Activated partial thromboplastin time
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The partial thromboplastin time (PTT), also known as the activated partial thromboplastin time (aPTT or APTT), is a blood test that characterizes
coagulation Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanis ...
of the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
. A historical name for this measure is the kaolin-cephalin clotting time (KCCT), reflecting
kaolin Kaolinite ( ) is a clay mineral, with the chemical composition Al2 Si2 O5( OH)4. It is an important industrial mineral. It is a layered silicate mineral, with one tetrahedral sheet of silica () linked through oxygen atoms to one octahedral ...
and
cephalin Phosphatidylethanolamine (PE) is a class of phospholipids found in biological membranes. They are synthesized by the addition of cytidine diphosphate- ethanolamine to diglycerides, releasing cytidine monophosphate. ''S''-Adenosyl methionine can ...
as materials historically used in the test. Apart from detecting abnormalities in blood clotting, partial thromboplastin time is also used to monitor the treatment effect of heparin, a widely prescribed drug that reduces blood's tendency to clot. The PTT measures the overall speed at which blood clots form by means of two consecutive series of biochemical reactions known as the ''intrinsic'' pathway and common pathway of
coagulation Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanis ...
. The PTT indirectly measures action of the following
coagulation factor Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...
s: I (fibrinogen), II (prothrombin), V (proaccelerin), VIII (anti-hemophilic factor), X (Stuart–Prower factor), XI (plasma thromboplastin antecedent), and XII (Hageman factor). The PTT is often used in conjunction with another measure of how quickly blood clotting takes place called the
prothrombin time The prothrombin time (PT) – along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) – is an assay for evaluating the ''extrinsic'' pathway and common pathway of coagulation. This blood test is als ...
(PT). The PT measures the speed of clotting by means of the ''extrinsic'' pathway and common pathway.


Methodology

Partial thromboplastin time is typically analyzed by a
medical technologist A medical laboratory scientist (MLS) or clinical laboratory scientist (CLS) or medical technologist (MT) performs diagnostic testing of blood and body fluids in clinical laboratories. The scope of a medical laboratory scientist's work begins wit ...
or a
laboratory technician A laboratory technician is a person who works in a laboratory performing analytical or experimental procedures, maintaining laboratory equipment and assisting scientists with their work. According to the Oxford English Dictionary, the first use o ...
on an automated instrument at 37 °C (as a nominal approximation of normal
human body temperature Normal human body-temperature (normothermia, euthermia) is the typical temperature range found in humans. The normal human body temperature range is typically stated as . Human body temperature varies. It depends on sex, age, time of day, exert ...
). The test is termed "partial" due to the absence of tissue factor from the reaction mixture. * Blood is drawn into a
test tube A test tube, also known as a culture tube or sample tube, is a common piece of laboratory glassware consisting of a finger-like length of glass or clear plastic tubing, open at the top and closed at the bottom. Test tubes are usually placed in ...
containing
oxalate Oxalate (IUPAC: ethanedioate) is an anion with the formula C2O42−. This dianion is colorless. It occurs naturally, including in some foods. It forms a variety of salts, for example sodium oxalate (Na2C2O4), and several esters such as dimethyl ...
or
citrate Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the ...
, molecules which act as an anticoagulant by binding the calcium in a sample. The blood is mixed, then centrifuged to separate blood cells from plasma (as partial thromboplastin time is most commonly measured using
blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intr ...
). * A sample of the plasma is extracted from the test tube and placed into a measuring test tube. * Next, an excess of
calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...
(in a phospholipid suspension) is mixed into the plasma sample (to reverse the anticoagulant effect of the oxalate enabling the blood to clot again). * Finally, in order to activate the intrinsic pathway of coagulation, an activator (such as
silica Silicon dioxide, also known as silica, is an oxide of silicon with the chemical formula , most commonly found in nature as quartz and in various living organisms. In many parts of the world, silica is the major constituent of sand. Silica is ...
,
celite Diatomaceous earth (), diatomite (), or kieselgur/kieselguhr is a naturally occurring, soft, siliceous sedimentary rock that can be crumbled into a fine white to off-white powder. It has a particle size ranging from more than 3 μm to les ...
,
kaolin Kaolinite ( ) is a clay mineral, with the chemical composition Al2 Si2 O5( OH)4. It is an important industrial mineral. It is a layered silicate mineral, with one tetrahedral sheet of silica () linked through oxygen atoms to one octahedral ...
,
ellagic acid Ellagic acid is a polyphenol found in numerous fruits and vegetables. It is the dilactone of hexahydroxydiphenic acid. Name The name comes from the French term ''acide ellagique'', from the word ''galle'' spelled backwards because it can be ...
) is added, and the time the sample takes to clot is measured optically. Some laboratories use a mechanical measurement, which eliminates interferences from lipemic and
icteric Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metab ...
samples.


