Factor X deficiency: An overlooked cause of bleeding in the newborn.

Introduction

Inherited clotting factor X (FX) deficiency is one of the rarest coagulation defects. Its prevalence is estimated to be 1:1,000,000, comprising 10% of all rare bleeding diseases. A total or partial deficiency of FX leads to impaired clot formation with various hemorrhagic symptoms of varying severity.[ 1 ] The congenital form has an autosomal recessive inheritance, while the acquired form (even rarer) is seen in patients having amyloidosis, liver disease, multiple myeloma, and leprosy.[ 2 ] The treatment comprises definitive FX replacement therapy and supportive care.

This case report describes a newborn with FX deficiency who presented with unexplained frank bleeding from the umbilical stump, emphasizing the importance of this uncommon but important differential.

Case Report

A 10-day-old female child presented to us with a complaint of frank bleeding from the umbilical stump. There was no history of irritability, seizures, petechiae, or bleeding from any site. The patient had a similar complaint on day 3 of life, for which suturing of the stump was done by a local practitioner. She was a full term-baby with a birth weight of 3100 g, born to third-degree consanguineous parents at a local hospital by spontaneous vaginal delivery (The obstetric score of the mother was G2P1 + 0). She cried immediately after birth, had a normal birth weight, was not given an injection of Vitamin K at birth, and had an uneventful antenatal period. There was a history of male sibling death at 6 years of age due to some undiagnosed bleeding disorder. One male sibling of 4 years of age was healthy and alive [ Figure 1 ].

On examination, the baby had significant pallor, heart rate was 180/min, respiratory rate was 62/min, capillary refill time was prolonged (4 s), and saturation was 97% on room air with active umbilical stump bleeding. The anterior fontanelle was slightly depressed, with normal tone and power in all four limbs. Packed red blood cells were transfused to resuscitate the baby and a Vitamin K injection was also given. She was also transfused fresh frozen plasma @ 10 ml/kg twice in 24 h as the bleeding continued. Suturing and compression of the umbilical stump were also done to stop the bleeding. Investigations [ Table 1 ] showed normal sepsis screen, normal platelet count but prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), and clotting time which improved after plasma transfusion [ Table 1 ]. Bleeding persisted in spite of Vitamin K administration, HPLC-based PIVKA estimation was unreliable, and liver function tests were normal, so the possibility of classic and late hemorrhagic disease of newborns was ruled out. The cranial ultrasound was normal. Furthermore, mixing studies revealed full correction of PT and aPTT on mixing with control plasma, pointing toward the suspicion of FX deficiency. Functional activity of FX was quantified by performing a PT–based assay, using rabbit thromboplastin and FX deficient plasma, and the levels were found to be 2 percent with normal factor V and II levels [ Table 1 ]. The rest of the Vitamin K-dependent factors were normal (the sample was sent 2 days after the vitamin K injection). Next-generation sequencing was planned, but due to financial constraints could not be done. The patient was referred to a higher center with advice to transfuse FX concentrate (nonavailability at our center) or fresh frozen plasma as per the availability in case of any bleeding with the advice to the parents for genetic counseling while planning future pregnancies.

Discussion

Coagulation FX, also known as the Stuart-Prower factor (named after first individual patients), is a Vitamin K-dependent protease glycoprotein, whose deficiency can present at any age and with variable manifestations. The common bleeding symptoms are easy bruising, epistaxis, gum bleeding, umbilical stump bleeding, menorrhagia, hemarthrosis, and intracranial bleeding.[ 3 ] Our patient presented with frank bleeding from the umbilical stump on day 10 of life, with a similar episode on day 3 of life. Similarly, Al-Mouqdad et al . reported a newborn born out of consanguineous marriage, who presented with intracranial and umbilical stump bleeding.[ 4 ] Various cases have been reported with bleeding manifestations as severe as fatal intracranial hemorrhage[ 4 5 6 7 ] [ Table 2 ]. The diagnosis of FX deficiency is usually suspected when both the PT and aPTT are abnormal and get corrected with a 1:1 mix with normal plasma.[ 8 ] Diagnosis should be confirmed by FX assays and mutation analysis is also recommended.[ 9 ] Laboratory findings supporting FX deficiency in our patient are mentioned in Table 1 . In our patient, PT and aPTT were prolonged; mixing studies revealed full correction with control plasma and aged serum and no correction with adsorbed plasma, suggesting FX deficiency. Factor assay came 2%, establishing severe disease in our patient. However, fortunately, the newborn did not have any intracranial bleeding, contrary to many of the reported cases of severe congenital FX deficiency with intracranial hemorrhage.[ 4 10 11 ] Wetzel and Kingma. have reported subgaleal hemorrhage and bilateral pneumothoraces in a newborn having FX deficiency following a nontraumatic cesarean section.[ 12 ] Treatment should be individualized and focused on preventing morbidities and complications with the aim of restoring FX levels up to 10%–40% of normal. FX replacement is the mainstay of therapy, along with fresh frozen plasma and prothrombin complex concentrates.

This case report highlights that FX deficiency is a treatable disorder that can present in the neonatal period in varying severity and it should be considered a differential in a bleeding newborn. Genetic counseling should be offered to the parents of the affected cases in subsequent pregnancies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

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