Neonatal hematology.

Neonatal hematology is a complex and dynamic process in the pediatric population. Surgeons frequently encounter hematologic issues regarding hemostasis, inflammation, and wound healing. This publication provides a surgeon-directed review of hematopoiesis in the newborn, as well as an overview of the current understanding of their hemostatic profile under normal and pathologic conditions.

Intracranial hemorrhages and late hemorrhagic disease associated cholestatic liver disease.

Deficiency of vitamin K predisposes to early, classic or late hemorrhagic disease of the newborn (HDN); of which late HDN may be associated with serious and life-threatening intracranial hemorrhage. Late HDN is characterized intracranial bleeding in infants aged 1 week to 6 months due to severe vitamin K deficiency. Late HDN is still an important cause of mortality and morbidity in developing countries where vitamin K prophylaxis is not routinely practiced. Children with cholestatic liver disease are at risk for developing secondary vitamin K deficiency because of fat malabsorbtion and inadequate dietary intake. In this study, we described 11 infants with cholestatic liver disease with different etiologies exhibiting intracranial hemorrhage (ICH). Six patients underwent surgical evacuation of ICH, following the administration of vitamin K and/or fresh frozen plasma. The possibility of cholestatic liver disease should be considered in the treatment of ICH due to vitamin K deficiency.

Intracranial hemorrhage associated with vitamin K-deficiency bleeding in patients with biliary atresia: focus on long-term outcomes.

BACKGROUND AND AIM: The prophylactic oral administration of vitamin K to newborns has markedly reduced the incidence of vitamin K deficiency (VKD); however, intracranial hemorrhage (ICH) is still one of the complications found in biliary atresia (BA) patients and is associated with VKD bleeding. Therefore, we aimed to investigate the incidence and long-term outcome of ICH in patients with BA who previously received prophylactic vitamin K during the neonatal period. METHODS: Eighty-eight consecutive infants with BA were treated and followed up at Kyushu University Hospital from 1979 to 2009. The clinical records and imaging study results were retrospectively reviewed in the infants with BA who presented with ICH. RESULTS: ICH occurred in 7.95% of patients with BA. The onset of ICH occurred at 47 to 76 days after birth, before the patients underwent surgery for BA (9-37 days after the onset of ICH). Coagulopathy was found upon admission in all of the cases with available data and improved after intravenous administration of vitamin K. A craniotomy was required in 2 cases before the surgery for BA. During the 22 to 278 months of follow-up, some neurologic sequelae persisted in 5 of 7 cases. Follow-up head computed tomography scans showed a low-density area in the left hemisphere in 5 cases. CONCLUSIONS: Although vitamin K prophylaxis had been given during the neonatal period, ICH-associated VKD bleeding was still found in 7.95% of patients with BA. Persistent neurologic sequelae were found in 5 of 7 cases, with low-density area in the left hemisphere.

Late vitamin K deficiency bleeding leading to a diagnosis of cystic fibrosis: a case report.

Vitamin K deficiency bleeding (VKDB) in infants still occurs despite worldwide use of prophylaxis. Clinical manifestations can be dramatic with over 50% of patients presenting with intracranial haemorrhage and a mortality rate of 20% in late vitamin K deficiency bleeding. Special attention should be given to infants with a high risk profile (preterm, breast feeding, cholestasis, malabsorption). A tentative diagnosis can be made observing quick normalisation of some easy-to-perform haemostatic parameters (PT, aPTT) after administration of vitamin K. Nowadays, VKDB can still be the first clinical sign of diseases causing malabsorption of fat-soluble vitamins. In this case report, VKDB led to the diagnosis of cystic fibrosis, the most common fatal autosomal recessive disease among Caucasian people.

Maternal-neonatal vitamin K deficiency secondary to maternal biliopancreatic diversion.

Bariatric surgery has become a common therapeutic approach for severe obesity, in case of unsuccessful behavioural and/or medical interventions. During the past years, the number of obese women who underwent bariatric surgery in childbearing age has progressively increased. We report a case of vitamin K deficiency, due to maternal biliopancreatic diversion, resulting in a symptomatic clinical presentation in the mother and in a hypocoagulable state in her neonate.

Intracranial bleeding due to vitamin K deficiency: advantages of using a pediatric intensive care registry.

