Sections

Workup

Approach Considerations

A full coagulopathy work-up and hematology consultation are required if clinical and laboratory findings are suggestive of non–vitamin K deficiency bleeding.

If liver disease is suspected, a work-up that includes functional tests and imaging are mandatory.

Hereditary defects in the coagulation system must always be considered among the differential diagnosis.

If the cause of bleeding is not straightforward, clinicians may need to perform other procedures like endoscopic retrograde cholangiopancreatography (ERCP) to rule out hepatobiliary diseases.

If liver biopsy is indicated, histopathology with and without special stains or biochemical analyses may be helpful to rule out hepatitis, biliary atresia,^{[27, 28]} tumors, and inherited metabolic diseases of the liver.

Coagulations studies

A prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen levels, and a platelet count should be included in the initial workup for vitamin K deficiency bleeding (VKDB) in a newborn. A thrombin clotting time (TCT) is optional.

Note the following:

A prolonged PT is usually the first laboratory test result to be abnormal in vitamin K deficiency bleeding; however, no laboratory test result can confirm the diagnosis of vitamin K deficiency bleeding.
A direct blood measurement of vitamin K is not useful, because its levels normally are low in newborns.
Levels of protein induced by vitamin K antagonism (PIVKA II) are increased in vitamin K deficiency bleeding, but this study is generally not available outside of research laboratories.
Infants with vitamin K deficiency bleeding typically have a prolonged PT with platelet counts and fibrinogen levels within the normal range for newborns. The presence of thrombocytopenia or a prolonged aPTT should prompt workup for other causes of bleeding during the neonatal period. For example, maternal transfer of antiplatelet antibodies in mothers with immune thrombocytopenia via breastfeeding may be associated with persistent neonatal thrombocytopenia.^[29]

The diagnosis of vitamin K deficiency bleeding is confirmed if administration of vitamin K halts the bleeding and reduces the PT value.

There appears to be a significant association between median platelet count and platelet mass with intracranial hemorrhage in neonates at days 1, 2, and 3 after diagnosis of gram-negative sepsis.^[30]

Imaging Studies

Intracranial bleeding is rare and usually associated with other causes of bleeding, particularly thrombocytopenia; however, intracranial hemorrhage has been reported in vitamin K deficiency bleeding (VKDB) and can be fatal.

Neonatal sepsis due to gram-negative bacteria (eg, Enterobacter species) is also a cause of intracranial bleeding.^[30]

Investigate any neurologic symptoms with imaging. Magnetic resonance imaging (MRI) does not expose the neonate to radiation, and this imaging modality is becoming the preferred way to study the brain because tissue damage can be better defined.

Treatment & Management

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Media Gallery

Vitamin K cycle. CO<sub>2 </sub> = carbon dioxide; NAD+ = oxidized nicotinamide adenine dinucleotide; NADH = reduced nicotinamide adenine dinucleotide; O<sub>2 </sub> = oxygen; and PIVKA = protein-induced by vitamin K absence.

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Author

Dharmendra J Nimavat, MD, FAAP Associate Professor of Clinical Pediatrics, Department of Pediatrics, Division of Neonatology, Southern Illinois University School of Medicine; Staff Neonatologist, Clinical Director, NICU Regional Perinatal Center, HSHS St John's Children's Hospital

Dharmendra J Nimavat, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association of Physicians of Indian Origin

Disclosure: Nothing to disclose.

Coauthor(s)

Michael P Sherman, MD, FAAP † Former Professor, Department of Child Health, University of Missouri-Columbia School of Medicine; Neonatologist, Women’s and Children’s Hospital; Professor Emeritus, Department of Pediatrics, University of California, Davis, School of Medicine

Michael P Sherman, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, American Thoracic Society, European Society for Paediatric Research, Pediatric Infectious Diseases Society, Perinatal Research Society, Society for Pediatric Research, Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David A Clark, MD Professor and Martha Lepow Chairman of Pediatrics, Professor of Obstetrics and Gynecology, Albany Medical College; Director, Children's Hospital at Albany Medical Center

David A Clark, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Forestry Association, American Pediatric Society, Capital District Pediatric Society, Christian Medical and Dental Associations, European Society for Paediatric Research, Eastern Society for Pediatric Research, Floyd W Denny Pediatric Alumni Society, Medical Society of the State of New York, New York Academy of Sciences, Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Santina A Zanelli, MD Associate Professor, Department of Pediatrics, Division of Neonatology, University of Virginia Health System

Santina A Zanelli, MD is a member of the following medical societies: American Academy of Pediatrics, American Epilepsy Society, Society for Neuroscience, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Oussama Itani, MD, FAAP, FACN Clinical Associate Professor of Pediatrics and Human Development, Michigan State University; Medical Director, Department of Neonatology, Borgess Medical Center

Oussama Itani, MD, FAAP, FACN is a member of the following medical societies: American Academy of Pediatrics, American Association for Physician Leadership, American Heart Association, American College of Nutrition

Disclosure: Nothing to disclose.

Acknowledgements

The authors appreciate the review of this article and helpful suggestions for improvement from Professor Daniel Batton, the Director of the Neonatology Division at Southern Illinois University School of Medicine.

Vitamin K Deficiency Bleeding Workup

Approach Considerations

Laboratory Studies

Coagulations studies

Imaging Studies

Vitamin K Deficiency Bleeding Workup

Approach Considerations

Laboratory Studies

Coagulations studies

Imaging Studies

References

Tables

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