Retrospective evaluation of patients with intracranial bleeding due to late vitamin K deficiency

Authors

Abstract

AimIn this study, we share our clinical experience and raise awareness about the importance of vitamin K prophylaxis. We evaluated
MethodsWe retrospectively evaluated the demographic characteristics, clinical and radiological findings of 9 patients with late vitamin K deficiency bleeding (VKDH) who were we followed in our clinic in 2020.
ResultsIt was determined that none of the 9 patients received postpartum vitamin K prophylaxis. The mean admission international normalized ratio (INR) of the patients was 4.2 + 1.1. Vitamin K was administered to all patients, and the mean of INR values decreased to 1.1 + 0.1. The most common complaint of the patients was convulsion (77.8%). Subarachnoid hemorrhage (SAH) + subdural hemorrhage (SDH) were detected in 4 patients, SAH + SDH + intraparenchymal hemorrhage (IPH) in 3 patients, SAH + IPH in 1 patient, and SAH in 1 patient. Surgery was performed on 3 patients. Two patients who were not operated died during their intensive care follow-up. Seven patients were discharged. Hemiplegia developed in 2 patients, and these patients were included in the physical therapy program.
ConclusionLate VKDB is most commonly seen between 2-12 weeks after birth. It causes serious morbidity and mortality. It is difficult to treat, time consuming and costly. It is possible to prevent late VKDB with intramuscular vitamin K prophylaxis after delivery.

Keywords

Introduction

Vitamin K is a fat-soluble vitamin required for the synthesis of functional molecules of Factor II, Factor VII, Factor IX, and Factor X produced by the liver. In the newborn period, sufficient vitamin K cannot be produced or stored. Reasons include low transfer of vitamin K through the placenta, low bioavailability due to the short half-life of liver stores, low levels of vitamin K in breast milk compared to other milks, and insufficient production of intestinal flora due to immaturity. Bleeding due to coagulation disorder secondary to vitamin K deficiency is divided according to time of occurrence. Bleeding between 24 hours and 14 days after birth (days 2 to 14) is called early vitamin K deficiency bleeding (VKDB), and bleeding between weeks 2 to 12 is called late VKDB.^1,2,3,4
VKDB can lead to a wide range of clinical presentations from mild nose bleeding, bleeding from the umbilical cord, gastrointestinal bleeding to severe brain hemorrhages. An important feature of late VKDB is that intracranial hemorrhages may be the first sign of presentation. According to the study by Klironomy et al., the incidence in those who did not receive prophylaxis was 4.4 to 7.2/100,000.^2,5
Late VKDB can cause 30% to 60% of intracerebral hemorrhage. In developed countries, stroke is among the top 10 causes of death in children. It constitutes 50% of non-traumatic hemorrhages. Trauma is the most common cause of intracerebral hemorrhages, but vitamin K deficiency and hemostatic disorders should also be considered. In infants 2 to 24 weeks of age, findings may sometimes be subtle. Intracranial hemorrhage may develop due to vitamin K deficiency in mothers who use antibiotics for a long time and in children who are exclusively breastfed. Intracranial hemorrhage has a high morbidity and mortality rate.^6,7,8
We examined n = 9 patients who were followed in our clinic for intracranial hemorrhage due to late vitamin K deficiency in 2020. In this study, we aimed to increase awareness of intracranial hemorrhages due to late vitamin K deficiency, which causes significant morbidity and mortality in the neonatal period.

Materials and Methods

Between January 2020 and December 2020, 9 patients who applied to the emergency department with intracranial hemorrhage due to late vitamin K deficiency and were later referred to us were evaluated retrospectively. Vitamin K prophylaxis was not applied to all patients, and other causes of bleeding disorders were excluded. Computer tomography (CT) was taken and types of bleeding on CT, operation status, presence of complications and survival were evaluated. All patients were followed up during their hospitalization. Statistical analysis
Descriptive statistics were used to describe continuous variables (mean, standard deviation, minimum, median, maximum). Frequency and percentage values were calculated for the descriptive statistics of categorical variables. Comparison of dependent and non-normally distributed continuous variables was made using the Wilcoxon Signed Rank test. Statistical significance level was determined as 0.05. Analyzes were performed using MedCalc Statistical Software version 12.7.7 (MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org; 2013).
Ethical ApprovalEthics Committee approval for the study was obtained.

Results

Four patients were female and 5 were male. The mean age of the patients was 8.2 ± 2.7 weeks. Upon admission to the emergency clinic, convulsions were observed in 7 patients (77.8%), fontanel swelling in 6 patients (66.7%), vomiting in 5 patients (55.6%), restlessness in 4 patients (44.4%), irritability in 3 patients (33.3%), and poor sucking in 3 patients (33.3%). Among the symptoms, convulsions were observed most frequently with 25%, followed by swelling in the fontanel in 21.4%, vomiting in 17.9%, restlessness in 14.3%, irritability in 10.7%, and poor sucking in 10.7% (Table 1).
It was determined that all patients included in the study did not receive prophylactic postnatal vitamin K. International normalized ratio (INR) values of the patients at admission were checked, and the mean was found to be 4.2 ± 1.1. Control INR values of the patients were checked after vitamin K was administered. The mean of the control INR value was found to be 1.1 ± 0.1 (Table 2). The change in INR value was found to be statistically significant.
Radiological imaging detected subarachnoid hemorrhage (SAH) and subdural hemorrhage (SDH) in 4 patients, SAH + SDH + intraparenchymal hemorrhage (IPH) in 3 patients, SAH + IPH in 1 patient, and SAH in 1 patient (Table 3) (Figure a, b, c, d).
In the follow-up of the cases, surgical intervention was performed in 3 patients (33.3%). Hydrocephalus developed in one patient who underwent surgery during the follow-up period, and a ventriculoperitoneal shunt system was applied. Two patients who were not operated on died due to general complications during the intensive care follow-up period. The remaining 7 patients survived. Hemiplegia developed in 2 patients who did not undergo surgery. These patients were included in the physical therapy program for rehabilitation. In the follow-up, the patients’ strengths recovered almost completely (Table 3).
There was a statistically significant difference between INR on arrival and INR after vitamin K (p=0.05).