AIM: To determine the incidence of late intracranial vitamin K deficiency bleeding (VKDB) in The Netherlands using the Dutch Pediatric Intensive Care Evaluation (PICE) registry. METHODS: The PICE registry was used to identify all infants who were admitted to a Dutch pediatric intensive care unit (PICU) with intracranial bleeding between 1 January 2004 and 31 December 2007. Cases of confirmed late intracranial VKDB were used to calculate the incidence for each year. To estimate the completeness of ascertainment of the PICE registry, data from 2005 were compared with general surveillance data from that year. RESULTS: In the 4-year study period, 16/64 (25%) of the infants admitted with intracranial bleeding had late intracranial VKDB, resulting in an overall incidence of 2.1/100,000 live births (95% confidence interval 1.2-3.5). The single-year incidence varied markedly between 0.5 and 3.3 per 100,000 live births. All five ascertained cases in 2005 were identified using the PICE registry, while general surveillance identified only three. CONCLUSIONS: The PICE registry allows ongoing monitoring of the incidence of late intracranial VKDB and appears to be associated with a higher rate of completeness than general surveillance. We propose the use of pediatric intensive care registries to assess the efficacy of national vitamin K prophylactic regimens.

Intracerebral hemorrhage despite prophylactic administration of vitamin K in infants--two case reports.

The incidence of vitamin K deficiency in infancy has decreased markedly, due to prophylactic administration of vitamin K during the neonatal period. However, vitamin K deficiency bleeding may occur during or after the neonatal period despite prophylactic administration in Japan. Two cases are reported of intracranial hemorrhage associated with coagulopathy in full-term infants who had received prophylactic administration of vitamin K. More reliable methods for prophylactic administration should be established.

Late hemorrhagic disease of the newborn.

BACKGROUND: Late hemorrhagic disease of the newborn (HDN) may occur without an underlying disorder or as a secondary manifestation of an underlying disorder. It may be seen in fully breast-fed infants without a routine supplementation of vitamin K. In contrast, idiopathic late HDN is defined as HDN without the presence of any risk factor, such as gastroenteritis or use of antibiotics. Severe hemorrhagic symptoms frequently occur. METHODS: Between March 1987 and May 1997, we evaluated 15 infants with idiopathic late HDN, who were diagnosed by detailed history, physical examination and laboratory findings. RESULTS: The age (mean +/- SD) at onset of symptoms was 62.4 +/- 33.9 days. All children were breast-fed infants and were born at term from healthy mothers. The delivery histories were uneventful. There was no history of vitamin K administration at birth. Signs and symptoms of the patients were convulsions (47%), feeding intolerance and poor sucking (47%), irritability (33%) and pallor (20%). In physical examination; there was bulging or full fontanel in 10 patients (67%), diminished or absent neonatal reflexes in nine patients (60%) and ecchymosis in three patients (20%). Before administration of vitamin K, prothrombin time (PT) was 76.1 +/- 43.0 s and partial thromboplastin time (PTT) was 123.4 +/- 68.8 s. Six to 12 h after administration of vitamin K, PT was 15.6 +/- 1.8 s and PTT was 33.4 +/- 1.0 s. Neurologic, gastrointestinal and skin hemorrhagic findings were found in 11 (73%), three (20%) and three patients (20%), respectively. There were both neurologic and skin bleeding symptoms in two patients. The mortality in the present study was 33%. CONCLUSIONS: Late HDN results in severe hemorrhage, especially hemorrhage in the central nervous system. Administration of vitamin K (1 mg, i.m.) at the birth can reduce these severe complications.

Vitamin K deficiency bleeding (VKDB) in infancy. ISTH Pediatric/Perinatal Subcommittee. International Society on Thrombosis and Haemostasis.

