Antithrombin III (SERPINC1)
Serine Protease Inhibitors (Serpins)

Author: Gianpiero Pescarmona
Date: 03/06/2010



Antithrombin III is a small protein molecule that inactivates several enzymes of the coagulation system. It is a glycoprotein produced by the liver and consists of 464 aminoacids (m.w.: 58 kD).



When relevant for the function

  • Primary structure
  • Secondary structure
  • Tertiary structure
  • Quaternary structure

Protein Aminoacids Percentage


mRNA synthesis
protein synthesis
post-translational modifications


cellular localization,
biological function

A clotting factor is activated when the factor that precedes it in the clotting cascade splits off a protein fragment and thereby exposes an enzymatic center. The latter can again be inactivated physiologically by complexing with antithrombin III (AT III), a circulating glycoprotein. Heparin acts to inhibit clotting by accelerating formation of this complex more than 1000-fold. Heparin is present (together with histamine) in the vesicles of mast cells.



2015-06-07T14:03:14 - Gianpiero Pescarmona

Antithrombin is a member of the serine protease inhibitor (serpin) superfamily. It is the principal plasma anticoagulant serpin mediating inactivation of serine protease procoagulant enzymes, chiefly thrombin and coagulation factors Xa and IXa( 1) Heparin and certain other naturally occurring glycosaminoglycans markedly enhance antithrombin's anticoagulant activity (approximately 1,000-fold) by providing a template to catalyze formation of covalently bonded, inactive complexes of serine protease and antithrombin that are subsequently cleared from circulation. Antithrombin is the mediator of heparin's anticoagulant activity.

The antithrombin gene on chromosome 1 encodes a glycoprotein of approximately 58,000 molecular weight that is syn= thesized in the liver and is present in a relatively high plasma concentration (approximately 2.3 umol/L).
The biological half-life of antithrombin is 2 to 3 days.

Antithrombin is also termed Antithrombin III (AT III). The designations Antithrombin I through to Antithrombin IV originate in early studies carried out in the 1950s by Seegers, Johnson and Fell (An antithrombin reaction to prothrombin activation, 1956)

Only AT III and possibly AT I are medically significant. AT III is generally referred to solely as "Antithrombin" and it is Antithrombin III that is discussed in this page.


Figure 1. The location of the four potential glycosylation sites within the tertiary structure of an antithrombin monomer are shown, as taken from the protein data bank file 2ANT. In this structure only Asn 155 is glycosylated by the addition of a single N-acetylglucosamine residue.

Antithrombin has a half-life in blood plasma of around 3 days. (Metabolism of antithrombin III (heparin cofactor) in man: Effects of venous thrombosis of heparin administration,1977)
The normal antithrombin concentration in human blood plasma is high at approximately 0.12 mg/ml, which is equivalent to a molar concentration of 2.3 μM. Antithrombin has been isolated from the plasma of a large number of species additional to humans. As deduced from protein and cDNA sequencing, cow, sheep, rabbit and mouse antithrombins are all 433 amino acids in length, which is one amino acid longer than human antithrombin. The extra amino acid is thought to occur at amino acid position 6. Cow, sheep, rabbit, mouse, and human antithrombins share between 84 and 89% amino acid sequence identity. (Regulation of thrombin activity by antithrombin and heparin,1994 Six of the amino acids form three intramolecular disulfide bonds, Cys8-Cys128, Cys21-Cys95, and Cys248-Cys430. They all have four potential N-glycosylation sites. These occur at asparagine (Asn) amino acid numbers 96, 135, 155, and 192 in humans and at similar amino acid numbers in other species. All these sites are occupied by cova= lently attached oligosaccharide side-chains in the predominant form of human antithrombin, α-antithrombin, resulting in a molecular weight for this form of antithrombin of 58,200. The potential glycosylation site at asparagine 135 is not occupied in a minor form (around 10%) of antithrombin, β-antithrombin (see Figure 1) (Physiological variant of antithrombin-III lacks carbohydrate side-chain at Asn 135,1987)
Recombinant antithrombins with properties similar to those of normal human antithrombin have been produced using baculovirus-infected insect cells and mammalian cell lines grown in cell culture . These recombinant antithrombins generally have different glycosylation patterns to normal antithrombin and are typically used in antithrombin structural studies. For this reason many of the antithrombin structures stored in the protein data bank and presented in this article show variable glycosylation patterns.
Antithrombin begins in its native state, which has a higher free energy compared to the latent state, which it decays to on average after 3 days. The latent state has the same form as the activated state - that is, when it is inhibiting thrombin. As such it is a classic example of the utility of kinetic vs thermodynamic control of protein folding.


