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A Practical Guide to Haemostasis


Venous Occlusion Test


Introduction

The venous occlusion test is an approach for studying fibrinolysis. Impaired fibrinolysis, determined by low fibrinolytic activity [e.g. a decreased Euglobulin Clot Lysis Time - ECLT] following venous occlusion has been reported to be associated with a variety of clinical problems including spontaneous or recurrent deep vein thromboses.
Deficient Fibrinolysis may be due to:
    - ↑Plasminogen activator inhibitor (PAI) levels
    - ↓Release of tissue plasminogen activator (t-PA) from the vascular endothelium
    - A functionally abnormal t-PA

Historically the venous occlusion test was a commonly performed test but it rarely performed today. The test relies upon the observation that following a period of venous occlusion there is an increase in the fibrinolytic activity of plasma, The mechanisms underlying the fibrinolytic response are poorly understood - it is possible that venous occlusion stimulates t-PA release but alternatively it may be due to an accumulation of t-PA that it secreted by endothelial cells.

Principles & Method

The test involves placing a BP cuff around the arm and inflating it to mid-way between the systolic and diastolic blood pressures [but <100mm Hg] for a period of 10-20 minutes. Blood samples are collected before and after the venous occlusion [distal to the cuff with the cuff still inflated] and the fibrinolytic activity of the plasma established.

Interpretation & Reference Ranges

The interpretation of the results is difficult:
1. In healthy individuals, a shortening of the ECLT will be observed and in general this is reduced by at least 30 minutes.
2. In most healthy individuals there will be increase in t-PA:Ag and t-PA activity and a decrease in PAI-1 antigen and PA-1 activity.
3. 'Poor responders' are commonly defined as those who after venous occlusion defined as patients who, after venous occlusion shows defective release of t-PA activity or t-PA:Ag (calculated as below the lowest value measured in a control population.

What Test Next

Individuals with defective fibrinolysis measured by venous occlusion and global tests of fibrinolytic activity e.g. ECLT and fibrin plate lysis , may go on to have specific assays of t-PA and PAI-1 [or plasminogen] measured.  

The Venous Occlusion Test is a rarely performed test and sequence analysis of the genes involved in Haemostasis and Thrombosis are more likely to be of benefit in cases where defective fibrinolysis is suspected.

The TEG & ROTEM are increasingly used to assess global fibrinolytic capacity.

What Test Next

In individuals with an abnormal venous occlusion test, specific assays of the components of the Fibrinolytic pathway should be undertaken and in addition , to perform sequence analysis of the relevant genes.