TERMINOLOGY: Replace the term "Hemorrhagic Disease of the Newborn" (HDN) by "Vitamin K Deficiency Bleeding" (VKDB), as neonatal bleeding is often not due to VK-deficiency and VKDB may occur after the 4-week neonatal period. DEFINITION: VKDB is bleeding due to inadequate activity of VK-dependent coagulation factors (II, VII, IX, X), correctable by VK replacement. DIAGNOSIS: In a bleeding infant a prolonged PT together with a normal fibrinogen level and platelet count is almost diagnostic of VKDB; rapid correction of the PT and/or cessation of bleeding after VK administration are confirmative. WARNING SIGNS: The incidence of intracranial VKDB can be reduced by early recognition of the signs of predisposing conditions (prolonged jaundice, failure to thrive) and by prompt investigation of "warning bleeds". CLASSIFICATION: VKDB can be classified by age of onset into early (<24 h), classical (days 1-7) and late (>1 week <6 months), and by etiology into idiopathic and secondary. In secondary VKDB, in addition to breast feeding, other predisposing factors are apparent, such as poor intake or absorption of VK. VK-PROPHYLAXIS: BENEFITS: Oral and intramuscular VK (one dose of 1 mg) protect equally well against classical VKDB but intramuscular VK is more effective in preventing late VKDB. The efficacy of oral prophylaxis is increased with a triple rather than single dose and by using doses of 2 mg vitamin K rather than 1 mg. Protection from oral doses repeated daily or weekly may be as high as from i.m. VK. VK-PROPHYLAXIS: RISKS: VK is involved in carboxylation of both the coagulation proteins and a variety of other proteins. Because of potential risks associated with extremely high levels of VK and the possibility of injection injury, intramuscular VK has been questioned as the routine prophylaxis of choice. Protection against bleeding should be achievable with lower peak VK levels by using repeated (daily or weekly) small oral doses rather than by using one i.m. dose. BREAST FEEDING MOTHERS TAKING COUMARINS: Breast feeding should not be denied. Supervision by pediatrician is prudent. Weekly oral supplement of 1 mg VK to the infant and occasional monitoring of PT are advisable. CONCLUSION: VKDB as defined is a rare but serious bleeding disorder (high incidence of intracranial bleeding) which can be prevented by either one i.m. or multiple oral VK doses.

Enfermedad hemorrágica del recién nacido, Vitamina K y cáncer

Pensamos que la enfermedad hemorragica del recien nacido se prevenia de una forma simple y sin ninguna complicación, sin embargo el estudio de Golding en 1992, planteó serias dudas en cuanto a la asociación entre la aplicació IM de vitamina K y diversas formas de cáncer en la infancia. Paises como el reino unido, Alemania, y Australioa suspendieron su aplicación , administrandola por via oral, pero desafortunadamente se han incrementado los casos de la enfermedad. Aparecieron posteriormente dos estudios que no encontraron relación entre cáncer y vitamina K, y se plantea ahora una intensa discusión , la cual se revisa brevemente junto con las formas de presentación de la enfermedad y las mediciones de la vitamina K1 en la leche humana y las leches de formula. en conclusion se requieren más investigaciones para aclarar si existe o no relación entre vitamina K y cáncer, y por el momento debe continuarse su administración por vía intramuscular, y se reafirma la importancia de la lactancia materna, apesar de que la cantidad de vitamina K disponible en ella es menor que la de las leches de fórmula

Vitamin K during infancy: current status and recommendations.

PIP: Vitamin K is needed to synthesize coagulation factors II (prothrombin), VII, IX, and X through the carboxylation of glutamic acid in vitamin K-dependent proteins which results in the creation of effective calcium binding sites which, in turn, facilitates the coagulation process. Vitamin K exists as naturally occurring vitamin K-I (phylloquinone) in green leafy vegetables and vegetable oils, vitamin K-II (menaquinone) as produced in the gut by bacteroides fragilis and E. coli, and synthetic vitamin K-III (menadoine sodium bisulfite) which is water-soluble and capable of producing serious jaundice in newborns, especially those with instability of glutathione and deficiency of G6PD. Humans require about 5 mcg of vitamin K daily. Since it is indigenously produced in the gut by bacterial flora, dietary deficiency of vitamin K in healthy subjects is rare. Vitamin K is usually the first vitamin given at birth. Newborn babies, however, absorb only approximately 30% of ingested vitamin K, compared to 50-70% in adults. Hemorrhagic disease is a manifestation of vitamin K deficiency in newborn infants. Hemorrhagic disease of the newborn (HDN), early HDN, classical HDN, and late HDN are discussed. The American Academy of Pediatrics recommended in 1961 that all healthy term newborn babies receive 0.5-1.0 mg of vitamin K-I intramuscularly at birth. However, while the authors have not followed those recommendations in their neonatal unit for 15 years, they have experienced only a 0.1% incidence of classical HDN. High-risk newborns at the unit are routinely given the recommended dose of K-I at birth.^ieng

The relevance of developmental hemostasis to hemorrhagic disorders of newborns.

The hemostatic system is a dynamic evolving process that is age-dependent. Components of the hemostatic system are synthesized in early fetal life and do not cross the placenta from mother to fetus. However, plasma concentrations of proteins involved in hemostasis significantly differ from adults. Physiological reference ranges are available for premature infants, full-term infants and children from ages 1 to 16 years. In the coagulation system, plasma concentrations of the vitamin K-dependent and contact factors are decreased at birth, whereas other factors such as fibrinogen, FV, FVIII, and FXIII are similar or increased compared with adults at birth. In the fibrinolytic system, plasma concentrations of plasminogen are decreased at birth, whereas tissue plasminogen activator and plasminogen activator inhibitor are increased. Clinically, the hemostatic system of the young is effective and healthy infants do not suffer from spontaneous hemorrhagic complications. However, infants are more vulnerable, compared with older patients, for bleeding in the presence of either congenital or acquired haemostatic defects. Severe congenital bleeding disorders, although rare, frequently present in the newborn period. The most common acquired causes of bleeding newborns include disseminated intravascular coagulation, vitamin K deficiency, and liver disease. A description of these disorders and treatment guidelines are provided.

Vitamin K deficiency, intracranial hemorrhage, and a subgaleal hematoma: a fatal combination.

An exclusively breast-fed infant, who did not receive vitamin K prophylaxis at birth, presented with signs of raised intracranial pressure. Her clinical course was compounded by a lumbar puncture, which revealed blood in the cerebrospinal fluid, and a large subgaleal hematoma, which developed at the puncture site of an attempted scalp vein catheterization, resulting in coning, hypovolemic shock, and death. A major coagulopathy was present, probably caused by vitamin K deficiency. The necessity for vitamin K prophylaxis in all newborns and the timing of lumbar puncture in the critically ill child are discussed.

Prophylaxis of vitamin K deficiency in infancy.

A prospective study was performed in Okazaki, Japan, to attempt to establish a more effective system of prophylaxis for vitamin K deficiency in infancy (VKDI). During the first year, a Normotest (Hepaplastintest) was performed in all infants at one week and at one month of age. Two mg of vitamin K was administered orally to those whose Normotest values were below 40%. i.e., the non-prophylactic administration of vitamin K (NPVK). During the second year of the study, all newborn infants received prophylactic vitamin K (PVK) within 24 hours of birth and at one week of age. The dosage was repeated at one month of age depending on the Normotest value. A total of 7,059 infants, comprising 93.3% of the live births in the city of Okazaki, were enrolled in this study. Data from 5,431 of these infants were used in the analysis of the results. In the NPVK group, 20 of the 2,791 infants had Normotest values below 40% at one month of age while 20 of the 2,640 in the PVK group had low values despite the prophylactic administration of vitamin K. Considering the prevalence of low Normotest values (less than or equal to 40%) at one month of age and the predicted Normotest values, it was concluded that the month of birth (June-September), the age of the mother (21-29 years), the birth order (first-born) and male sex are risk factors for vitamin K deficiency in infancy.

Subclinical liver dysfunction in one-month-old infants with a low activity of vitamin K dependent coagulant factors assessed by normotest.

To clarify features of late vitamin K deficiency hemorrhagic disease in Japanese infants, seventeen of 1,687 infants screened by normotests were examined for signs and symptoms suggesting hepatobiliary diseases. Clinical observations disclosed findings suggesting hepatobiliary diseases in 7 of the 17 selected infants with normotest values of less than 40%, and 11 infants had abnormal results in one or more liver function tests. Taken together, 14 of the 17 infants had findings suggesting hepatobiliary diseases. Upon vitamin K supplementation normotest values improved in various degrees in all infants, whether or not they had signs or symptoms of hepatobiliary diseases. Late vitamin K deficiency hemorrhagic disease of infancy may be related to subclinical hepatobiliary diseases.

Hemorragia periventricular neonatal / Neonatal periventricular hemorrhage

De las hemorragias, la periventricular neonatal es una de las que ocurren con mayor frecuencia en prematuros con menos de 32 semanas de gestación. Asimismo, en este estudio se consideran otros factores de riesgo que incrementan la irrigación sanguínea cerebral y que provocan sangrado en la región subepindimaria de la matriz germinativa. Se distinguen dos síndromes clínicos fundamentales: el catastrófico y el saltatorio, determinados por la magnitud de la hemorragia. El diagnóstico definitivo se lleva a cabo mediante tomografía computada o ultrasonografía, aunque el tratamiento preventivo debe ser el de primera elección. En cuanto a la hidrocefalia posthemorrágica, la derivación ventriculo-peritoneal es el tratamiento final