Figure 2. The reactive arg 393 - ser 394 bond is located on an exposed loop at the surface of the molecule. This loop is termed the reactive site loop (RSL) or reactive centre loop (RCL).

Figure 3. The amino acid sequence of the reactive site loop of human antithrombin is shown (Conformational changes in serpins: II. The mechanism of activation of antithrombin by heparin,2000)

The reactive site loop comprises amino acid sequence numbers 377 to 400 (numbers shown below the above sequence) or amino acids P1 to P17 and P1' to P7' using the Schechter and Berger convention (number shown above the above sequence). The reactive bond is indicated by an arrow.
Antithrombin is a serpin (serine protease inhibitor) and is thus similar in structure to most other plasma protease inhibitors, such as alpha 1-antichymotrypsin, alpha 2-antiplasmin and Heparin cofactor II.

The physiological target proteases of antithrombin are those of the contact activation pathway (formerly known as the intrinsic pathway), namely the activated forms of Factor X (Xa), Factor IX (IXa), Factor XI (XIa), Factor XII (XIIa) and, to a greater extent, Factor II (thrombin) (IIa), and also the activated form of Factor VII (VIIa) from the tissue factor pathway (formerly known as the extrinsic pathway) ( Substitution of valine for leucine 305 in factor VIIa increases the intrinsic enzymatic activity, 2001) The inhibitor also inactivates kallikrein and plasmin, also involved in blood coagulation. However it inactivates certain other serine proteases that are not involved in coagulation such as trypsin and the C1s subunit of the enzyme C1 involved in the classical complement pathway.
Protease inactivation results as a consequence of trapping the protease in an equimolar complex with antithrombin in which the active site of the protease enzyme is inaccessible to its usual substrate(chemistry). The formation of an antithrombin-protease complex involves an interaction between the protease and a specific reactive peptide bond within antithrombin. In human antithrombin this bond is between arginine (arg) 393 and serine (ser) 394 (see Figure 2 and Figure 3).
It is thought that protease enzymes become trapped in inactive antithrombin-protease complexes as a consequence of their attack on the reactive bond. Although attacking a similar bond within the normal protease substrate results in rapid proteo= lytic cleavage of the substrate, initiating an attack on the antithrombin reactive bond causes antithrombin to become activated and trap the enzyme at an intermediate stage of the proteolytic process. Given time, thrombin is able to cleave the reactive bond within antithrombin and an inactive antithrombin-thrombin complex will dissociate, however the time it takes for this to occur may be greater than 3 daysn.However bonds P3-P4 and P1'-P2' can be rapidly cleaved by neutrophil elastase and the bacterial enzyme thermolysin respectively, resulting in inactive antithrombins no longer able to inhibit thrombin activity.
The rate of antithrombin's inhibition of protease activity is greatly enhanced by its additional binding to heparin as is its inactivation by neutrophil elastase. (Probing serpin reactive-loop conformations by proteolytic cleavage,1996)

Antithrombin and heparin

Antithrombin inactivates its physiological target enzymes, Thrombin, Factor Xa and Factor IXa with rate constants of 7–11 × 103, 2.5 × 103 M−1 s−1 and 1 × 10 M−1 s−1 respectively. The rate of antithrombin-thrombin inactivation increases to 1.5 - 4 × 107 M−1 s−1 in the presence of heparin, i.e. the reaction is accelerated 2000-4000 fold."The kinetics of hemostatic enzyme-antithrombin interactions in the presence of low molecular weight heparin": Factor Xa inhibition is accelerated by only 500 to 1000 fold in the presence of heparin and the maximal rate constant is 10 fold lower than that of thrombin inhibition. The rate enhancement of antithrombin-Factor IXa inhibition shows an approximate 1 million fold enhancement in the presence of heparin and physiological levels of calcium.
AT-III binds to a specific pentasaccharide sulfation sequence contained within the heparin polymer
Upon binding to this pentasaccharide sequence, inhibition of protease activity is increased by heparin as a result of two distinct mechanisms. In one mechanism heparin stimulation of Factor IXa and Xa inhibition depends on a conformational change within antithrombin involving the reactive site loop and is thus allosteric. (Allosteric activation of antithrombin critically depends upon hinge region extension,2004) In another mechanism stimulation of thrombin inhibition depends on the formation of a ternary complex between AT-III, thrombin, and heparin.

