Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K

There is consensus that late vitamin K deficiency bleeding (VKDB) should be prevented by vitamin K prophylaxis. One single dose of 1 mg vitamin K₁ is effective if given i.m. or s.c., but not if given orally. Repeated oral doses might be as effective as the parenteral dose but the optimal dose regimen remains to be established. Different oral dose schedules are presently used in different countries. In Australia, Germany, The Netherlands and Switzerland active surveillance data on late VKDB were collected in a similar manner and failure rates compared. Identical case definitions were used. There were three basic strategies for oral and one for parenteral vitamin K prophylaxis for healthy newborns in the four countries: (1) daily supplementation of low dose vitamin K (25 μg) for breast-fed infants (The Netherlands); (2) 3 × 1 mg orally [Australia (January 1993 – March 1994) and Germany (December 1992 – December 1994)]; (3) 1 mg vitamin K i.m. (Australia since March 1994); and (4) 2 × 2 mg vitamin K (new mixed micellar preparation) (Switzerland). The respective failure rates per 100,000 live births (including cases given all recommended doses and those given incomplete prophylaxis) were for strategy: (1) 0.2 (0–1.3) in The Netherlands; (2) 2.3 (95% CI 1.6–3.4) in Germany and 2.5 (1.1–4.8) in Australia (oral prophylaxis); (3) Australia (i.m. prophylaxis) 0 (0–0.9); and (4) 3.6 (0.7–10.6) in Switzerland. The failure rates for complete prophylaxis only were: strategy (1) 0 (0–0.7) in The Netherlands; (2) 1.8 (1.1–2.8) in Germany and 1.5 (0.5–3.6) in Australia; (3) Australia (i.m.) 0 (0–0.9); and (4) 1.2 (0–6.5) in Switzerland. Conclusions The Australian data confirm that three oral doses of 1 mg vitamin K are less effective than i.m. vitamin K prophylaxis. A daily low oral dose of 25 μg vitamin K₁ following an initial oral dose of 1 mg after birth for exclusively breast-fed infants may be as effective as parenteral vitamin K prophylaxis. The effectiveness of the “mixed-micellar” preparation of vitamin K₁ needs further study. Received: 12 April 1996 / Accepted: 21 July 1996     

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.     

Intracranial haemorrhage due to late onset vitamin K deficiency bleeding in Hanoi province, Vietnam

BACKGROUND: In many developing countries vitamin K prophylaxis is not routinely administered at birth. There are insufficient data to assess the cost effectiveness of its implementation in such countries. OBJECTIVE: To estimate the burden of intracranial haemorrhage caused by late onset vitamin K deficiency bleeding in Hanoi, Vietnam. METHODS: Cases of intracranial haemorrhage in infants aged 1-13 weeks were identified in Hanoi province for 5 years (1995-1999), and evidence for vitamin K deficiency was sought. The data were compared with those on vitamin K deficiency bleeding in developed countries and used to obtain an approximation to the incidence of intracranial haemorrhage caused by vitamin K deficiency bleeding in Hanoi. RESULTS: The estimated incidence of late onset vitamin K deficiency bleeding in infants who received no prophylaxis was unexpectedly high (116 per 100,000 births) with 142 and 81 per 100,000 births in rural and urban areas respectively. Mortality was 9%. Of the surviving infants, 42% were neurologically abnormal at the time of hospital discharge. Identified associations were rural residence, male sex, and low birth weight. A significant reduction in the incidence was observed in urban Hanoi during 1998 and 1999, after vitamin K prophylaxis was introduced at one urban obstetric hospital. CONCLUSIONS: Vitamin K deficiency bleeding is a major public health problem in Hanoi. The results indicate that routine vitamin K prophylaxis would significantly reduce infant morbidity and mortality in Vietnam and, costing an estimated 87 US dollars (48 pounds, 72 Euro) per disability adjusted life year saved, is a highly cost effective intervention.     

