Severe Coagulopathy and Intra-Alveolar Haemorrhage Due to Fat Malabsorption in Celiac Disease.

Celiac disease, a prevalent autoimmune disorder, can present atypically with fat malabsorption and coagulopathy due to vitamin K malabsorption. A 64-year-old male presented with haemoptysis and severe anaemia (Hb 6 g/dl). Despite normal previous coagulation tests, admission laboratory tests revealed an international normalised ratio (INR) of 7.0 and iron deficiency anaemia. Initial blood products and vitamin K treatment corrected the INR temporarily, but the patient's haemoptysis returned, and his INR values continued to rise. Further investigation revealed celiac disease with fat malabsorption, leading to vitamin K malabsorption and along with a previously prescribed antiplatelet aggregation therapy, this led to diffuse alveolar haemorrhage. A gluten-free diet and vitamin supplementation normalised the patient's INR and stopped the bleeding. This case highlights the importance of considering celiac disease in unexplained coagulopathies and the effectiveness of dietary management. LEARNING POINTS: Celiac disease can cause severe coagulopathy due to fat malabsorption and vitamin K deficiency.High suspicion is required for atypical presentations of celiac disease.A gluten-free diet is essential for managing celiac disease and normalising coagulation profiles.

Rapid diagnosis of coagulopathies from vitamin K deficiency in a consecutive case cohort evaluated by comparative assessment of factor II by 1-stage assays with prothrombin time vs Ecarin reagents.

BACKGROUND: Vitamin K (VK) deficiency (VKD) impairs γ-carboxylation of VK-dependent factors (VKDFs), resulting in higher factor (F)II levels measured by Ecarin (FIIE) reagents (that convert des-γ-carboxylated FII to meizothrombin) than by prothrombin time (FII) reagents. OBJECTIVES: To evaluate FII/FIIE abnormalities among patients assessed for coagulopathies and identify findings predictive of coagulopathy improvement after VK. METHODS: We retrospectively assessed consecutive cases from 2002 to 2021 with FII/FIIE tests and the sensitivity and specificity of FII/FIIE ratios and FIIE-FII differences for VKD defined as international normalized ratio correction/improvement of ≥0.5 after VK. RESULTS: Two hundred ninety-two patients (males, 58.2%; adults, 85.6%; median age, 73 years) were evaluated (84.2% hospitalized, 48.3% in intensive care, 71.6% with active liver disease, and 28% deceased at discharge) and 25% to 38% had FII/FIIE findings suggestive of VKD. Among 170 patients assessed for response to VK, FII/FIIE ratios of ≤0.84 to 0.91 and FIIE-FII differences of >0.04 U/mL had similar modest sensitivity (47.7%-69.3%) and modest to good specificity (67.1%-91.5%) for VKD. FII/FIIE ratios of <0.86, suggestive of VKD (sensitivity, 47.7%; specificity, 90.2%), were more common in patients deficient in only VKDF (P = .0001), but were detected in 16% with non-VKDF deficiencies. Low FIIE was commonly associated with active liver disease (P = .0002). Patients with and without probable VKD (based on FII/FIIE ratios of <0.86) had similar mortality, bleeding, and rates of prothrombin complex concentrate and red cell transfusions (P ≥ .78), but fewer with probable VKD received plasma and fibrinogen replacement (P ≤ .024). CONCLUSION: FII/FIIE comparison aids the diagnosis of VKD and predicts clinical responses to VK treatment among patients with coagulopathies.

A Case of Significant Coagulopathy Due to Vitamin K Deficiency Caused by the Administration of Cefazolin and Rifampicin and Hyponutrition After a Postoperative Infection of the Lumbar Spine.

