History

The clinical manifestations of vitamin K (VK) deficiency are evident only if hypoprothrombinemia is present. Bleeding is the major symptom, especially in response to minor or trivial trauma. Any site can be involved, so manifestations can include mucosal and subcutaneous bleeding, such as epistaxis, hematoma, gastrointestinal bleeding, menorrhagia, hematuria, gum bleeding, and oozing from venipuncture sites. Easy bruisability also is observed.^[20]

Physical Examination

Ecchymosis, petechiae, hematomas, and oozing of blood at surgical or puncture sites are observed. In infants, some birth defects, such as underdevelopment of the face, nose, bones, and fingers, are linked to a VK-deficient state. Infants may present with nontraumatic intracranial bleeding with signs such as vomiting, poor intake, anemia, seizures, and bleeding in mucosal sites.

Complications

The characteristics of vitamin K (VK) deficiency vary according to the age of onset. In infants, its deficiency causes hemorrhagic disease of newborn, resulting in intracranial and retroperitoneal bleeding, which can occur at 1-7 days postpartum. Late hemorrhagic disease of newborn can occur as late as 3 months postpartum. (See Presentation and Workup.)^{[21, 22]}

Because VK is involved in gamma carboxylation of osteocalcin, which is important in bone synthesis, osteoporosis is associated with VK deficiency.^{[23, 24, 25]} Osteocalcin is important in the remodeling and mineralization of bone.

