Answer

Bleeding related to vitamin K deficiency: Nonenhanced CT scan shows an

acute right-sided subdural hematoma (SDH) (see Image 1) associated with
extensive infarction involving the entire right cerebral hemisphere and the
medial portion of the left frontal lobe. Extensive subfalcine herniation changes
are present, with entrapment of the left foramen of Monro and enlargement of
the left lateral ventricle. The sutures are separated due to the acute increase in
intracranial pressure.

Given the prolonged PT of >50 s and the aPTT of 90.6 s, a bleeding disorder
was determined to be the etiology of the patient's SDH. The differential
diagnosis included vitamin K deficiency bleeding (VKDB) or an inherited
deficiency of factor II, V, or X. To prepare for evacuation of her SDH, the patient
was given vitamin K 2 mg intramuscularly (IM) and fresh frozen plasma (FFP)
20 mL/kg over 2 h. Surgical evacuation of the SDH was completed without
complication except for excessive oozing for which intraoperative recombinant
activated factor VII (Novo-7) 1200 g was administered, with good effect.
Repeat assessment of her PT and aPTT resulted in values of 8.3 and 24.6 s,
respectively. Her coagulation parameters remained normal for the subsequent
duration of the patient's hospitalization. On admission, the patient's factor II, VII,
and X levels were <10% and her factor V level was 89% (within normal limits),
and a diagnosis of VKDB was confirmed.

Vitamin K is central to the coagulation cascade, and its absence or consumption

can result in bleeding. Vitamin K activates clotting factors II, VII, IX, and X,
which are collectively known as the prothrombin complex, as well as
anticoagulant proteins C and S. In mild or early stages of vitamin K deficiency,
only the PT is substantially prolonged because of the short half-life of factor VII.
However, in severe or prolonged deficiency, both PT and aPTT are markedly
elevated because of the deficiency of factors II, IX, and X. In infants, vitamin K
deficiency should be confirmed by the resolution of the bleeding symptoms and
by the correction of PT and aPTT with the administration of vitamin K and by
ruling out other causes of bleeding, such as inherited deficiency of common
pathway factors (II, V, or X), liver disease, and disseminated intravascular
coagulation (DIC). Assays of factors II, V, VII, and X help in differentiating
congenital factor deficiency from vitamin K deficiency.

Newborns are particularly at risk for vitamin K deficiency because of poor

placental transmissibility (30:1 maternal-infant gradient), absent hepatic
menaquinones (vitamin K2 produced by gut bacteria), and low levels of vitamin
K in breast milk (relatively low compared with supplemented infant formula).
The deficiency leads to unexpected bleeding in otherwise healthy neonates if
adequate vitamin K prophylaxis is not administered at birth. According to an
American Academy of Pediatrics policy statement in 2003, a single IM dose of
0.5-1 mg should be given to all newborns.

VKDB can be categorized into early (in the first week of life) and late (from 8
days to 6 months) onset. The frequency of early VKDB in the United States is
0.25-1.7% without vitamin K prophylaxis. Late-onset VDKB, which has a
prevalence of 5-20 cases per 100,000 live births with no vitamin K prophylaxis,
occurs almost exclusively in breastfed infants; intracranial hemorrhage (ICH) is
a complication in 30-50% of patients. Additional risk factors for vitamin K
deficiency include diarrhea, hepatitis, cystic fibrosis, celiac disease, and alpha1-
antitrypsin deficiency. Vitamin K deficiency without bleeding may occur in up to
50% of infants younger than 5 days. Finally, VKDB occurring within 24 hours of
birth is usually due to maternal medications, such as use of anticonvulsants,
antituberculosis medications (eg, rifampin, isoniazid), or warfarin. In these
cases, postnatal vitamin K prophylaxis does not help in preventing VKDB.

Therapy for VKDB depends on the severity of the bleeding. Minor bleeding can
effectively be corrected with IM or subcutaneous administration of vitamin K.
Intravenous administration is not recommended because of a risk of
anaphylactoid reactions. The PT and aPTT normalize 4-8 hours after the
administration of vitamin K. In cases of severe or life-threatening bleeding (eg,
ICH), the patient should receive FFP 10-15 mL/kg and/or prothrombin complex
concentrate or recombinant factor preparations (eg, Novo-7) in addition to
vitamin K.

The neurologic condition of the infant in this case improved rapidly after surgery.
She was able to breastfeed well within 24 hours, and brain imaging studies
obtained on days 2 and 8 after surgery showed no recurrence of the SDH (see
Image 2 for CT obtained 2 days after surgery). Her neurologic status greatly
improved by day 13, and she was discharged home with vitamin K
supplementation 2 mg by mouth once a week until 6 months of age. The infant
was born at home and therefore did not receive vitamin K prophylaxis at birth or
any time during the 5 weeks before her presentation.

