Late Hemorrhagic Disease Research Articles

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.

Association hémorragies cérébrales et rétiniennes chez 2 enfants : ne pas conclure trop vite au diagnostic d’enfant secoué

We report on 2 cases associating retinal (RH) and cerebral hemorrhages (CH), which first suggested the diagnosis of shaken baby syndrome (SBS). After an etiologic search, the diagnosis was corrected: the first case was a late hemorrhagic disease of the newborn and the second case hemophilia A. RH is a major feature of SBS, although not pathognomonic. There is no specific RH of SBS but they usually affect the posterior retinal pole. Typically, RHs of SBS are present in both eyes, although unilateral RHs do not exclude the diagnosis of SBS. The relationship between RH and CH has been reported in SBS but also in other diseases. Thus, one must search for hemostasis abnormalities, even though the clinical presentation suggests SBS. Ignoring SBS as well as coming to the conclusion of SBS too quickly should be avoided. Diagnostic difficulties may be related to the number of physicians involved and their interpretation of the facts. These 2 cases underline the need for working as a team that includes hematologists able to interpret coagulation parameters.

Intracranial hemorrhage: Clinical and demographic features of patients with late hemorrhagic disease

This retrospective study presents clinical, demographical features and radiological findings as well as outcomes of 31 infants with intracranial hemorrhage (ICH) due to vitamin K deficiency and hence evaluates the risk factors involved. Thirty-one cases (17 males and 14 females) having a mean age of 52.52 ± 20.80 days with intracranial hemorrhage due to late hemorrhagic disease of the newborn (LHDN), hospitalized in our clinics were included in the study. Cranial computerized tomography (CT) was performed in all patients for the diagnosis and evaluation of ICH. It was found that the most frequent presenting symptoms were pallor (77.4%), seizures (58%), altered consciousness (58%), vomiting (44%) and poor feeding (35%). Pulsatile fontanel was found in 61% and bulging in 26%. Seven (22.5%) patients had prior history of antibiotic usage. All patients (93.5%) except two were breast fed. Sixteen (51.6%) were delivered at home. Eighteen (58%) had a history of single-dose vitamin K prophylaxis on the first day of delivery. Parenchymal (44%), subdural (39%) or subarachnoidal (22.5%) bleeding was observed. Seven (22.6%) were exitus. During the follow-up period (ranging from 3 months to 18 months) neurological examination findings were recorded. Our results indicate that it may be questionable whether single-dose vitamin K prophylaxis at birth is adequate for the prevention of LHDN and if a different timing of this prophylaxis should be made for the exclusively breast fed infants.

783 Intracranial Hemorrhages and Late Hemorrhagic Disease Associated Cholestatic Liver Disease

783 Intracranial Hemorrhages and Late Hemorrhagic Disease Associated Cholestatic Liver Disease

Case of toluene abuse

Haemorrhagic disease of the newborn (HDN) can be defined as vitamin K deficiency related bleeding. HDN is one of the most frequent bleeding disorders in infancy [1]. It is classified as early, classical and late - onset disease according to the time bleeding occurs. Early HDN is diagnosed when the bleeding begins in the first 24 hours of postnatal period. It is frequently seen in babies whose mothers are on antitubercular (isoniazid and/or rifampicin), or antiepileptic (such as phenytoin and phenobarbitol) drugs. Classical HDN occurs between 2-5 days of neonatal period and life-threatening bleeding is rare. Late-onset disease can be seen during infancy but predominantly at 4-8 weeks of life. Its incidence is 4-25/1,00,000 births in the western countries but as high as 25-80/1,00,000 in eastern countries [2]. Late haemorrhagic disease is diagnosed if bleeding occurring after the 7th day of life with normal platelet count, prolonged prothrombin time (PT) and partial thromboplastin time (PTT) associated with stopping of bleeding and PT/PTT returning to normal after giving vitamin K [3].