Differential Diagnoses

Suttie JW. Vitamin K. Machlin L, ed. Handbook of Vitamins. New York, NY: Marcel Dekker; 1984. 147.
Van Winckel M, De Bruyne R, Van De Velde S, et al. Vitamin K, an update for the paediatrician. Eur J Pediatr. 2008 Nov 4. [QxMD MEDLINE Link].
Shearer MJ. Vitamin K deficiency bleeding (VKDB) in early infancy. Blood Rev. 2008 Sep 18. [QxMD MEDLINE Link].
van Hasselt PM, de Koning TJ, Kvist N, et al. Prevention of vitamin K deficiency bleeding in breastfed infants: lessons from the Dutch and Danish biliary atresia registries. Pediatrics. 2008 Apr. 121(4):e857-63. [QxMD MEDLINE Link].
Burke CW. Vitamin K deficiency bleeding: overview and considerations. J Pediatr Health Care. May-June 2013. 27:215-21. [QxMD MEDLINE Link].
Maldonado M, Alhousseini A, Awadalla M, Idler J, Welch R, Puder K, et al. Intrahepatic Cholestasis of Pregnancy Leading to Severe Vitamin K Deficiency and Coagulopathy. Case Rep Obstet Gynecol. 2017. 2017:5646247. [QxMD MEDLINE Link].
Mihatsch WA, Braegger C, Bronsky J, Campoy C, Domellöf M, Fewtrell M, et al. Prevention of Vitamin K Deficiency Bleeding in Newborn Infants: A Position Paper by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2016 Jul. 63 (1):123-9. [QxMD MEDLINE Link].
Krasinski SD, Russell RM, Furie BC. The prevalence of vitamin K deficiency in chronic gastrointestinal disorders. Am J Clin Nutr. 1985 Mar. 41(3):639-43. [QxMD MEDLINE Link]. [Full Text].
Liebman HA, Furie BC, Tong MJ. Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med. 1984 May 31. 310(22):1427-31. [QxMD MEDLINE Link].
[Guideline] American Academy of Pediatrics Committee on Fetus and Newborn. Controversies concerning vitamin K and the newborn. American Academy of Pediatrics Committee on Fetus and Newborn. Pediatrics. 2003 Jul. 112 (1 Pt 1):191-2. [QxMD MEDLINE Link].
Vitamin K Shot – Essential in Preventing Serious Bleeding in Newborns. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/healthcommunication/toolstemplates/entertainmented/tips/kvitamin.html. June 23, 2014; Accessed: August 30, 2017.
Beutler E, Lichtman MA, Coller BS. Disorders of the vitamin K dependent coagulation factors. Williams Hematology. 5th ed. New York, NY: McGraw-Hill; 1995. 1481-5.
Furie B, Furie BC. Molecular basis of vitamin K-dependent gamma-carboxylation. Blood. 1990 May 1. 75(9):1753-62. [QxMD MEDLINE Link]. [Full Text].
Udall JA. Human sources and absorption of vitamin K in relation to anticoagulation stability. JAMA. 1965 Oct 11. 194(2):127-9. [QxMD MEDLINE Link].
Booth SL, Al Rajabi A. Determinants of vitamin K status in humans. Vitam Horm. 2008. 78:1-22. [QxMD MEDLINE Link].
Ansell JE, Kumar R, Deykin D. The spectrum of vitamin K deficiency. JAMA. 1977 Jul 4. 238(1):40-2. [QxMD MEDLINE Link].
Kristin M McCabe, Michael A. Adams, Rachel M. Holden. Vitamin K Status in Chronic Kidney Disease. Nutrition. November 2013. 5:4390-4398.
Jagannath VA, Fedorowicz Z, Thaker V, Chang AB. Vitamin K supplementation for cystic fibrosis. Cochrane Database Syst Rev. January 18, 2015. 1:1-33. [QxMD MEDLINE Link].
Martin J. Shearer, Xueyan Fu, Sarah L. Booth. Vitamin K Nutrition, Metabolism, and Requirement: Current Concept and Future Research. Advances in Nutrition. 2012. 3:182-195.
Lee GR, Bithell TC, Forester J. Acquired coagulation disorders. Wintrobe's Clinical Hematology. Baltimore, Md: Williams & Wilkins; 1993: 1473-80.
Ozdemir MA, Karakukcu M, Per H, Unal E, Gumus H, Patiroglu T. Late-type vitamin K deficiency bleeding: experience from 120 patients. Childs Nerv Syst. 2011 Sep 18. [QxMD MEDLINE Link].
Takahashi D, Shirahata A, Itoh S, Takahashi Y, Nishiguchi T, Matsuda Y. Vitamin K prophylaxis and Late Vitamin K deficiency bleeding in infants: The 5th nation-wide survey in Japan. Pediatr Int. 2011 Apr 22. [QxMD MEDLINE Link].
Furie B. Vitamin K: metabolism and disorders. Hoffman R, Benz EJ, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone; 2000. 1958-62.
Nakajima S, Iijima H, Egawa S, Shinzaki S, Kondo J, Inoue T, et al. Association of vitamin K deficiency with bone metabolism and clinical disease activity in inflammatory bowel disease. Nutrition. 2011 Oct. 27(10):1023-8. [QxMD MEDLINE Link].
Vermeer C, Theuwissen E. Vitamin K, osteoporosis and degenerative diseases of ageing. Menopause Int. 2011 Mar. 17(1):19-23. [QxMD MEDLINE Link].
van Hoorn JH, Hendriks JJ, Vermeer C, Forget PP. Vitamin K supplementation in cystic fibrosis. Arch Dis Child. 2003 Nov. 88 (11):974-5. [QxMD MEDLINE Link].
Phillippi JC, Holley SL, Morad A, Collins MR. Prevention of Vitamin K Deficiency Bleeding. J Midwifery Womens Health. 2016 Jul 7. 9:25-6. [QxMD MEDLINE Link].
Sankar MJ, Chandrasekaran A, Kumar P, Thukral A, Agarwal R, Paul VK. Vitamin K prophylaxis for prevention of vitamin K deficiency bleeding: a systematic review. J Perinatol. 2016 May. 36 Suppl 1:S29-35. [QxMD MEDLINE Link].
Golding J, Paterson M, Kinlen LJ. Factors associated with childhood cancer in a national cohort study. Br J Cancer. 1990 Aug. 62 (2):304-8. [QxMD MEDLINE Link].
Klebanoff MA, Read JS, Mills JL, et al. The risk of childhood cancer after neonatal exposure to vitamin K. N Engl J Med. 1993 Sep 23. 329(13):905-8. [QxMD MEDLINE Link]. [Full Text].
Centers for Disease Control and Prevention (CDC). Notes from the field: late vitamin K deficiency bleeding in infants whose parents declined vitamin K prophylaxis--Tennessee, 2013. MMWR Morb Mortal Wkly Rep. 2013 Nov 15. 62 (45):901-2. [QxMD MEDLINE Link]. [Full Text].
Weddle M, Empey A, Crossen E, Green A, Green J, Phillipi CA. Are Pediatricians Complicit in Vitamin K Deficiency Bleeding?. Pediatrics. 2015 Oct. 136 (4):753-7. [QxMD MEDLINE Link]. [Full Text].
Witt M, Kvist N, Jørgensen MH, Hulscher JB, Verkade HJ, also., et al. Prophylactic Dosing of Vitamin K to Prevent Bleeding. Pediatrics. 2016 May. 137 (5):[QxMD MEDLINE Link]. [Full Text].
Routine administration of vitamin K to newborns. Joint position paper of the Canadian Paediatric Society and the Committee on Child and Adolescent Health of the College of Family Physicians of Canada. Can Fam Physician. 1998 May. 44:1083-90. [QxMD MEDLINE Link].
[Guideline] World Health Organization. Guidelines on Maternal, Newborn, Child and Adolescent Health: Recommendations on newborn health. World Health Organiation. Available at http://www.who.int/maternal_child_adolescent/documents/guidelines-recommendations-newborn-health.pdf. 2012; Accessed: August 30, 2017.
Merli GJ, Fink J. Vitamin K and thrombosis. Vitam Horm. 2008. 78:265-79. [QxMD MEDLINE Link].

Media Gallery

of 0

Author

Dieu-Thu Nguyen-Khoa, MD, FACP Associate Clinical Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Physician Specialist, Department of Primary Care and Community Medicine, ValleyCare Olive View-UCLA Medical Center

Dieu-Thu Nguyen-Khoa, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Pankaj Patel, MD Fellow, Department of Gastroenterology, Winthrop University Hospital and The School of Medicine at Stony Brook University Medical Center

Pankaj Patel, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians-American Society of Internal Medicine

Disclosure: Nothing to disclose.

Mageda Mikhail, MD Assistant Professor, Department of Medicine, Division of Endocrinology, The School of Medicine at Stony Brook University Medical Center

Mageda Mikhail, MD is a member of the following medical societies: Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for Physician Leadership, American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society, International Society for Clinical Densitometry, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Hampton Roy, Sr, MD † Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Acknowledgements

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, and Endocrine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment