Hemorrhagic Disease Of Newborn

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Continuing Education Activity

Hemorrhagic disease of the newborn is a life-threatening condition that is due to insufficient vitamin K levels in newborns as a result of various causes. Proper management of the disease can help reduce disease incidence. This activity outlines the evaluation and treatment of hemorrhagic disease of the newborn and explains the role of the interprofessional team in managing patients with this condition.


  • Identify the etiology of hemorrhagic disease of the newborn.
  • Outline the presentation of a patient with hemorrhagic disease of the newborn.
  • Describe the management options available for hemorrhagic disease of the newborn.
  • Explain the importance of improving care coordination amongst the interprofessional team to enhance the delivery of care for patients with hemorrhagic disease of the newborn.


Hemorrhagic disorder of the newborn is a bleeding disorder that manifests in the first few weeks of life after delivery. The term hemorrhagic disorder of the newborn encompasses all hemorrhagic diseases, i.e., due to vitamin K deficiency, trauma, clotting factor deficiency, etc. When the cause is vitamin K deficiency, it is referred to as vitamin K deficiency bleeding or VKDB. Vitamin K is a fat-soluble vitamin mainly synthesized in adults by gut bacteria. Newborns, however, have minimal vitamin K reserves in their liver during the time of delivery and are not able to synthesize vitamin K due to a sterile gut. Hence they are at risk of developing the hemorrhagic disease of the newborn. One of the main functions of vitamin K is gamma-carboxylation of coagulant factors- 2,7,9 and 10. This converts inactive clotting factors into an active state. Deficiency leads to the inadequate activity of these clotting factors, which results in bleeding.

Hemorrhagic disease of the newborn can be categorized into three groups. These groups are separated based on the age of onset.[1]

  1. Early: Occurs within the first 24 hours of birth, can also occur in-utero or during delivery.
  2. Classical: 1 week of neonatal life (2nd through 7th day)
  3. Late: From 8 days to up to 6-12 months.[2]


The etiology for vitamin K deficiency can be grouped as idiopathic or secondary. The etiology of idiopathic causes is not known, but a few of the secondary causes have been explored. Vitamin K deficiency leads to decreased activity of clotting factors, resulting in hemorrhagic disease of the newborn. Adults can synthesize vitamin K in the large intestine through the gut bacteria, but neonates have reduced stores of vitamin K due to insufficient placental transfer and a sterile gut that fails to synthesize the necessary levels of vitamin K. Additionally, breast milk is deficient in vitamin K and poor hepatic storage.[3][4]

Vitamin K deficiency can manifest in babies born to mothers on anti-tubercular drugs (isoniazid, rifampicin), antiepileptics (phenytoin, barbiturates, and carbamazepine), broad-spectrum antibiotics (cephalosporins), or vitamin K antagonists such as warfarin.[2] Infants born with malabsorption diseases such as cystic fibrosis or hepatobiliary diseases such as biliary atresia have also been shown to develop vitamin K deficiency. Mutations in genes encoding for the gamma-glutamyl carboxylase and epoxide reductase have also been reported.[5]


All infants irrespective of race, sex, color, religion, national origin, etc. are known to be affected by vitamin K deficiency bleeding. However, in a study conducted on 50 newborns, VKDB was found to have an increased incidence amongst male infants, breastfed infants, and those born via spontaneous vaginal delivery.[6]

In early VKDB, the incidence in infants who have not received vitamin K prophylaxis ranges from about 6% to 12%. In classic VKDB, the incidence has gone down from 0.25% to 1.5% in earlier studies to 0.01% to 0.44% in recent studies. This has been achieved due to the inclusion of vitamin K prophylaxis in routine newborn care. In late VKDB, the incidence is 1 in 15,000 to 1 in 20,000 births and is seen predominantly in exclusively breastfed babies or babies with cholestasis or malabsorption (as vitamin K absorption is dependent on bile). The most common presenting symptom of late VKDB is intracranial bleeding, which has a mortality of 20%–50% and associated morbidity.[4]


Vitamin K is a fat-soluble vitamin that occurs in 2 forms- vitamin K1 or phylloquinone (present in green leafy vegetables) and vitamin K2 or menaquinone (synthesized by the gram-negative bacteria in the intestines).[7][8] Although vitamin K has many other roles in the body, its major role involves the activation of clotting factors. It does so by gamma-carboxylation of glutamic acid residues of clotting factors 2,7,9 and 10 via post-translational modification.[9]

A deficiency of vitamin K in the body leads to inadequate activation of these clotting factors and hence leads to bleeding in the body, which manifests as hemorrhagic disease of the newborn or, more specifically, known as VKDB.

