Take the Shot: A Review of Vitamin K Deficiency.

Vitamin K is essential for the process of coagulation. In its absence, severe and sometimes fatal bleeding events can occur, especially in newborns. Vitamin K prophylaxis at birth has been shown to prevent morbidity and mortality associated with vitamin K deficiency bleeding (VKDB) and is recommended by multiple organizations including the American Academy of Pediatrics and the World Health Organization. Pediatricians should feel comfortable explaining the risks and benefits of vitamin K prophylaxis to families and should be equipped to recognize signs of VKDB, especially given increasing rates of parental refusal. This article aims to improve understanding of VKDB, including prevention, early recognition, and treatment. [Pediatr Ann. 2023;52(2):e42-e45.].

Hemorrhagic Disease of the Newborn: A Case Series Illustrating Preventable Harm.

Newborns are susceptible to postnatal Vitamin K deficiencies from limited placental transfer, gastrointestinal absorption, and bioavailability in breast milk and formula preparations. For over 50 years, the American Academy of Pediatrics has recommended prophylactic vitamin K to prevent hemorrhagic disease in newborns. Yet, public skepticism contributes to increasing refusal rates. We present three cases of vitamin K-dependent bleeding following parental refusal of postnatal prophylaxis. Two patients experienced intracranial hemorrhage with resultant neurological devastation and mortality, respectively. The third child presented with symptomatic hematuria. Perinatal providers must partner with families and advocate vitamin K prophylaxis to limit unnecessary morbidity and mortality.

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.

Intracranial Hemorrhage Secondary to Vitamin K Deficiency Bleeding in a Newborn.

We present a case of a 6-week-old infant who presented with seizure-like activity. Workup revealed abnormal coagulation and imaging confirmed intracranial hemorrhage. Parental refusal of vitamin K treatment at birth suggested vitamin K deficiency bleeding (VKDB) in this newborn. Though VKDB is rare in developed countries, rates have been rising which coincides with an increasing trend of parental refusal of vitamin K prophylaxis at birth.

Laboratory assessment of vitamin K status.

Vitamin K is required for the É£-carboxylation of specific glutamic acid residues within the Gla domain of the 17 vitamin K-dependent proteins (VKDPs). The timely detection and correction of vitamin K deficiency can protect against bleeding. Vitamin K also plays a role in bone metabolism and vascular calcification. Patients at increased risk of vitamin K deficiency include those with a restricted diet or malnutrition, lipid malabsorption, cancer, renal disease, neonates and the elderly. Coagulation assays such as the prothrombin time have been used erroneously as indicators of vitamin K status, lacking sufficient sensitivity and specificity for this application. The measurement of phylloquinone (K1) in serum is the most commonly used marker of vitamin K status and reflects abundance of the vitamin. Concentrations <0.15 µg/L are indicative of deficiency. Disadvantages of this approach include exclusion of the other vitamin K homologues and interference from recent dietary intake. The cellular utilisation of vitamin K is determined through measurement of the prevalence of undercarboxylated VKDPs. Most commonly, undercarboxylated prothrombin (Protein Induced by Vitamin K Absence/antagonism, PIVKA-II) is used (reference range 17.4-50.9 mAU/mL (Abbott Architect), providing a retrospective indicator of hepatic vitamin K status. Current clinical applications of PIVKA-II include supporting the diagnosis of vitamin K deficiency bleeding of the newborn, monitoring exposure to vitamin K antagonists, and when used in combination with α-fetoprotein, as a diagnostic marker of hepatocellular carcinoma. Using K1 and PIVKA-II in tandem is an approach that can be used successfully for many patient cohorts, providing insight into both abundance and utilisation of the vitamin.

Vitamin K deficiency bleeding in an apparently healthy newborn infant: the compelling need for evidence-based recommendation.

