Vitamin K Deficiency Bleeding (Hemorrhagic Disease of the Newborn)

What is the hemorrhagic disease of the newborn?

Hemorrhagic disease of the newborn (HDN) is a bleeding disorder that occurs in newborns. It is caused by a deficiency of vitamin K, which is an essential nutrient for blood clotting.

What causes vitamin K deficiency in newborns?

In haemorrhagic disease of the newborn, vitamin K-dependent factors are low at birth and fall further in breast-fed infants in the first few days of life. Newborns are born with low levels of vitamin K because the placenta does not transfer vitamin K well from the mother to the fetus. Vitamin K is also not well absorbed from breast milk. Liver cell immaturity, lack of gut bacterial synthesis of the vitamin and low quantities in breast milk may all contribute to a deficiency which may cause hemorrhage, usually on the 2nd – 4th day of life. 

Vitamin K is needed for the production of several clotting factors, including prothrombin and factors VII, IX, and X. These clotting factors are needed for the formation of a blood clot.

Without enough vitamin K, newborns are at risk of bleeding. This bleeding can occur anywhere in the body, but it is most common in the brain and intestines.

The vitamin K cycle

The vitamin K cycle is a complex biochemical process that is essential for blood clotting. It is also involved in bone health and other cellular functions.

The vitamin K cycle can be divided into two main parts: the carboxylation of vitamin K-dependent proteins and the recycling of vitamin K epoxide.

Image depicting the intricate Vitamin K cycle, highlighting the roles of vitamin K epoxide reductase, vitamin K quinone, and γ-carboxyglutamate carboxylase
This illustration reveals the interplay of key players, including vitamin K epoxide reductase, vitamin K quinone, and γ-carboxyglutamate carboxylase, as they orchestrate the production of essential coagulation factors.

Carboxylation of vitamin K-dependent proteins

Vitamin K is required for the carboxylation of glutamic acid residues in certain proteins, including clotting factors, bone matrix proteins, and other cellular proteins. Carboxylation is the addition of a carboxyl group (COO-) to a molecule.

Vitamin K is converted into hydroquinone by a vitamin K reductase. The hydroquinone is an essential cofactor utilized by the vitamin K-dependent carboxylase to catalyze the oxidative fixation of carbon dioxide to specific glutamic acid residues for example a prothrombin precursor to form a γ-carboxyglutamic acid (Gla) residue e.g. prothrombin.  Gla residues are essential for the biological activity of many vitamin K-dependent proteins. Gla residues are also required for the binding of bone matrix proteins to calcium, which is essential for bone health.

 The carboxylation of vitamin K-dependent proteins is catalyzed by a group of enzymes called gamma-glutamyl carboxylases (GGCXs). GGCXs require vitamin K, carbon dioxide, and oxygen to function.

During this reaction, vitamin K is converted to an epoxide, which is then converted back to the quinone by a vitamin K epoxide reductase. This vitamin K-dependent post-translational modification takes place in the Golgi apparatus of many cell types and is restricted to specific domains on a small number of vitamin K-dependent proteins. 

Vitamin K-dependent γ-carboxylation in hepatocytes is necessary for the biologic activity of a number of coagulation factors, including the zymogens prothrombin, factors VII, IX and X, as well as protein C and S. 

Vitamin K dependent factors which are involved in the coagulation pathway. These are important to prevent bleeding in hemorrhagic disease of the newborn
Vitamin K-dependent coagulation factors, including factors II, VII, IX, and X, play a pivotal role in the intricate process of blood clotting. They act as catalysts, orchestrating a series of reactions that culminate in the formation of a fibrin clot, effectively halting bleeding. Vitamin K deficiency in newborns, often resulting from limited placental transfer and underdeveloped gut flora, can lead to hemorrhagic disease of the newborn, characterized by excessive bleeding. Administration of vitamin K at birth effectively prevents this potentially devastating condition.

Recycling of vitamin K epoxide

When vitamin K is used to carboxylate a protein, it is converted to vitamin K epoxide. Vitamin K epoxide is the inactive form of vitamin K.

Vitamin K epoxide can be recycled back to vitamin K by an enzyme called vitamin K epoxide reductase (VKOR). VKOR requires NADPH, a cofactor, to function.

Once vitamin K is recycled, it can be used to carboxylate another protein.

What happens in vitamin K deficiency?

The vitamin K cycle is important for:

  • Blood clotting: Vitamin K is required for the production of several clotting factors, which are essential for blood clotting.
  • Bone health: Vitamin K is required for the binding of bone matrix proteins to calcium, which is essential for bone health.
  • Other cellular functions: Vitamin K is also involved in other cellular functions, such as cell growth and differentiation.

Vitamin K deficiency can lead to a number of problems, including:

  • Bleeding problems: Vitamin K deficiency can lead to bleeding problems, such as easy bruising, nosebleeds, and heavy menstrual periods.
  • Bone problems: Vitamin K deficiency can lead to bone problems, such as osteoporosis and fractures.
  • Other health problems: Vitamin K deficiency has also been linked to other health problems, such as heart disease and cancer.