Incidence of late vitamin K deficiency bleeding in newborns in the Netherlands in 2005: evaluation of the current guideline

Vitamin K prophylaxis is recommended to prevent the hazard of haemorrhage caused by vitamin K deficiency in newborns. The present Dutch guideline recommends 1 mg of vitamin K₁ orally at birth, followed by a daily dose of 25 μg of vitamin K₁ from 1 to 13 weeks of age for breastfed infants. Since the introduction of this prophylaxis, the incidence of vitamin K deficiency bleeding (VKDB) has decreased; however, late VKDB is still reported. From 1 January to 31 December 2005, a nationwide active surveillance was performed by the Netherlands Paediatric Surveillance Unit (NSCK) to study the current incidence and aetiology of late VKDB in infants. Six cases could be validated as late VKDB: all were breastfed, one fatal idiopathic intracranial haemorrhage at the age of 5 weeks and five bleedings secondary to an underlying cholestatic liver disease between the age of 3 and 7 weeks. The total incidence of late VKDB and idiopathic late VKDB was calculated to be 3.2 (95% CI: 1.2–6.9) and 0.5 (95% CI: 0–2.9) per 100,000 live births, respectively. With the current Dutch guideline, idiopathic late VKDB is rare but late VKDB secondary to cholestasis still occurs in breastfed infants. Doubling the daily dose of vitamin K₁ to 50 μg, as is comparable to formula-feeding, may possibly prevent VKDB in this group. Further research, however, is needed to prove this hypothesis.     

Intracranial Hemorrhage in a Previously Healthy Infant

We describe a 5-week-old infant who presented in cardiac arrest and was later found to have intracranial hemorrhage due to late vitamin K deficiency bleeding. The infant had not received vitamin K prophylaxis following a home birth. Because of worsening direct hyperbilirubinemia and transaminitis, she was subsequently found to have biliary atresia. This case allows us to review the differential diagnosis of intracranial hemorrhage in infants and underscores the importance of considering whether infants presenting with any source of bleeding had received vitamin K prophylaxis. As refusal of vitamin K prophylaxis has increased in the United States over the last decade, pediatricians now play an increasingly vital role in promoting strong adherence to universal prophylaxis for newborns in their practice.     

Late form of vitamin K deficiency bleeding. Description of four cases with various clinical picture and outcome

Late form of vitamin K deficiency bleeding (VKDB) occurs in infants who received none, or inadequate vitamin K prophylaxis after birth. Exclusively breastfed infants are especially prone to development of this disease. We present 4 cases of late VKDB with different clinical picture and outcome. In two patients intracranial bleeding of variable magnitude was detected, in one, bleeding into pleural cavity and in the fourth severe bleeding from injection sites without internal haemorrhage. Diagnosis was based on the clinical picture with special emphasis on the child's past history and results of coagulation tests. Treatment consisted mainly of vitamin K administration and infusion of fresh frozen plasma. One patient developed severe and definite brain damage after intracranial bleeding, the second only a mild brain dysfunction, the remaining two infants recovered fully. These observations and literature data suggest that in exclusively breastfed infants who did not receive vitamin K after birth, late VKDB should be taken into account as a cause of haemorrhage with different localization and magnitude. There is a need for more emphasis on teaching of physicians about late VKDB and for parenteral vitamin K prophylaxis programme for all newborn infants.     

Oral mixed micellar vitamin K for prevention of late vitamin K deficiency bleeding

OBJECTIVE: To determine whether the use of mixed micellar vitamin K improves the efficacy of the 3 x 2 mg oral vitamin K prophylaxis schedule. DESIGN: Nationwide active surveillance for vitamin K deficiency bleeding (VKDB) complemented with two surveys on the use of the mixed micellar preparation in hospitals and by paediatricians. SETTING AND PATIENTS: Infants in Germany in 1997-2000. INTERVENTION: Prophylaxis with three oral doses of 2 mg mixed micellar vitamin K. MAIN OUTCOME MEASURE: Confirmed VKDB between day 8 and week 12 and no condition requiring specific vitamin K supplementation known before the onset of bleeding. RESULTS: Twenty nine reports met the case definition: seven had not received any vitamin K prophylaxis; for three, vitamin K prophylaxis was unknown; two had insufficient vitamin K prophylaxis for their age; 17 had been given the recommended doses. The mixed micellar preparation had been given to seven, other preparations to nine, and one had been given both. These cases did not differ with respect to the site of bleeding and cholestasis detected at bleeding. Estimates of the use of the mixed micellar preparation in birth hospitals and by paediatricians yielded 1 817 769 newborns exposed to the mixed micellar preparation and 1 320 926 newborns exposed to other preparations. The rate of late VKDB was 0.44/100 000 (95% confidence interval (CI) 0.19 to 0.87) in children given mixed micellar vitamin K compared with 0.76/100 000 (95% CI 0.36 to 1.39) in children given other preparations. CONCLUSION: Mixed micellar vitamin K did not significantly improve the efficacy of the 3 x 2 mg oral vitamin K prophylaxis schedule.     

