Neonatal factor XIII deficiency

We describe a patient diagnosed in the neonatal period as having factor XIII deficiency who presented with persistent umbilical bleeding. Factor XIII deficiency is the only coagulation factor deficiency that cannot be detected by classical hemostatic tests, and a rapid diagnosis is vital during the first decade of life. A newborn presenting with persistent umbilical stump bleeding should be screened for factor XIII deficiency when routine coagulation tests prove normal.     

Intracranial hemorrhage in congenital deficiency of factor XIII

We describe a male infant with congenital deficiency of coagulation Factor XIII who presented in the immediate postnatal period with umbilical stump bleeding and suffered a severe intracranial hemorrhage at 2 months of age. Factor XIII, also known as "fibrin-stabilizing factor," is a transpeptidase that produces strong covalent bonds between soluble fibrin monomers formed during coagulation. Presumptive diagnosis of Factor XIII deficiency was made with a clot solubility screening test, and confirmation was accomplished by demonstrating the absence of cross-linked fibrin chains by electrophoresis. This patient had received replacement therapy for 2 years, initially with intravenous fresh frozen plasma, and recently with Fibrogammin (Hoechst-Roussel Pharmaceuticals), a European Factor XIII concentrate soon to be available in the United States. Factor XIII deficiency is associated with a high incidence of life-threatening complications, notably intracranial hemorrhage. In light of the long half-life of this factor and the relatively low risk associated with new Factor XIII concentrates, such as Fibrogammin, prophylactic life-long replacement therapy should be considered for patients with severe Factor XIII deficiency.     

Hereditary factor XIII deficiency

Twelve cases of hereditary factor XIII (FX III) deficiency diagnosed over five years (1986–1990) at Christian Medical College and Hospital, Vellore are presented here. Although all the cases had a history of umbilical cord bleeding and subsequent frequent bleeding episodes, diagnosis was considerably delayed. All but two patients required transfusions for bleeding episodes. Ten patients had a history of consanguinity in parents. Clinical features and family history are described in detail here. The ease of performing the Urea solubility test and problems in it's interpretation are highlighted. The role of prophylactic transfusion is also discussed.     

Activity of blood coagulation Factor XIII as a prognostic indicator in patients with Henoch-Schönlein purpura

Determination of coagulation Factor XIII (F XIII)-related parameters in 21 patients with Henoch-Schönlein purpura documented a significant decrease of F XIII activity as well as of the F XIII-related antigenic determinants. Subgroup analysis with regard to the clinical symptoms showed an even further decrease of these parameters in patients with gastrointestinal complications. Stimulated by these findings a substitution therapy with a F XIII concentrate was initiated in those patients whose F XIII activity in plasma remained low and who developed severe abdominal pain accompanied by persisting gastrointestinal bleeding. This therapeutic approach not only corrected the laboratory data, but more important led to a cessation of pain and bleeding. A rapid decrease of F XIII levels after transfusion below 40 U/ml was indicative of relapse of abdominal symptoms, while increasing values were associated with the recovery of the patients. In conclusion: F XIII activity determinations appear to have a predictive value in patients with Henoch-Schönlein purpura, and the administration of F XIII concentrates may contribute to the improvement of gastrointestinal complications.Abbreviations F XIII Factor XIII - SHP Henoch-Schönlein purpura - XIII-act Factor XIII activity - MCA monochloroacetic acid - XIII-A Factor XIII subunit A antigen - XIII-S Factor XIII subunit S antigen - F VIII R:AG Factor VIII related antigen - FDP Fibrin degradation products - F VIII:C Factor VIII coagulant activity     

Prenatal diagnosis in factor XIII-A deficiency

Congenital factor XIII deficiency is a severe bleeding disorder that is inherited as an autosomal recessive trait. The condition is commonly due to absence of the factor XIII-A subunit protein in the plasma. The case of a baby is reported who showed typical clinical features of factor XIII-A deficiency, including recurrent bleeding from the umbilical stump and a life threatening haemorrhage after circumcision. Family studies were performed and molecular analysis, using a Short Tandem Repeat (STR) marker closely linked to the A subunit gene, allowed antenatal exclusion diagnosis to be undertaken in a subsequent pregnancy. The case highlights the importance of seeking a family history of bleeding disorders before surgery in the neonatal period, particularly if the parents are consanguineous.     