Serebral Kitle Görünümünden Dolayı Ameliyat Edilen Geç Hemorajik Hastalık Olgusu

Serebral Kitle Görünümünden Dolayı Ameliyat Edilen Geç Hemorajik Hastalık Olgusu

Hemorrhagic disease of the newborn despite vitamin K prophylaxis at birth

Late hemorrhagic disease of the newborn (HDN) presents 0.5-6 months after birth with mucocutaneous and intracranial bleeding. We describe here two cases of late HDN in infants who received vitamin K. The first case is a previously healthy breastfed male who received one dose of oral vitamin K at birth and developed an intracranial hemorrhage 5 weeks later. He was treated with intravenous vitamin K and recombinant factor VIIa prior to emergent craniectomy. An unrelated infant presented at 5 months of age with diarrhea and easy bruising despite IM vitamin K at birth. These cases illustrate the morbidity associated with late HDN.

CPP013 Late hemorrhagic disease of newborn and neurologic sequelae in Kayseri

CPP013 Late hemorrhagic disease of newborn and neurologic sequelae in Kayseri

Late haemorrhagic disease of the newborn

Late haemorrhagic disease of the newborn (HDN) can occur owing to a lack of vitamin K prophylaxis, as a manifestation of an underlying disorder or idiopatically from the 8th day to 12 weeks after birth. Eight infants admitted to Kocaeli University Hospital with nine episodes of late HDN between January 2002 and April 2005 were evaluated retrospectively from hospital records. The median age at presentation was 46 (26-111) days. All the infants were born at full-term to healthy mothers and were exclusively breast-fed. All had an uneventful perinatal history, except one who had meconium aspiration. Four patients had received no vitamin K prophylaxis and another three had uncertain histories. At presentation, six had intracranial bleeding and the remainder had bleeding either from the venepuncture site or the gastro-intestinal tract. The presenting signs and symptoms were irritability, vomiting, bulging or full fontanelle, convulsions and diminished or absent neonatal reflexes. Galactosaemia was detected in a 2-month-old infant with prolonged jaundice. There was no surgery-related mortality or complications but one survived for only 2 days on ventilatory support following surgery. Only one of the six survivors had severe neurological sequelae. Late HDN frequently presents with intracranial haemorrhage, leading to high morbidity and mortality. HDN can be the manifestation of an underlying metabolic disorder. Vitamin K prophylaxis of the newborn should be routine in developing countries.

Intracranial hemorrhage due to late hemorrhagic disease in two siblings

Deficiency of vitamin K predisposes to early, classic or late hemorrhagic disease of the newborn (HDN); late HDN may be associated with serious and life-threatening intracranial hemorrhage. Late HDN is characterized by intracranial bleeding in infants aged 1 week to 6 months due to severe vitamin K deficiency, occurring particularly in exclusively breastfed infants. Late HDN is still an important cause of mortality and morbidity in developing countries where vitamin K prophylaxis is not routinely practiced. In this study, we report on two siblings with intracranial bleeding who were fully breastfed without a routine supplementation of vitamin K. Vitamin K should be given to all newborns as a single, intramuscular dose of 1 mg.

The impact of national and international guidelines on newborn care in the nurseries of Piedmont and Aosta Valley, Italy.

BackgroundCare procedures for preventing neonatal diseases are carried out according to nurseries' traditions and may be not consistent with the evidence based medicine issues.MethodsA multi-centric survey was conducted in 2 Regions located in NW Italy (Piedmont and Aosta Valley) in order to collect information on some healthy newborn care procedures. During 2001, a questionnaire was sent to the chief pediatrician in charge to the all 33 nurseries of the region asking the methods used during 2000 as prevention of ophthalmia neonatorum, early and late hemorrhagic disease of newborn, umbilical cord care and recommendations of vitamin D administration. Thereafter, during 2004 the same questionnaire was sent to the 34 chief pediatrician of nurseries to evaluate if the procedures were changed during 2003 according to guidelines. The nurseries care for 32,516 newborns in 2000 and 37,414 in 2003.ResultsAminoglycoside eyes drops as prevention of ophthalmia neonatorum were the first choice in both periods (23 out 33 nurseries in 2000 and 24 out 34 in 2003 p > 0.05; the corresponding figures for newborns were18,984 out 32,516 newborns vs. 28,180 out of 37,414 p < 0.05). The umbilical cord care was carried out with alcohol in 12/33 centers (13,248 newborns) and dry gauze in 3/33 centers (2,130 newborns) in 2000, the corresponding figures in 2003 were 6/34 centers (p > 0.05), (6,380 newborns, p < 0.05) and 12/34 centers (p < 0.05), (18,123 newborns, p < 0.05). The percentage of newborns receiving of i.m. vitamin K. at birth increased during the study period (15,923/32,104 in 2000 vs. 19,684/37,414 in 2003, p < 0.01), but not the number of nurseries (16 in 2000 and 17 in 2003 p > 0.05). The numbers of parents of newborns who receive the recommendations of oral vitamin K during the first months life decreased from 2000 (25,516/30,606) to 2003 (29,808/37,414, p < 0.01) as well as for Vitamin D recommendation (14,582/30,616 in 2000 vs. 11,051/37,414 in 2003, p < 0.01). Oral vitamin K during the first months of life was recommended by 25 nurseries in 2000 and 27 in 2003 (p > 0.05), the corresponding figures for Vitamin D were 15 and 14 (p > 0.05).ConclusionIn the present study a large variability of procedures among the nurseries was observed. During the study periods, guidelines and evidence based medicine issues have only partially modified the neonatal care procedures In Piedmont and Aosta Valley nurseries. These observations suggest to implement local forum/consensus conference to standardized procedures as much as possible.

