Vitamin K deficiency bleeding (VKDB) of the newborn, previously known as haemorrhagic disease of the newborn, is a rare form of bleeding disorder that affects newborns and young infants due to low stores of

vitamin K Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation ...

at birth. It commonly presents with

intracranial haemorrhage Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. Subtypes are intracerebral bleeds (intraventricular bleeds and intraparenchymal bleeds), subarachnoid bleeds, epidural bleeds, and subdural bleeds ...

with the risk of brain damage or death. Newborn infants have low stores of vitamin K, and human breast milk has low concentrations of the vitamin. This combination can lead to vitamin K deficiency and later onset bleeding. Vitamin K deficiency leads to the risk of blood coagulation problems due to impaired production of clotting factors II, VII, IX, X,

protein C Protein C, also known as autoprothrombin IIA and blood coagulation factor XIX, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and cell death and maintainin ...

and protein S by the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

. More rarely VKDB can be caused by maternal medicines causing vitamin K deficiency in the newborn. VKDB can largely be prevented by prophylactic supplementation of vitamin K, which is typically given shortly after birth by intramuscular injection. Most national health organisations recommend routine vitamin K supplementation after birth. Widespread use of this has made this a rare disease.

Classification

VKDB is classified as early, classical or late depending on when it first starts with each having somewhat different types of bleeding and underlying cause:

Signs and symptoms

VKDB presents typically in the first month of life with bleeding which can be from various locations. Late onset VKDB presents with bleeding into the brain (

) in more than half of cases.

Causes

Newborns are relatively vitamin K deficient for a variety of reasons: They have low vitamin K stores at birth as vitamin K passes the

placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mate ...

poorly. Levels of vitamin K in human

breast milk Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by mammary glands located in the breast of a human female. Breast milk is the primary source of nutrition for newborns, containing fat, protein, carbohydrates ( la ...

are low.

Gut flora Gut microbiota, gut microbiome, or gut flora, are the microorganisms, including bacteria, archaea, fungi, and viruses that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut m ...

, that in adults produces vitamin K, has not yet developed. Early VKDB is rare and caused by maternal medications that interact with vitamin K such as

warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent st ...

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The in ...

, or

rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. It is almost always used t ...

. Classical VKDB is more common and caused by the relative deficiency at birth with inadequate vitamin K intake. This is often termed idiopathic as no one cause is found. Late VKDB presents after day 8 and up to 6 months of age, coinciding with the typical age for exclusive breast feeding due to the low levels of vitamin K in human breast milk. Many of these infants have poor vitamin K absorption due to

cholestasis Cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system that can occur from a gallstone or malig ...

which compounds low intake.

Diagnosis

Bleeding in an infant without vitamin K supplementation with elevated

prothrombin time The prothrombin time (PT) – along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) – is an assay for evaluating the ''extrinsic'' pathway and common pathway of coagulation. This blood test is als ...

(PT) that is corrected by vitamin K administration is typically sufficient to make the diagnosis. Confirmation, or investigation of minor deficiency, can be performed by testing proteins produced in the absence of vitamin K, the most established assay being for PIVKA-II.

Prevention

Late onset VKDB is nearly completely prevented by early supplementation of vitamin K which is typically given to newborns shortly after birth. The most effective method of administration is by intramuscular injection shortly after birth but it can be given orally in three doses over the first month. It is not possible to reliably distinguish which infants are at high risk of late VKDB and the potential consequences are high, as such most national health organisations recommend routine supplementation in the first 24 hours of life.

Controversy

Controversy arose in the early 1990s regarding routine supplementation, when two studies suggested a relationship between

parenteral A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...

administration of vitamin K and childhood cancer. However, both studies have been discredited on the basis of poor methodology and small sample sizes, and a review of the evidence published in 2000 by Ross and Davies found no link between the two.

Treatment

Treatment of established bleeding depends on the location but includes vitamin K₁ (phylloquinone; phytomenadione; phytonadione) administration which restores the prothrombin time rapidly. Severe bleeding may require blood products such as fresh frozen plasma (FFP), a

prothrombin complex concentrate Prothrombin complex concentrate (PCC), also known as factor IX complex, is a medication made up of blood clotting factors II, IX, and X. Some versions also contain factor VII. It is used to treat and prevent bleeding in hemophilia B if pure ...

(PCC).

References

External links

{{Certain conditions originating in the perinatal period Haemorrhagic and haematological disorders of fetus and newborn Neonatology