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Hemorrhagic Disease of the Newborn
Hemorrhagic Disease of Newborn Due to Vitamin K Deficiency

Hemorrhagic disease of the newborn, also known as vitamin K deficiency bleeding affects term and preterm infants and causes unexpected blood loss at various sites, including cerebral bleeding, with potentially severe consequences. Traumatic birth and hemophilia are predisposing factors.

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WIKIDATA, Public Domain

Presentation

While assessing hemorrhagic disease of the newborn, the physician should first inquire about maternal conditions, medication and feeding preferences, in order to determine a deficiency of vitamin K during the pregnancy. In the infant, the classical signs may present during the 2nd and 7th day. The illness is classified based on the timing the initial blood loss event is observed [1]. In early-onset, bleeding starts during the first 24 hours of life. This is the case if mothers used anticonvulsant or antituberculosis drugs during gestation. The severe type may be partly prevented by administering vitamin K to the mother during the last 2 to 4 weeks of pregnancy.

Affected children exhibit gastrointestinal, brain, skin or mucous membrane bleeding or blood loss from the umbilical stump. Late-onset symptoms usually appear between 2nd and 12th week. However, they can be noticed till 6 months of age. It affects breastfed babies who failed to receive prophylactic vitamin K at birth and have undiagnosed cholestasis leading to vitamin K malabsorption [2] and may also cause intracranial hemorrhage [3]. This manifests as apnea, seizures, and shock, while other parenchymal organs blood loss may be difficult to detect by clinical examination. However, if suspicion arises, urgent imaging evaluation is required. Cases have been reported in Europe [4] and Australia [5] [6].

Infants may report with blood-stained sputum, respiratory distress, irritability or melena. If the hemorrhage is significant, the baby will be tachycardic and the blood pressure will be low. The late form of the illness may also be a manifestation of several underlying conditions, such as cystic fibrosis, diarrhea, hepatitis, alpha 1-antitrypsin deficiency, Alagille syndrome, galactosemia, and abetalipoproteinemia.

Entire Body System

  • Anemia

    Werner Cambridge University Press, ١٨‏/٠٨‏/٢٠٠٥ - 452 من الصفحات Neonatal hematology : a historical overview -- Disorders of the fetomaternal unit -- Erythropoiesis, red cells, and the approach to anemia -- Anemia of prematurity and indications for erythropoietin [books.google.com]

    Hemolytic disease of the newborn (HDN) results when maternal antibodies attack the fetal red blood cells, leading to a hemolytic anemia and accumulation of bilirubin in the fetus or newborn. It can affect the newborn to varying degrees of severity. [radiopaedia.org]

    Children and adolescents with all forms of non-malignant blood disorders, including anemias, bleeding problems, blood clots, platelet disorders and red and white blood cell disorders, are treated through our Pediatric Hematology service. [childrenshospital.org]

    […] age infant (LGA) + Physical maturity + Pathology of prematurity + Gross appearance of premature infant + Difficulties in maintaining homeostasis + Thermoregulation + Hypoglycemia + Hyperbilirubinemia + Fluids and electrolytes + Apnea of prematurity + Anemia [atlases.muni.cz]

  • Ecchymosis

    In physical examination; there was bulging or full fontanel in 10 patients (67%), diminished or absent neonatal reflexes in nine patients (60%) and ecchymosis in three patients (20%). [ncbi.nlm.nih.gov]

    Presentation ▪ Gastrointestinal haemorrhage ▪ Prolonged bleeding after circumcision ▪ Epistaxis ▪ Ecchymosis (bruising) ▪ Intracranial haemorrhage ▪ Bleeding from umbilicus ▪ Cephalohematoma….. 11. [slideshare.net]

    In physical examination; there was bulging or full fontanel in three patients (8.5%), diminished or absent neonatal reflexes in nine patients (24%) and ecchymosis in 25 patients (71%). [pjms.com.pk]

    The usual presentation is a manifestation of haemorrhage; melena, umbilical bleeding, haematuria, epistaxis, generalized ecchymosis, and circumcision site bleeding are possible manifestations, and the neonate also may bleed from iatrogenic puncture sites [panafrican-med-journal.com]

