Antithrombin

 

I asked a colleague who is very experienced in thrombophilia testing and interpretation, how I could improve my…er.....not so good knowledge! She suggested Practical-Haemostasis.com. It’s a free website and I’ve found it really useful.

So my task tonight is Antithrombin.

Antithrombin (AT) s a natural anticoagulant and has a very important role in stopping the action of Thrombin ( IIa), Factor Xa (FXa) and to a lesser extent XIa (FXIa) and IXa (FIXa). These are called Serine Proteases which means they cut peptide bonds in specific proteins. So basically AT is involved in preventing the body from clotting to much which can lead to thrombosis. If a patient is deficient in this, Venous Thromboembolic disease (VTE) can occur.

I didn’t realise that there are six types of AT. The most significant was known as Antithrombin III, but the III has been dropped and is now known simply as antithrombin.

The laboratory I work in measures this by a chromogenic method, so in short by a colour change, which allows the absorbance (light at a particular wavelength) to pass through a volume of liquid. Plasma is incubated with an excess of the relevant substrate. In my labs case it is with an excess of FXa in the presence of excess heparin.

The heparin changes the structure of the AT to increase it’s activity as an inhibitor. A chromogenic substrate is the added which is specific for the enzyme FXa. Any residual cause the substrate to be cleaved and a colour change. The absorbance at 405nm is inversely proportional to the amount of antithrombin activity in the plasma.

AT can also be measured immunologically.

Result interpretation should always bear in mind the limitations of a particular method. The bovine FIIa method is suggested to be the best at detecting all AT variants. The human FIIa and bovine FXa may not detect all clinically significant variants.

So it seems that AT deficiency can be inherited or acquired. Acquired causes can be seen in liver dysfunction, Sepsis, DIC, Pre-eclampsia, AML, Heparin therapy, Proteinuria, in association with L-Asparaginase,, Chron’s Ulcerative Colitis, Poor nutrition and dilutional reasons such as haemodialysis , Cardiopulmonary bypass and Plasmaphoresis.

I’ve been reading my Trust’s guidance for thrombophilia testing and acquired AT deficiency is not tested for. Inherited deficiencies are investigated if diagnosis will affect patient management. So for example patients who will be on long term anticoagulants due to recurrent VTE and unprovoked DVT or PE. Also decisions regarding thrombophylaxis in pregnancy. Unusual sites for thrombosis and arterial thrombosis may also warrant thrombophillua screening.

Thrombophillia testing is not recommended in decisions regarding contraception using oestrogen but instead a progesterone only preparation is recommended. 

In pregnancy morbidity, it is suggested that just Antiphospholipid antibodies are tested on two separate occasions at least six weeks apart. Whilst patients developing warfarin skin necrosis,  a Protein C and Protein S are indicated.

And I'll leave today's learning there and move on next time to another part of thrombophillia screening.