Hereditary Coagulation Factor X Deficiency the Results of Screening Test, Diagnostic Test

Stuart Prower factor (Factor X) deficiency is a rare hereditary autosomal recessive coagulation disorder. We have come across three cases in the course of last 20 years at our institute. These patients presented with prolonged bleeding after minor trauma, epistaxis, subcutaneous bluish black nodules and two of them presented with history of consanguinity in parents. Hematological findings in correlation with clinical manifestations revealed severe factor-X deficiency. The rare disorder of factor X deficiency was described independently by Telfer, et al. (1) and Hougie, et al.(2), in Prower and Stuart Kinships respectively (hence the nomenclature Stuart Prower Factor). Incidence in general population is approximately one in two million(3). In heterozygous state it remains asymptomatic, but in autosomal recessive condition it presents symptomatically(4) with bleeding manifestations, resembling moderate haemo-philia (easy bruising, subcutaneous bleeding from mucous membranes and menorrhagia in females). Marked deficiency may present as severe post-traumatic bleeding or even hemarthrosis. Cases with intracranial bleed have been reported(5). The optimum level of factor X required for hemostasis is 10%(6). The laboratory diagnosis is based upon correction studies of PT and APTT with various plasma/serum reagents and specific factor X assays. Till now 50 cases have been reported in the world literature inclusive of Indian references(3,6-8). A 15-year-old Hindu boy presented with repeated episodes of epistaxis, gum bleeds and profuse bleeding after tooth extraction (the presenting complaint). There was history of prolonged bleeding after cuts and formation of bluish black nodules since age of 3 years. There was no history of similar complaint in maternal or paternal side. A 2-year-old Muslim child presented with severe epistaxis and bleeding from tongue bite. There was history of subcutaneous nodules and prolonged bleeding after minor trauma. Apart from bleeding manifestation there was no other clinical finding except for mild anemia. Family history revealed consan-guinity (1st cousin). Earlier, a female sibling had died with similar bleeding manifestations. An 8-month-muslim male child born of consanguinous marriage (1st cousin) presented with severe bleeding manifestations in the form of subcutaneous nodules and spontaneous epistaxis. One of the female cousins of the patient died due to CNS bleed in early child hood.

The rare disorder of factor X deficiency was described independently by Telfer, et al. (1) and Hougie, et al. (2), in Prower and Stuart Kinships respectively (hence the nomenclature Stuart Prower Factor).
Incidence in general population is approximately one in two million (3).In heterozygous state it remains asymptomatic, but in autosomal recessive condition it presents symptomatically(4) with bleeding manifestations, resembling moderate haemophilia (easy bruising, subcutaneous bleeding from mucous membranes and menorrhagia in females).Marked deficiency may present as severe post-traumatic bleeding or even hemarthrosis.Cases with intracranial bleed have been reported (5).The optimum level of factor X required for hemostasis is 10% (6).
The laboratory diagnosis is based upon correction studies of PT and APTT with various plasma/serum reagents and specific factor X assays.Till now 50 cases have been reported in the world literature inclusive of Indian references (3,(6)(7)(8).

Case Reports
Case 1 A 15-year-old Hindu boy presented with repeated episodes of epistaxis, gum bleeds and profuse bleeding after tooth extraction (the presenting complaint).There was history of prolonged bleeding after cuts and formation of bluish black nodules since age of 3 years.There was no history of similar complaint in maternal or paternal side.

Case 2
A 2-year-old Muslim child presented with severe epistaxis and bleeding from tongue bite.There was history of subcutaneous nodules and prolonged bleeding after minor trauma.Apart from bleeding manifestation there was no other clinical finding except for mild anemia.Family history revealed consanguinity (1st cousin).Earlier, a female sibling had died with similar bleeding manifestations.

Case 3
An 8-month-muslim male child born of consanguinous marriage (1st cousin) presented with severe bleeding manifestations in the form of subcutaneous nodules and spontaneous epistaxis.One of the female cousins of the patient died due to CNS bleed in early child hood.
The results of screening test, diagnostic test A. Kumar K.L. Mishra A. Kumar* D. Mishra and factor assay all the 3 cases are given in Table-I.The screening and diagnostic tests of coagulation suggested defect in common pathway; factor X deficiency.Factor assays revealed level to be 10% in case 1 and <1% in cases 2 & 3 (Table-I).The factor assay was performed using commercial factor X deficient plasma.
Collection, processing and analysis of the samples was done according to the standard method as described by Dacie & Lewis (9).All the samples were assessed in duplicate.Control values in comparison to the tests have been shown in Table I.

Discussion
Factor X deficiency is an extremely rare hereditary bleeding disorder with prevalence of approximately 1 in 2 million in general population (6).The disease is more common in communities with social acceptability of consanguinity.Some of the large series have been reported from countries like Iran which form number of patients registered at National Hemophilia Centre London uptil 1998 (6).
Majority of these patients (56%) were with severe deficiency (<1%), 28% presented with moderate (1-5%) and only 15% of them were suffering from mild (6-10%) deficiency of factor X. In India there has been sporadic reports (7,8).These cases in Indian series presented with severe manifestation correlating with factor level <1%.In the present group of patients the clinical and hematological findings are identical with the previous case reports and add to the numbers of Remarks Raised APTT Correction with aged serum indicates factor X deficiency along with and no correction with adsorbed plasma confirms the same.raised PT: indicates defect in common pathway * The method used for factor X assay, was manual technique using commercial factor X deficient plasma (from Diagnostic Stago) as described by Dacie & Lewis(9) (Semi quantitative assay).cases.Also, clinically presenting bleeds with resemblance to mild/moderate hemophilias and with the background of consanguinity a possibility of factor X should always be kept in mind and analysed for.
Given the higher incidence of consanguinity in minority community, it shall be worth while to fully investigate for factor X in cases not other wise turning out to be Hemophilia A or Hemophilia B. In some cases where there is difficulty in diagnosis, correction of coagulation abnormality following vitamin K administration may also help in establishing the diagnosis of its deficiency.Not only it helps in establishing the diagnosis but also prevents erroneous labeling of vitamin K deficiency to a congenital factor deficiency state (10).
Contributors: AK performed clinicohematological analysis as incharge of hematology and coagulation lab, department of pathology.KLM performed laboratory work up and analysis of results.Clinical examination was done by AK.DM helped in laboratory workup.

TABLE I -
Screening and Diagnostic Tests of 3 Cases