A 5-week-old full-term female infant is presented to the emergency department (ED) by her parents. The mother states that the baby had been doing well until a few days ago, when she started to become fussy and irritable; since then, she has had episodes of vomiting, and swelling has developed around her right eye. She was feeding poorly the day before presentation, and the parents state that the infant 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 fontanelle is bulging and her right pupil is dilated and unresponsive.
A nonenhanced computed tomography (CT) scan of the infant’s head is ordered, but during preparation for scanning, the patient develops shallow breathing and hypoxia, with an oxygen saturation of 80% while breathing room air. This condition progresses to apnea and a decrease in her heart rate to 60 bpm. Atropine is administered, and the patient is intubated.
The CT scan of the infant’s head is performed (see Image).
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Laboratory investigations are initiated, and they show the following values: on complete blood count, the white blood cell count (WBC) is 20.6 × 109/L (20,600/mm3); hemoglobin (Hgb), 89 g/L (8.9 g/dL); hematocrit (Hct), 0.273 (27.3%); and platelets (Plt), 516 × 109/L (516 × 103/mL). Additionally, blood urea nitrogen (BUN) is 5 mmol/L (14 mg/dL); creatinine, 17.7 mmol/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); and albumin, 46 g/L (4.6 g/dL). Prothrombin time (PT) is >50 s, and activated partial thromboplastin time (aPTT) is 90.6 s. What is the diagnosis?
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HINT
The patient was a full-term female infant delivered at home and breastfed.
Authors:
Anusuya Mokashi, MD, Department of Medicine Residency, Westchester Medical Center, New York Medical College, Valhalla, NY
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 Editors:
Ada Jain Kumar, MD, Department of Radiology, Advocate Lutheran General Hospital, Park Ridge, IL
Rick G. Kulkarni, MD, FACEP, Assistant Professor, Yale School of Medicine, Section of Emergency Medicine, Department of Surgery, Attending Physician, Medical Director, Department of Emergency Services, Yale-New Haven Hospital, CT
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ANSWER
Bleeding related to vitamin K deficiency: The nonenhanced CT scan shows an acute right-sided subdural hematoma (SDH; see Image 1) associated with an extensive infarct 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 because of 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 mg 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 resolution of the bleeding symptoms and correction of the PT and aPTT with the administration of vitamin K, as well as 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 these 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 after birth is usually caused by maternal medications, such as anticonvulsants, antituberculosis medications (eg, rifampin, isoniazid), or warfarin. In these cases, postnatal vitamin K prophylaxis does not prevent 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 within 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.
In this case, the neurologic condition of the infant rapidly improved 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 the CT scan obtained 2 days after surgery). Her neurologic status greatly improved by day 13, and she was discharged to 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 at any time during the 5 weeks before presentation.
References:
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