  • Poor Feeding

    Symptoms of VKDB can include vomiting, overt bleeding, poor feeding, lethargy, pallor and bruising. Mark and Melissa Knotowicz declined the shot for their twins, Silas and Abel, following their birth in July at a local Nashville hospital. [news.vanderbilt.edu]

    In a study of Turkey convulsion and poor feeding were seen in 47% patient and pallor in 20% [ 8 ]. Bulging fontanel was seen in a comparable proportion of patients. [alliedacademies.org]

    Common clinical presentations were irritability, convulsions, poor reflexes and poor feeding. Mostly recovery was within 24 hours after vit K. Conclusion: Late HDN results in severe hemorrhage especially hemorrhage in the central nervous system. [pjms.com.pk]

  • Surgical Procedure

    During the 2.5-hour surgical procedure, the estimated blood loss was 50 mL. Two hours after the initial dose, a second dose of rFVIIa (100 [micro]g/kg) was administered in the operating room. [thefreelibrary.com]

    Some institutions will choose to refuse circumcision and other elective surgical procedures to infants who have not received vitamin K prophylaxis. References Lippi G, Franchini M (2011) Vitamin K in neonates: facts and myths. Blood Transfus 9:4-9. [omicsonline.org]

Hematological

  • Hemophilia A

    Previously, the term "hemorrhagic disease of the newborn" was used to describe bleeding disorders in neonates associated with a traumatic birth or hemophilia. [1] The current proper diagnostic term that has been adopted is "vitamin K deficiency bleeding [emedicine.com]

    Traumatic birth and hemophilia are predisposing factors. [symptoma.com]

    Hemophilia is an inherited bleeding disorder. Bleeding disorders can also be a side effect of medicines such as blood thinners. Various blood tests can check for a bleeding disorder. You will also have a physical exam and history. [icdlist.com]

  • Easy Bruising

    An unrelated infant presented at 5 months of age with diarrhea and easy bruising despite IM vitamin K at birth. [ohsu.pure.elsevier.com]

    An unrelated infant presented at 5 months of age with diarrhea and easy bruising despite IM vitamin K at birth. These cases illustrate the morbidity associated with late HDN. [ncbi.nlm.nih.gov]

Gastrointestinal

  • Diarrhea

    An unrelated infant presented at 5 months of age with diarrhea and easy bruising despite IM vitamin K at birth. [ohsu.pure.elsevier.com]

    An unrelated infant presented at 5 months of age with diarrhea and easy bruising despite IM vitamin K at birth. These cases illustrate the morbidity associated with late HDN. [ncbi.nlm.nih.gov]

    The late form of the illness may also be a manifestation of several underlying conditions, such as cystic fibrosis, diarrhea, hepatitis, alpha 1-antitrypsin deficiency, Alagille syndrome, galactosemia, and abetalipoproteinemia. [symptoma.com]

    […] disease — less than 24 hours after birth, occurs rarely with maternal medication that interferes with vitamin K Classic onset — 2 – 7 days after birth in breastfed neonates Late onset — after 2 weeks of life, risk factors besides breastfeeding include diarrhea [atlases.muni.cz]

    Newborns and infants with the following problems involving the gastrointestinal system are more likely to develop this disorder: Alpha1-antitrypsin deficiency Biliary atresia Celiac disease Cystic fibrosis Diarrhea Hepatitis The condition causes bleeding [nlm.nih.gov]

  • Melena

    Infants may report with blood-stained sputum, respiratory distress, irritability or melena. If the hemorrhage is significant, the baby will be tachycardic and the blood pressure will be low. [symptoma.com]

    Under this term the author includes all conditions that involve bleeding in the newborn, as cephalatoma, cerebral hemorrhage, various forms of melena and umbilical hemorrhage. [jamanetwork.com]

    Bleeding commonly occurs in the umbilicus, gastrointestinal (GI) tract (ie, melena), skin, nose, surgical sites (ie, circumcision) and, uncommonly, in the brain. [3] Late-onset vitamin K deficiency bleeding in the newborn Late-onset vitamin K deficiency [emedicine.com]

