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Introduction: Bleeding in neonates is a significant cause of morbidity and mortality in the neonatal period. The early identification of bleeding and its cause (bleeding or clotting disorder) is very important for the appropriate management and for prognostication. Material & Methods: After obtaining institutional ethics committee approval, 21 patients with diagnosis of onset of hemorrhagic disorder were recruited from 550 patients admitted to the Neonatal Intensive Care Unit (NICU) after obtaining written informed consent from their parents/guardians. A detailed history including family history, maternal history and perinatal history was recorded. Thorough assessment and relevant investigations were done for all 21 patients diagnosed with bleeding disorder out of 550 patients. Duration of hospital stay and immediate outcome i.e.-Morbidity and mortality in such neonates were noted. Results: The incidence of bleeding in neonates was 3.8%. Thrombocytopenia was major cause for bleeding [8(38.1%)] followed by VKDB [5 (24%)]. VLBW babies (19.04%) and preterm babies (11.1%) had a statistically significant risk of bleeding. 71.4% (15/21) of neonates had bleeding in the first week of life. 14.3% (3/21) of NICU deaths were in the neonates with bleeding which indicates that bleeding constituted a significant risk factor for mortality in NICU. The outcome in the VKDB was dismal (67% mortality and 33% neurologic sequelae) A statistically significant correlation was found between maternal factors such as Gestational Age<34 weeks, History of Instrumental delivery, history of maternal fever and Anaemia Conclusion: Early and prompt diagnosis of hemorrhagic disease of the newborn can alleviate the devastating consequences. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

Austin Pereira,1 R Damilola Adekunle,2,&ast; Michele Zaman,3,&ast; Michael J Wan1 1University of Toronto Department of Ophthalmology & Vision Sciences, Toronto, Ontario, Canada; 2Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada; 3Queen’s School of Medicine, Kingston, Ontario, Canada&ast;These authors contributed equally to this workCorrespondence: Michael J Wan, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada, Tel +1 416-813-1836, Fax +1 416-813-7040, Email michael.wan@sickkids.caAbstract: 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.Keywords: vitamin A deficiency, vitamin B deficiency, vitamin C deficiency, vitamin D deficiency, vitamin E deficiency, vitamin K deficiency

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.

Prolonged prothrombin time increases the risk of bleeding complications in proportion to prolongation severity. We reported the case of a 72-year-old woman with a recent hospitalization for methicillin-susceptible Staphylococcus aureus endocarditis complicated by spondylodiscitis who developed a severe prolongation of clotting time during treatment with cefazolin due to a vitamin K deficiency. Cefazolin is a first-generation cephalosporin active against gram-positive bacteria. Like other cephalosporins, it is potentially able to inhibit the enzymes involved in recycling vitamin K metabolites, leading to a fall in gamma-carboxylation of vitamin K-dependent clotting factors. Clinicians should be aware of the necessity of regular monitoring of clotting times for the duration of antimicrobial therapy, especially in those patients with several risk factors for a poor vitamin K nutritional status. Prompt detection of vitamin K deficiency should be recognized and adequately supplemented.

Prolonged prothrombin time increases the risk of bleeding complications in proportion to prolongation severity. We reported the case of a 72-year-old woman with a recent hospitalization for methicillin-susceptible Staphylococcus aureus endocarditis complicated by spondylodiscitis who developed a severe prolongation of clotting time during treatment with cefazolin due to a vitamin K deficiency. Cefazolin is a first-generation cephalosporin active against gram-positive bacteria. Like other cephalosporins, it is potentially able to inhibit the enzymes involved in recycling vitamin K metabolites, leading to a fall in gamma-carboxylation of vitamin K-dependent clotting factors. Clinicians should be aware of the necessity of regular monitoring of clotting times for the duration of antimicrobial therapy, especially in those patients with several risk factors for a poor vitamin K nutritional status. Prompt detection of vitamin K deficiency should be recognized and adequately supplemented. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

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., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

