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Case Reports Indian Pediatrics 2001; 38: 183-186 |
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Factor X Deficiency
and Hemophilia A : Occurrence of Two Different |
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Manuscript received: May 3, 2000; Hemophilia A is the commonest inherited coagulation defect in human beings. Factor X deficiency is a much rarer disease(1). Occurrence of these two inherited diseases in the same family has not been reported so far.
A 1½-year-old female child born of third degree consanguinity presented with a 2-day history of spontaneous bruising over the back and thigh. There was no history of bleeding from any other site. Besides the ecchymosis over the medial aspect of the left thigh (4 Χ 3 cm) and the interscapular region (2 Χ 1 cm), the clinical examination was unremarkable. Significant in the history was an admission at the age of 3 months for the refusal of feeds, altered sensorium and seizures due to subdural hematoma. She was found to have prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) but was pro-visionally diagnosed to have late hemorrhagic disease of the newborn. It was managed conservatively with the administration of fresh frozen plasma. The child made an uneventful recovery and no further investigations were carried out by the treating physician. Her elder brother was a case of Hemophilia A diagnosed on the basis of prolonged APTT, factor VIII level of less than 1 IU/ml and a normal von Willebrand Factor (VWF). Another 6-months-old male sibling had died of an unexplained cause. Apart from an affected elder brother there was no family history of any bleeding disorder. A detailed coagulation work up of the patient (Table I) showed prolonged PT and APTT and a low factor X of 2.2 IU/ml (Normal 50-150 IU/ml). The factor VIII level was normal (72 IU/ml). Factor XIII activity fibrinogen and platelet aggregation were normal. A diagnosis of severe congenital factor X deficiency was made. In both parents, the factor VIII and factor X levels were normal (Table I). Maternal carrier screening for hemophilia A judged by factor VIII:C/VWF ratio was negative. The patient was managed conservatively. The patient was seen again at 2½ years of age with hematoma on forehead following trivial fall, which was managed conservatively.
Factor X deficiency is a rare coagulation defect that is inherited as an autosomal recessive trait. Its prevalence is estimated to be 1 in 500,000 population(2). The genetic locus of the trait is situated on the chromosome 13 and the gene has been sequenced(2). Acquired factor X deficiency has been described in association with primary amyloidosis and malignancies like multiple myeloma, gastric carcinoma, and acute non-lymphocytic leukemia(3-6). The disease presents like any other inherited coagulation defect with easy bruisability, epistaxis, gastrointestinal bleeding and menorrhagia. However, these patients have a higher tendency to present with sponta-neous intracerebral or intraspinal hemorrhage(7-9), as noticed in our patient. Similar to our case, the homozygotes have consanguineous parents and appreciable symptoms while the heterozygotes have mild symptoms if at all. Cases of factor X deficiency presenting later in life may have to be differentiated from acquired factor X deficiency resulting from diverse etiologies (vide supra) before ascribing it to be a congenital deficiency state. As our patient had presented early in life the diagnosis of congenital factor X deficiency, in the absence of clinical evidence of secondary etiology, was not difficult. Familial multiple factor deficiency (FMFD) is a known phenomenon wherein sibs have inherited deficiencies of several coagulation factors(1). However, sibs having deficiencies of different coagulation factors have not been described. Our patient had deficiency of factor X, while her brother had deficiency of factor VIII. Although, such an occurrence of two different coagulation defects in two siblings could be purely coincidental, it emphasizes the need to carry out complete coagulation profile in each patient even if there is an already diagnosed case in the family. This is also necessary so that patients are not erroneously labeled to have vitamin K deficiency, as it occurred in our case. Although, level of factor X is normally low in neonate(10), careful analysis of factor X level with respect to age is of great help. In dubious cases with difficulty in diagnosis, correction of coagulation abnormal-ity following vitamin K administration may also help in establishing the diagnosis of its deficiency. This will also help in prevention of erroneous labeling of vitamin K deficiency to a congenital factor deficiency state. Differentiation of factor X deficiency from factor VIII deficiency is also important for the management. The former can be managed by plasma infusion or by infusion of factor X concentrate in major bleeding episodes. In contrast, the latter requires infusion of factor VIII concentrate or cryoprecipitate for the management of bleeding episode. Prothrombin complexes have been variably used for its ease of storage; decreased risk of viral contami-nation; home administration; and lesser volume of infusion. However, it is associated with variable rise in factor X levels. Presence of two defects in the family has implications for prenatal diagnosis too. One will have to antenatally screen for both the defects and possibly for other coagulation factor deficiency too. This may be possible only at specialized centers.
The authors thank Mrs. Shrimati Shetty, Scientific Officer, Institute of Immuno-hematology, I.C.M.R., K.E.M. campus for her help in carrying out the coagulation profiles. Contributors: RCP did the collection of data, drafting of manuscript and will act as a guarantor. SBB helped in the revision of the manuscript. DRS assisted in collection of data and drafting of manuscript. JRK helped in revision of the manuscript.
Funding:
None.
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