    ▪ Hematomas, melena, and post-circumcision and umbilical cord bleeding may be present; only 5-35% of cases of factor VIII and IX deficiency become clinically apparent in the newborn period. [slideshare.net]

  • Chronic Diarrhea

    Risk factors include: low levels of vitamin K in breast milk biliary atresia, which causes slow bile flow cystic fibrosis celiac disease chronic diarrhea hepatitis A1-antitrypsin deficiency, which may cause lung and liver disease If your baby’s doctor [healthline.com]

    Late hemorrhagic disease (onset between 8days to 12 weeks) occurs in exclusively breast fed infants who have not received VK prophylaxis at birth or have suffered from chronic diarrhea or cholestatic liver disease [2]. [medresearch.in]

    diarrhea A1-antitrypsin deficiency Hepatitis 0.5mg – 1mg vitamin K IM at birth If Parents Refuse IM Vitamin K: 2 – 4mg PO vitamin K after first feeding then 2mg at 2 – 4 weeks and again at 6 – 8 weeks OR 2 – 4mg PO vitamin K after first feeding then [med.stanford.edu]

    Lack of vitamin K administration at birth, exclusive breast feeding, chronic diarrhea and prolonged use of antibiotics make them more prone to vitamin K deficiency bleeding [ 4 ]. [panafrican-med-journal.com]

    Lack of vitamin K administration on birth, exclusive breast feeding, chronic diarrhea and prolong use of antibiotics make them more prone to vitamin K deficiency. [alliedacademies.org]

  • Hematemesis

    […] posterior fossa hemorrhage of newborn P52.8 Other intracranial (nontraumatic) hemorrhages of newborn P52.9 Intracranial (nontraumatic) hemorrhage of newborn, unspecified P53 Hemorrhagic disease of newborn P54 Other neonatal hemorrhages P54.0 Neonatal hematemesis [icd10data.com]

    It can present as umbilical stump hemorrhage, hematemesis, malena, ecchymoses, epistaxis, bleeding from venepuncture sites, etc. It can also present with convulsion, poor sucking, irritability and pallor. [alliedacademies.org]

  • Rectal Bleeding

    The remaining had skin haemorrhage and rectal bleeding. [pjms.com.pk]

    ( K29.01 ) ulcerative enterocolitis with rectal bleeding ( K51.01 ) disease D69.9 ICD-10-CM Diagnosis Code D69.9 Hemorrhagic condition, unspecified 2016 2017 2018 2019 Billable/Specific Code newborn P53 Icterus - see also Jaundice hemorrhagic (acute) [icd10data.com]

Skin

  • Petechiae

    At that time, he was noted to have palatal petechiae and a rapid strep was performed which was negative. He was discharged home with the diagnosis of a possible viral infection versus onset of colic. [thefreelibrary.com]

Neurologic

  • Intracranial Hemorrhage

    Isolated intracranial hemorrhage is a common mode of presentation. [ncbi.nlm.nih.gov]

    A qualitative assessment of platelets concerning mass, as well as their total number is a reliable predictor for intracranial hemorrhage in gram-negative sepsis newborns. [symptoma.com]

    The first case is a previously healthy breastfed male who received one dose of oral vitamin K at birth and developed an intracranial hemorrhage 5 weeks later. [ohsu.pure.elsevier.com]

    At 4 weeks she began bleeding at the umbilicus and 4 days after she suffered an intracranial hemorrhage. [link.springer.com]

  • Irritability

    Signs and symptoms of the patients were convulsions (47%), feeding intolerance and poor sucking (47%), irritability (33%) and pallor (20%). [ncbi.nlm.nih.gov]

    Infants may report with blood-stained sputum, respiratory distress, irritability or melena. If the hemorrhage is significant, the baby will be tachycardic and the blood pressure will be low. [symptoma.com]

    Studies on the initial serum sample revealed vitamin K dependent factors II, VII, IX, and X to be Patient No. 2 A 5-week old infant who was the product of a home birth developed irritability. [thefreelibrary.com]

    It can also present with convulsion, poor sucking, irritability and pallor. Hemorrhagic disease of newborn is seen in 0.25-1.7% of neonates during the first week of life [ 2 ]. [alliedacademies.org]