Postoperative surgical site infection in the lumbar spine is one of the serious complications that sometimes results in death. Herein, we describe a case in which a patient was found to have coagulopathy due to vitamin K deficiency when he was transferred to a hospital for treatment for a postoperative infection of the lumbar spine. The coagulation disorder was caused by antimicrobial agents administered to the patient, who was suffering from hyponutrition. The patient was a 70-year-old man with a history of diabetes mellitus. He was diagnosed with lumbar spinal canal stenosis and underwent posterior decompression of the L2-L5 and S1 laminae at a previous hospital five months before transfer to our hospital. Four months before transfer, purulent discharge was observed from the wound, and methicillin-susceptible Staphylococcus aureus was detected in the wound culture. Cefazolin was administered for two weeks, resulting in initial improvement. However, one month before the transfer, the wound infection recurred, accompanied by bacteremia and a psoas abscess. He had been treated with cefazolin, levofloxacin, rifampicin, trimethoprim, and sulfamethoxazole, but the antibiotics' effects were insufficient. Upon transfer for debridement surgery due to uncontrolled infection, his coagulation parameters were as follows: prothrombin time (PT) 74.0 sec, PT-international normalized ratio (INR) 6.69, PT% 9.0, activated partial thromboplastin time (APTT) 138 sec, fibrinogen (FIB) 664 mg/dl, fibrin degradation products (FDP) 7.1 µg/ml, and protein induced by vitamin K absence-II (PIVKA-II) 34400 mAU/ml. Because we suspected vitamin K deficiency, vitamin K 40 mg was administered as a test dose, and coagulation function improved to PT 16.4 sec, PT-INR 1.30, PT% 65.2, and APTT 79 sec after four hours. The diagnosis of vitamin K deficiency was confirmed, vitamin K was administered for four days, and the coagulation status normalized five days after transfer. Debridement was performed for the left psoas abscess. Cefazolin was administered for eight weeks, and administration was completed. The coagulation abnormality did not recur due to careful attention to his nutrition. We experienced a case of coagulopathy due to vitamin K deficiency caused by antimicrobial agents administered to a hyponourished patient with a postoperative infection of the lumbar spine. The cause of vitamin K deficiency, in this case, was thought to be low nutrition, suppression of vitamin K-producing bacteria by cefazolin and rifampicin, and the use of cefazolin with a methyl-thiadiazole thiol group. It should be kept in mind that severe coagulopathy due to vitamin K deficiency caused by antimicrobial treatment with hyponutrition can occur in postoperative infections.

A Case of Vitamin K Deficiency Bleeding in a Newborn: Catastrophic Yet Preventable.

A four-week-old full-term male infant presented to the emergency department with blood in the diaper, increasing lethargy, and vomiting and was found to have multiple intracranial hemorrhages on CT. He was delivered at home and did not receive vitamin K. Coagulation studies were abnormal, and des-gamma carboxyprothrombin (DCP) was 481, diagnostic of vitamin K deficiency. He received vitamin K and required multiple antiepileptic medications for seizure control. Vitamin K deficiency bleeding (VKDB) is a preventable disease that can have devastating consequences and could present as early, classical, or late-onset. The typical presentation manifests with cutaneous, gastrointestinal, or intracranial hemorrhage most commonly in fully breastfed infants. Vitamin K prophylaxis has proven to be effective. With increasing out-of-hospital delivery and online misinformation, there is a declining administration of intramuscular vitamin K at birth. It is the responsibility of healthcare providers to properly inform patients and their families of the importance of vitamin K prophylaxis at or before the time of delivery.

Hemorrhagic Disease of the Newborn as a Consequence of Vitamin K Refusal Due to Language Barrier.

Newborns are prone to hemorrhagic disease due to vitamin K deficiency for multiple reasons, including vitamin K absence in breast milk and formula preparation, sterile gut with limited absorption, and lack of placental transfer. Despite the importance of vitamin K administration at birth in preventing hemorrhagic disease in infants, some parents still refuse administration to their newborns. One of the unexpected but preventable reasons is the language barrier related to special dialects, resulting in misunderstanding the benefits of vitamin K administration and complications related to vitamin K deficiency. We present a case of hemorrhagic disease of the newborn due to vitamin K deficiency following the parental refusal of postnatal prophylactic vitamin K due to a language barrier that resulted in miscommunication. Although appropriate education was provided to the family via Spanish interpreter as requested, it was later revealed that the family was speaking a special dialect, and they did not fully understand the importance of vitamin K prophylaxis. The patient experienced intracranial hemorrhage with full recovery after treatment and surgical intervention. Upon reviewing the case, the parents were speaking a rare dialect of Spanish, that was not known to the Spanish medical interpreters. A combination of a Spanish medical translator and a family friend was necessary for effective communication with the family.

Coagulopathy Induced by Antibiotics Usage and Bowel Obstruction With Colon Cancer: Report of a Rare Case.

This case report presents a rare occurrence of coagulopathy induced by antibiotics in a woman in her 90s with chronic bowel obstruction and massive colon cancer. The patient developed vitamin K deficiency-related coagulopathy following antibiotic administration, resulting in bleeding complications. Despite initial consideration of disseminated intravascular coagulation, further investigations revealed antibiotic-induced vitamin K deficiency. Prompt discontinuation of antibiotics and IV vitamin K2 administration led to the resolution of coagulopathy. The case emphasizes the importance of cautious antibiotic use in patients with chronic bowel obstruction and prolonged fasting. The protein induced by vitamin K absence-II (PIVKA-II) proved valuable in diagnosing vitamin K deficiency. The learning points include the potential for coagulopathy with antibiotics in prolonged bowel obstruction and the utility of PIVKA-II in assessing vitamin K deficiency. Healthcare providers should exercise caution when administering antibiotics in similar clinical scenarios.

Severe Early-Onset Vitamin K Deficiency Bleeding in a Neonate Born to a Mother with Crohn's Disease in Clinical Remission: A Case Report.

Vitamin K deficiency bleeding (VKDB) in neonates is a significant disorder that causes skin, gastrointestinal, and intracranial hemorrhaging. Early-onset VKDB occurs within 24 hours of birth, and its prognosis is poor due to severe hemorrhage. The causes of early-onset VKDB include maternal intake of warfarin and anticoagulants, and maternal vitamin K deficiency. We report the case of a neonate with early-onset VKDB born to a mother with Crohn's disease. The neonate developed severe cerebellar hemorrhage on the day of birth and subsequent noncommunicating hydrocephalus requiring a ventriculoperitoneal shunt. The mother had a 14-year history of Crohn's disease and short bowel owing to intestinal resection. She was in complete remission during pregnancy according to the Crohn's Disease Activity Index. Endoscopic examination performed shortly before pregnancy revealed inflammatory findings in the residual small intestine. Her blood tests at delivery showed an elevated prothrombin induced by vitamin K deficiency or antagonist II (PIVKA-II) level of 26,900 mAU/mL. A definitive protocol to prevent early-onset VKDB in mothers with Crohn's disease complicated by a short bowel is lacking. Administering vitamin K to mothers with elevated PIVKA-II levels before delivery may help prevent early-onset VKDB.

Clinical outcome and neurological development of patients with biliary atresia associated with a bleeding tendency: a single institution experience.

PURPOSE: We compared the clinical features of patients with biliary atresia (BA) associated with a bleeding tendency (BT) at the time of the diagnosis with those of patients without a bleeding tendency (NBT). METHODS: The patients' background characteristics, age in days at the first visit, Kasai portoenterostomy (KPE), and postoperative course were retrospectively analyzed. RESULTS: Nine of the 93 BA patients (9.7%) showed a BT, including 7 with intracranial hemorrhaging (ICH), 1 with gastrointestinal bleeding, and 1 with a prothrombin time (PT) of 0%. The age at the first visit was 62 ± 12 days old for BT patients and 53 ± 27 days old for NBT patients (p = 0.4); the age at KPE was 77 ± 9 days old for BT patients and 65 ± 24 days old for NBT patients (p = 0.2); the time from the first visit to surgery was 13 ± 7 days for BT patients and 11 ± 10 days for NBT patients (p = 0.5); and the native liver survival rate was 56% for BT patients and 58% for NBT patients (p = 1), with no significant difference in any of the parameters. The neurological outcomes of survivors of ICH were favorable. CONCLUSIONS: Appropriate BT correction allowed early KPE even after ICH, resulting in native liver survival rates comparable to those of NBT patients without significant neurological complications.

