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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 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 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,

Principles & Methods for Screening for abnormalities of Platelet Procoagulant Activity

Two tests are may be used to screen for abnormalites 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.

Comments

Disorders of platelet procoagulant activity are rare!

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 ABCtransporter A1 [ABCA1] gene should be undertaken but also consideration of the other causes of an abnormal screen for PCA.

Useful Links & References

1. Brooks, M.B., et al., Exclusion of ABCA-1 as a candidate gene for canine Scott syndrome. J Thromb Haemost, 2008. 6(9): p. 1608-10.

2. Zwaal, R.F., P. Comfurius, and E.M. Bevers, Scott syndrome, a bleeding disorder caused by defective scrambling of membrane phospholipids. Biochim Biophys Acta, 2004. 1636(2-3): p. 119-28.

3. Zhou, Q., P.J. Sims, and T. Wiedmer, Expression of proteins controlling transbilayer movement of plasma membrane phospholipids in the B lymphocytes from a patient with Scott syndrome. Blood, 1998. 92(5): p. 1707-12.

4. Weiss, H.J. and B. Lages, Platelet prothrombinase activity and intracellular calcium responses in patients with storage pool deficiency, glycoprotein IIb-IIIa deficiency, or impaired platelet coagulant activity--a comparison with Scott syndrome. Blood, 1997. 89(5): p. 1599-611.

5. Weiss, H.J. and B. Lages, Family studies in Scott syndrome. Blood, 1997. 90(1): p. 475-6.

6. Toti, F., et al., Scott syndrome, characterized by impaired transmembrane migration of procoagulant phosphatidylserine and hemorrhagic complications, is an inherited disorder. Blood, 1996. 87(4): p. 1409-15.

7. Weiss, H.J., Scott syndrome: a disorder of platelet coagulant activity. Semin Hematol, 1994. 31(4): p. 312-9.

Data Interpretation

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