BACKGROUND: Vitamin K is a key point for guarantee normal blood clotting and its level in newborns is commonly low, so a supplementation after delivery is mandatory. Vitamin K prophylaxis in newborns is still an open field of debate: many types of protocol have been proposed in different years and Countries, and sometimes with great variability inside the same Nation (for instance, in Italy a national consensus is not available, so different protocols are employed). Recommendations include different protocols for healthy newborns born at term, but the unpreventable presence of bleeding favouring factors (i.e. blood vessels malformations) or limiting intestinal absorption of liposoluble vitamins (i.e. cholestasis), which could be unrecognized or subclinical in the perinatal period, rises some concerning about the most precautionary route of administration and the timing of further doses after the first one given at birth. The purpose of this report is to underline the most recent evidences available in literature and to arise a debate about this topic, in order to stimulate the production of evidence-based guidelines concerning the prophylaxis with vitamin K1 in newborn infants, considering that many bleeding risk factors are not recognizable at birth. CASE PRESENTATION: We are hereby presenting an emblematic case concerning the risk of intracranial bleeding in an apparently healthy newborn: the described infant did not show any pathological elements in pregnancy history or perinatal life which suggest a possible increased risk of bleeding and the needing of a particular approach in the administration of vitamin K1, but at the end of the first week of life presented an intracranial bleeding with neurological symptoms that required treatment for vitamin K deficiency. CONCLUSIONS: Univocal recommendations about vitamin K prophylaxis are not available and the contrast between oral and intramuscular routes persists unsolved. The difficulty to certainly identify an infant eligible for oral administration of vitamin K1 at birth suggests that the intramuscular route should be preferred. How to prosecute the supplementation in the first months of life is still an open topic of debate.

The Presentation of a Fussy Infant With Bruising: Late-Onset Vitamin K Deficiency Bleeding.

Vitamin K plays an integral role in the clotting cascade. Deficiency, specifically in vulnerable neonates with insufficient stores, can lead to spontaneous bleeding and devastating effects. In this case, we report a young infant with late-onset vitamin K deficiency bleeding who did not receive vitamin K prophylaxis after birth. Initially presenting with bruising and fussiness, the patient was later found to have intracerebral hemorrhage with midline shift and uncal herniation. The infant was not a surgical candidate and died shortly thereafter. Laboratory studies confirmed the diagnosis of late-onset vitamin K deficiency bleeding as the cause of hemorrhage and death.

Gastrointestinal bleeding secondary to trimethoprim-sulfamethoxazole-induced vitamin K deficiency.

There is a well-known association between vitamin K deficiency and haemorrhagic events including gastrointestinal bleeding. There is also a well-known association between both poor dietary intake of vitamin K and chronic antibiotic use and the development of vitamin K deficiency. Although the medical literature notes that cephalosporin antibiotics have a propensity to cause vitamin K deficiency due to the molecular structure of the medications and their ability to suppress the synthesis of clotting factors, there are other antibiotics that have also been implicated in the development of vitamin K deficiency. There are very few reports of trimethoprim/sulfamethoxazole causing vitamin K deficiency and further leading to bleeding episodes. We present such a case and discuss the risk factors leading to such complications.

Late Vitamin K Deficient Bleeding in 2 Young Infants--Renaissance of a Preventable Disease.

INTRODUCTION: Late vitamin K deficiency bleeding in young infants is a rare disorder which occurs almost exclusively in breast-fed infants who did not receive proper vitamin K prophylaxis at birth and who might additionally suffer from cholestasis. Its impact on morbidity is high since in 50% of the cases it presents with intracranial hemorrhage with a mortality rate of 20% and life-long neurologic sequelae in 30% of the affected infants. CASE REPORTS: 2 male infants were both admitted to our unit at the age of 5 weeks with subdural hematoma with midline shift due to late vitamin K deficiency bleeding. Both infants did not receive the recommended Vitamin K prophylaxis in Germany. One patient presented with cholestatic jaundice on admission as an additional risk factor. DISCUSSION: Parents who in the apparent best interest for their children refuse the recommended and well established vitamin K prophylaxis at birth leading to the reappearance of late vitamin K deficiency bleeding. These parents also tend to refuse routine immunizations of childhood in later life, which not only have an impact on their own child but might bear a risk for the whole community. CONCLUSION: It is the responsibility of health-care takers to show increased awareness to the growing number of parents refusing vitamin K prophylaxis at birth and educate them properly about the devastating consequences of late vitamin K deficiency bleeding.