Allosteric activation

Figure 4. Two crystal structures for antithrombin. Model A is taken from the pdb file 2ANT and model B from pdb file 1AZX. Model B is complexed with a pentasaccharide while model A is uncomplexed.

Increased Factor IXa and Xa inhibition requires the minimal heparin pentasaccharide sequence. The conformational changes that occur within antithrombin in response to pentasaccharide binding are well documented. (The intact and cleaved human antithrombin III complex as a model for serpin-proteinase interactions,1994)
In the absence of heparin, amino acids P14 and P15 (see Figure 3) from the reactive site loop are embedded within the main body of the protein (specifically the top of beta sheet A). This feature is in common with other serpins such as heparin cofactor II, alpha 1-antichymotrypsin and MENT.

The conformational change most relevant for Factor IXa and Xa inhibition involves the P14 and P15 amino acids within the N-terminal region of the reactive site loop (circled in Figure 4 model B). This region has been termed the hinge region. The conformational change within the hinge region in response to heparin binding results in the expulsion of P14 and P15 from the main body of the protein and it has been shown that by preventing this conformational change, increased Factor IXa and Xa inhibition does not occur. It is thought that the increased flexibility given to the reactive site loop as a result of the hinge region conformational change is a key factor in influencing increased Factor IXa and Xa inhibition. It has been calculated that in the absence of the pentasaccharide only one in every 400 Antithrombin molecules (0.25%) is in an active conformation with the P14 and P15 amino acids expelled.

Non-allosteric activation

Figure 5. The structure of an antithrombin-thrombin-heparin ternary complex taken from pdb 1TB6.

Increased thrombin inhibition requires the minimal heparin pentasaccharide plus at least an additional 13 monomeric units. This is thought to be due to a requirement that antithrombin and thrombin must bind to the same heparin chain adjacent to each other. This can be seen in the series of models shown in Figure 5.
In the structures shown in Figure 5 the C-terminal portion (P' side) of the reactive site loop is in an extended conformation when compared with other un-activated or heparin activated antithrombin structures. The P' region of antithrombin is unusually long relative to the P' region of other serpins and in un-activated or heparin activated antithrombin structures forms a tightly hydrogen bonded β-turn. P' elongation occurs through the breaking of all hydrogen bonds involved in the β-turn.
The hinge region of antithrombin in the Figure 5 complex could not be modelled due to its conformational flexibility, and amino acids P9-P14 are not seen in this structure. This conformational flexibility indicates an equilibrium may exist within the complex between a P14 P15 reactive site loop inserted antithrombin conformation and a P14 P15 reactive site loop expelled conformation. In support of this, analysis of the positioning of P15 Gly in the Figure 5 complex (labelled in model B) shows it to be inserted into beta sheet A (see model C).

Effect of glycosylation on activity
α-Antithrombin and β-antithrombin differ in their affinity for heparin. The difference in dissociation constant between the two is threefold for the pentasaccharide and greater than tenfold for full length heparin, with β-antithrombin having a higher affinity.
The higher affinity of β-antithrombin is thought to be due to the increased rate at which subsequent conformational changes occur within the protein upon initial heparin binding. For α-antithrombin, the additional glycosylation at Asn-135 is not thought to interfere with initial heparin binding, but rather to inhibit any resulting conformational changes.
Even though it is present at only 5–10% the levels of α-antithrombin, due to its increased heparin affinity, it is thought that β-antithrombin is more important than α-antithrombin in controlling thrombogenic events resulting from tissue injury. Indeed, thrombin inhibition after injury to the aorta has been attributed solely to β-antithrombin. (Thrombin inhibition by antithrombin III on the subendothelium is explained by the isoform AT beta,1996)

Role in disease

Evidence for the important role antithrombin plays in regulating normal blood coagulation is demonstrated by the correlation between inherited or acquired antithrombin deficiencies and an increased risk of any affected individual developing thrombotic disease. Antithrombin deficiency generally comes to light when a patient suffers recurrent venous thrombosis and pulmonary embolism.