History and Physical

If VKDB is suspected, it is important to take a proper history. The following points in the history that could lead to a proper diagnosis include:

  1. Drugs taken during pregnancy- anticonvulsants, anti-tubercular drugs, warfarin, salicylates, etc.
  2. Gestation period- preterm babies are at a higher risk of having VKDB.
  3. If breastfed or bottle-fed- as bottle/formula-fed infants are at lower risk due to fortified feedings with essential vitamins and minerals.
  4. Place of delivery- generally home-delivered infants do not have access to immediate vitamin K prophylaxis and hence are at a greater risk.

Physical findings in a patient with VKDB are:

  1. Cephalhematoma
  2. Intracranial bleeding
  3. Intrathoracic bleeding, which can cause hemoptysis, and associated respiratory distress
  4. Intra-abdominal bleeding- melena or hematemesis
  5. Bleeding from the skin- petechiae present over the skin
  6. Bleeding from mucous membranes, including the gums, nose, etc.
  7. Bleeding after circumcision
  8. Bleeding from the umbilical stump after cutting the umbilical cord at birth
  9. Bleeding from vaccination sites[10]

Intracranial bleeding is mostly associated with late VKBD and presents with a floppy baby, lethargy, feeding difficulties, bulging fontanelles, decreased respiratory rate, altered consciousness, convulsions, or pallor.[11]


History, physical examination, and laboratory investigations, along with any significant radiological findings, can help to arrive at the diagnosis early and start treatment.

Most commonly advised laboratory tests are:

1. Complete blood count- will have normal platelet levels (1.5-4 lacs/cubic mm)

2. Clotting profile:

  • International normalized ratio (INR) greater than or equal to 4
  • Prothrombin time (PT) more than 4 times the normal[4]
  • Prothrombin time will be increased due to decreased activity of factor 7
  • Partial thromboplastin time (PTT) will also be increased due to decreased activity of factors 2,9 and 10
  • Clotting time will be increased due to clotting factor deficiency
  • Fibrinogen levels will remain normal

3. Protein induced by vitamin K antagonist (PIVKA) estimation- PIVKA are proteins induced in vitamin K absence. These are evaluated by HPLC (high-pressure liquid chromatography), ELISA (enzyme-linked immunosorbent assay), or immuno-electrophoresis. Any amount of PIVKA is abnormal and indicates vitamin K deficiency.[3] It disappears around day 5 of the administration of vitamin K.[12]

4. Chest X-ray or ultrasound to determine if there is bleeding in body cavities- intrathoracic, intra-abdominal

5. Computed tomography (CT) and magnetic resonance imaging (MRI) studies to evaluate for intracranial hemorrhage

Treatment / Management

Treatment of VKDB mainly focuses on prompt administration of vitamin K to the infant and then further investigation for the cause of the disease.

In cases of severe life-threatening bleeding, immediate blood transfusions can be given along with fresh frozen plasma to reduce the bleeding.

Late VKDB can present with intracranial hemorrhage. The most common form being sub-dural hemorrhage may require surgical evacuation or intracranial shunting to relieve increased intracranial pressure and associated symptoms.[13]

Late VKDB can also present with neurological abnormalities despite treatment that will require regular follow-up and continuous monitoring. Physiotherapy can be advised to retain/strengthen neural function. If unable to suck or swallow, babies may require nutritional assistance.

Nonetheless, a single intramuscular (IM) dose of 1 mg of vitamin K is known to improve the coagulation profile within 1 to 7 days.[14]

Infants not protected from VKBD through prophylaxis may have unrecognized liver disease.

Differential Diagnosis

The most common differential for VKDB is trauma- accidental or non-accidental injury. Other differentials include:

  • Clotting factor deficiencies such as hemophilia A or hemophilia B. Non-reversal of condition despite administering clotting factors may help to determine the exact cause.
  • Disseminated intravascular coagulation (DIC)- running laboratory studies will help to differentiate between DIC and VKDB.
  • Thrombocytopenia, especially maternal immune thrombocytopenia as antibodies to platelets, can cross the placenta and decrease infant platelet count manifesting as purpura. However, in VKDB, the platelet count is generally normal.
  • For infants presenting with isolated gastrointestinal bleed, intussusception can be a differential.

