LATE ONSET ACQUIRED PROTHROMBIN COMPLEX DEFICIENCY (APCD) IN A 27 DAYS OLD INFANT: A RARE CASE REPORT

ABSTRACT


INTRODUCTION
Acquired prothrombin complex deficiency (APCD) is a disease that occurs due to a deficiency in the coagulation factors that make up the prothrombin complex (II, VII, IX, and X), which are highly dependent on the presence of vitamin K in carrying out their functions (Pantiyasa, 2011).Some studies suggest that this disorder is caused by vitamin Farahdina Farahdina, Ima Sri Wahyuni, Vatine Adila Late Onset Acquired Prothrombin Complex Deficiency (APCD) in a 27 Days Old Infant: a Rare Case Report 983 K deficiency in infancy, but vitamin K supplementation alone cannot solve the problem (Bhanchet et al., 1977).Global findings regarding this disease vary widely.Due to the lack of understanding of the underlying etiology, prevention in high-risk groups is difficult to provide.Published epidemiological studies were conducted in Thailand, with an incidence of 35.5 per 100,000 live births (Unghusak, Tishyadhigama, Choprapawon, Sawadiwutiping, & Varintarawat, 1988) with a mortality rate of 35%, indicating a fairly large number as a cause of infant mortality (Bhanchet-Israngkura & Kashemsant, 1975).
Most cases that are brought to the hospital are caused by spontaneous bleeding that occurs in the early stages of life, which is less than three months of age (Koojaroenprasit, 2012).It is very rare for the parents to check neonates' complaints at the earliest possible condition which results in the treatment given to the patient being a little late and worsening the patient's prognosis (Gunawan & YOESTINI, 2011).
This case report will report the incidence of late onset APCD to increase awareness when there are early symptoms that appear in patients even though the symptoms seem vague.So that treatment can be given as early as possible before more massive bleeding occurs (Bruck, 1992) (Fristadi & Bharata, 2015) (Scholes, 1998).
A 27-days-old neonatus looked hypoactive was taken by his parents to the hospital because decreased of consciousness, and his body was bluish since 1 hour ago after drinking milk.Alloanamnesis from the parents found that the patient often turned blue and was not breathing suddenly.Then after being awakened, the patient breathes again.No previous history of vomiting and seizures.There is no history of fever, bowel disorders and the urination within normal limits.The history of pregnancy and delivery was a normal delivery at hospital with 35 weeks of preterm pregnancy and was assisted by a midwife.There is no history of taking drugs during pregnancy such as excessive antibiotics, anticonvulsants, anti-tuberculosis drugs, or anticoagulants.After delivery, the baby was quite good, there was no history of jaundice, head trauma, or previous excessive swinging.The patient was given breast milk and sometimes given formula milk.The history of postnatal vitamin K injection is unknown.
Physical examination showed the baby looked pale and somnolent with the Children Coma Scale (CSS) 7 (E1M4V2).Examination of vital signs showed the pulse rate was 158 beats / minute (sufficient, strong, and regular filling), an irregular breath rate of 10 times / minute, and the body temperature was 36.8 ° C. The neonatal weight was 2.5 kilograms and the birth weight now was 2.6 kilograms.The baby's head looks normal, with isochore pupils 3mm and 3mm, and the mouth looks bluish with the suction and swallow reflex was weak.Neurological examination shows there is no spasticity in the extremities.Physical examination of the chest and abdomen within normal limits.There was no gastrointestinal bleeding from the orogastric tube.There is a bluish appearance on the skin and there is no wound on the skin and the turgor returns normal.
On the hemostatic status examination, it was found that normal prothrombin time (PT) (13 seconds) but the activated partial thromboplastin time (aPTT) was extended by http://eduvest.greenvest.co.id 63 seconds.Head ultrasound imaging shows there is a bleeding on appointed from the picture below.

Figure 1. Ultrasound examination of the head
The patient was diagnosed with low onset of Acquired prothrombin complex deficiency condition and was given therapy according to the protocol.The patient was treated with intubation procedure.The patient was infused using Dextrose-10 / Normal Saline (1/5) with 290 mL / 24 hours.Infusion of NS 0.9% 30cc / kg.PRC transfusion 30cc / 2tpm, ranitidine 2x3 mg, ampisulbactam2x150mg, phenytoin 60mg if seizures (+) midazolam inj 0.1-0.4mg / kg / hour.2x3 mg furosemide injection.Pro furosemide 1.5 mg post cg 0.2 cc.The patient also was given 3meqdrip natrium bicarbonate correction, dobutamine 5meq / kg / hr, miloz 0.1-0.4mg/ kg / hr.The patient was observed in the neonatal room and a CT scan is planned if the patient has been stable condition.

