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A Practical Guide to Laboratory Haemostasis

 

Platelet Function Testing: Platelet Procoagulant Activity [PCA] Assays



Scott Syndrome and Platelet Procoagulant Activity

The procoagulant activity of platelets has previously been designated Platelet Factor-3 (PF3) or Platelet Factor-3 availability (PF3a).  Scott syndrome is named after the first patient described with this disorder [Anne Scott] in 1973.

It is a rare disorder of platelet procoagulant activity (to date only 3 cases have been reported) which appears to be due to, at least in some cases, to a mutation within the ABCtransporter A1 [ABCA1] gene or to a trans-acting regulatory gene sequence that controls its expression.

Scott syndrome patients suffer from a moderate-to-severe haemorrhagic disorder.  However, there are other disorders of platelet procoagulant activity including Quebec Platelet Disorder (Platelet Factor V Quebec), Platelet Factor V-New York, some patients with Storage Pool Disorder [SPD], Glanzmann’s Thrombasthenia and Bernard Soulier Syndrome.  The findings in Glanzmann’s Thrombasthenia and Bernard Soulier Syndrome suggest that the abnormalities in the platelet membrane glycoproteins may also interfere with platelet PCA and the bleeding tendency is not due entirely to lack of the relevant glycoprotein.

At least some of the patients with Scott Syndrome show impaired binding of factor Va to ionophore-activated platelets. The changes in the phospholipid membrane that occur with activation of the platelet are crucial for the formation of the ‘tenase’ and ‘prothrombinase’ complexes and hence the defective Va binding demonstrated by flow cytometry,

Method

Several tests may be used to screen for abnormalities of platelet procoagulant activity:

1. Prothrombin Consumption Index [PCI]:
This is based on the finding that that the prothrombin time of serum is longer than that of plasma, as prothrombin is normally consumed during its conversion to thrombin.
          PCI = [Serum Clotting Time/Plasma Clotting Time] x 100%
If thrombocytopenia is excluded, then an abnormal PCI which is corrected by normal platelets or phospholipid raises the possibility of a defect in platelet PCA.

2. Platelet Factor 3 Availability (PF3a) Assay:
The PF3a assay relies on the principle that incubation of platelet-rich plasma (PRP) with kaolin activates the procoagulant activity of platelets, resulting in a progressive shortening of both the recalcification time and Russell viper venom time. By appropriate mixing of normal PPP and PRP from a patient, the PF3a test can be made specific for assessing the PCA of platelets
Abnormal PF3a has been reported in patients with both congenital and acquired bleeding disorders and may be associated with other defects in platelet function.
PF3a is a useful screening test for detecting an abnormality in platelet PCA but is not diagnostic of any specific disorder.

3. Annexin V binding:
Annexin V is a protein with a high affinity and a specificity for aminophospholipids at physiologic calcium concentrations and can be used as a marker of platelet activation and the development of procoagulant activity. The use of annexin V in flow cytometry provides a rapid method to assess procoagulant activity in platelets and the loss of phospholipid asymmetry in cell membranes.

What Test Next

If the Prothrombin Consumption Index [PCI] or the Platelet Factor 3 Availability (PF3a) assay suggests an abnormality - then the cause of this should be sought. A screen for mutations within the ABC transporter A1 [ABCA1] gene should be undertaken but also consideration of the other causes of an abnormal screen for PCA.

Data Interpretation

Click HERE to go to the Data Interpretation Exercises.