Interpretation

The typical
reference range In medicine and health-related fields, a reference range or reference interval is the range or the interval of values that is deemed normal for a physiological measurement in healthy persons (for example, the amount of creatinine in the blood, o ...
is between 30 seconds and 50 s (depending on laboratory). Shortening of the PTT is considered to have little clinical relevance, but some research indicates that it might increase risk of
thromboembolism Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (t ...
. Normal PTT requires the presence of the following coagulation factors: I, II, V, VIII, IX, X, XI and XII. Notably, deficiencies in factors VII or XIII will not be detected with the PTT test. Prolonged aPTT may indicate: * use of heparin (or contamination of the sample) * antiphospholipid antibody (especially lupus anticoagulant, which paradoxically increases propensity to
thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (t ...
) * coagulation factor deficiency (e.g., hemophilia) *
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
— coagulation factor consumption * presence of antibodies against coagulation factors (factor inhibitors) To distinguish the above causes,
mixing test Mixing studies are tests performed on blood plasma of patients or test subjects to distinguish factor deficiencies from factor inhibitors, such as lupus anticoagulant, or specific factor inhibitors, such as antibodies directed against factor VIII. ...
s are performed, in which the patient's plasma is mixed (initially at a 50:50 dilution) with normal plasma. If the abnormality does not disappear, the sample is said to contain an "inhibitor" (either heparin, antiphospholipid antibodies or coagulation factor specific inhibitors), while if it does disappear a factor deficiency is more likely. Deficiencies of factors VIII, IX, XI and XII and rarely
von Willebrand factor Von Willebrand factor (VWF) () is a blood glycoprotein involved in hemostasis, specifically, platelet adhesion. It is deficient and/or defective in von Willebrand disease and is involved in many other diseases, including thrombotic thrombocytope ...
(if causing a low factor VIII level) may lead to a prolonged aPTT correcting on mixing studies. The aPTT is usually normal in
pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...
but tends to slightly decrease in late pregnancy.


aPTT-based APC resistance test

The aPTT-based
activated protein C Protein C, also known as autoprothrombin IIA and blood coagulation factor XIX, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and cell death and maintaini ...
(APC) resistance test is used in the diagnosis of APC resistance (APCR). It involves a modified aPTT test performed in the presence and absence of APC. The ratio of these aPTT values is calculated and is called the APC sensitivity ratio (APCsr) or simply APC ratio (APCr). This ratio is inversely related to the degree of APC resistance. The aPTT-based APC resistance test was developed in 1993.


History

The aPTT was first described in 1953 by researchers at the
University of North Carolina at Chapel Hill A university () is an institution of higher (or tertiary) education and research which awards academic degrees in several academic disciplines. Universities typically offer both undergraduate and postgraduate programs. In the United States ...
. This is the reason why the color of the
Vacutainer A vacutainer blood collection tube is a Sterilization (microbiology), sterile glass or plastic test tube with a colored rubber stopper creating a vacuum seal inside of the tube, facilitating the drawing of a predetermined volume of liquid. Vacut ...
tube top is Carolina blue.


See also

* Thromboplastin


References

{{Myeloid blood tests Blood tests Medical signs