Intraspinal hemorrhage in a child with factor XIII deficiency.

The rarity of spinal cord injuries and hemorrhages and of fibrin-stabilizing factor XIII deficiency during childhood has induced us to report the case of this two-year-old boy with factor XIII deficiency who presented with cervical intraspinal hemorrhage between the C4 and C7 levels as well as paraplegia presumably following a minor trauma. The findings in this patient, who was brought in two weeks after the appearance of the first symptoms, indicate the importance of early diagnosis and early intervention to minimize the extent of the damage from the injury in such cases. The case also points to the need for close follow-up of patients with factor XIII deficiency for CNS bleeding.     

Congenital factor XIII deficiency.

Clinical and hematological data of 9 cases with factor XIII deficiency is highlighted. The age at first bleed ranged from 3 days of life to 1 year. Seven of these 9 cases had bleeding from the umbilicus, 3 had recurrent subcutaneous and muscle hematomas, while 4 cases had CNS bleeds of which 3 expired. Routine coagulogram was normal, while clot solubility in 5 molar urea solution was abnormal in all cases. Factor XIII assay was not done in any. Patients were treated with plasma transfusion during episodes of bleeding. No patient received plasma transfusion as prophylactic therapy. The cumulative Indian data so far documented, inclusive of this series, shows a very high incidence of CNS bleeds (33%) in patients with this inherited coagulation disorder.     

Treatment of refractory hemorrhage with factor XIII in a patient with hemophilia A with inhibitor

An 11‐year‐old male with hemophilia A and a known high‐titer Factor VIII inhibitor was admitted with retroperitoneal hemorrhage. The patient was receiving infusions of recombinant activated Factor VII (rFVIIa) for a recent elbow hemorrhage when retroperitoneal bleeding commenced. Despite increased dosing of rFVIIa and a dose of activated prothrombin complex concentrate (aPCC), he continued to hemorrhage and required several blood transfusions. Factor XIII was administered 1 hour after rFVIIa and the patient demonstrated cessation of bleeding and normalization of clot strength. Factor XIII may act as an adjuvant in effective clot stabilization in patients with hemophilia and inhibitory antibodies. Pediatr Blood Cancer 2013; 60: E23–E25. © 2013 Wiley Periodicals, Inc.     

Cephalohemoatoma as the first manifestation of congenital factor XIII deficiency

Congenital factor XIII deficiency is a rare hereditary disorder characterized by a marked tendency to bleeding. We describe a male newborn with inherited factor XIII deficiency. The patient was from a family without known antecedents and presented cephalohematoma as the first manifestation of the disease. This presentation is very unusual. The patient was diagnosed during the neonatal period and was successfully treated with substitution therapy. Early diagnosis and treatment of this disorder are important to prevent complications of severe bleeding.     

Intracranial haemorrhage due to factor V deficiency

Factor V deficiency is a rare coagulation disorder which is inherited autosomal recessively. Factor V deficiency should be considered in infants with bleeding disorders and prolonged prothrombin and activated partial thromboplastin times if bleeding continues in spite of vitamin K injection. In this article, the case of an infant with an intracranial haemorrhage due to congenital factor V deficiency is reported.     

Hereditary heterozygote factor VII deficiency]

Hereditary Factor VII deficiency is one of the rare congenital coagulopathies. Prolonged prothrombin time (PT) with normal partial prothrombin time (PTT) may be an indicator for Factor VII deficiency. A family with hereditary heterozygous Factor VII deficiency is presented in whom no symptoms of a bleeding disorder were clinically detectable. A discussion of the therapeutic options follows.     