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., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hyperemesis gravidarum (HG), severe nausea and vomiting in pregnancy, can lead to vitamin deficiencies. Little is known about HG-related vitamin K deficiency. We aimed to summarise available evidence on the occurrence of HG-related vitamin K deficiency and corresponding maternal and neonatal complications. A systematic review was conducted, searching Medline and EMBASE from inception to 12 November 2020. We identified 1564 articles, of which we included fifteen in this study: fourteen case reports (n 21 women) and one retrospective cohort study (n 109 women). Nine out of twenty-one women reported in case reports had a prolonged prothrombin time (PT). The cohort study measured PT in 39/109 women with HG, of whom 10/39 women (26 %) had prolonged PT. In total, 30–50 % women received vitamin K supplementation after vitamin K deficiency had been diagnosed. Four case reports (n 4 women) reported corresponding maternal complications, all consisting of coagulopathy-related haemorrhage. Nine case reports (n 16 neonates) reported corresponding neonatal complications including intracranial haemorrhage (n 2 neonates) and embryopathy (n 14 neonates), which consisted of Binder phenotype (n 14 neonates), chondrodysplasia punctata (n 9 neonates) and grey matter heterotopia (n 3 neonates). In conclusion, vitamin K deficiency and related complications occur among women with HG. In our systematic review, we were unable to assess the incidence rate. [ABSTRACT FROM AUTHOR]

Background: Short bowel syndrome (SBS) refers to a malabsorptive state caused by extensive resection of the intestinal tract that leads to chronic diarrhea, electrolyte disturbances, and malnutrition. Although relatively uncommon, patients with SBS can present to the emergency department with more serious complications that are potentially life-threatening. Among these complications, coagulopathy secondary to SBS is an underrecognized condition.Case Report: We present a case of severe coagulopathy secondary to vitamin K deficiency in SBS. The patient presented with unexplained coagulopathy and spontaneous bleeding in multiple organs. With a review of surgical history and detailed clinical evaluation, SBS complicated with vitamin K deficiency was diagnosed, and the patient was treated successfully. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When a patient with a history of repeated intestinal surgery presents with diarrhea, malnutrition, or electrolyte abnormalities, emergency physicians should suspect SBS. Among complications of SBS, vitamin K deficiency is a rare but serious cause of unexplained coagulopathy presenting to the emergency department. Understanding the pathophysiology of SBS facilitates early identification of complications and improves patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: An algorithmic approach, termed the prolonged clot time profile (PROCT), consisting of initial screening with prothrombin time (PT) and activated partial thromboplastin time (aPTT), reflexive mixing studies if indicated, and follow‐up assays depending on initial testing results, offers an efficient approach to delineate the etiology of a prolonged PT/aPTT. Herein, we present the outcomes of the PROCT in the outpatient setting. Methods: In this retrospective study, we reviewed medical records of consecutive outpatients who had prolonged PT and/or aPTT noted in the routine coagulation laboratory and who had PROCT ordered in our institutional Special Coagulation Laboratory between 2010 and 2017. Results: One hundred and six patients, median age 55 years (IQR 30‐67), met our study criteria. Twenty‐nine patients had normal PT/aPTT, while 77 had persistent abnormalities and underwent reflexive testing. A prolonged PT, aPTT, or PT and aPTT was noted in 27 (35%), 27 (35%), and 23 (30%) respectively. Forty‐nine (64%) had an acquired condition, 17 (22%) had a congenital condition, 7 (9%) had unclear etiology, and 4 (5%) were the result of laboratory artifact. The most common known cause of an isolated prolonged PT in our study was vitamin K deficiency in 8 (10%), the most common cause of an isolated prolonged aPTT was lupus anticoagulant in 4 (5%), and the most common cause of prolonged PT and aPTT was liver disease in 11 (14%). Conclusion: Prolonged PT/aPTT have a wide range of causes, including artifactual prolongation or abnormalities in secondary hemostasis due to both inherited and acquired conditions. [ABSTRACT FROM AUTHOR]

