Hereditary Factor X (Stuart-Prower Factor) Deficiency

Introduction

Inherited deficiency of Factor X was first reported way back in mid 1950s by workers who were studying patients with a haemorrhagic disease resembling factor VII deficiency. It is also known by the surnames of the patients who were first found to manifest the defect (Stuart and Prower). Congenital Factor X deficiency is inherited as an autosomal recessive condition [1]. The exact frequency of the defect has not been established although a homozygous incidence of 1:1,000,000 has been described [2]. About 50 affected families have since been described [3].

Factor X is one of the vitamin K dependent factors, which is synthesized in the liver parenchymal cell and found in the plasma in a concentration of about 1 mg/dl [4]. It is a rare coagulation disorder in which both males and females are equally affected. We present a case that manifested with bleeding diathesis at 20 years of age post-operatively.

Case Report

A 20 year old male presented with episodic fullness of upper abdomen with colicky pain and altered bowel habits for two years. He had low to moderate grade fever associated with chills, four to five times a week. Since last one year, he also had five to six episodes of spontaneous epistaxis that lasted for few minutes with the loss of approximately 10-15 ml of blood loss. There was a history of weight loss, easy fatigability and decreased appetite. He also had easy bruisability, but no history of purpuric spots, mucous membrane bleeding from any other site or deep tissue and joint bleeding. Clinical and radiological examination revealed pallor, cervical, axillary, mesenteric and retroperitoneal lymphadenopathy. All biochemical metabolic parameters, chest radiograph and stool for occult blood were negative. He was provisionally diagnosed as Non-Hodgkin's lymphoma or disseminated tuberculosis. He was planned for axillary lymph node biopsy for a definitive diagnosis. Post-operatively, after the axillary node biopsy he had continuous bleeding/oozing from the operated site and developed a haematoma at the biopsy site. His haematoma was evacuated but he continued to have local bleeding at the biopsy site. He was investigated further. A detailed coagulation work up revealed normal bleeding time, prolonged prothrombin time (PT), prolonged activated partial thromboplastin time (APTT) and prolonged Russel viper venom time (RVVT). Platelet count, fibrinogen level, thrombin time and clot solubility were normal. Tests for fibrinogen degradation product (FDP) and D-dimer were negative. Apart from the acquired causes, the prolonged PT and APPT could be due to inherited deficiency of Factors V, X, II and combined deficiency of Factor V and VIII. Mixing studies with normal pooled plasma (determined immediately after incubation at 37°C, 60 minutes and 120 minutes incubation) and aged serum was done which showed correction of the prolonged PT and APTT. As the mixing studies showed correction with aged serum with prolonged RVVT, a provisional diagnosis of Factor X deficiency was made. However, individual factor assays (Factor V, II, VIII & X) were performed using factor deficient plasma and Factor X levels were found to be < 1% (Table 1).

Table 1.

Laboratory data of the patient

Test	Patient (seconds)	Control (seconds)
P T	36	10.8 – 13
APTT	67	28 – 33
T T	12	12
RVVT	51	15.5
Factor X	<1%	100%
Other clotting assays	Normal	Normal
(Factors II, V, VIII)

The patient was diagnosed as severe Factor X deficiency along with the underlying disorder (which was finally diagnosed as disseminated tuberculosis). He was managed with transfusion of fresh frozen plasma (FFP). Plasma was given as an initial dose of 15-20 ml/kg of body weight, followed by 3-6 ml/kg body weight every 24 hours. The biologic half-life of Factor X is about 40 hours, so administration of FFP every 12 hours results in a progressive increase in Factor X concentrations. The patient responded and the wound oozing stopped with healing of wound.

Discussion

Factor X deficiency is an extremely rare hereditary disorder with prevalence of approximately 1 in 2 million in general population [5]. Affected patients may manifest with severe haemorrhagic symptoms early in life, whereas, ‘symptomatic’ heterozygote may bleed only after severe challenge to the haemostatic system, as in trauma or surgery. Bleeding sites vary according to the severity of the deficiency [5]. Umbilical stump bleeding may be an early manifestation of Factor X deficiency. Soft tissue haemorrhages, including menorrhagia in women, are common in affected patients. Haemarthrosis, exsanguinating post operative haemorrhage, pseudotumours and central nervous haemorrhage have been reported in severely affected patients. The disease is more common in communities with social acceptability of consanguinity. Given the higher incidence of consanguinity in minority community, it will be prudent to investigate patients with bleeding diathesis for Factor X deficiency that are not diagnosed as Factor VIII/IX deficiency.

The acquired causes of prolonged PT and APTT could be due to specific inhibitors of Factors V, II or X, disseminated intravascular coagulation (DIC), liver disease, vitamin K deficiency (malabsorption, warfarin ingestion, propylthiouracil administration), paraproteinemia and amyloidosis. Our case had severe Factor X deficiency (<1%), who presented with exsanguinating post-operative bleeding, which is characteristic of this disorder. In our country, sporadic cases of severe Factor X deficiency have been reported [6, 7].

Peyuandi et al [5], revealed the spectrum of bleeding manifestations of 32 Iranian patients and reported that epistaxis occurred in patients with all degrees of deficiency. But other bleeding manifestations in mucosal tracts, such as haematuria and gastrointestinal bleeding occurred almost exclusively in patients with unmeasurable Factor X levels. The same findings are also highlighted by other workers [8, 9]. Epistaxis is unusual in patients of other coagulation factor deficiencies such as Factor VIII and IX but is prevalent in Factor X deficiency, the cause of which is not clear.

Amyloidosis is also associated with acquired deficiency of Factor X. It is hypothesized that the development of Factor X deficiency depends on the affinity of the particular amyloid protein for Factor X and the quantity of amyloid directly exposed to the circulating blood [10]. As the inheritance pattern of Factor X deficiency is autosomal recessive, our case was diagnosed as hereditary Factor X deficiency, since his only live parent (father) and brother had normal Factor X levels, and the patient did not have any of the underlying acquired causes of Factor X deficiency.

Treatment consists of FFP or PCC which contains significant amounts of activated vitamin K – dependent factors. When administered at frequent intervals or over a prolonged period, PCCs may produce hypercoagulable complications, such as DIC, venous thromboembolism, stroke or myocardial infarction. The use of these products in patients with liver dysfunction is especially hazardous, as the activated factors in the PCCs are not cleared efficiently by a diseased liver and thrombosis may be induced. Factor levels of 10 – 40% have been considered adequate for haemostasis. Due to the risk of thromboembolic phenomenon, Factor X levels should not exceed 50% of normal.

Conflicts of Interest

None identified