Segmental uniparental disomy as a rare cause of congenital severe factor XIII deficiency in a girl with only one heterozygous carrier parent

Abstract

Uniparental disomy (UPD) refers to a situation when a person inherits both homologs of a region or complete part of a chromosome from only one parent. Here, we present an unusual case of UPD in congenital severe factor (F) XIII deficiency. A 6-year-old girl experienced cephalhematoma and umbilical bleeding after birth and easy bruising, and postextraction bleeding since early infancy. FXIII activity was 0% [mother 53.7% and father 132.5% (normal 70–140%)] and the FXIII antigen level was 2.5% [mother 38.9% and father 151% (normal 75–155%)]. The washed platelet FXIII activity was 0.1% in the patient (normal 64–144%), suggesting a deficiency of FXIII-A subunit. The FXIII-A subunit genetic analysis detected a homozygous p.Arg382Ser mutation. A similar heterozygous mutation was detected in the mother but surprisingly, not in the father. Kinship was confirmed by a paternity test. To confirm the possibility of UPD, a test using four markers in the vicinity of the F13A1 gene revealed that she inherited duplicate mutations from a heterozygous mutation in her mother, presenting a unique case of unusual maternal segmental UPD in otherwise unexplained congenital (homozygous) severe FXIII deficiency. UPD as a rare cause of autosomal recessive bleeding disorder when only one parent is affected is critical for genetic counseling.     

Subgaleal hematoma presenting as a manifestation of Factor XIII deficiency

Extracranial hematoma without significant head trauma is uncommon. We discuss a 9-year-old girl who presented with sudden head swelling, bilateral proptosis, extraocular muscle palsy, and progressive visual disturbance after hair braiding. The diagnosis of a large subgaleal hematoma with extension into the superior aspect of the orbits was made, requiring surgical drainage. Hematologic workup revealed an underlying Factor XIII deficiency.     

Leukocyte adhesion deficiency in a female patient without delayed umbilical cord separation

Leukocyte adhesion deficiency type 1 (LAD-1), a rare disorder of neutrophil function, is classically characterised by delayed umbilical cord separation. We report a case of LAD-1 in a female infant whose umbilical cord separated within 2 weeks of birth and review the literature pertaining to the timing of umbilical cord separation.     

Umbilical cord stricture and overcoiling are common causes of fetal demise.

Although umbilical cord stricture and umbilical cord overcoiling have been established as causes of intrauterine fetal demise, relatively few studies addressed this issue, most of them being case reports. We reviewed a total of 268 fetal autopsies during a 3-year period from 1998 to 2001. One hundred thirty nine cases of fetal demise including spontaneous abortion were identified. Nineteen percent (26 of 139) were associated with umbilical cord stricture, overcoiling, or a combination of both. Stricture of the umbilical cord was defined as a decrease in diameter in relation of the remaining umbilical cord; overcoiling as 0.3 coil/cm or greater. Fetal demise most commonly occurred in the second trimester, with a mean gestation age of 21 weeks. The average maternal age was 33 years; 15% had a prior fetal demise. We found that 77% (20 of 26) of these cases had umbilical cord stricture only or with overcoiling, 23% (6 of 26) had umbilical cord overcoiling alone. Localized deficiency of Wharton's jelly and increased collagen were found in all cases with umbilical cord stricture with or without overcoiling. In patients with umbilical cord overcoiling alone, 25% had Wharton's jelly deficiency; half of them had increased collagen deposition in the umbilical cords. The placenta was reviewed for secondary thrombosis of the vessels of the chorionic plate. Thrombosis of the vessels of the chorionic plate was noted in 54% of the patients. Our study suggests that umbilical cord stricture and cord overcoiling may represent two distinct pathological entities commonly causing fetal demise. This observation reinforces the importance of a fetal autopsy with careful examination of the placenta and umbilical cord with documentation of the cord coil index.     