To analyze the use of vitamin K1 in 638 pregnant women and their newborns. Methods A questionnaire was distributed to obstetricians and neonatologists in hospitals of all levels in Shandong province. The clinical data of 638 pregnant women and their newborns with vitamin K1 medication were collected and analyzed. Results Among the 638 pregnant women, 540 cases（84. 63%）did not regularly take vitamin K1 before delivery and 559 cases（87. 58%） did not regularly take vitamin K1 after delivery. All healthy neonates were given vitamin K1 by intramuscular injection. The gestational age/body weight was not considered in 198 cases, and the dosage was different in 79 cases due to "different gestational age/body weight". The dosage was temporarily decided in 14 cases due to uncertain reasons such as prolonged labor or placental abruption. A total of 263 cases were given once, 9 cases were given twice, and 18 cases were given three times or more；190 cases were given immediately after birth, 99 cases within 24 h and 13 cases after 24 h. Among all diseased neonates, there are 226 cases of intramuscular injection of vitamin K1, 67 cases of intravenous drip, 50 cases of intravenous injection and 4 cases of oral administration; in 149 cases, we did not consider the gestational age/body weight, 171 cases were given different doses due to "different gestational age/body weight", and in 27 cases, we temporarily decided the dosage of vitamin K1 according to the conditions at admission, such as abnormal coagulation, severe infection, etc. After admission, 289 cases were routinely treated with vitamin K1 injection, and 58 cases were depended on whether they had been used before, whether they had bleeding, diarrhea, long-term use of antibiotics, breastfeeding, and the time of more than 1 week since the last application, etc；272 cases were used within 3 days of admission, 74 cases were used within 3 days of admission and thereafter, and 1 case was used after 3 days. Among all newborns, 501 cases were not routinely supplemented after discharge, 111 cases were unaware of that, and 26 cases were routinely supplemented after discharge. Conclusions A total of 638 pregnant women were deficient in vitamin K1 supplementation prenatally and postnatally. The dosage of vitamin K1 used in healthy children and sick children is different, the healthy children have insufficient vitamin K1 supplement after discharge, and the sick newborn have excessive vitamin K1 supplement during hospitalization but insufficient vitamin K1 supplement after discharge. [ABSTRACT FROM AUTHOR]

Objective: Despite operational guidelines, anecdotal evidence suggests that newborn vitamin K1 prophylaxis is not practiced routinely in India. This study determined the coverage of vitamin K1 prophylaxis among newborns in the country.Design: Nationwide cross-sectional data on live births and newborns receiving vitamin K1 during the 2019-2020 reporting period were abstracted from the Health Management Information System (HMIS). The coverage estimates of newborn vitamin K1 prophylaxis were derived nationally and also for individual states and union territories (UT). Additionally, coverage heterogeneities were investigated using classifiers, viz. geography, socio-demographic index (SDI), special developmental categories and institutional birth rate (IBR).Setting: India.Participants: 20 208 804 newborns documented with HMIS.Results: Vitamin K1 was administered to overall 62·36 % newborns (95 % CI: 62·34 to 62·38 %). The Central zone (49·0 %), low SDI states (54·39 %), Empowered Action Group states (53·32 %) and states with low IBR (44·69 %) had the lowest coverage amongst their respective groupings. Across the individual states and UT, the coverage ranged widely from 22·18 % (in Tripura) to 99·38 % (in Puducherry), exhibiting considerable variability (coefficient of variation: 33·74 %) and inequality (Gini coefficient: 0·17). While the coverage in eight states/UT (i.e. Arunachal Pradesh, Manipur, Nagaland, Tripura, Uttar Pradesh, Uttarakhand, Telangana and Andaman & Nicobar Islands) was below 50 %; only five states/UT (i.e. Chandigarh, Gujarat, Goa, Puducherry and Tamil Nadu) achieved above 90 % coverage.Conclusion: Vitamin K1 prophylaxis was not practiced in more than one-third newborns in India. It calls for identifying the barriers, addressing the gaps and implementing newborn vitamin K1 prophylaxis more effectively throughout the country. [ABSTRACT FROM AUTHOR]