Intrauterine fetal death due to fetal intracranial hemorrhage associated with maternal vitamin K deficiency: A case report.

Vitamin K deficiency can cause coagulopathy; therefore, supplementation is recommended to prevent intracranial hemorrhage in newborns. Some reports have shown that maternal vitamin K deficiency is associated with intracranial hemorrhage in the fetus. However, no clear guidelines exist for the diagnosis and treatment of maternal vitamin K deficiency to prevent fetal intracranial hemorrhage. We report a case of intrauterine fetal death due to intracranial hemorrhage associated with maternal vitamin K deficiency resulting from hyperemesis gravidarum. In this case, maternal protein induced by vitamin K absence II (PIVKA-II) was high at the time of intrauterine fetal death. Therefore, measuring maternal PIVKA-II levels in high-risk cases may help determine the timing of therapeutic interventions for vitamin K deficiency during pregnancy.

Higher levels of circulating desphospho-uncarboxylated matrix Gla protein over time are associated with worse survival: the prospective Maastricht Intensive Care COVID cohort.

BACKGROUND: Extra-hepatic vitamin K-status, measured by dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), maintains vascular health, with high levels reflecting poor vitamin K status. The occurrence of extra-hepatic vitamin K deficiency throughout the disease of COVID-19 and possible associations with pulmonary embolism (PE), and mortality in intensive care unit (ICU) patients has not been studied. The aim of this study was to investigated the association between dp-ucMGP, at endotracheal intubation (ETI) and both ICU and six months mortality. Furthermore, we studied the associations between serially measured dp-ucMGP and both PE and mortality. METHODS: We included 112 ICU patients with confirmed COVID-19. Over the course of 4 weeks after ETI, dp-ucMGP was measured serially. All patients underwent computed tomography pulmonary angiography (CTPA) to rule out PE. Results were adjusted for patient characteristics, disease severity scores, inflammation, renal function, history of coumarin use, and coronary artery calcification (CAC) scores. RESULTS: Per 100 pmol/L dp-ucMGP, at ETI, the odds ratio (OR) was 1.056 (95% CI: 0.977 to 1.141, p = 0.172) for ICU mortality and 1.059 (95% CI: 0.976 to 1.059, p = 0.170) for six months mortality. After adjustments for age, gender, and APACHE II score, the mean difference in plasma dp-ucMGP over time of ICU admission was 167 pmol/L (95% CI: 4 to 332, p = 0.047). After additional adjustments for c-reactive protein, creatinine, and history of coumarin use, the difference was 199 pmol/L (95% CI: 50 to 346, p = 0.010). After additional adjustment for CAC score the difference was 213 pmol/L (95% CI: 3 to 422, p = 0.051) higher in ICU non-survivors compared to the ICU survivors. The regression slope, indicating changes over time, did not differ. Moreover, dp-ucMGP was not associated with PE. CONCLUSION: ICU mortality in COVID-19 patients was associated with higher dp-ucMGP levels over 4 weeks, independent of age, gender, and APACHE II score, and not explained by inflammation, renal function, history of coumarin use, and CAC score. No association with PE was observed. At ETI, higher levels of dp-ucMGP were associated with higher OR for both ICU and six month mortality in crude and adjusted modes, although not statistically significantly.

Association Between Vitamin Deficiencies and Ophthalmological Conditions.