    […] and symptoms of gastrointestinal bleeding causing bloody stools, abdominal bleeding causing distended abdomen, bleeding into the lung cavity causing breathing difficulty, genitourinary bleeding causing bloody urine, and bleeding into the brain causing irritability [thedoctorwillseeyounow.com]

Workup

When facing a child with evident bleeding, the physician should order a complete coagulation panel, including a complete cell blood count, fibrinogen level, fibrin degradation products, prothrombin time, activated partial thromboplastin time and thrombin clotting time, as well as the international normalized ratio (INR). These tests have orientation values and only point to the existence of a vitamin K deficiency, they do not directly establish the diagnosis. The prothrombin time will be increased, while fibrinogen and platelets are normal. A more useful test is represented by protein induced by vitamin K antagonism, that will be increased, but it is not widely available. Thrombocytopenia or an increased activated partial thromboplastin time are not consistent with hemorrhagic disease of the newborn diagnosis, but rather with antiplatelet antibody maternal transmission by breastfeeding, for instance [7]. Fibrin degradation products are increased in liver diseases, after blood transfusion or in disseminated intravascular coagulation in children. An INR 1.4 or less excludes vitamin K deficiency. Factor VIII may be congenitally low or decreased due to disseminated intravascular coagulation.

A qualitative assessment of platelets concerning mass, as well as their total number is a reliable predictor for intracranial hemorrhage in gram-negative sepsis newborns [8]. If suspected, liver pathology can be demonstrated using classical biochemistry tests and imaging methods like endoscopic retrograde cholangiopancreatography. A liver biopsy is occasionally needed in order to exclude biliary atresia or inherited metabolic liver diseases [9]. In case neurologic symptoms are present and intracranial hemorrhage is suspected, a magnetic resonance imaging cranio- cerebral scan should be performed. Intrathoracic bleeding is ruled out using radiographs and ultrasound examination.

Treatment

This case highlighted the good prognosis of an uncommon complication when prompt diagnosis and appropriate treatment are instituted. The importance of vitamin K prophylaxis to all newborns is emphasized. [ncbi.nlm.nih.gov]

Treatment for vitamin K deficiency bleeding: Specific treatment for VKDB will be determined by your baby's physician based on: your baby's gestational age, overall health, and medical history extent of the disease your baby's tolerance for specific medications [medcentral.org]

Vitamin K deficiency is rare in adults, except in syndromes with poor fat absorption, in liver disease, or during treatment with certain anticoagulant drugs, which interfere with vitamin K metabolism. [britannica.com]

Prognosis

This case highlighted the good prognosis of an uncommon complication when prompt diagnosis and appropriate treatment are instituted. The importance of vitamin K prophylaxis to all newborns is emphasized. [ncbi.nlm.nih.gov]

Prognosis ▪ In the absence of intracranial haemorrhage, the prognosis for vitamin K deficiency bleeding in an otherwise healthy infant is excellent. ▪ Prognosis after intracranial haemorrhage depends on the extent and location of the haemorrhage. ▪ Long-term [slideshare.net]

It contains a complete discussion of the history, etiology, pathology, forms, diagnosis, prognosis and treatment of the group of diseases designated as the syndrome of hemorrhagic disease of the newborn. [jamanetwork.com]

(MCA) Doppler time average mean velocity (TAMV): may occur before precipitation of fetal hydrops 1 increase in fetal middle cerebral arterial (MCA) Doppler peak systolic velocity (PSV): may occur before precipitation of fetal hydrops 2 Treatment and prognosis [radiopaedia.org]

Prognosis The prognosis is good for most affected babies. Intracranial haemorrhage and late VKDB account for the mortality associated with VKDB [ 11 ]. Prevention All forms of VKDB are now far less common due to understanding of the aetiology. [patient.info]

Etiology

Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10coded.com]

Emergency physicians may encounter presentations of bleeding in the neonate that have multifactorial etiologies. [ncbi.nlm.nih.gov]

