparation of blood for blood transfusion. The donor's and recipient's blood must be ABO and Rh D compatible. Donor blood for transfusion is also screened for infections in separate processes.

Antibody screening

A blood sample from the recipient and a blood sample from every unit of donor blood are screened for antibodies with the indirect Coombs test. Each sample is incubated against a wide range of RBCs that together exhibit a full range of surface antigens (i.e. blood types).

Cross matching

The indirect Coombs test is used to test a sample of the recipient's serum for antibodies against a sample of the blood donor's RBCs. This is sometimes called cross-matching blood.

Antenatal antibody screening

The indirect Coombs test is used to screen pregnant women for IgG antibodies that are likely to pass through the placenta into the fetal blood and cause haemolytic disease of the newborn.

Laboratory method

The IAT is a two-stage test. (A cross match is shown visually in the lower half of the schematic as an example of an indirect Coombs test).

First stage

Washed test red blood cells (RBCs) are incubated with a non human serum. If the serum contains antibodies to antigens on the RBC surface, the antibodies will bind onto the surface of the RBCs.

Second stage

The RBCs are washed three or four times with isotonic saline and then incubated with antihuman globulin. If antibodies have bound to RBC surface antigens in the first stage, RBCs will agglutinate when incubated with the antihuman globulin (also known Coombs reagent) in this stage, and the indirect Coombs test will be positive.

Titrations

By diluting a serum containing antibodies the quantity of the antibody in the serum can be gauged. This is done by using doubling dilutions of the serum and finding the maximum dilution of test serum that is able to produce agglutination of relevant RBCs.

Coombs reagent

Coombs reagent (also known as Coombs antiglobulin or antihuman globulin) is used in both the direct Coombs test and the indirect Coombs test. Coombs reagent is antihuman globulin. It is made by injecting human globulin into animals, which produce polyclonal antibodies specific for human immunoglobulins and human complement system factors. More specific Coombs reagents or monoclonal antibodies can be used.

Enhancement media

Both IgM and IgG antibodies bind strongly with their antigens. IgG antibodies are most reactive at 37 °C. IgM antibodies are easily detected in saline at room temperature as IgM antibodies are able to bridge between RBC’s owing to their large size, efficiently creating what is seen as agglutination. IgG antibodies are smaller and require assistance to bridge well enough to form a visual agglutination reaction. Reagents used to enhance IgG detection are referred to as potentiators. RBCs have a net negative charge called zeta potential which causes them to have a natural repulsion for one another. Potentiators reduce the zeta potential of RBC membranes. Common potentiators include low ionic strength solution (LISS), albumin, polyethylene glycol (PEG), and proteolytic enzymes.

History of the Coombs test

The Coombs test was first described in 1945 by Cambridge immunologists Robin Coombs (after whom it is named), Arthur Mourant and Rob Race.^[3] Historically, it was done in test tubes. Today, it is commonly done using microarray and gel technology.

References

^ "Hemolytic Anemia - Wikipedia".
^ F. Rosen and R. Geha, Case Studies in Immunology, 4th ed., Garland Science, p.173.
^ Coombs RRA, Mourant AE, Race RR. A new test for the detection of weak and "incomplete" Rh agglutinins. Brit J Exp Path 1945;26:255-66.

External links

Coombs testing - Institute for Transfusion Medicine.
Coombs’ test - direct - Medlineplus.org.
Coombs’ test - indirect - Medlineplus.org.
Acute Anemia - emedicine.com
Drugs that cause haemolytic anemia - Merck Manual.
Coombs' Test at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 自己免疫性溶血性貧血の病因：温暖凝集素と薬剤 pathogenesis of autoimmune hemolytic anemia warm agglutinins and drugs
2. 自己免疫性溶血性貧血の臨床的特徴および診断：温暖凝集素 clinical features and diagnosis of autoimmune hemolytic anemia warm agglutinins
3. 胎児および新生児における溶血性疾患の出生後診断およびマネージメント postnatal diagnosis and management of hemolytic disease of the fetus and newborn
4. 自己免疫性溶血性貧血の病因：寒冷凝集素症 pathogenesis of autoimmune hemolytic anemia cold agglutinin disease
5. 小児および思春期における自己免疫性溶血性貧血 autoimmune hemolytic anemia in children and adolescents

English Journal

Indication of Mild Hemolytic Reaction Among Preterm Infants With ABO Incompatibility.

Yogev-Lifshitz M1, Leibovitch L1,2, Schushan-Eisen I1,2, Taran C2, Strauss T1,2, Maayan-Metzger A1,2.
Pediatric blood & cancer.Pediatr Blood Cancer.2016 Feb 3. doi: 10.1002/pbc.25926. [Epub ahead of print]
BACKGROUND: Among term infants, ABO incompatibility is a leading cause of hemolytic disease and neonatal jaundice. With respect to preterm infants, data are lacking.OBJECTIVE: To evaluate the incidence and severity of ABO incompatibility hemolytic disease among preterm infants with respect to hemoly
PMID 26841084

Giant cell hepatitis with autoimmune hemolytic anemia in a Korean infant.

Cho MH1, Park HS2, Han HS3, Bae SH1.
Pediatrics international : official journal of the Japan Pediatric Society.Pediatr Int.2016 Feb 3. doi: 10.1111/ped.12874. [Epub ahead of print]
Giant cell hepatitis (GCH) with autoimmune hemolytic anemia (AHA) is a very rare disease characterized by early onset and severe clinical manifestations, including immune hemolytic anemia and hepatitis with cholestasis. The prognosis is poor despite aggressive immunosuppressive therapy. We report he
PMID 26841192

Linking dispositional mindfulness and positive psychological processes in cancer survivorship: a multivariate path analytic test of the mindfulness-to-meaning theory.

Garland EL1,2, Thielking P1, Thomas EA2, Coombs M2, White S1, Lombardi J1, Beck A1.
Psycho-oncology.Psychooncology.2016 Jan 22. doi: 10.1002/pon.4065. [Epub ahead of print]
BACKGROUND: Research indicates that dispositional mindfulness is associated with positive psychological functioning. Although this disposition has been linked with beneficial outcomes in the broader mental health literature, less is known about dispositional mindfulness in cancer survivors and how i
PMID 26799620

Japanese Journal

肝細胞癌の治療中に自己免疫性溶血性貧血を発症した1例

医学検査 65(1), 51-54, 2016
NAID 130005133681

Intravascular Hemolytic Anemia in a Patient with Antibodies Related to Meropenem

Internal Medicine 54(10), 1291-1295, 2015
NAID 130005069794

Levofloxacinによると推測される薬剤性免疫性溶血性貧血の1例

医学検査 64(1), 60-65, 2015
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