RESEARCH METHOD
This study uses a qualitative method with the type of case report.The sampling technique used in this study the author uses the Random Sampling technique or by using the Slovin formula in Husein Umar.Where each population has the same opportunity to be selected as a sample in this study.

RESULT AND DISCUSSION
The case that we present is a 27-day-old baby with drowsiness and decreased consciousness.Initial suspicion needs to be explored, especially the patient's body and lips become bluish in color and occasionally do not breathe.The age of our patient is still the age at riskof the first onset of APCD, considering that some studies have an average age of onset of 40 days although it can be longer than that up to three months.Most of the complaints of APCD patients when they first come to the hospital are seizures, coma, drowsiness, or the presence of focal neurological abnormalities.These symptoms arise due to the process of abnormalities that occur in the intracranial so that it can cause an increase in intracranial pressure and affect consciousness and breathing (Wahab, 2020) (Bhanchet-Israngkura & Kashemsant, 1975).
Our patients have been breastfed since birth and occasionally get formula milk.A study showed that babies who only consumed breastmilk had a higher risk of developing APCD compared to babies who were alternated with formula or formula alone.Although breastmilk has complete nutrition, vitamin K is not able to penetrate the breastmilk Farahdina Farahdina, Ima Sri Wahyuni, Vatine Adila Late Onset Acquired Prothrombin Complex Deficiency (APCD) in a 27 Days Old Infant: a Rare Case Report 985 barrier so it is found in breast milk at low concentrations (Gretz & Basuroy, 2013).In infants who do not have abnormalities in their coagulation conditions, consumption of breast milk alone is sufficient to meet daily vitamin K needs, but in infants with APCD, additional vitamin K is necessary.In addition, there are doubts about the history of postpartum intramuscular vitamin K administration, so that it can increase the suspicion of vitamin K deficiency in patients.On physical examination, our patient found somnolence of consciousness with some bluish spots.In some areas of the skin appear bruising that is bluish in color.This color can be one of the manifestations of APCD on the skin, the emergence of purpura which can be an early sign of APCD symptoms.Although often overlooked, purpura is an early sign before the appearance of more severe symptoms such as intracranial hemorrhage or GI tract bleeding.In one study purpura was found in 32% of patients with APCD, even though purpura was not found even though bleeding at other sites persisted.
GI tract and intracranial hemorrhage are dangerous complications in infants born with coagulation disorders.The mortality in both cases is quite high, even if the patient survives, he or she will experience an accompanying disability for the rest of his life (Pitriyani, Noch, & AK, 2019) (Wahab, 2020).Somnolence appearance of the patient shows that the problems that occur are not only local, but there have been problems in the intracranial that cause decreased consciousness.In addition, the apneic period can be a seizure process that is often overlooked (Bruck, 1992).So an intracranial examination needs to be done.Due to the condition of the frontanella that has not closed, an ultrasound examination can be carried out through the gap and it is found that there is intracerebral hemorrhage.
The results of the hematological examination showed a decrease in the level of platelets which is also one of the components of blood hemostasis.In several previous studies, APCD was not associated with a decrease in platelets, so the findings in this case were unique (Sipayung, Pakpahan, Widiyani, & Devi, 2019).One of the possible processes that cause a decrease in platelets in our patient is the possibility of consumptive coagulopathy that occurs in the intracranial as a form of compensation for the bleeding that occurs.In locations that occurs bleeding, many platelets recruited to carry out hemostasis which causes platelets in the peripheral veins to decrease (Krismen, 2014).
In our case we had a normal PT result and a prolonged aPTT.Although in many studies related to APCD, PT and aPTT are found to be prolonged, but it is necessary to carry out a more in-depth evaluation of what factors are experiencing the disorder.Because only looking at PT and aPTT alone could not assess the abnormality of the coagulation factors that occur in the patient.
The therapy given focuses on providing life-support to the patient.Giving mechanical ventilation to help the patient when there is apnea phase.Giving phenytoin and midazolam aims to prevent seizures in which the manifestations of seizures that occur are apneic seizures.Giving PRC transfusion is a support to overcome on-going bleeding that occurs in patients.New definitive therapy will be given when the patient's condition has stabilized.

CONCLUSION
Based on the analysis and discussion, it can be concluded that APCD is a disease with a high mortality rate, and those who survive are also threatened with disability for the rest of their lives.So that early detection and holistic treatment need to be done to prevent death and disability.