Factor X Deficiency Presenting As Intracranial Hemorrhage in a Newborn

Case Presentation:

A full term female neonate born out of consanguineous marriage with unremarkable prenatal labs and prenatal ultrasound (US) studies, was found to have a large cephalohematoma at birth. On day of life (DOL) one, she had an episode of melena. On DOL2 the cephalohematoma increased in size with a 2.5 cm increase in head circumference. She was noted to be pale. Oozing noted from the heel stick site. Complete blood count (CBC) showed significant drop in hemoglobin and hematocrit from 18.5/ 56 at birth to 5.4/ 16.4. She was noted to have seizure activity and was given a loading dose of phenobarbital. Non‐contrast computed tomography (CT) of the head showed a left intracranial parieto‐occipital hematoma. A comprehensive workup for a bleeding disorder was undertaken. The initial Factor X result was inconclusive but repeat test showed Factor X level between 12‐14% of normal factor activity in blood. Grossly abnormal coagulation panel was noted as well. See table:

She was transferred to an outside hospital for further management. She received multiple transfusions of fresh frozen plasma (FFP). On DOL 7 she was started on Prothrombin Complex Concentrate (PCC) that was given daily for a week. Once started on PCC, coagulation tests slowly trended back to normal levels. She was discharged home on DOL 23 with a central venous catheter in place and was scheduled for PCC injections three times a week. Seizures controlled with maintenance phenobarbital.

Discussion:

Inherited Factor X deficiency (FXD) is an extremely rare autosomal recessive bleeding disorder with an incidence of 1: 1,000,000 in the general population. Factor X (FX) is a vitamin K‐dependent plasma protein with a major role in the coagulation cascade. Homozygous FXD has variable presentation ranging from umbilical cord bleeding, hematuria, hemarthrosis to severe gastrointestinal or intracranial hemorrhage. Consanguinity is often associated with FXD. It gives prolongation of both PT and activated partial prothrombin time (aPTT), which correct with a 1:1 mix with normal plasma. In this case, FXD was suspected based on the postnatal clinical manifestations and the prolongation of PT/ aPTT. FXD can be easily misdiagnosed as hemorrhagic disease of the newborn, based on their similar clinical manifestations. Because there is no purified FX concentrate available, whole blood, FFP and PCC have been used for the treatment of FXD. Future studies are needed to standardize preventive and therapeutic approach for patients with FXD. Determination of the underlying mutation is helpful in providing genetic counseling for families at risk.

Conclusions:

Rare autosomal recessive disorders of coagulation can present with significant hemorrhage in newborn. It is important for the clinician to include them in the differential diagnoses especially when consanguinity is involved.

Case Presentation:

TT is a FT new born girl born NSVD conceived by first cousins. Prenatal labs were unremarkable and prenatal sonogram did not showed any abnormalities. Physical exam at birth was significant for a large cephalohematoma. On DOL1 the new born had one episode of melena. On DOL2 the cephalohematoma was found to be increasing in size and head circumference increased from 32 cm at birth to 34.5 cm. The patient started bleeding from the heel stick site and presented a significant drop in hemoglobin and hematocrit from 18.5g/dl/ 56% at birth to 5.4g/dl/ 16.4%. Patient presented one seizure episode that resolved with phenobarbital and CT head scan without contrast showed a large left parieto‐occipital hematoma. Initial Factor X (FX) levels were 12‐14% of normal factor activity and presented prolonged PT/INR and PTT with increased Fibrinogen and D‐Dimer levels. On DOL7 the patient initiated treatment with Prothrombin Complex Concentrate daily and after 5 days of treatment FX level increased to18%. Coagulation test normalized after 14 days of treatment with fresh frozen plasma and Prothrombin Complex concentrate without any further complication.

Discussion:

Inherited Factor X deficiency (FXD) is a rare autosomal recessive bleeding disorder. Factor X (FX) is a vitamin K‐dependent plasma protein with a major role in the coagulation cascade. Homozygous FXD usually presents with variable mucosal bleeding ranging from umbilical cord bleeding, epistaxis, hematuria and menorrhagia to severe gastrointestinal bleeding, hemarthrosis, and intracranial hemorrhages. It is considered extremely rare with an incidence of 1: 1,000 000 in the general population. Consanguinity is often associated with it. FXD gives prolongation of both prothrombin time (PT) and activated partial prothrombin time (APTT) which corrects with a 1:1 mix with normal plasma.

In this presented case, the diagnosis of FX deficiency was suspected based on the postnatal clinical manifestations and the prolongation of PT/ PTT. Prenatal fetal US results were within normal limits without any evidence of bleeding. FXD can be easily misdiagnosed as a hemorrhagic disease of the new born, based on their similar clinical manifestations. Because there is no purified FX concentrate available, blood, fresh frozen plasma and prothrombin complex concentrate (PCC) have been used for the treatment of FXD. Determination of the underlying mutation is helpful in providing genetic counseling for families at risk.

Conclusions:

FXD is a extremely rare autosomal bleeding disorder. Future studies are needed to standardize preventive and therapeutic approach for patients with FXD