Acquired antithrombin deficiency

Acquired antithrombin deficiency occurs as a result of three distinctly different mechanisms. The first mechanism is increa= sed excretion which may occur with renal failure associated with proteinuria nephrotic syndrome. The second mechanism results from decreased production as seen in liver failure or cirrhosis or an immature liver secondary to premature birth. Liver dysfunction, premature birth. The third mechanism results from accelerated consumption which is most pronounced as consequence of severe injury trauma but also may be seen on a lesser scale as a result of interven= tions such as major surgery or cardiopulmonary bypass

Inherited antithrombin deficiency

The incidence of inherited antithrombin deficiency has been estimated at between 1:2000 and 1:5000 in the normal popula= tion, with the first family suffering from inherited antithrombin deficiency being described in 1965). Subsequently it was proposed that the classification of inherited antithrombin deficiency be designated as either type I or type II, based upon functional and "immunochemical": antithrombin analyses. Maintenance of an adequate level of antithrombin activity, which is at least 70% that of a normal functional level is essential to ensure effective inhibition of blood coagulation proteases. Typically as a result of type I or type II antithrombin deficiency, functional antithrombin levels are reduced to below 50% of normal. (Antithrombin III: summary of first database update,1994)

Type I antithrombin deficiency

Type I antithrombin deficiency is characterised by a decrease in both antithrombin activity and antithrombin concen= tration in the blood of affected individuals. Type I deficiency was originally further divided into two subgroups, Ia and Ib, based upon heparin affinity. The antithrombin of subgroup Ia individuals showed a normal affinity for heparin while the antithrombin of subgroup Ib individuals showed a reduced affinity for heparin. Subsequent functional analysis of a group of 1b cases found them not only to have reduced heparin affinity but multiple or 'pleiotrophic' abnormalities affecting the reactive site, the heparin binding site and antithrombin blood concentration. In a revised system of classification adopted by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis, type Ib cases are now designated as type II PE, Pleiotrophic effect.
Most cases of type I deficiency are due to point mutations, deletions or minor insertions within the antithrombin gene. These genetic mutations result in type I deficiency through a variety of mechanisms:

* Mutations may produce unstable antithrombins that either may be not exported into the blood correctly upon completion biosynthesis or exist in the blood for a shortened period of time, e.g., the deletion of 6 base pairs in codons 106-108.
* Mutations may affect mRNA processing of the antithrombin gene.
* Minor insertions or deletions may lead to frame shift mutations and premature termination of the antithrombin gene.
* Point mutations may also result in the premature generation of a termination or stop codon e.g. the mutation of codon 129, CGA→TGA (UGA after transcription), replaces a normal codon for arginine with a termination codon. ( A common point mutation producing type 1A antithrombin III deficiency: AT129 CGA to TGA (Arg to Stop) 1991 )

Type II antithrombin deficiency

Type II antithrombin deficiency is characterised by normal antithrombin levels but reduced antithrombin activity in the blood of affected individuals. Originally it was proposed that type II deficiency be further divided into three subgroups IIa, IIb and IIc depending upon which antithrombin functional activity is reduced or retained.

* Subgroup IIa - Decreased thrombin inactivation, decreased factor Xa inactivation and decreased heparin affinity.
* Subgroup IIb - Decreased thrombin inactivation and normal heparin affinity.
* Subgroup IIc - Normal thrombin inactivation, normal factor Xa inactivation and decreased heparin affinity.
In the revised system of classification again adopted by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis, type II antithrombin deficiency remains subdivided into three subgroups: the already mentioned type II PE, along with type II RS, where mutations effect the reactive site and type II HBS, where mutations effect the antithrombin heparin binding site.
For the purposes of an antithrombin mutational database compiled by members of the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis, type IIa cases are now classified as type II PE, type IIb cases as type II RS and type IIc cases as type II HBS.


Presently it is relatively easy to characterise a specific antithrombin genetic mutation. However prior to the use of modern characterisation techniques investigators named mutations for the town or city where the individual suffering from the deficiency resided i.e. the antithrombin mutation was designated a toponym. Modern mutational characterisation has since shown that many individual antithrombin toponyms are actually the result of the same genetic mutation, for example Antithrombin-Toyama, is equivalent to Antihrombin-Kumamoto, -Amien, -Tours, -Paris-1, -Paris-2, -Alger, -Padua-2 and -Barcelona.

As medication

Antithrombin is used as a protein therapeutic that can be purified from human plasma or produced recombinantly (for example, Atryn, which is produced in the milk of genetically modified goats.)

Antithrombin is approved by the FDA as an anticoagulant for the prevention of clots before, during, or after surgery or birthing in patients with hereditary antithrombin deficiency.