Aim: Intracranial haemorrhage (ICH) in infancy is a rare life‐threatening event. The aim of this review is to highlight the association of ICH and potentially preventable vitamin K deficiency and to describe risk factors, presentation and outcome. Methods: Original published data on ICH related to vitamin K deficiency during 2008–2012 were extracted from records of participating centres in Egypt (Cairo and Delta region). Full data on 70 infants (0–24 weeks) have been reported in three publications. Results: The first study involved premature infants where ICH was potentially preventable with administration of parenteral vitamin K prophylactic doses to mothers ahead of imminent preterm delivery. The other 2 studies involved term newborns and infants. ICH due to early or classic vitamin K deficiency was reported in nine patients while 44 were due to late vitamin K deficiency. Main risk factors for late onset were exclusive breastfeeding, persistent diarrhoea and/or prolonged antibiotic therapy. Conclusion: Vitamin K deficiency bleeding is a relatively frequent problem underlying ICH in infancy. Prophylactic vitamin K to mothers when anticipating preterm labour or a vitamin K boost in exclusively breast‐fed infants with prolonged antibiotic usage and, or, persistent diarrhoea might have an impact on prevention and outcome. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. IRB Review Board of Tsukuba University Hospital Mito Clinical Education and Training Center/Mito Kyodo General Hospital issued approval (24-06). Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tatsumura et al.)

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., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Thomas Nakagawa declare(s) royalties from Wolters-Kluwer, UpToDate. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nmadu et al.)

BackgroundVitamin K-dependent (VKD) proteins, including the mineralization inhibitor matrix-gla protein (MGP), are found in joint tissues including cartilage and bone. Previous studies suggest low vitamin K status is associated with higher osteoarthritis (OA) prevalence and incidence.ObjectiveTo clarify what joint tissues vitamin K is relevant to in OA, we investigated the cross-sectional and longitudinal association between vitamin K status and knee OA structural features measured using magnetic resonance imaging (MRI).MethodsPlasma phylloquinone (PK, vitamin K1) and dephosphorylated-uncarboxylated MGP ((dp)ucMGP) were measured in 791 older community-dwelling adults who had bilateral knee MRIs (mean ± SD age = 74 ± 3 y; 67% female). The adjusted odds ratios (and 95% confidence intervals) [OR (95%CI)] for presence and progression of knee OA features according to vitamin K status were calculated using marginal models with generalized estimating equations (GEEs), adjusted for age, sex, body mass index (BMI), triglycerides and other pertinent confounders.ResultsLongitudinally, participants with very low plasma PK (

• Intracranial hemorrhage in a patient with X-linked myotubular myopathy (XLMTM). • XLMTM is associated with vitamin K deficiency and coagulopathy. • Vitamin K deficiency related to cholestasis and intercurrent acute illness. • Consensus is needed for cholestasis and nutritional deficiency screening in XLMTM. • Further studies should investigate the cause of intrahepatic cholestasis in XLMTM. X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy characterized by profound hypotonia and poor respiratory effort at birth. The condition is associated with multiple morbidities including chronic respiratory insufficiency, feeding tube dependence, and rarely, vitamin K deficiency leading to bleeding and coagulopathy. We report a case of a 6-month-old boy with X-linked myotubular myopathy who experienced a fatal intracranial hemorrhage due to vitamin K deficiency without prior clinical evidence of cholestasis or micronutrient deficiency. We propose clinically non-apparent cholestasis in combination with acute illness and poor weight gain led to his vitamin K deficiency and intracranial hemorrhage. However, the etiology and mechanism of his cholestasis remains unclear. We conclude that children with X-linked myotubular myopathy, especially with gene therapy on the horizon, may benefit from routine hepatic, coagulation, and nutritional screening to prevent potentially catastrophic bleeding. [ABSTRACT FROM AUTHOR]