P0181 ORAL VITAMIN K PROPHYLAXIS DOES NOT PREVENT LATE HEMORRHAGIC DISEASE OF THE NEWBORN IN PIZZ ALPHA-1 ANTITRYPSIN DEFICIENCY.

Introduction: Late hemorrhagic disease (LHD) of the newborn is defined as a bleeding episode due to vitamin (vit) K deficiency which occurs between 2–12 weeks of age. It is seen in exclusively breastfed infants who received inadequate vit K prophylaxis and in babies with intestinal malabsorption. Intramuscular (IM) administration of a single dose of 1 mg vit K has been shown to prevent LHD. The reported association between IM vit K administration and childhood cancer has caused worldwide concern. Although still unconfirmed, it prompted the change to schedules of repeated oral doses of vit K. Until now there’s no uniform policy and different regimens are used. The Dutch protocol, providing a daily oral dose of 25 microgram vit K following an initial oral dose of 1 mg immediately after birth, has been shown to approach the effectiveness of IM vit K. Methods: We report on 2, exclusively breastfed, 5 week old babies (1 boy, 1 girl), who presented with acute bleeding after correct oral vit K following the Dutch protocol. Results: The girl presented with spontaneous bruising and epistaxis. She was found to have severe coagulopathy (PT<10%, aPTT>180 sec, fibrinogen 305 mg/dl, platelets 701 109/l) and a subcutaneous hemorrhage of the thoracic wall was diagnosed on CT scan. Mild cholestasis (total bilirubin 3.5 mg/dl, direct bilirubin 2.76 mg/dl) was also noted, AST was 80 IU/l, GGT 288 IU/l. The boy was admitted with shock and respiratory distress. Blood results showed a PT<10%, aPTT>180 sec, fibrinogen 326 mg/dl, platelets 404 109/l. Total bilirubin was 6.3 mg/dl, direct bilirubin 3.6 mg/dl, AST 184 IU/l and GGT 988 IU/l. CT scan revealed a hemothorax. The vit K dependent coagulation factors were reduced in both babies. Both infants were treated with intravenous vit K and fresh frozen plasma. The coagulation normalised within hours. Further investigations led to the diagnosis of PiZZ alpha-1 antitrypsin deficiency (AAT) in both children. Conclusion: LHD of the newborn can be the first life threatening symptom of undiagnosed cholestatic liver disease, with AAT and biliary atresia as most common causes. Vit K is essential in the prevention of LHD. Despite correct oral vit K administration following the Dutch regimen, our patients developed LHD. Our limited experience indicates that oral vit K prophylaxis may be inadequate to prevent bleeding diathesis in children with liver disease. LHD is unpredictable and warning signs are often unrecognized. Therefore developing screening methods identifying patients at risk is a challenge for the future, meanwhile however it might be safer to prefer parenteral vit K prophylaxis.