Vitamin K prophylaxis and vitamin K deficiency bleeding (VKDB) in early infancy

The efficacy of vitamin K prophylaxis (1 mg im or sc, or 1-2 mg orally both given as a single dose at birth) in the prevention of vitamin K deficiency bleeding in early infancy was estimated in Germany during a 15-month period between 1988 and 1989. Cases were identified by a survey of all paediatric hospitals and population denominators by a survey of all obstetric hospitals. Response rates were 85% and 68%, respectively. Thirteen cases of vitamin K deficiency bleeding in early infancy with confirmed prophylactic states were confirmed, seven of whom had intracranial haemorrhage. The estimated efficacy of single parenteral administration of vitamin K versus no prophylaxis was 96.7% (95% confidence interval: 74-99.6%) and for single oral administration versus no prophylaxis 80.4% (9.1-95.6%). Single parenteral vitamin K prophylaxis gave substantial protection against vitamin K deficiency bleeding in early infancy. Single oral prophylaxis appeared to be less effective, although the difference was not significant, as indicated by the wide overlap of the respective 95% confidence intervals.     

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-onset holocarboxylase synthetase-deficiency: pre- and post-natal diagnosis and evaluation of effectiveness of antenatal biotin therapy

The clinical and biochemical findings in a family with late-onset holocarboxylase synthetase (HCS) deficiency are described. The index patient had two life-threatening episodes of metabolic decompensation at the age of 13 and 18 months with ketotic hypoglycaemia, vomiting and progressive loss of consciousness. The child recovered without biotin therapy. Organic aciduria characteristic of multiple carboxylase deficiency (MCD) was found, however, the key metabolites were only slightly elevated in some samples. Biotinidase deficiency was considered but excluded by the finding of normal plasma biotinidase activity. The correct diagnosis was made only at the age of 19 months when severe MCD was found in lymphocytes in the presence of normal plasma biotin concentration. HCS deficiency was confirmed by fibroblast studies. Biotin therapy (20 or 40 mg/day) prevented further episodes and normalized biochemical parameters with so far normal development. During two subsequent pregnancies, 10 mg biotin/day was administered to the mother from the 20th week of gestation. At delivery plasma biotin in cord blood samples was 3–4 times higher than in maternal plasma. The 2nd child was unaffected. In the 3rd pregnancy prenatal diagnosis was performed at 16 weeks of gestation. The concentration of methylcitrate in amniotic fluid was within the normal range and that of 3-hydroxyisovalerate only slightly elevated. However, enzyme assays in cultured amniotic fluid cells were consistent with an affected fetus. At birth, carboxylase activities in lymphocytes of this newborn were only moderately decreased to 37% of mean normal. HCS deficiency was confirmed postnatally in fibroblasts. Development remains normal on biotin therapy (20 mg/day). Conclusion Prenatal diagnosis in families with milder forms of HCS deficiency has to be performed by enzyme assays in cultured amniotic cells since organic acid analysis of amniotic fluid may be inconclusive in affected fetuses. Biotin administered prenatally is effectively taken up by the fetus and prevents functional deficiency of the carboxylases in an affected newborn. Received: 4 August 1997 / Accepted in revised form: 21 November 1997     

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

Background: 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. Methods: 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. Results: 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. Conclusion: Our results indicate that it may be questionable whether single‐dose vitamin K prophlaxis 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.     

Italian multicentre study on retinopathy of prematurity

The aim of this prospective multicentre study was to evaluate the influence of a number of perinatal factors on the development of ROP in high risk preterm infants with gestational age ≤30 weeks. All infants consecutively born in, or transferred to, one of the 14 participating centres from 1 January 1992 through 31 December 1993, who had a gestational age of 30 weeks or less and no congenital anomalies and survived to the age of 6 months, were included in the study. Of the 380 infants with mean ± SD gestational age of 28.4 ± 1.6 weeks (range 23–30 weeks) and birth weight of 1157 ± 335 g (range 485–2480 g) that were eligible for the study, 82 (21.5%) developed ROP stage 1 or 2 and 57 (15%) ROP stage 3 or 3+. Step-wise logistic regression analysis showed that the following factors had a significant predictive value for the development of ROP stage 3 or 3+: gestational age (Odds Ratio (OR)=0.6144 for each increment of 1 week of gestational age), birth weight (OR=0.843 for each increment of 100 g of birth weight), prenatal steroids (OR 4.044 for lacking or incomplete prophylaxis), RDS (OR 2.294), oxygen dependency at 60 days (OR 2.085), necrotising enterocolitis (OR 2.597). Conclusion This study confirms the role of prematurity, low birth weight and RDS in the pathogenesis of ROP, and emphasises the importance of prenatal steroid prophylaxis of RDS in very preterm infants. Furthermore, our data suggest that infants with oxygen dependency at 60 days or necrotising enterocolitis are at very high risk of developing ROP. Received: 29 September 1996 and in revised form: 28 January 1997 / Accepted: 1 April 1997     