Another Disease Re-emerges Due to Parental Shot Refusal: Case Report of a Fussy Infant with Blood in Stool.

BACKGROUND: Infants may present to the emergency department (ED) with vague complaints worrisome to parents and may initially appear well, despite serious underlying pathology. Whereas sepsis and nonaccidental trauma are high on most providers' diagnostic considerations, we report a case representative of a worrisome trend secondary to the refusal of parenteral vitamin K at birth leading to significant neurologic sequelae. CASE REPORT: A 10-week-old boy presented to the ED with gradual increase in fussiness for 2 weeks and new onset of blood flecks in the stool on the day of presentation. Careful physical examination revealed a pale-appearing infant, leading to diagnostic evaluation demonstrating profound anemia and intracranial bleeding. The patient was diagnosed with late-onset vitamin K-deficient bleeding (VKDB) secondary to parental refusal of the vitamin K shot at birth. Why Should Emergency Physicians be Aware of This? Emergency Medicine providers need to add this serious treatable disease into their diagnostic consideration for fussy infants, infants with unexplained bruising or bleeding, or infants with new-onset seizures. Rapid identification of VKDB can lead to prompt treatment and halt the rapid progression of symptoms. Emergency Medicine providers should ask all parents if their infant received parenteral vitamin K in the newborn period, especially if they are exclusively breastfed or born out of the hospital.

Early vitamin K deficiency bleeding in a neonate associated with maternal Crohn's disease.

We report herein a case of early vitamin K deficiency bleeding (VKDB) in a neonate associated with maternal Crohn's disease. A female neonate was born at 37 weeks' gestation and weighed 2778 g. She developed broad purpura on her back on day 1. Laboratory data showed anemia, prolonged coagulation time and elevated protein induced by vitamin K absence or antagonist-II. Early VKDB has not been reported in a neonate born from mother with active Crohn's disease. It is essential to give vitamin K selectively as soon as possible after birth to prevent early VKDB in neonates.

Evaluation of risk factors in patients with vitamin K-dependent coagulopathy presumed to be caused by exposure to brodifacoum.

BACKGROUND/AIMS: Recently, many cases of vitamin K-dependent coagulopathy of unknown origin have been reported. Such patients lack any relevant family history and have no systemic disease, raising suspicion of superwarfarin intoxication. We evaluated individual risk factors causing coagulopathy and hemorrhagic symptoms in patients with suspected superwarfarin intoxication. In addition, we determined how to effectively treat vitamin K-dependent coagulopathy caused by suspected superwarfarin intoxication. METHODS: Seven patients with suspected superwarfarin intoxication who lacked any definitive history of rodenticide ingestion were included. Thirty-one patients initially diagnosed with rodenticide poisoning were also included. We performed a retrospective chart review of all subjects and examined clinical data including patient demographics and medical histories. RESULTS: Patients initially diagnosed with rodenticide poisoning were divided into two groups, one of which had a laboratory abnormality (prothrombin time [PT] > 13 seconds) and another group with PTs in the normal range. There was no significant difference between the two groups in any of age, gender, the extent of chronic alcohol consumption, the causative rodenticide, psychiatric problems, ingestion of drugs interacting with warfarin, the extent of intoxication, or the type of ingestion attempt. The albumin level of the former group was significantly lower than that of the latter group (p = 0.014). Furthermore, a significant difference between the two groups was evident in terms of simultaneous ingestion of rodenticide and alcohol (p = 0.023). CONCLUSIONS: Most patients with superwarfarin poisoning did not exhibit any complication. When such complications were evident, they were associated with serum albumin level and coingestion of rodenticide and alcohol.