Background. Are breast-fed infants vitamin K deficient? F.R. Greer raised this question in 2001 in his classic study. The purpose of the study was to determine the concentration of prothrombin induced by vitamin K absence II (PIVKA-II) and prothrombin complex indices as latent vitamin K deficiency markers in exclusively breastfed infants (first 6 months of life). Materials and me­thods. A total of 264 children aged 0 to 6 months were examined, they were in a satisfactory state and had unchanged general blood tests and hepatobiliary tests. Results. In the early neonatal period, 62 (83.8 %) of 74 children who did not receive vitamin K had ­PIVKA-II score above 40 mAU/ml. In 17 (77.3 %) of 22 babies aged 8 to 28 days who did not receive vitamin K after birth, PIVKA-II was within normal limits. In 92 % of 31 infants who received prophylactic vitamin K1 boluses, PIVKA-II was normal in the first week of life, in 12 (54.5 %) of 22 children aged 28 to 180 days who were examined after antibiotic treatment, PIVKA-II is higher than normal. The use of antibiotics in children was associated with elevated concentrations of PIVKA-II, which may indicate a latent acquired vitamin K deficiency or one, which is renewed after birth. The study of the prothrombin complex according to median and quartile estimates (Me, 25–75) in these children established a decrease in prothrombin content by Quick to 62 % (18–91 %), an increase in prothrombin time to 18 s (13–22 s), and an increase in international normalized ratio to 1.4 (1.1–2.6). Conclusions. Thus, children of this group deve­loped hypocoagulation that together with other adverse conditions may lead to the development of late hemorrhagic disease.

Abstract Background Patients with extensive burns usually develop pro-coagulation soon after the injury if there is no sepsis occurred. We describe the case of an extensive burn adult suffering from hypocoagulation not related to sepsis, but secondary to antibiotic treatment. Case presentation Here, we report a case of an adult male patient suffering from flame burns of 45% total body surface area (40% full thickness) combined with inhalation injury. Hypocoagulopathy with soaring prolonged activated partial thromboplastin time value occurred on third week post-burn while systemic infection had been under control by application of broad-spectrum antibiotics. Investigations showed that not the infection but vitamin K-related coagulation factor deficiency were responsible for unexpected bleeding. However, supplemental vitamin K was not the key as we expected, which prompted us trying to decode the underlying cause of coagulation disturbance in this patient and pick out the most effective treatment for live-saving. After the withdrawal of highly suspected broad-spectrum antibiotic, Meropenem®, disturbed vitamin K related coagulation factors gradually restored to their optimal levels so as to maintain normal coagulation status. Therefore, surgical procedures without further risk of bleeding could be carried out in time for wound recovery. The patient was discharged on post-burn day 67 and transferred to a secondary hospital for his rehabilitation. Conclusion Hypocoagulopathy may be devoted to different reasons other than sepsis in extensive burns. Early recognition of the cause for coagulation disturbance is critical to make appropriate treatment and save patients’ lives. This case illustrated the importance of unveiling the mist cause for coagulation disturbance occurred in extensive burn patient, which paved the way for optimal life-saving treatments. And we also recommend burn surgeons to be alerted to antibiotic-induced vitamin K deficiency-related coagulopathy among critical burn patients.