A bleeding tendency as the first symptom of a choledochal cyst

We report an 8-month-old male presenting with gingival hemorrhages and nasal bleeding as the first symptom of a choledochal cyst (CC). On physical examination, there was a large cystic mass in the right upper abdominal quadrant. Laboratory studies on admission revealed moderate liver dysfunction and a bleeding tendency due to vitamin K deficiency. After administration of 5 mg vitamin K the bleeding tendency disappeared. At laparotomy, a large CC 5 cm in diameter was found and the liver showed moderate cholestasis. The sudden onset of a bleeding tendency in infants with congenital liver or biliary-tract disease may suggest not only biliary atresia, but also CC. Accepted: 10 October 1998     

Prevention of vitamin K deficiency bleeding with oral mixed micellar phylloquinone: results of a 6-year surveillance in Switzerland

In 1995, a new form of vitamin K prophylaxis with two oral doses of 2 mg mixed micellar phylloquinone (Konakion MM) on the 1st and 4th day of life was introduced in Switzerland. It was hoped that this new galenic preparation of phylloquinone would protect infants with insufficient or absent bile acid excretion from late vitamin K deficiency bleeding (VKDB). Subsequently, the occurrence of VKDB was monitored prospectively between July 1, 1995 and June 30, 2001 with the help of the Swiss Paediatric Surveillance Unit (SPSU). Over a period of 6 years (475,000 deliveries), there were no cases of early (<24 h of age), one case of classical (2–7 days of life), and 18 cases of late (1–12 weeks) VKDB fulfilling standard case definitions. In 13/18 patients with late VKDB there was pre-existing liver disease and in 4/18 patients, parents had refused prophylaxis. The incidence of late VKDB for infants with completed Konakion MM prophylaxis was 2.31/100,000 (95% CI: 1.16–4.14) and for the entire population 3.79/100,000 (95% CI: 2.24–5.98). There was only one case of late VKDB after complete prophylaxis in an infant without underlying liver disease. Conclusion: two oral doses of 2 mg of a mixed micellar vitamin K preparation failed to abolish VKDB. The recommendations for vitamin K prophylaxis in Switzerland have therefore been changed to include a third dose at 4 weeks of age. Starting on January 1, 2004, the incidence of vitamin K deficiency bleeding will again be monitored prospectively by the Swiss Paediatric Surveillance Unit.Abbreviations CI confidence interval - SPSU Swiss Paediatric Surveillance Unit - VKDB vitamin K deficiency bleeding     

Life-Threatening Intracranial Bleeding in a Newborn with Congenital Cytomegalovirus Infection: Late-Onset Neonatal Hemorrhagic Disease

The authors present a case of a 36-day-old infant with intracranial and intramuscular hemorrhage due to vitamin K deficiency bleeding, who received intramuscular vitamin K prophylaxis at birth. In this case, laboratory tests showed anemia, liver dysfunction with cholestasis, and coagulopathy, consistent with vitamin K deficiency abnormality. Serological analyses showed that cytomegalovirus immunoglobulin (Ig)M and IgG avidity were both positive. The infant was treated successfully with intravenous ganciclovir and blood products. This case suggests that it is imperative to meticulously investigate the etiology in neonates with late-onset hemorrhagic disease of the newborn. Cholestatic liver disease caused by congenital cytomegalovirus infection should be in mind in term infants who presented with late-onset hemorrhagic disease.     

