The "Thrombophilic Screen"

The "Thrombophilic Screen" is as series of tests launched when the question arises as to why a person is found to be clotting excessively. For instance, as in Question 21 from the second paper of 2011, somebody turns up to the ED with a proximal DVT. You ask yourself, "how did that get there?"

A good article exists to guide investigations of inherited thrombophilia.

In brief, the tests you would do include the following:

  • Antithrombin levels
  • Protein C
  • Protein S
  • APC clotting time
  • Lupus anticoagulant
  • Anti-β2-glycoprotein-I antibody
  • Anticardiolipin antibody
  • Prothrombin gene mutation
  • Fasting homocysteine levels
Causes and Diagnostic Tests for Thrombophilia
Thrombophilia Diagnostic test Causes
Antithrombin deficiency

Antithrombin levels

Hereditary

Liver disease

DIC

Vasculitis

Protein C deficiency

Protein C level

Hereditary
Protein S deficiency

Protein S level

Hereditary
Factor V Leiden

APC clotting time

Hereditary
Antiphospholipid syndrome

Lupus anticoagulant

Anti-β2-glycoprotein-I antibody

Anticardiolipin antibody

SLE
Prothrombin gene mutation

G20210A test

Hereditary
Hyperhomocysteinaemia

Fasting homocysteine assay

Hereditary

Yet another portal vein thrombosis SAQ (Question 27 from the first paper of 2012) asked specifically about the causes of antithrombin-III deficiency. The table below has been condensed out of the UpToDate article about Antithrombin III deficiency.

Causes of Antithrombin III Deficiency

Inherited AT-III defects

  • Type I (reduced level)
  • Type II (functionally defective AT-III)
    • Reactive site defect
    • Heparin binding site defect
    • Pleiotropic effect mutations

Acquired 

Reduced production

  • Liver disease
  • Asparginase therapy (for ALL)
  • Oral contraceptive use
  • Preeclampsia or eclampsia

Loss of protein

  • Nephrotic syndrome
  • Plasmapheresis, replaced with albumin
  • Major surgery with extensive blood loss 
  • Heparin therapy (by increasing AT clearance)- however, this does not pose an increased thrombotic risk - only a false positive result on the thrombophilia screen

Increased consumption

  • Disseminated intravascular coagulation (DIC)
  • Acute thrombosis, eg. lage PE
  • Extracorporeal circuits, eg. ECMO and CRRT

The consequences of AT-III deficiency are thrombosis and loss of heparin effect. Heparin needs antithrombin to act upon as its primary mode of action. No AT, and heparin becomes pointless.

The management of AT-III deficiency is, predictably, supplementation with AT-III. If the expensive purified factor is not available, FFP will suffice.

References

For this sort of really basic stuff, no matter where you look you will find essentially the same information.
I used chapters from From "William Hematology" by Lichtman et al, especially chapter 115 by Monroe III

Kamal, Arif H., Ayalew Tefferi, and Rajiv K. Pruthi. "How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults." Mayo Clinic Proceedings. Vol. 82. No. 7. Elsevier, 2007.

DeMuro, J. P., and A. F. Hanna. "Trauma Induced Coagulopathy: Prevention and Intervention."Scand J Trauma Resusc Emerg Med 20.47 (2014): 4.

White, Julian. "Snake venoms and coagulopathy." Toxicon 45.8 (2005): 951-967.

Kashuk, Jeffry L., et al. "Primary fibrinolysis is integral in the pathogenesis of the acute coagulopathy of trauma." Annals of surgery 252.3 (2010): 434-444.

De Stefano, Valerio, Guido Finazzi, and Pier Mannuccio Mannucci. "Inherited thrombophilia: pathogenesis, clinical syndromes, and management [see comments]." Blood 87.9 (1996): 3531-3544.

Hunt, Beverley J. "Bleeding and coagulopathies in critical care." New England Journal of Medicine 370.9 (2014): 847-859.

UpToDate offers a good article about Antithrombin III deficiency, for a price.

Beresford, C. H. "Antithrombin III deficiency." Blood reviews 2.4 (1988): 239-250.