Vitamin K can be obtained from food and supplements. Good sources of vitamin K include green leafy vegetables, vegetable oils, and meats.

The recommended daily intake of vitamin K for adults is 120 micrograms for men and 90 micrograms for women. Pregnant and breastfeeding women need more vitamin K, 90 micrograms and 120 micrograms per day, respectively.

Most people can get enough vitamin K from their diet. However, some people may need to take a vitamin K supplement, such as people who are taking certain medications that interfere with the absorption of vitamin K.

How is hemorrhagic disease of the newborn diagnosed?

Hemorrhagic disease of the newborn is diagnosed based on the newborn’s medical history, physical examination, and laboratory tests.

Medical history

The doctor will ask the parents about the newborn’s birth history, including the mother’s diet during pregnancy and any medications she took. The doctor will also ask about the newborn’s family history of bleeding disorders.

Physical examination

The doctor will perform a physical examination of the newborn to look for signs of bleeding, such as bruising, nosebleeds, and bleeding from the umbilical cord. The doctor will also check the newborn’s vital signs, such as heart rate, respiratory rate, and blood pressure.

Laboratory tests

The most important laboratory test for diagnosing hemorrhagic disease of the newborn is the prothrombin time (PT). The PT measures how long it takes for blood to clot. A prolonged PT is a sign of a bleeding disorder, such as hemorrhagic disease of the newborn. However, the platelet count is normal. Both the PT and APTT time are abnormal with normal platelet count and fibrinogen and absence of fibrin degradation products. 

Other laboratory tests that may be helpful in diagnosing this disorder include:

  • Activated partial thromboplastin time (APTT): This test measures how long it takes for blood to clot in the presence of certain clotting factors. A prolonged APTT may be a sign of a bleeding disorder.
  • Vitamin K level: This test measures the amount of vitamin K in the blood. A low vitamin K level may be a sign of hemorrhagic disease of the newborn.
  • Fibrinogen count is normal.
  • Absence of fibrin degradation products: The presence of FDPs in the blood indicates that fibrin clots are being broken down, which can lead to further bleeding. Therefore, the absence of FDPs in this disorder is a good sign, indicating that the newborn’s blood clotting system is working properly and that the bleeding is likely to stop on its own.

Differential diagnosis

There are a number of other conditions that can cause bleeding in newborns, including:

  • Thrombocytopenia: This is a condition in which there is a low platelet count. Platelets are blood cells that help blood clots.
  • Disseminated intravascular coagulation (DIC): This is a condition in which blood clots form throughout the body, blocking blood vessels and preventing blood from flowing properly.
  • Liver disease: The liver produces several clotting factors. Liver disease can damage the liver and reduce the production of clotting factors.
  • Genetic bleeding disorders: There are a number of genetic bleeding disorders that can cause bleeding in newborns, such as hemophilia and von Willebrand disease.

If the newborn has a bleeding disorder that is not caused by HDN, the doctor will recommend additional tests and treatment to manage the disorder.

How do we treat hemorrhagic disease of the newborn?


The treatment for HDN is a single injection of vitamin K. The injection is usually given to the newborn within a few hours of birth.

In some cases, newborns with HDN may need to be given additional injections of vitamin K, or they may need to be given blood transfusions.


HDN can be prevented by giving all newborns a single injection of vitamin K shortly after birth. The injection is safe and effective.

Key points of hemorrhagic disease of the newborn


A bleeding disorder that occurs in newborns caused by vitamin K deficiency. 


  • Liver cell immaturity
  • Lack of gut bacterial synthesis
  • Low quantities in breastmilk

Laboratory diagnosis

  • Abnormal PT and APTT
  • Platelet count and fibrinogen normal
  • FDP absent


  • IM prophylaxis

Disclaimer: This article is intended for informational purposes only and is specifically targeted towards medical students. It is not intended to be a substitute for informed professional medical advice, diagnosis, or treatment. While the information presented here is derived from credible medical sources and is believed to be accurate and up-to-date, it is not guaranteed to be complete or error-free. See additional information.


  1. Kher P, Verma RP. Hemorrhagic Disease of Newborn. 2023 Jun 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 32644420.
  2. Ng E, Loewy AD. Guidelines for vitamin K prophylaxis in newborns. Paediatr Child Health 2018, 23(6):394–397. 
  3. Goldberg S, Hoffman J. Clinical Hematology Made Ridiculously Simple, 1st Edition: An Incredibly Easy Way to Learn for Medical, Nursing, PA Students, and General Practitioners (MedMaster Medical Books). 2021.
  4.  Keohane EM, Otto CN, Walenga JM. Rodak’s Hematology 6th Edition (Saunders). 2019.
  5. Hoffman R, Benz EJ, Silberstein LE, Heslop H,Weitz J, Anastasi J. Hematology: Diagnosis and Treatment E-Book (Hematology Basic Principles and Practice) 6th Edition (Churchill Livingstone). 2013.

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