Factor XIII deficiency in a newborn]

Factor XIII deficiency is an uncommon inherited disorder which is characterized by umbilical cord bleeding and an unusually high incidence of intracranial hemorrhage. We report here a case of Factor XIII deficiency in a child that presented a caput. succedaneum as the first manifestation of the disease and then an umbilical cord bleeding. The importance of performing a quantitative FXIII assay in the presence of strong clinical suspicion is strengthened because of the normality of the standard screening tests and the important therapeutic consequences.     

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.     

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.     

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     

A rare cause of intracranial hemorrhage: factor X deficiency.

Congenital factor X deficiency is a rare inherited coagulation disorder, characterized by prolonged prothrombin time and partial thromboplastin time. For the definite diagnosis, specific factor X level should be investigated. We describe a patient with factor X deficiency who had intracranial hemorrhage. Hematologic tests showed prolonged prothrombin time, partial thromboplastin time, and a factor X level of 5%. The patient's hemorrhage resolved with fresh frozen plasma replacement. In this article, we discuss the clinical features and management of factor X deficiency.     

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.     

Factor V inhibitor in neonatal intracranial hemorrhage secondary to severe congenital factor V deficiency

We report a newborn infant girl, born to consanguineous parents, with recurrent intracranial hemorrhage secondary to congenital factor V deficiency with factor V inhibitor. Repeated transfusions of fresh-frozen plasma (FFP) and platelet concentrates, administrations of immunosuppressive therapy (prednisolone and cyclophosphamide), and intravenous immunoglobulin failed to normalize the coagulation profiles. Exchange transfusion followed-up by administrations of activated prothrombin complex and transfusions of FFP and platelet concentrates caused a temporary normalization of coagulation profile, enabling an insertion of ventriculoperitoneal (VP) shunt for progressive hydrocephalus. The treatment was complicated by thrombosis of left brachial artery and ischemia of left middle finger. The child finally died from another episode of intracranial hemorrhage 10 days after insertion of the VP shunt.     

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.     

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.     

INTRAVASCULAR COAGULATION IN GENERALIZED HERPES SIMPLEX INFECTION OF THE NEWBORN

A case of disseminated herpes simplex virus infection in a newborn associated with a fatal bleeding diathesis is reported. The presence of intravascular coagulation was suggested by thrombocytopenia, fibrinogenopenia, and reduced Factor V level. At necropsy localized fibrin and platelet deposition was found in liver and lung. It is postulated that intravascular coagulation resulted from local tissue necrosis and the subsequent release of thrombo-plastin-like substances into the general circulation. Heparin therapy did not alter the fatal outcome.     

Intracranial endodermal sinus tumors associated with growth hormone replacement therapy in a girl

The primary intracranial endodermal sinus tumor (EST) is regarded as a rare histological subtype that is often associated with components of other germ cell tumors, and there are no reports on the onset of intracranial ESTs after growth hormone (GH) replacement therapy. The authors report an extremely rare case of pure primary EST associated with GH replacement therapy. A 15-year-old girl with GH deficiency experienced headache, nausea, and vomiting after GH replacement therapy for a 17-month period. Magnetic resonance imaging showed 2 tumor masses located in the pineal region and frontal horn of the right lateral ventricle, respectively. Before surgery, the authors administered 1 cycle of neoadjuvant chemotherapy, which shrank the tumor and facilitated surgical intervention. The larger mass located in the pineal region was removed via a right occipital transtentorial approach, and postoperative histopathological analysis revealed a pure EST. While there is a clear association between the initiation of GH replacement therapy and the development of the EST in this case, the causal effect cannot be specified. Nevertheless, this case demonstrates that GH replacement therapy must be used cautiously.     

口服抗凝剂治疗以新生儿暴发性紫癜或颅内出血为首发表现的遗传性复合杂合突变的重度蛋白C缺乏症2例病例报告并文献复习

背景：既往国内报道的重度遗传性蛋白C缺乏症(PCD)患儿大多放弃救治而死亡。 目的：探索口服抗凝剂对重度PCD患儿的长期救治效果。 设计：病例报告。 方法：报道并分析2例新生儿期起病的遗传性复合杂合突变的重度PCD患儿的诊断、治疗及预后,检索PubMed、中国知网和万方数据库,行文献复习。 主要结局指标：血栓或出血缓解。 结果：1例首发表现为新生儿暴发性紫癜（PF）;1例因存在继发性慢性DIC,以新生儿颅内出血、肺出血为首发表现。2例经基因测序均明确蛋白C(PROC)基因复合杂合突变。每日应用新鲜冷冻血浆及低分子肝素抗凝获得初步缓解后,分别序贯口服维生素K拮抗剂华法林或直接口服抗凝剂利伐沙班作为长期治疗,预防血栓及出血事件,随访3~6年,2例均存活至今,生存质量尚好,且无明显不良反应。 结论：重度遗传性PCD可以新生儿PF、颅内出血和肺出血为首发表现,应改变观念积极救治;华法林和利伐沙班等口服抗凝剂可以作为长期维持治疗时安全有效的选择,改善预后。     

Role of coagulopathy in newborn intracranial hemorrhage

Fifty newborn infants of less than 33 weeks' gestation were followed prospectively from birth with serial coagulation and real-time ultrasound studies. A significant association of hypocoagulability in the first four hours of life with subsequent onset or progression of intraventricular or other clinical hemorrhages was documented. Abnormalities included lower values for fibrinogen, platelet count, antithrombin III, and factor VIII with higher values for fibrin monomer and longer Laidlaw whole blood clotting times. These abnormalities tended to correct spontaneously in surviving infants. An association between gestational complications and incidence of hypocoagulability and intracranial hemorrhage (ICH) was noted. Babies of preeclamptic mothers had fewer abnormalities and babies born to mothers with premature rupture of membranes and suspected amnionitis manifested more hypocoagulability and more severe intracranial hemorrhages.     