Abstract Background Vitamin K deficiency results in serious coagulation dysfunction, but hemorrhagic shock is rare. Herein, we describe a case of vitamin K deficiency and abnormality in the path of the intercostal artery, the combination of which led to hemorrhagic shock. Case presentation An 83-year-old woman was hospitalized for suspected gallstones. She developed septic shock after 4 days of hospitalization. We considered cholecystitis or cholangitis and performed abdominal ultrasonography, which revealed gallbladder enlargement, biliary sludge, and hyperplasia of the bile duct wall. Antibiotic treatment with sulbactam/ampicillin (SBT/ABPC) was initiated on day four, and percutaneous transhepatic gallbladder drainage (PTGBD) was performed on day five. The treatment was successful, but the patient developed bilateral pleural effusion because of hypoalbuminemia. We performed drainage for bilateral pleural effusion on days 13 and 17. The patient developed hypotension on day 18; blood tests showed anemia and severe coagulation dysfunction but a normal platelet count. We suspected vitamin K deficiency-induced coagulation dysfunction because of previous antibiotic treatment and restricted diet, and it led to hemorrhagic shock. Massive right hemothorax was observed by computed tomography, and urgent interventional radiology was performed. We observed no injury to the intercostal artery truncus but confirmed an abnormality in the course of the intercostal artery; therefore, we inferred that the cause of hemothorax in this case was injury to a small vessel, not truncus because of the abnormality. Because of the likelihood of rebleeding, we performed coil embolization from the seventh to the ninth intercostal artery. Because we confirmed vitamin K deficiency-induced coagulation dysfunction, we referred to the concentration of protein induced by vitamin K absence/antagonist-II (PIVKA-II), and it was found to increase by 23,000. Conclusions A combination of vitamin K deficiency and abnormality in the course of the intercostal artery led to hemorrhagic shock. When using certain antibiotics and restricting diet, it is important to measure coagulation function, even if the platelet count is normal. Further, when thoracentesis is performed, abnormalities in the course of the intercostal artery should be identified. Thoracentesis with ultrasound may prevent hemothorax.

Introduction The American Academy of Pediatrics recommends vitamin K prophylaxis at birth for all newborns to prevent vitamin K deficiency bleeding (VKDB). Despite a lack of evidence for serious harms, barriers to prophylaxis, including parental refusal, are rising, as are cases of VKDB. Methods This simulation involved an infant presenting to the emergency department who decompensated due to a cerebral hemorrhage caused by VKDB and was treated by pediatric and emergency providers. The case was incorporated into the fellow and division monthly curricula, and participants completed postsimulation surveys. The patient required a secure airway, seizure management, vitamin K, and a fresh frozen plasma infusion upon suspicion of the diagnosis, plus a coordinated transfer to definitive care. The case included a description of the simulated case, learning objectives, instructor notes, an example of the ideal flow of the scenario, anticipated management mistakes, and educational materials. Results The simulations were carried out with 48 total participants, including 40 fellows and eight attendings, from five different training institutions over 1 year. In surveys, respondents gave overall positive feedback. Ninety-four percent of participants gave the highest score on a Likert scale indicating that the simulation was relevant, and over 80% gave the highest score indicating that the experience helped them with medical management. Discussion This simulation trained physicians how to recognize and treat a distressed infant with VKDB. The case was perceived to be an effective learning tool for both fellow and attending physicians.

BackgroundOsteoarthritis is the most common form of arthritis, with knee osteoarthritis being the leading cause of lower extremity disability among older adults in the US. There are no treatments available to prevent the structural pathology of osteoarthritis. Because of vitamin K's role in regulating skeletal mineralization, it has potential to be a preventative option for osteoarthritis. We therefore examined the relation of vitamin K to new-onset radiographic knee osteoarthritis and early osteoarthritis changes on magnetic resonance imaging (MRI).MethodsSubjects from the Multicenter Osteoarthritis (MOST) Study had knee radiographs and MRI scans obtained at baseline and 30 months later, and plasma phylloquinone (vitamin K) measured at baseline. We examined the relationship of subclinical vitamin K deficiency to incident radiographic knee osteoarthritis and MRI-based cartilage lesions and osteophytes, respectively, using log binomial regression with generalized estimating equations, adjusting for potential confounders.ResultsAmong 1180 participants (62% women, mean age 62±8 years, mean body mass index 30.1±5.1 kg/m(2)), subclinical vitamin K deficiency was associated with incident radiographic knee osteoarthritis (risk ratio [RR] 1.56; 95% confidence interval [CI], 1.08-2.25) and cartilage lesions (RR 2.39; 95% CI, 1.05-5.40) compared with no deficiency, but not with osteophytes (RR 2.35; 95% CI, 0.54-10.13). Subclinically vitamin K-deficient subjects were more likely to develop osteoarthritis in one or both knees than neither knee (RR 1.33; 95% CI, 1.01-1.75 and RR 2.12; 95% CI, 1.06-4.24, respectively).ConclusionIn the first such longitudinal study, subclinical vitamin K deficiency was associated with increased risk of developing radiographic knee osteoarthritis and MRI-based cartilage lesions. Further study of vitamin K is warranted given its therapeutic/prophylactic potential for osteoarthritis.