It contains a complete discussion of the history, etiology, pathology, forms, diagnosis, prognosis and treatment of the group of diseases designated as the syndrome of hemorrhagic disease of the newborn. [jamanetwork.com]

Etiologies and risk factors of three types of hemorrhagic diseases of newborn have been shown in Table 1. [alliedacademies.org]

Etiology Vitamin K is required for production of coagulation factors II., VII., IX. and X. in the liver Newborns are relatively vitamin K deficient because of low vitamin K stores at birth low levels of vitamin K in the breast milk sterility of the intestine [atlases.muni.cz]

Epidemiology

Robison, Epidemiology of Leukemia in Childhood, Oncology of Infancy and Childhood, 10.1016/B978-1-4160-3431-5.00001-7, (1-25), (2009). Martin J. Shearer, Vitamin K deficiency bleeding (VKDB) in early infancy, Blood Reviews, 23, 2, (49), (2009). [doi.org]

Epidemiology [ 2 ] In the UK, VKDB is very rare with most cases occurring in breastfed babies whose parents have refused prophylaxis. The incidence internationally of early VKDB of at-risk neonates (see Risk factors, below) ranges from 6-12%. [patient.info]

A few case reports are available of late HDN in babies even after receiving injection vitamin K. 14 An epidemiological study from Germany by von Kries 15 showed a failure rate (occurrence of late HDN) of 0.25 per 100,000 infants after IM administration [pjms.com.pk]

Our purpose was to describe the epidemiological, diagnostic, and common causes of new-bornhaemorrhagic syndrome in paediatric emergency medical department of the Rabat Children's Hospital. [panafrican-med-journal.com]

Prevention

The early onset form of the disease may be prevented by giving vitamin K shots to pregnant women who take anti-seizure medications. [nlm.nih.gov]

Our conclusions are that physicians must be alert to mild bleeding in newborns and that prophylaxis with 1 mg of intramuscular vitamin K at birth may be insufficient to prevent late HDN. [ncbi.nlm.nih.gov]

Prevention of vitamin K deficiency in newborns. Br J Haematology. 1999104430-437. [powershow.com]

Although the efficacy of vitamin K prophylaxis in either oral or parenteral forms has been shown to be effective in preventing the early form of VKDB, more research needs to be conducted on the prevention of late VKDB with oral vitamin K. (19-21) If the [thefreelibrary.com]

References

  1. Pichler E, Pichler L. The neonatal coagulation system and the vitamin K deficiency bleeding - a mini review. Wien Med Wochenschr. 2008;158(13-14):385-95.
  2. Shearer MJ. Vitamin K deficiency bleeding (VKDB) in early infancy. Blood Rev. 2009;23(2):49-59.
  3. Pereira SP, Shearer MJ, Williams R, et al. Intestinal absorption of mixed micellar phylloquinone (vitamin K1) is unreliable in infants with conjugated hyperbilirubinaemia: implications for oral prophylaxis of vitamin K deficiency bleeding. Arch Dis Child Fetal Neonatal Ed. 2003;88:F113–18.
  4. von Kries R, Göbel U. Oral vitamin K prophylaxis and late haemorrhagic disease of the newborn. Lancet. 1994;343:352.
  5. Loughan PM, McDougall PN. The efficacy of oral vitamin K1: Implications for future prophylaxis to prevent haemorrhagic disease of the newborn. J Paediatr Child Health. 1993;29:171-6.
  6. Loughnan PM, McDougall PN. Epidemiology of late onset haemorrhagic disease: A pooled data analysis. J Paediatr Child Health. 1993;29:177-81.
  7. Hauschner H, Rosenberg N, Seligsohn U, et al. Persistent neonatal thrombocytopenia can be caused by IgA antiplatelet antibodies in breast milk of immune thrombocytopenic mothers. Blood. 2015;126(5):661-4.
  8. Mitsiakos G, Pana ZD, Chatziioannidis I, et al. Platelet mass predicts intracranial hemorrhage in neonates with gram-negative sepsis. J Pediatr Hematol Oncol. 2015;37 (7):519-23.
  9. Bellini S. What parents need to know about vitamin K administration at birth. Nurs Womens Health. 2015;19(3):261-5.
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