Coagulation abnormalities associated with localized hemorrhage in the neonate.

Serial coagulation studies were completed on six neonates with apparent or inapparent localized hemorrhage. The sites of the hemorrhages were intracranial (2), gastrointestinal (2), subperiosteal (1), and pulmonary (1). The studies revealed an increased factor VIII level, decreased platelet count, and a short PTT. Since similar findings occur in disseminated intravascular coagulation, it is possible that coagulation abnormalities associated with localized hemorrhage result from similar mechanisms. These observations suggest that occult and clinically unrecognized hemorrhage can be suspected by serial coagulation studies of sick infants.     

Intracranial Hemorrhage as the First Manifestation of Severe Congenital Factor X Deficiency in a 20‐Month‐Old Male: Case Report and Review of the Literature

Factor X deficiency (FXD) is a rare bleeding disorder, which can result in severe bleeding symptoms such as intracranial hemorrhage (ICH). The most common bleeding symptoms are epistaxis and gum bleeding. ICH is reported in 9–26% of all patients with FXD, mostly during the first month of life. Here, we present a rare case of a male presenting with ICH at the age of 20 months as the first manifestation of FXD. Secondary prophylaxis with factor X substitution once weekly prevented further bleeding.     

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.     

晚发性维生素K缺乏致颅内出血危险因素分析

目的探讨晚发性维生素K缺乏致颅内出血发病的危险因素。方法对57例晚发性维生素K缺乏致颅内出血进行了总结,并应用非条件Logistic回归分析,对8项可能的危险因素进行分析。结果晚发性维生素K缺乏致颅内出血发病危险模型Y=-4.405 1.652X1 2.418X2 2.076X3 2.782X7 1.617X8,X1=性别,X2=年龄,X3=喂养方式,X7=CMV感染,X8=肝功能异常。结论男性、年龄<3个月、纯母乳喂养、有CMV感染、肝功能异常者易发生晚发性维生素K缺乏致颅内出血。     

Risk factors of renal involvement and significant proteinuria in Henoch-Schönlein purpura

Risk factors of renal involvement and significant proteinuria in patients with Henoch-Sch?nlein purpura (HSP) were retrospectively evaluated by univariate and multivariate analyses. The analysis was performed in 134 patients with HSP. Renal involvement was found in 65 patients (49%) and 97% of the renal involvement was found within 3 months of disease onset. Moderate or severe proteinuria was recognised in 25 patients. A univariate analysis revealed that an age of more than 4 years at the onset, severe abdominal pain with gastrointestinal bleeding, persistent purpura over a month, coagulation factor XIII activity < 80%, and treatment with factor XIII concentrate were associated with developing renal involvement. A multivariate analysis showed that severe abdominal symptoms, an age of more than 4 years, and persistent purpura increased the risk of renal involvement. Risk factors of moderate or severe proteinuria were also examined. The risk factors in a univariate analysis were severe abdominal symptoms, persistent purpura, decreased factor XIII activity, treatment with steroids, and treatment with factor XIII concentrate. Of those, persistent purpura, treatment with factor XIII concentrate, and factor XIII activity < 80% were associated with significant proteinuria in a multivariate analysis. Among the patients with severe abdominal symptoms, factor XIII activity was significantly decreased in patients with significant proteinuria compared to other patients without significant proteinuria. CONCLUSION: Long-term prognosis of Henoch-Sch?nlein purpura is dependent on the severity of renal involvement. In those patients who have the risk factors of renal involvement, especially significant proteinuria, close attention should be paid to a urinalysis for at least 3 months from the onset of the disease.     

Spontaneous splenic rupture in a patient with factor XIII deficiency and a novel mutation

We report a novel mutation in factor XIIIA gene that caused severe congenital factor XIII deficiency in a 6 year and 8 month old male. The mutation is a GA deletion in the core domain leading to a premature stop at codon 502. The child had severe deficiency with two episodes of intracerebral hemorrhage. He also developed spontaneous splenic rupture, an unusual complication of this disorder.     

Intracranial hemorrhage and vitamin K deficiency in early infancy

We report late-onset (1/2 to 6 months of age) intracranial hemorrhage related to vitamin K deficiency in 32 breast-fed infants, 31 of whom received no prophylactic vitamin K at birth. Computerized tomography showed mild to severe intracranial hemorrhage. Most (90.6%) had subarachnoid hemorrhage, either alone or in combination with subdural hemorrhage (37.5%), parenchymal hemorrhage (31.3%), or intraventricular hemorrhage (12.5%). In three (9.4%) the infratentorial region was involved.