Vitamin deficiencies can have adverse effects on health, including on the visual system. The ocular manifestations of a vitamin deficiency are related to the underlying biochemical function of the particular nutrient. While vitamin deficiencies are not common in developed counties, they are still prevalent in parts of the developing world and in specific, vulnerable populations. Vitamin deficiencies can cause or contribute to many ophthalmological conditions and eye diseases may even be the first presenting finding of a vitamin deficiency. As such, it is important for ophthalmologists to be aware of the ocular manifestations of vitamin deficiencies, especially given that the complications can be severe and effectively treated if identified early. This review summarizes the literature on the main vitamins known to have characteristic ocular manifestations: vitamins A, B1, B2, B9, B12, C, D, E and K. The function, epidemiology, manifestations, workup, and management of each vitamin is discussed in detail.

The Legal Limits of Parental Autonomy: Do Parents Have the Right to Refuse Intramuscular Vitamin K for Their Newborn?

Description The American Academy of Pediatrics recommends that all newborns receive an intra-muscular (IM) dose of vitamin K within 6 hours of delivery for the prevention of vitamin K deficiency bleeding (VKDB). There has been an increase in the number of parents who have refused the IM vitamin K dose for their infant based on its possible link to leukemia, preservatives that may lead to adverse reactions, and wanting to avoid pain for the infant. When newborns do not receive IM vitamin K, the most serious feared potential complication is intracranial hemorrhage with potential neurologic sequela including seizures, developmental delay, and death. Recent studies support the contention that parents are making the choice to refuse IM vitamin K without sufficient knowledge of the potential consequences. Parental decisions typically align with the best interest of the child; however, when parental decisions veer from the child's best interest, the limit of parental autonomy is tested. The precedent set by previous cases in which parental autonomy was challenged suggests parents should not be able to refuse IM vitamin K because the therapy has nearly no burden and forgoing this therapy has the potential for substantial harm. It has been argued that as long as the degree of intrusion is modest (a single IM injection) and the benefit substantial (prevention of possible death), states are granted the power to mandate the use of such an intervention. Mandated IM vitamin K for all newborns, regardless of parental approval, would rescind some parental autonomy but improve overall beneficence, nonmaleficence, and justice in the care of newborns.

Radial nerve palsy caused by a rapidly growing intramuscular hematoma in an infant with biliary atresia: a case report.

BACKGROUND: Biliary atresia (BA) is a rare cause of persistent jaundice in infants that can result in vitamin K malabsorption and vitamin K deficiency bleeding (VKDB). We present an infant with BA who developed a rapidly growing intramuscular hematoma in her upper arm after a vaccination which caused a radial nerve palsy. CASE PRESENTATION: An 82-day-old girl was referred to our hospital because of a rapidly growing left upper arm mass. She had received three doses of oral vitamin K before age 1 month. At age 66 days, she received a pneumococcal vaccination in her left upper arm. On presentation, she showed no left wrist or finger extension. Blood examination revealed direct hyperbilirubinemia, liver dysfunction, and coagulation abnormalities, indicating obstructive jaundice. Magnetic resonance imaging showed a hematoma in the left triceps brachii. Abdominal ultrasonography revealed an atrophic gallbladder and the triangular cord sign anterior to the portal vein bifurcation. BA was confirmed on cholangiography. VKDB resulting from BA in conjunction with vaccination in the left upper arm were considered the cause of the hematoma. The hematoma was considered the cause of her radial nerve palsy. Although she underwent Kasai hepatic portoenterostomy at age 82 days, the obstructive jaundice did not sufficiently improve. She then underwent living-related liver transplantation at age 8 months. The wrist drop was still present at age 1 year despite hematoma resolution. CONCLUSIONS: Delayed detection of BA and inadequate prevention of VKDB can result in permanent peripheral neuropathy.

Type 3 of progressive familial intrahepatic cholestasis (PFIC-3): Case report.

Genetic testing should always be advised in both parents and children of families with progressive familial intrahepatic cholestasis as early detection will provide more options to a better qualitative life.

Vitamin K Deficiency in the Setting of Blenderized Tube Feeding Regimen in a Teenager: A Case Report.