However, based on laboratory studies, it becomes easier to arrive at the diagnosis and treat the disease accordingly.

Treatment Planning

For early and classic forms of hemorrhagic disease of the newborn, the treatment is with oral vitamin K (2mg dose) repeated at 2-4 weeks and at 6-8 weeks.

For the late form of the disease, oral vitamin K is not as efficacious as parenteral, and hence currently, 0.5-1 mg single IM dose is administered to infants.[2] 

For infants weighing less than 1500 gm, 0.5 mg IM single dose is given.

For infants weighing more than 1500 gm, 1 mg IM single dose is given.[12]

All breastfed babies with diarrhea and malabsorption require an additional post-natal dose of vitamin K to prevent late vitamin K deficiency bleeding.[3]

In the case of life-threatening hemorrhages, 10-20 ml/kg of fresh frozen plasma should also be administered.

More than 20% of blood loss and features of shock require immediate blood transfusions.[3]

Toxicity and Side Effect Management

There is no known toxicity or side effects associated with vitamin K1. Vitamin K1 is a naturally occurring, fat-soluble form of vitamin K. Before the introduction of vitamin K1, vitamin K3 was used. Vitamin K3 is a synthetic, water-soluble derivative of menadione. In higher doses, it has been associated with kernicterus, hemolytic anemia, and hyperbilirubinemias.[3]

Vitamin K was earlier thought to be associated with an increased risk of childhood cancers. However, studies have shown no such association.[15]

Due to having a safe profile, vitamin K1 is widely accepted as routine prophylaxis in most countries.[1]


Vitamin K prophylaxis at birth has proven to significantly improve the prognosis by decreasing mortality. Patients presenting with intracranial hemorrhage might have associated morbidity in the form of neurological damage. However, vitamin K has reduced the incidence of hemorrhagic disease of the newborn, and its usage should be continued as effective prophylaxis.[14]


The most important complication of hemorrhagic disease of the newborn is bleeding, which can often be fatal in infants. It is one of the most important causes of intracranial hemorrhage in the first year of life.[16]

Morbidity is generally seen with late vitamin K deficiency bleeding, and it manifests as neurological defects such as hydrocephalus, encephalopathy, cerebral atrophy, seizures, and severe developmental delay.[4]


Consultations with neonatology, pediatrics, transfusion medicine, clinical pathology, and hematology are critical for the early detection and diagnosis of vitamin K deficiency bleeding. Routine follow-up should be scheduled to reduce morbidity and mortality.

Deterrence and Patient Education

Healthcare workers should work closely with the parents to make them understand the need for vitamin K prophylaxis and the severity of the disease. The benefit of using IM vitamin K injections should be explained to the parents. For those who refuse injection, counseling about the adverse effects of vitamin K deficiency should be explained. The alternate oral dose (2 mg) should also be recommended, along with the repetition of the dose at 2 to 4 and 6 to 8 weeks of age.[17]

Pearls and Other Issues

Breast milk is particularly deficient in vitamin K, and hence prophylaxis at birth will go a long way in preventing the disease. However, as certain studies have found, formula-fed babies do not suffer from vitamin K deficiency as formula milk is already fortified with minerals and vitamins in sufficient quantities.[8] According to a study conducted, formula-fed infants were found to have higher vitamin K1 fecal concentrations than breast-fed infants.

Enhancing Healthcare Team Outcomes

Hemorrhagic disease of the newborn is a life-threatening condition associated with high mortality and morbidity. But, it can easily be prevented by administering 1 mg IM of vitamin K within 1 hour of birth.

Early and prompt diagnosis of hemorrhagic disease of the newborn can alleviate the devastating consequences. Strong interprofessional communication and care coordination by clinicians, nurses, and pharmacists can help improve outcomes and ensure patient safety. Parents should be counseled regarding the condition, and the severity and follow-up routine with the clinician should be scheduled on a regular basis to check the well-being of the patient.

Article Details

Article Author

Pawani Kher

Article Editor:

Rita P. Verma


6/27/2022 11:48:32 PM



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