Cleaved and latent antithrombin

Figure 6. Latent antithrombin

Cleavage at the reactive site results in entrapment of the thrombin protease, with movement of the cleaved reactive site loop together with the bound protease, such that the loop forms an extra sixth strand in the middle of beta sheet A. This move= ment of the reactive site loop can also be induced without cleavage, with the resulting crystallographic structure being identical to that of the physiologically latent conformation of plasminogen activator inhibitor-1 (PAI-1). For this reason the conformation of antithrombin in which the reactive site loop is incorporated uncleaved into the main body of the protein is referred to as latent antithrombin. In contrast to PAI-1 the transition for antithrombin from a normal or native conformation to a latent conformation is irreversible.
Native antithrombin can be converted to latent antithrombin (L-antithrombin) by heating alone or heating in the presence of citrate. (Commercial antithrombin concentrate contains inactive L-forms of antithrombin, 1997 ) However, without extreme heating and at 37°C (body temperature) 10% of all antithrombin circulating in the blood is converted to the L-antithrombin over a 24-hour period. The structure of L-antithrombin is shown in Figure 6.
The 3-dimensional structure of native antithrombin was first determined in 1994. Unexpectedly the protein crystallized as a heterodimer composed of one molecule of native antithrombin and one molecule of latent antithrombin. Latent antithrombin on formation immediately links to a molecule of native antithrombin to form the heterodimer, and it is not until the concentration of latent antithrombin exceeds 50% of the total antithrombin that it can be detected analytically. Not only is the latent form of antithrombin inactive against its target coagulation proteases, but its dimerisation with an otherwise active native antithrombin molecule also results in the native molecules inactivation. The physiological impact of the loss of antithrombin activity either through latent antithrombin formation or through subsequent dimer formation is exacerbated by the preference for dimerisation to occur between heparin activated β-antithrombin and latent antithrombin as opposed to α-antithrombin.
A form of antithrombin that is an intermediate in the conversion between native and latent forms of antithrombin has also been isolated and this has been termed prelatent antithrombin. (A novel anti-angiogenic form of antithrombin with retained proteinase binding ability and heparin affinity,2001 )

Antiangiogenic antithrombin
Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. Under normal physiological conditions angiogenesis is tightly regulated and is controlled by a balance of angiogenic stimulators and angiogenic inhibitors. Tumor growth is dependent upon angiogenesis and during tumor development a sustained production of angiogenic stimulatory factors is required along with a reduction in the quantity of angiogenic inhibitory factors tumor cells produce. The cleaved and latent form of antithrombin potently inhibit angiogenesis and tumor growth in animal models. The prelatent form of antithrombin has been shown to inhibit angiogenesis in-vitro but to date has not been tested in experimental animal models.



Laboratory evaluation

Also known as: Functional Antithrombin III; AT III; AT 3 Formal name: Antithrombin (Activity and Antigen)

"The Test":

How is it used?
What does the test result mean?
Is there anything else I should know?

How is it used?
Antithrombin testing is primarily ordered, along with other tests for excessive clotting disorders, to investigate the cause of recurrent blood clot formation (thrombosis). Testing evaluates the activity (function) and the amount (quantity) of antithrombin.
The activity test is performed first, to evaluate whether the total amount of functional antithrombin is normal. If the antithrombin activity is low, then the antithrombin antigen test is performed to determine the quantity of antithrombin present. These two tests can be used to differentiate between type 1 and type 2 antithrombin deficiencies. If a deficiency is detected, both antithrombin tests are typically repeated at a later date to confirm test findings.
Antithrombin testing may sometimes be used to evaluate people who are not responding as expected to heparin. Heparin is an anticoagulant drug that is given to people who have a blood clot or are at an increased risk of forming inappropriate blood clots. Heparin can greatly increase antithrombin activity, thus inhibiting formation of blood clots, but those who are antithrombin deficient are resistant to heparin treatment.

Is there anything else I should know?
If a person with an antithrombin deficiency also has other coagulation risks, such as a Protein C or S deficiency, a Factor V Leiden mutation, or oral contraceptive use, then she may be at a significantly elevated risk of developing a blood clot.

Antithrombin deficiency can increase the risk of recurrent miscarriage.

People with antithrombin deficiency may need preventive anticoagulation therapy prior to medical or surgical procedures.
Antithrombin concentrates and recombinant antithrombin are now available as a medication to temporarily correct acute or chronic antithrombin deficiencies.