Vitamin K acts a cofactor for the gamma-carboxylation of several proteins in the coagulation cascade. The clinical spectrum of vitamin K deficiency (VKD) can be asymptomatic to a significant bleeding. VKD is classically seen in newborns. However, this can manifest later in patients with risks such as sub-optimal nutrition, fat malabsorption, medications including antibiotics. A 17-year-old male with spinal muscular atrophy (SMA) Type 1, tracheostomy with ventilator dependent, gastrostomy tube feeding was seen by the gastroenterologist following treatment for small intestinal bacterial overgrowth (SIBO). Investigations showed coagulopathy following which he was transferred to the Pediatric ICU. Labs revealed prothrombin time (PT) 114 s [Normal 9.4-12.5 s], INR (International normalized ratio) 12.6 [Normal < 1.1] and partial thromboplastin time (PTT) 90 s [Normal 25.1-36.5 s]. Mixing studies and coagulation assays were consistent with VKD (low Factor VII and Factor IX with normal Factor V). His home blenderized feeding regimen met the caloric requirement but not the adequate intake (AI) values for vitamin K and other minerals. He received intravenous vitamin K (phytonadione) for five consecutive days with resolution of the coagulopathy (PT 13.2 s, PTT 37.1 s, INR 1.2). The patient was discharged on enteral vitamin K and additional supplements following dietary review by a nutritionist. Clinicians should be cognizant of VKD in patients on blenderized tube feeds which may not meet the adequate intake (AI) goals. In patients who are not receiving nutritionally complete formulas or receiving inadequate volumes, it is important to monitor macro and micronutrients.

Three Different Regimens for Vitamin K Birth Prophylaxis in Infants Born Preterm: A Randomized Clinical Trial.

OBJECTIVE: To study the efficacy of 3 different vitamin K birth prophylaxis regimens in infants born premature. STUDY DESIGN: This was an open-label, parallel-group, randomized clinical trial conducted in a tertiary neonatal care unit in India. Infants born very preterm (≤32 weeks) and/or with very low birth weight (≤1500 g) were included. In each arm, 25 babies were enrolled. Babies were randomized to receive 1.0 mg, 0.5 mg, or 0.3 mg intramuscular (IM) vitamin K1 at birth. Protein induced by vitamin K absence - II (PIVKA-II) levels were assessed at birth, and on days 5 and 28, along with the frequency of death, bleeding manifestations, intraventricular hemorrhage, necrotizing enterocolitis, bilirubin levels, and duration of phototherapy. The primary outcome was comparison of PIVKA-II levels on day 5 of life. RESULTS: All the 3 regimens resulted in similar proportion of vitamin K subclinical sufficiency (PIVKA-II < 0.028 AU/mL) infants on day 5 (1 mg - 100%; 0.5 mg - 91.7%; 0.3 mg - 91.7%, P = .347), with no significant difference in median (IQR) PIVKA-II levels (AU/mL): 1 mg 0.006 (0.004, 0.009); 0.5 mg 0.008 (0.004, 0.009); 0.3 mg 0.006 (0.003, 0.009), P = .301. However, on day 28, there was a significant decrease in the proportion of vitamin K-sufficient infants in the 0.3-mg IM group (72.7%) compared with the 1.0-mg (100%) or 0.5-mg (91.3) groups. The 1.0-mg group had significantly greater bilirubin levels and duration of phototherapy. None of the other clinical outcomes were statistically different. CONCLUSIONS: Both 1-mg and 0.5-mg IM vitamin K birth prophylaxis resulted in high sufficiency on follow-up, compared with 0.3 mg. The current recommendation of 0.5-1 mg IM vitamin K birth prophylaxis for infants born preterm, needs to be continued. TRIAL REGISTRATION: CTRI/2022/02/040396.

Gastrointestinal bleeding due to idiopathic early onset of vitamin K deficiency bleeding in a girl baby 50 min after birth: a rare case.

