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The partial thromboplastin time (PTT), also known as the activated partial thromboplastin time (aPTT or APTT), is a
blood test A blood test is a medical laboratory, laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose ...
that characterizes
coagulation Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a thrombus, blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of co ...
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 is com ...
. A historical name for this measure is the Kaolin-cephalin clotting time (KCCT), reflecting
kaolin Kaolinite ( ; also called kaolin) is a clay mineral, with the chemical composition Al2 Si2 O5( OH)4. It is a layered silicate mineral, with one tetrahedral sheet of silica () linked through oxygen atoms to one octahedral sheet of alumina (). ...
and cephalin 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 Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Heparin is a blood anticoagulant that increases the activity of antithrombin. It is used in the treatment of myocardial infarction, ...
, 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 thrombus, blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of co ...
. The PTT indirectly measures action of the following coagulation factors: 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 Coagulation#Extrinsic pathway, extrinsic pathway and Coagulation#Common pathway, ...
(PT). The PT measures the speed of clotting by means of the ''extrinsic'' pathway and common pathway.


Methodology

Activated partial thromboplastin time (APTT) is typically analyzed by a medical technologist or laboratory technician, either manually or using an automated instrument at 37°C, which approximates normal human body temperature.
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 Coagulation#Extrinsic pathway, extrinsic pathway and Coagulation#Common pathway, ...
utilizes complete thromboplastin, a combination of
tissue factor Tissue factor, also called platelet tissue factor or Coagulation factor III, is a protein present in subendothelial tissue and leukocytes which plays a major role in coagulation and, in humans, is encoded by ''F3'' gene. Its role in the blood c ...
and
phospholipids Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typi ...
. In contrast, APTT employs partial thromboplastin, containing only phospholipids and no tissue factor—hence the term "partial thromboplastin time." An activator is used in the APTT test to initiate the intrinsic pathway of blood coagulation. Common activators include kaolin, silica, celite, and ellagic acid. * 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 s ...
containing
oxalate Oxalate (systematic IUPAC name: ethanedioate) is an anion with the chemical formula . This dianion is colorless. It occurs naturally, including in some foods. It forms a variety of salts, for example sodium oxalate (), and several esters such as ...
or
citrate Citric acid is an organic compound with the formula . It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry Biochemistry, or biological chemistry, is the study of chemical processes within and relati ...
, molecules which act as an
anticoagulant An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which ...
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 (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...
). * 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; it has 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 to it ...
(in a
phospholipid Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
suspension) is mixed into the plasma sample (to reverse the anticoagulant effect of the citrate enabling the blood to clot again). * Finally, in order to activate the intrinsic pathway of coagulation, an activator 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 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 ...
is between 25
second The second (symbol: s) is a unit of time derived from the division of the day first into 24 hours, then to 60 minutes, and finally to 60 seconds each (24 × 60 × 60 = 86400). The current and formal definition in the International System of U ...
s and 33 s (depending on laboratory). Longer times of up to 50 s do apply to infants. Shortening of the PTT is considered to have little clinical relevance, but some research indicates that it might increase risk of
thromboembolism Thromboembolism is a condition in which a blood clot (thrombus) breaks off from its original site and travels through the bloodstream (as an embolus) to obstruct a blood vessel, causing tissue ischemia and organ damage. Thromboembolism can affe ...
. 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 Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Heparin is a blood anticoagulant that increases the activity of antithrombin. It is used in the treatment of myocardial infarction, ...
or
warfarin Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...
(or contamination of the sample) * Vitamin K deficiency * Antiphospholipid antibody (especially
lupus anticoagulant Lupus anticoagulant is an immunoglobulin that binds to phospholipids and proteins associated with the cell membrane. Its name is a partial misnomer, as it is actually a prothrombotic antibody ''in vivo''. The name derives from their properties ''i ...
, which paradoxically increases propensity to
thrombosis Thrombosis () is the formation of a Thrombus, 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 (thrombocytes) and fib ...
) * Coagulation factor deficiency (e.g.,
haemophilia Haemophilia (British English), or hemophilia (American English) (), is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a long ...
,
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
,
von Willebrand disease Von Willebrand disease (VWD) is the most common heredity, hereditary coagulopathy, blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of ...
) * Coagulation factor consumption (e.g.,
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
,
disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking Microvessel, small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems ...
) * Presence of
antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
against coagulation factors (factor inhibitors) *
Von Willebrand disease Von Willebrand disease (VWD) is the most common heredity, hereditary coagulopathy, blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of ...
To distinguish the above causes, mixing tests 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 that promotes primary hemostasis, specifically, platelet adhesion. It is deficient and/or defective in von Willebrand disease and is involved in many other diseases, including thrombotic thro ...
(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 gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...
but tends to slightly decrease in late pregnancy.


aPTT-based APC resistance test

The aPTT-based activated protein C (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 partial thromboplastin time was first described in 1953 by researchers at the
University of North Carolina at Chapel Hill The University of North Carolina at Chapel Hill (UNC, UNC–Chapel Hill, or simply Carolina) is a public university, public research university in Chapel Hill, North Carolina, United States. Chartered in 1789, the university first began enrolli ...
. The initial exogenous phospholipid used in PTT testing was Cephalin.


See also

* Thromboplastin


References

{{DEFAULTSORT:Activated Partial thromboplastin time Blood tests Medical signs Hematology