What does the test result mean?
Decreased antithrombin activity and decreased quantities of antithrombin antigen suggest a type 1 antithrombin deficiency. In this case, the activity is decreased because there is less antithrombin available to participate in clotting regulation. Reduced antithrombin activity and normal levels of antithrombin antigen suggest a type 2 antithrombin deficiency. This means that there is sufficient antithrombin, but it is not functioning as it should. In either case, a deficiency increases the affected person's risk of developing an inappropriate blood clot.
If the antithrombin activity is normal, then the antithrombin antigen test is usually not performed. In this case, the antithrombin is functioning adequately and the recurrent thrombotic episodes being investigated are likely due to a cause other than an antithrombin deficiency.
Temporarily or chronically decreased antithrombin levels may be seen with conditions that affect its consumption or production, such as:

* DIC (Disseminated intravascular coagulation), an acute or chronic condition characterized by the consumption of clotting factors. An affected person may bleed and/or clot.
* DVT (deep vein thrombosis – a blood clot usually in a deep leg vein)
* Liver disease
* Nephrotic syndrome
* Protein-losing condition
* Pulmonary embolism
* Heparin therapy (transiently lower antithrombin level)
* Infants during the first few days of life (about 50% of healthy adult level)
* Estrogen therapy
Increased levels of antithrombin are not usually considered a problem. They may be seen with conditions such as "acute hepatitis" or a blocked bile duct (cholestasis), kidney transplant, vitamin K deficiency, or being on warfarin (COUMADIN®) anticoagulation therapy. Therefore, a normal level while a person in on warfarin does not absolutely rule out the presence of antithrombin deficiency.

Antithrombin Antigen, Plasma
Useful For
Assessing abnormal results of the antithrombin activity assay. (ATTF / Antithrombin Activity, Plasma), which is recommended as the primary (screening) antithrombin assay

Diagnosing antithrombin deficiency, acquired or congenital, in conjunction with measurement of antithrombin activity

As an adjunct in the diagnosis and management of carbohydrate-deficient glycoprotein syndromes

Reference Values
Adults: 80-130% Normal, full-term newborn infants may have decreased levels (> or =35-40%) which reach adult levels by 180 days postnatal. Healthy, premature infants (30-36 weeks gestation) may have decreased levels which reach adult levels by 180 days postnatal.*

Hereditary antithrombin deficiency is much less common than acquired deficiency. Diagnosis of hereditary deficiency requires clinical correlation, testing of both antithrombin activity and antithrombin antigen, and may be aided by repeated testing and by family studies. DNA-based diagnostic testing may be helpful, but is generally not readily available.

Acquired antithrombin deficiency may occur in association with a number of conditions (see Clinical Information). The clinical significance (thrombotic risk) of acquired antithrombin deficiency is not well established, but accumulating information suggests possible benefit of antithrombin replacement therapy in carefully selected situations.(4)

Increased antithrombin activity has no definite clinical significance.

Antithrombin activity (ATTF / Antithrombin Activity, Plasma) is usually used for monitoring treatment of antithrombin deficiency disorders, including infusion of antithrombin therapeutic concentrate.

Antithrombin antigen results are potentially affected by:
-Heparin (unfractionated or low-molecular-weight) >4 U/mL

-Heparin therapy may temporarily decrease plasma antithrombin antigen into the abnormal range

-Hemoglobin >7 g/L

-Bilirubin >500 mg/L

-Lipemia; may lead to an over-estimation of the antithrombin antigen level

-Rheumatoid factor (RF) >800 IU/mL; may lead to over-estimation of the antithrombin antigen level

-Antirabbit antibodies; in certain subjects leads to aberrant results

Clinical Reference
1. Bock SC: Antithrombin III and heparin cofactor II. In Hemostasis and Thrombosis. Fourth edition. Edited by RW Colman, J Hirsh, VJ Marder, et al. Philadelphia, Lippencott Williams and Wilkins, 2001, pp 321-333
2. Viazzer H: Hereditary and acquired antithrombin deficiency. Semin Thromb Hemost 1999;25(3):257-263
3. Conrad J: Antithrombin activity and antigen. In Laboratory Techniques in Thrombosis-A Manual. Second edition. Boston, MA, Kluwer Academic Publishers, 1999, pp 121-128
4. Lane DA, Bayston T, Olds RJ, et al: Antithrombin mutation database: update. For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thr

Carolina Pianetta 15/03/15

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