BACKGROUND: The incidence of early-onset vitamin K deficiency bleeding (VKDB) in at-risk neonates who did not receive vitamin K supplementation varied from 6 to 12%. This case report aims to show that VKDB can occur abruptly after birth despite vitamin K1 1 mg IM being given immediately after birth. CASE PRESENTATION: A term female baby was born through vaginal delivery of a 28 years old mother, G1P0A0, 39-40 weeks gestation with normal APGAR score, and birth weight was 3445 g, birth length was 52 cm. During pregnancy, the mother did not take any drugs except vitamins. There are no abnormalities on the baby's physical examination. The anus is patent. Immediately after birth, the baby received a vitamin K1 1 mg intramuscularly. Abruptly, 50 min after delivery, there was meconium with lots of fresh blood. Laboratory results showed hemoglobin, 19.6 g/dL; leukocytes, 25,010/uL; platelets, 390,000/uL, with increased PT and aPTT. A peripheral blood smear showed a normal blood morphology. When 7 h old, the baby had much hematochezia. Laboratory results showed decreased hemoglobin to 17.5 g/dL and increased PT, aPTT, and INR. No abnormalities were found on the babygram and abdominal ultrasound. The working diagnosis was gastrointestinal bleeding due to idiopathic early-onset VKDB. The baby received vitamin K1 2 mg IM, Fresh Frozen Plasma, and a Packed Red Cells transfusion. The patient returned home in good clinical condition. CONCLUSION: Vitamin K1 1 mg IM prophylaxis should be given immediately after birth to prevent early-onset VKDB. In addition, pregnant women who receive drugs that interfere with vitamin K metabolism (anti-epileptic drugs, anti-tuberculosis drugs, vitamin K antagonist drugs) should be given prophylactic vitamin K1, 20 mg/d orally, for at least two weeks before the expected time of delivery.

Exclusively breastmilk-fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth.

BACKGROUND: There is near-global consensus that all newborns be given parenteral vitamin K1 (VK1 ) at birth as prophylaxis against VK deficiency bleeding (VKDB). Breastmilk has a low VK content and cases of late VKDB are reported in exclusively breastmilk-fed preterm infants despite VK prophylaxis at birth. OBJECTIVES: To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under-γ-carboxylated (Glu) species of Gla proteins, factor II (PIVKA-II), and osteocalcin (GluOC), synthesized by liver and bone, respectively. PATIENTS/METHODS: Prospective, multicenter, observational study in preterm infants born <33 weeks' gestation. Blood samples and dietary history were collected before hospital discharge, and after discharge at 2-3 months' corrected age. Outcome measures were serum VK1 , PIVKA-II, and %GluOC (GluOC as a percentage of the sum of GluOC plus GlaOC) compared between exclusively breastmilk-fed and formula/mixed-fed infants after discharge. RESULTS: After discharge, breastmilk-fed babies had significantly lower serum VK1 (0.15 vs. 1.81 µg/L), higher PIVKA-II (0.10 vs. 0.02 AU/ml) and higher %GluOC (63.6% vs. 8.1%) than those receiving a formula/mixed-feed diet. Pre-discharge (based on elevated PIVKA-II), only one (2%) of 45 breastmilk-fed infants was VK insufficient. After discharge, eight (67%) of 12 exclusively breastmilk-fed babies were VK insufficient versus only one (4%) of 25 formula/mixed-fed babies. CONCLUSIONS: Preterm infants who remain exclusively or predominantly human breastmilk-fed after neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine postdischarge VK1 supplementation of breastfed infants to provide intakes comparable to those from formula milks should prevent this deficiency.

No child should suffer from vitamin K deficiency-induced bleeding disorders.

We encountered an 11-day-old male neonate with vitamin K deficiency-induced intracranial hemorrhage, despite receiving oral vitamin K2 (menaquinone-4) prophylaxis according to Japanese guidelines. This case suggests that the current vitamin K deficiency-bleeding prophylaxis programs cannot prevent bleeding completely. Better prophylaxis programs using both intramuscular and oral administration should be considered.