A 40-year-old woman presents 7 days after a pan-colectomy for Crohn’s disease. She has a past history of antithrombin III deficiency. She has increasing abdominal pain and vomiting. There is marked tenderness in the right upper quadrant. An abdominal CT scan is performed.

  • What does the CT scan show?
  • What is the most likely cause for the appearances seen in the CT?
  • What are the causes of anti-thrombin III deficiency?
  • What further investigations would you order to help manage this lady’s condition?
  • What treatment would you order for this lady’s condition?

[Click here to toggle visibility of the answers]

College Answer

a) CT Scan:

    • Extensive hypodense areas in liver consistent with hepatic infarction
    • Splenomegaly
    • Hypodense areas in spleen consistent with splenic infarcts
    • Free fluid in abdomen

b) Cause:

•  Portal venous thrombosis

c) Causes of anti-thrombin III deficiency:

•   Hereditary

•   Acquired

o Post-operative state

o Liver disease

o Disseminated intravascular coagulation

o Nephrotic syndrome

o Vasculitis

  • Further investigations:
    • Ultrasound of hepatic/abdominal vasculature.
    • ATIII activity on blood sample … Prothombotic screen also acceptable

e) Treatment:

    • Heparinisation
    • If there is heparin resistance or low ATIII activity, either antithrombin III concentrate or fresh frozen plasma.
    • Referral for advice regarding surgical (endovascular Vs open) options

Discussion

The CT scan I used was mined shamelessly from Google Images. It is not the one which appeared in the paper.

The first two parts of this question are straightforward.

The CT features of portal vein thrombosis are as follows:

  • Direct visualisation of the clot:
    • Usually seen as a hypodense filling defect in the portal vein lumen
    • The decreased density inside the portal vessels is best seen in the contrast phase
    • Non-contract CT will not pick this up: you need portal venous phase contrast enhanced studies.
    • You can also sometimes see enhancement of the walls of the portal vein, which is either dilated vasa vasorum or a thin film of contrast flowing around the obstruction
    • The thrombus itself should not enhance with contrast. If there is enhancement, particularly in the arterial phase, the thrombus is probably malignant in origin (i.e a HCC has eroded into the lumen).
  • Sequelae of portal vein obstruction:
    • Venous infarcts of the liver and spleen
    • Cavernous transformation of the portal vein (looks like a varicocele!)
    • Posrtosystemic collateral vessels and arterioportal shunts
    • Gut ischaemia
    • Ascites

The second half of the question requires detailed knowledge of AT-III deficiency. One can arrive at at least half of a sensible answer by logically asking why AT-III might not be present in sufficient quantities. Either you hereditarily fail to synthesise enough of it, or your liver is so damaged that it cannot produce enough. Or, it has been used up somehow, eg. in the context of DIC, MAHA, or in a bypass circuit. Lastly, it is possible that you are losing it along with other proteins via your leaky nephrotic kidneys.

The chapter which discusses thrombophilia screening tests contains within it this table, which lists the causes of AT-III deficiency with greater granularity.

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 management of AT-III deficiency is, predictably, supplementation with AT-III. If the expensive purified factor is not available, FFP will suffice. Heparinisation for thrombosis actually will not work unless there is some antithrombin for the heparin to act upon.

Management options for PVT include the following:

  • Do nothing:  If the patient is asymptomatic, or if significant risks are associated with anticoagulation (eg. bleeding varices), one may also rely on portal cavernous transformation to divert venous flow around the thrombus. However, rate of spontaneous resolution is low (~ 17%).
  • Anticoagulate with heparin, LMWH or warfarin: Ideally, anticoagulation should be started in the first week (according to Basit et al, "Rate of recanalization is 69% if anticoagulation is started in the first week, but 25% if anticoagulation is started in second week").
  • Control portal venous hypertension: 
    • β-blockers, eg. propanolol
    • Diuretics, eg. spironolactone
    • TIPS procedure
    • Intraportal thrombolysis
    • Surgical thrombectomy

References

References

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.

Mathieu, Didier, Norbert Vasile, and P. Grenier. "Portal thrombosis: dynamic CT features and course." Radiology 154.3 (1985): 737-741.

Lee, Hae-Kyung, et al. "Portal vein thrombosis: CT features." Abdominal imaging 33.1 (2008): 72-79.

Denninger, Marie‐Hélène, et al. "Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors." Hepatology31.3 (2000): 587-591.\

Valla, Dominique-Charles, and Bertrand Condat. "Portal vein thrombosis in adults: pathophysiology, pathogenesis and management.Journal of hepatology 32.5 (2000): 865-871.

Boyer, Thomas D. "Management of portal vein thrombosis."Gastroenterology & hepatology 4.10 (2008): 699.

Basit, Syed Abdul, Christian D. Stone, and Robert Gish. "Portal vein thrombosis." Clinics in liver disease 19.1 (2015): 199-221.