For more information about vitamin K deficiency, see the eMedicine articles
Hemorrhagic Disease of Newborn (within the Pediatrics specialty) and Vitamin
K Deficiency (within the Internal Medicine specialty).

References
 AAP. American Academy of Pediatrics. Policy statement. Controversies
concerning vitamin K and the newborn. Pediatrics 2003;112(1):191-3.
Available at:
http://aappolicy.aappublications.org/cgi/reprint/pediatrics;112/1/191.pdf.
Accessed October 12, 2005.
 Agnelli G. Current issues in anticoagulation. Pathophysiol Haemost
Thromb 2005;34(suppl 1):2-9.
 Ansell J, Hirsh J, Poller L, et al. The pharmacology and management of
the vitamin K antagonists: the seventh ACCP conference on
antithrombotic and thrombolytic therapy. Chest 2004;126(3 suppl):204-
23.
 Edstrom CS, Christensen RD, Andrew M. Developmental aspects of
blood hemostasis and disorders of coagulation and fibrinolysis in the
neonatal period. In: Christensen RD, ed. Hematologic Problems of the
 Neonate. Philadelphia, PA: WB Saunders Co; 2001.
http://www.emedicine.com/med/topic2385.htm.
 Royal College of Physicians. Health and Social Policy. Design and
Content 2001, Revised September 2004.
http://www.emedicine.com/ped/topic966.htm.
 Watson H, Baglin T, Laidlaw SL, et al. A comparison of the efficacy and
rate of response to oral and intravenous Vitamin K in reversal of over-
anticoagulation with warfarin. Br J Haematol 2001;115:125-49.
 World Health Organization and Food and Agriculture Organization of the
United Nations. Chapter 10: Vitamin K. In: Human Vitamin and Mineral
Requirements. Report of a Joint FAO/WHO Expert Consultation. 2002.
Bangkok, Thailand.

BACKGROUND
Parents bring their full-term female infant, aged 5 weeks, to the emergency
department. The mother states that the baby had been doing well until a few
days ago, when she started to become fussy and irritable, with vomiting and
swelling around her right eye. She was feeding poorly yesterday and has been
"tired" for the last several hours.

On physical examination, the infant is irritable and listless. She has mild
swelling with ecchymosis around the right eye with an additional area of
ecchymosis on the right knee. Her anterior fontanel is bulging, and her right
pupil is dilated and unresponsive. Nonenhanced head CT is ordered, but during
preparation for scanning, the patient develops shallow breathing with hypoxia,
with an oxygen saturation of 80% on room air. This condition progresses to
apnea and slowing of her heart rate to 60 beats per minute. Atropine is
administered, and the patient is intubated.

Head CT is performed (see Image).

The patient's laboratory investigations show the following values: on CBC, WBC
of 20.6 X 109/L (20,600/mm3), hemoglobin (Hb) 89 g/L (8.9 g/dL), hematocrit
(Hct) 0.273 (27.3%), platelets 516 X 109/L (516 X 109/L); BUN 5 mmol/L (14
mg/dL), creatinine 17.7 mol/L (0.2 mg/dL), aspartate aminotransferase (AST)
121 U/L, alanine aminotransferase (ALT) 149 U/L, total protein 76 g/L (7.6 g/dL),
albumin 46 g/L (4.6 g/dL); prothrombin time (PT) >50 s and activated partial
thromboplastin time (aPTT) = 90.6 s.

Hint
The patient was a full-term female infant delivered at home and breastfed.
Authors: Anusuya Mokashi, Medical
Student, New York Medical
College, Valhalla

Avinash Mohan, MD, Department

of Neurosurgery Residency, New
York Medical College, Valhalla

Prithvi Narayan, MD, Assistant

Professor of Neurosurgery and
Pediatrics, Director of Pediatric
Neurosurgery, Department of
Neurosurgery, New York Medical
College, Valhalla

Somasundaram Jayabose, MD,

Chief, Section of Pediatric
Hematology/Oncology, New York
Medical College, Valhalla; Chief
of Pediatric Hematology-
Oncology, Westchester Medical
Center, NY

eMedicine Editor: Ada Jain Kumar, MD, Department

of Radiology, Evanston
Northwestern Healthcare

Rick Kulkarni, MD, Attending

Physician, Director of Informatics,
Department of Emergency
Medicine, Olive View - UCLA
Medical Center, Assistant
Professor of Medicine, David
Geffen School of Medicine at
UCLA