Intra-cranial hemorrhage in infants due to vitamin K deficiency - report of 2 cases

OBJECTIVE: Drive attention to the late form of the hemorrhagic disease of the newborn, secondary to vitamin K deficiency, as a cause of intracranial hemorrhage in young infants.METHODS: The authors describe and analyze two cases of late hemorrhagic disease of the newborn, secondary to vitamin K deficiency, producing intracranially hemorrhage during the second month of age. The most important publications on this subject are reviewed.RESULTS: Both infants had not received prophylaxis with vitamin K at birth. They were both being fed exclusively on breast milk. They developed intracranial hemorrhage, and the clotting defect was rapidly corrected with intramuscular vitamin K. At 3 and 4 years of age, one of them has showed normal psychomotor development, and the other has showed moderate developmental delay with microcephaly.CONCLUSION: Late hemorrhagic disease of the newborn must be considered in young infants, between 2 and 12 weeks of age, with intracranial hemorrhage, especially those fed exclusively on breast milk who did not receive vitamin K at birth. It may produce neurodevelopmental delay. The clotting defect is rapidly corrected with intramuscular vitamin K. This condition is preventable. The prophylaxis is recommended with 1 mg of intramuscular vitamin K to all newborns, at birth, even without risk factors.

Late hemorrhagic disease of the newborn.

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. 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. 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%. 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.

Prevention of vitamin K deficiency bleeding in newborns.

Newborn babies are born vitamin K deficient; however, the deficiency is not sufficiently severe to cause a vitamin K deficiency coagulopathy and haemorrhagic disease of the newborn (HDN). Severe vitamin K deficiency can develop quickly in breast-fed newborns and can result in the appearance of classic HDN during the first week of life or late HDN during the first 2 months of life. Both forms of the disease can be severe, causing brain damage and death. Classic and late HDN are prevented by the intramuscular administration of vitamin K at birth. Oral prophylaxis prevents classic HDN but is ineffective in preventing late HDN. Despite proven effectiveness of intramuscular vitamin K prophylaxis there have been concerns about the need for, and safety of, this therapy. This review provides evidence that there is need for intramuscular vitamin K prophylaxis for all babies in order to eradicate haemorrhagic disease of the newborn and concludes that there is no evidence that this therapy is harmful.

Effects of 2,3,7,8-tetrachlorodibenzo- p-dioxin or 2,2′,4,4′,5,5′-hexachloro-biphenyl on vitamin K-dependent blood coagulation in male and female WAG/rij-rats

Newborns are susceptible to hemorrhages (hemorrhagic disease of the newborn or HDN) due to vitamin K deficiency. Induction of cytochrome P450 in the fetal liver by maternal anticonvulsant therapy such as phenobarbital or phenytoin is considered to be a major cause. An observed increase in late hemorrhagic disease (LHD) in breast fed neonates gave rise to the hypothesis that PCBs and dioxins, P450-inducing contaminants present in human milk, might effect vitamin K-dependent blood coagulation. This hypothesis was studied in rats. Administration of a single oral dose of 0.003, 0.03, 0.3, 3 or 30 nmol 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) per kg bodyweight or 0.75, 4, 20, 100 or 500 μmol 2,2′,4,4′,5,5′-hexachlorobiphenyl/kg bw (HxCB) t0 female and male rats resulted in dose-related reductions of the vitamin K-dependent coagulation factor VII. The highest factor VII reduction in female rats was 44%, observed after TCDD exposure. The Lowest Observed Adverse Effect Level (LOAEL) of TCDD on female factor VII levels was 0.3 nmol/kg bw (96 ng/kg). There was a significant inverse correlation between Factor VII levels and induction of hepatic ethoxyresorufin O-deethylating (EROD) activity, reflecting CYP1A1, and total P450 content. HxCB had no effect on female coagulation factors. In contrast, in male rats only exposure to HxCB, which induces mainly CYP2B1 and 2B2, decreased both coagulation factors dramatically up to 88%. The LOAEL of HxCB on factor VII in male rats was 100 μmol/kg bw (36 mg/kg). In general, effects on coagulation factors in male rats exceeded those in females. In addition, sex-dependent differences of TCDD and HxCB were observed on the hepatic vitamin K cycle enzyme activities in female and male rats. Vitamin K-dependent (γ-glutamyl carboxylase activity was mainly induced in female rats; 2.3-fold in the highest dose group of TCDD. In male rats only vitamin K 2,3-epoxide reductase (KO-reductase) activity was induced 1.7-fold by the highest dose of HxCB. KO-reductase activity in female rats was also increased by TCDD, however, less pronounced than the carboxylase activity. Concluding, the hepatic vitamin K cycle still functions and is not blocked by TCDD or HxCB, thus explaining the observed reduction in factor VII. Finally, the possible role of P450 in vitamin K deficiency is discussed. Based on these results it is suggested to investigate the possible role of PCBs and dioxin-like compounds in LHD in more detail.

Coagulation problems in the newborn

In order to evaluate newborn infants with bleeding problems, it is necessary to be familiar with the physiology of neonatal hemostasis. Levels of many coagulation factors in healthy fullterm neonates are approximately 50% of the adult mean and are lower in preterm infants. Consideration of the clinical setting and appropriate laboratory tests can differentiate between vitamin K deficiency, disseminated intravascular coagulation, liver dysfunction and congenital coagulation factor deficiencies, thus allowing appropriate treatment to be selected. The use of oral vs intramuscular vitamin K for prevention of late hemorrhagic disease of the new born is discussed.

Vitamin K prophylaxis in less developed countries: policy issues and relevance to breastfeeding promotion.

Vitamin K prophylaxis prevents hemorrhagic disease of the newborn. The present review estimates the potential magnitude of this problem in less developed countries, assessing the need for prophylaxis, along with its cost-effectiveness and feasibility. Late hemorrhagic disease, occurring between 2 and 12 weeks, often leads to death or permanent disability. Its median incidence in developed countries is 7 per 100,000 births. Incidences in less developed countries may be much higher. Three incidence scenarios are proposed and the corresponding losses of disability-adjusted life-years (DALYs) calculated. Under the intermediate scenario, late hemorrhagic disease accounts for 0.1% to 0.2% of DALYs lost to children less than 5 years of age. Assuming a cost of +1.00 per injection, each DALY saved would cost +133. Decisions on prophylaxis must be made on a national basis, considering mortality levels and causes, health budgets, and feasibility. Comparison with the impact of diseases prevented by breast-feeding shows that concern with hemorrhagic disease should not affect breast-feeding promotion efforts, although strategies for supplementing breast-fed infants must be explored.

Late hemorragic disease of the newborn: case report

OBJECTIVE: In this study the authors review this subject, and call attention for the late hemorrhagic disease of the newborn, due to the severity and higher risk of mortality and neurological sequelae.METHODS: In this article, four cases of children, age raging from 12 to 21 days, with late hemorrhagic disease associated with vitamin K deficiency were reported. RESULTS: All newborns had multiple hemorrhagic manifestations of the disease. The systems more affected were digestive tract, urinary system, umbilical cord, respiratory system and nervous system.CONCLUSION: Three forms of hemorrhagic disease of newborn have been related with vitamin K deficiency. However, late vitamin K deficiency bleeding is not common and may not be diagnosed by pediatrician. This form of disease can be prevented by vitamin K prophylaxis administration after birth.

Vitamin K deficiency — Late onset intracranial haemorrhage

A retrospective study is presented of the clinical features and outcome of late onset haemorrhagic disease due to vitamin K deficiency in 11 babies who were admitted to the emergency or child neurology unit during a 4-year period (January 1994-December 1997). The disease occurred in infants between 30 and 119 days of age (mean: 56+/-24 days). None of them received vitamin K after birth and all were breastfed. The presenting complaints were seizures (91%), drowsiness (82%), poor sucking (64%), vomiting (46%), fever (46%), pallor (46%), acute diarrhoea (27%), irritability and high-pitched cry (18%). On examination, tense or bulging fontanelle (73%), anisocoria (36%), weak neonatal reflexes (18%), cyanoses (18%) were the most frequent findings. The localizations of the intracranial haemorrhage were as follows: intracerebral (91%), subarachnoid (46%), subdural (27%), and intraventricular (27%). No fatality was observed. However, after a follow-up period ranging from 6 to 48 months (mean: 21+/-13 months), only three (27%) infants remained neurologically normal. Seizure disorders (73%), severe psychomotor retardation (46%), cerebral palsy (46%) and microcephaly (46%) were observed in the remainder. Hydrocephalus developed in three (27%) babies but none of them required shunt replacement. The value is emphasized of vitamin K prophylaxis in the newborn to reduce the incidence of late onset intracranial haemorrhage and handicap in children.