Neonatal Congenital Factor X Deficiency

Four neonates with congenital Factor X deficiency presented soon after birth with bleeding episodes. Two of the newborns had intracranial hemorrhages; one of them also had antenatal ventricular dilatation and postnatal hydrocephalus and died of massive intracerebral hemorrhage at four months. One patient was lost for follow up. The two surviving infants were followed up for four years and two years respectively, while on replacement therapy with three injections of 40 units/kg prothrombin complex a month. In spite of markedly elevated prothrombin time and partial thromboplastin time, these two infants remain free of major bleeding manifestations except for troublesome petechiae and ecchymoses. A schedule for substitution therapy with Factor X is proposed for infants and children to prevent bleeding in severe Factor X deficiency.     

Intrapartum rupture of the falciform ligament and umbilical vein. A rare cause of hemoperitoneum in the newborn

Intra-abdominal hemorrhage in the newborn is uncommon, but it must be considered in the first 48 hours of life in the infant with pallor, anemia, abdominal distension, and shock. The injured liver is the most common source of bleeding, with the spleen and kidney less often involved. In the case presented, the hallmarks of intra-abdominal hemorrhage were evident. Exploratory laparotomy revealed intraperitoneal bleeding emanating from the disruption of the umbilical vein and its enveloping falciform ligament. There was no other site of intra-abdominal bleeding and there were no intrinsic abnormalities of the umbilical cord or the placenta. Disruption of the intra-abdominal umbilical vein represented the sole source of intra-abdominal bleeding in this patient. The case is reported to document disruption of the intra-abdominal umbilical vein as a rare cause of neonatal hemoperitoneum.     

Combination of von Willebrand disease type 1 and partial factor XII deficiency in children: clinical evidence for a diminished bleeding tendency

Factor XII deficiency can be associated with a thrombotic and VWF deficiency with a haemorrhagic clinical course. To study the potential influence of factor XII deficiency on bleeding tendency in patients suffering from VWD we retrospectively compared the clinical outcome of children with either an isolated factor XII deficiency, an isolated VWD, or a combination of both. Patients with the combined coagulation defect showed significantly fewer bleeding events when compared to patients with isolated VWD, although ristocetin cofactor activities were reduced to a comparable degree. As far as aPTT values are concerned, there were no significant differences among the three groups. Whether this combination of thrombophilic and haemorrhagic coagulation disorders is only coincidental or the result of an active modulation of one of the two counteracting coagulation factors is not known at present.     

Factor X Deficiency: A Rare Cause of Puberty Menorrhagia

Factor X deficiency is an extremely rare coagulation defect inherited as an autosomal recessive disorder with variable bleeding manifestations. The authors report case of a 16 y-old girl born from a consanguineous marriage who presented with excessive bleeding at the start of menarche. Investigations revealed severe anemia, prolongation of both prothrombin time and activated partial thromboplastin time and moderate deficiency of factor X (1 %). She was given multiple transfusions including packed cells and fresh frozen plasma and was advised to remain under regular follow up.     

Splitting of the umbilical cord in a 13-week-old fetus

There is an increasing interest in the physiology and pathology of the umbilical cord because it is recognized as an important source of placental and, consequently, fetal problems. During the postmortem examination of a severely macerated 13-week-old fetus, a split umbilical cord was noted. This rare finding was seen in the middle segment of the cord, the fetal and placental ends both being normal. The pathogenesis of this lesion is not fully understood, and it is possible that it results through focal degeneration of previously formed Wharton's jelly or secondary loss of Wharton's jelly due to incomplete fusion or hypoplasia of the amniotic covering. Whatever the pathogenesis, it is assumed that an umbilical vessel devoid of its protective Wharton's jelly is more prone to compression and thrombosis with all its deleterious effects. Death in this case was probably associated with the congenital heart defect also presented by the fetus. The rarity of this lesion is probably explained by the fact that it represents the end of the spectrum of longitudinal deficiency of Wharton's jelly, a relatively common finding.