Discussion

Late VKDB develops as a result of insufficient plasma concentration of active coagulation factors II, VII, IX, and X. Although it usually occurs between the 2nd and 12th weeks, literature reports that cases can be seen up to 6 months of age. Although vitamin K crosses the placenta, its serum level is not sufficient. The plasma concentration of vitamin K varies between 30% and 60% compared to normal adults. The concentration of vitamin K in breast milk is physiologically low (breast milk level 1 to 4 mg/L).⁵ According to the study by Pirinccioglu et al., 93.7% of babies are exclusively breastfed for the first 6 months.⁹ Considering this high rate, the risk of late VKDB due to vitamin K deficiency may rise significantly.¹⁰
It has been stated that there is a risk of bleeding between 50% and 80% in late VKDB, and the incidence of intracranial hemorrhages has increased. Literature shows different distributions of bleeding types. In the study by Visser et al. on n = 16 patients, SDH was detected most frequently in 50%.¹¹ In the study by Zidan et al. on n = 32 patients, SDH was observed in 56.3%, IPH in 31.3%, and mixed-type bleeding in 12.5%.¹² Ozdemir et al., in their study on n = 120 patients, found SDH in 28%, IPH in 23%, SAH in 14%, intraventricular bleeding in 8%, IPH + SDH in 10%, and SDH + SAH in 5%.² In our study, we found mixed-type bleeding most common at 88.9%. We observed only SAH in 1 patient (11.1%). The most common type of bleeding was SDH and SAH in n = 8 patients, followed by IPH in n = 4 patients. Compared with the literature, mixed-type bleeding was more common, but overall parallel in distribution.
Late VKDB clinical findings are non-specific. It may present with seizure, fever, vomiting, unconsciousness, generalized hypotonia, impaired sucking, irritability, pallor, and fontanel swelling.^9,12 Princcioglu et al., in their study with n = 31 patients, found pallor in 24 patients (77.4%), seizures in 18 patients (58%), confusion in 18 patients (18%), vomiting in 14 patients (44%), malnutrition in 11 patients (35%), fontanel pulsation in 19 patients (61%), and swelling in 8 patients (26%).⁹ Our study shows parallelism with the literature in terms of symptoms. Although seizure was the most common complaint, it was followed by swelling in the fontanel, vomiting, restlessness, poor sucking, and irritability.
Although late VKDB causes severe neurological sequelae and death, its incidence varies according to the development level of countries. In a study conducted in Germany, morbidity was 21% and mortality 19%. In Egypt, mortality was higher at 23.8%. In another study in our country, mortality was 20.8% and morbidity 48.1%.¹³ In our study, 2 patients (22.2%) died due to general complications during intensive care follow-up. Hemiplegia developed in 2 non-operated patients and hydrocephalus in 1 operated patient. Literature reports hydrocephalus incidence after intracerebral hemorrhage ranging from 8.9% to 50% depending on bleeding type.¹³ Hydrocephalus is accepted as a poor prognosis finding.^14,15 Our rate was 33.3%. A ventriculoperitoneal shunt system was applied to the patient who developed hydrocephalus. Our results showed parallelism with the literature.
Prothrombin time (PT) and active partial thromboplastin time (aPTT) values are prolonged in vitamin K deficiency. Bleeding values return to normal within 2 to 3 hours after vitamin K administration.³ In our study, reasons for not taking vitamin K prophylaxis included parental refusal and home births without access to health services. INR values were high at admission, but returned to normal after vitamin K administration. According to our findings, all newborn infants should be given vitamin K prophylaxis to avoid catastrophic effects of VKDB. Vitamin K prophylaxis can be administered orally or intramuscularly. The oral form is less effective in reducing the risk of ICH than the intramuscular form. Although some articles suggest vitamin K prophylaxis may increase incidence of certain childhood cancers, these discussions remain unclarified.^2,3,16

Conclusion

Although late VKDB is seen between the 2nd and 12th weeks on average, it can be seen up to the 6th month. The morbidity and mortality of late VKDB are high, and it mostly presents with intracranial hemorrhages. Breast milk is poor in terms of vitamin K content, and considering that the majority of newborn babies are fed only with breast milk for the first 6 months, it is seen how high the risk is. The way to reduce this risk is that it is important to administer vitamin K prophylaxis, especially in its intramuscular form. Prophylaxis should be made mandatory and should be applied to all newborns born in or out of the hospital. In this way, morbidity and mortality that may occur in VKDB can be prevented. We can prevent information pollution by providing pregnant women with accurate information about vitamin K prophylaxis during pregnancy follow-up.
Our study was conducted with a limited number of patients. Prophylaxis has become widespread with the increase in routine follow-ups in children. Its incidence has decreased in parallel with the developments in diagnosis and treatment. However, it should be kept in mind that when prophylaxis is not performed, it can cause all kinds of intracranial hemorrhage and lead to serious sequelae and death, as seen in our study.

Declarations

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About This Article

Received:

January 10, 2023

Accepted:

February 11, 2023

Published Online:

February 22, 2023

Printed:

March 25, 2023