Effects of heavy maternal smoking on intrauterine growth patterns in sudden infant death victims and surviving infants

Sudden infant death (SID) is associated with both intrauterine growth retardation and maternal smoking during pregnancy. Here, we investigated if the statistical association between maternal smoking and SID is direct or mediated through the well- known growth retarding effects of heavy maternal smoking on the fetoplacental unit. We analysed data from a population-based prospective cohort study (181 cases, total newborn population 227,791 births) within the Westphalian Perinatal Inquiry in Germany between 1990 and 1994. SID victims whose mothers did not smoke had a normal mean birth weight (mean 3415.5 vs 3431.5 g), length (mean 51.46 vs 51.66 cm), and body mass index (BMI) (mean 12.8 vs 12.8 kg/m²) when compared to surviving children. In contrast, SID victims of mothers who smoked heavily (>ten cigarettes per day) had a significantly lower birth weight (2911.21 g vs 3148.34 g), length (48.98 vs 50.39 cm), and BMI (11.8 vs 12.4 kg/m²) when compared to surviving children whose mothers smoked heavily. Stratification for gestational age revealed that these differences are mainly caused by preterm SID infants. Conclusion The statistical association between maternal smoking and SID mainly results from effects of tobacco smoke on the fetoplacental unit which, in later SID victims, appears to be more susceptible to the growth retarding effects of cigarette smoking. Received: 26 May 1997 / Accepted in revised form: 10 September 1997     

Life-threatening intracranial bleeding in a newborn with congenital cytomegalovirus infection: late-onset neonatal hemorrhagic disease

The authors present a case of a 36-day-old infant with intracranial and intramuscular hemorrhage due to vitamin K deficiency bleeding, who received intramuscular vitamin K prophylaxis at birth. In this case, laboratory tests showed anemia, liver dysfunction with cholestasis, and coagulopathy, consistent with vitamin K deficiency abnormality. Serological analyses showed that cytomegalovirus immunoglobulin (Ig)M and IgG avidity were both positive. The infant was treated successfully with intravenous ganciclovir and blood products. This case suggests that it is imperative to meticulously investigate the etiology in neonates with late-onset hemorrhagic disease of the newborn. Cholestatic liver disease caused by congenital cytomegalovirus infection should be in mind in term infants who presented with late-onset hemorrhagic disease.     

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.     

Vitamin K,an update for the paediatrician

Introduction  This review summarizes current knowledge on vitamin K for the paediatrician. Vitamin K is a fat-soluble vitamin, present in plants as phylloquinone and produced by bacteria as menaquinone. It is acting as a co-factor for γ-glutamyl carboxylase. This enzyme is responsible for post-translational modification of some glutamate side chains to γ-carboxyglutamate. The majority of γ-carboxylated proteins function in blood coagulation; others play a role in calcium homeostasis. Data  Newborn babies are at particular risk of vitamin K deficiency, as placental transfer is limited and human milk is a poor source. Vitamin K prophylaxis at birth effectively prevents vitamin K deficiency bleeding (VKDB), formerly known as “haemorrhagic disease of the newborn”. Recent epidemiological studies provide data on the effectiveness of different administration routes and dosing schemes. Infants of mothers taking drugs that inhibit vitamin K are at risk of early VKDB and should receive 1 mg intramuscular (IM) as soon as possible after birth. Classic VKDB is prevented by intramuscular as well as by oral administration of 1 mg vitamin K. In exclusively breast-fed infants, single IM administration at birth is also effectively preventing (rare) late VKDB but single oral administration is not. If given orally, prophylaxis should be continued by either weekly administration of 1 mg till 12 weeks or repeating 2 mg at weeks 1 and 4. Daily administration of 25 μg offers insufficient protection. The only infants not fully protected in this way are those with yet unrecognised liver disease. Conclusions  Further work is needed before firm recommendations can be made regarding dose in preterm infants and in patients with fat malabsorption/cholestasis or regarding the role of vitamin K in the prevention of osteoporosis.     

Thymic cyst haemorrhages and transient cholestasis in a 4-week-old infant

We report a 4-week-old boy with acute respiratory distress, due to massive haemorrhages in multiple thymic cysts. A right hemithymectomy was performed because of mechanical obstruction of the trachea by the cysts. The origin of the multilocular thymic cysts remained unclear. Most likely, these haemorrhages were caused by vitamin K deficiency, although the infant received vitamin K prophylaxis. In addition, he developed transient cholestasis, but the aetiology remained unclear. It is postulated that massive haemorrhages in thymic cysts produce large amounts of bilirubin, causing sludging of bile excretions in the liver. Four weeks after the operation, all laboratory findings were normal and 6 months after the operation the boy is still healthy. Conclusion This case report shows that respiratory distress in an infant can be caused by multiple haemorrhages in multilocular thymic cysts. Received: 12 June 1997 / Accepted in revised form: 4 September 1997