Patricia S Coffey, Emily Gerth-Guyette PATH, Seattle, WA, USABackground: Vitamin K prophylaxis can prevent vitamin K deficiency bleeding (VKDB), and current global recommendations support universal prophylactic use in newborns. Data about access to and use of vitamin K in low and middle income countries (LMIC) are scarce. To address this gap, we explored current perspectives and practices of newborn vitamin K administration in LMIC in order to better understand the barriers to more widespread coverage of this lifesaving preventative treatment.Methods: We conducted an online survey of stakeholders involved in newborn health. We sent the survey via e-mail to 109 individuals who were based primarily in LMIC and 23 responses were received, resulting in a response rate of 21%. Respondents were generally health or development professionals from sub-Saharan Africa and Asia. Results: Incidence rates at the country level were mostly unknown or not supported by adequate data. Many respondents (17/23) indicated that vitamin K prophylaxis is included in their national newborn care guidelines and policies, while 12 respondents indicated that administration at birth was widely practiced. Around half of respondents reported that health workers were trained in the diagnosis and treatment of VKDB. The most frequently cited barriers to more widespread vitamin K prophylaxis were (in rank order) high rates of home birth (which preclude injections that must be given by skilled health workers), lack of access to and availability of vitamin K, perception that vitamin K prophylactic treatment is not a priority among health workers, lack of vitamin K formulations appropriate for infants, cultural practices suggesting that injection at birth is not acceptable to parents, and vitamin K not being included in national guidelines and policies. There was no consensus as to the ideal formulation, respondents preferring both the current intramuscular (IM) injection and oral formulation. Reported product attributes of IM and oral formulations are summarized.Conclusion: Prophylactic administration of vitamin K to newborns is relatively well integrated into policy at the global and country levels, but its practice is underutilized. Barriers to use are access, supply chain logistics, provider attitudes, and restrictions on the use of injections by providers at the community level. Technology innovation may offer some promise to mitigate these barriers, although advocacy and health system strengthening might be more likely to yield improved coverage. Further investigation using in-depth bottleneck analysis at the country level could help identify specific health system improvements. Keywords: newborn, vitamin K, prophylaxis, LMIC

What is known and objective: Vitamin K deficiency is known to cause impaired coagulation. We report a case of marked prolongation of the prothrombin time‐international normalized ratio (PT‐INR) associated with warfarin and vitamin K deficiency caused by endoscopic nasobiliary drainage (ENBD). Case presentation: Oral administration of warfarin was initiated in a 67‐year‐old man after left hemihepatectomy. He developed a biliary fistula after surgery that was treated by ENBD, which resulted in significant prolongation of the PT‐INR. What is new and conclusion: The effect of warfarin was enhanced in this patient due to reduced absorption of vitamin K as a result of external biliary drainage. [ABSTRACT FROM AUTHOR]

Keywords: Celiac disease; Iron deficiency anemia; Vitamin D deficiency; Vitamin K deficiency; Hyposplenism EN Celiac disease Iron deficiency anemia Vitamin D deficiency Vitamin K deficiency Hyposplenism 322 331 10 06/18/20 20200601 NES 200601 Presentation of case Dr. Due to malabsorption of micronutrients, anemia and osteopenia or osteoporosis can most often be found in patients with newly diagnosed celiac disease. However, if you look at the chances of having celiac disease from the angle of iron deficiency anemia, a recent systematic review showed that 1 in 31 patients with iron deficiency anemia is found to have celiac disease [[55]]. Based on the prevalence of celiac disease of 1% in the general population and the fact that 90% of patients are HLA-DQ2 positive as compared to only 10% of the general population, calculation revealed a risk of 7.4% for the newborn to develop celiac disease in the future. [Extracted from the article]