Intracranial Hemorrhage in a Pregnant Woman on Low-Dose Aspirin: A Case Report

Introduction

Preeclampsia is new-onset hypertension and proteinuria or other end-organ damage after 20 weeks of gestation [1]. Severe complications include eclampsia, HELLP syndrome, pulmonary edema, myocardial infarction, acute respiratory distress syndrome, stroke, and renal and retinal damage. Pre-eclampsia complicates 2–8% of pregnancies worldwide, resulting in severe maternal and fetal complications and death [2]. It is responsible for more than 75 000 maternal deaths and more than 500 000 infant deaths worldwide each year [3]. The only definitive treatment for preeclampsia is delivery of the placenta and baby [4]. It is important to identify women at high risk of developing this disorder in early pregnancy so that timely therapeutic intervention can be initiated. In those at high risk for preeclampsia, aspirin at a dose of 50–150 mg daily during pregnancy can reduce perinatal mortality [5]. The American College of Obstetricians and Gynecologists, the Society for Maternal-Fetal Medicine, the World Health Organization, and the American Heart Association/American Stroke Association all recommend the use of low-dose aspirin to prevent preeclampsia in high-risk populations to improve maternal and perinatal outcomes [6].

Risk factors and determinants of preeclampsia include previous chronic hypertension, diabetes, renal disease, and obesity (BMI ≥30.0) kg/m2), short stature, nutritional deficiency, hypertension in previous pregnancy, heredity, autoimmune diseases (systemic lupus erythematosus and antiphospholipid antibody syndrome), hydatidiform mole, multiple pregnancy, macrosomia, primipara, advanced maternal age, and assisted reproduction [7].

We report a case of a 32-year-old pregnant woman who was obese before pregnancy, had a history of adverse pregnancy outcomes and hydatidiform mole, and risk factors for preeclampsia. She started taking aspirin 100 mg/day at 12 weeks of gestation and developed cerebral hemorrhage and intraventricular hemorrhage at 33 weeks 5 days of gestation.

Case Report

A 32-year-old pregnant woman, gestational 6, para 2, at 33 weeks 5 days of gestation, had a history of vaginal delivery. She had regular obstetric examinations and was free of gestational hypertension and other medical and surgical diseases. At about 7 AM, she suddenly developed severe headache, followed by 6 episodes of projectile vomiting of stomach contents, accompanied by unconsciousness and clammy limbs. She denied any head trauma. She was taken to a peripheral hospital by emergency services, and computed tomography (CT) and magnetic resonance imaging (MRI) were performed.

Acute cerebral hemorrhage was diagnosed and treated by lowering intracranial pressure, antiemetic, and hemostasis, and she was transferred to the intensive care unit of our hospital for treatment after fluid resuscitation. The patient was obese (pre-pregnancy body-mass index >30), had 2 previous adverse biochemical pregnancy outcomes, had a history of a hydatidiform mole, and was at high risk for preeclampsia. Therefore, oral aspirin 100 mg daily was started after 12 weeks of gestation and has been continued to this day. There was no other medical history, and the prenatal session was uneventful.

On arrival, her vital signs were temperature 36.1°C, heart rate 86 beats/min; respiratory rate 20 breaths/min. and blood pressure 138/66 mm Hg. The Glasgow Coma Scale (GCS) score was 15. Physical examination revealed that the patient was conscious, with free movement of the limbs, a distended abdomen, and a fetal heart sound of 145 beats/min between the fundus umbilica and xiphoid process. Blood analysis showed white blood cell 12.59×109/L, hemoglobin 98 g/L, platelet 214×109/L, and neutrophil ratio 88.6%. Blood coagulation testing showed that D-dimer was 10.43 mg/L. Blood lipids were elevated: total bile acid 6.01 mmol/L, triglyceride 3.56 mmol/L, high-density lipoprotein cholesterol 1.63 mmol/L, and low-density lipoprotein cholesterol 3.53 mmol/L. Liver function testing showed albumin 31.9 g/L, electrolytes K 3.36 mmol/L, and the other results were normal. Renal function and myocardial enzymes were normal. Antibodies to syphilis and human immunodeficiency virus were negative. CT showed a cerebral hemorrhage in the left frontal lobe that broke into the ventricular system, and a 59×30×49 mm high-density shadow was seen in the left frontal lobe (Figure 1). Head MRI showed acute cerebral hemorrhage in the left frontal lobe with cerebral herniation and hematomas in the posterior horn of the lateral ventricles and the third and fourth ventricles on both sides. After multidisciplinary discussion involving neurosurgery, neurology, obstetrics, and pediatrics, and communication with the patient’s family, the team decided to perform an emergency cesarean section to protect the mother and fetus. Her fetal outcome was a living baby boy, Apgar 1 min 4 points (heart rate 2 points, skin color 1 point, reaction 1 point), treated with warmth, positive-pressure ventilation, and tracheal intubation, 5 min 8 points, weight 2340 g, and the premature neonate was transferred to the neonatal intensive care unit. After cesarean section, the patient was transferred to the intensive care unit and received further medical conservative treatment, including intracranial pressure reduction, sedation, and anti-infection treatment. CT angiography (CTA) image reconstruction of the head was performed within 2 days, and no vascular malformations were detected. Five days later, the patient recovered and was transferred to the general ward for treatment. After 25 days of treatment, a repeat CT scan showed a reduction in left frontal intracerebral hemorrhage, measuring 47×28×37 mm (Figure 2). The patient improved and was discharged from the hospital. A follow-up visit was made to the neurosurgery and obstetrics departments 42 days later.

Discussion

ICH during pregnancy is a rare emergency event with an incidence of 7.18 per 100 000 pregnancies and is one of the leading causes of maternal death worldwide [8]. The most common cause of ICH is systemic disease with different manifestations of preeclampsia in one-third, structural vascular lesions in about one-third, and the etiology of ICH is undetermined in about one-third [9]. Other common risk factors include hypertension, HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome, diabetes mellitus, and dyslipidemia [9]. Pregnancy status causes changes in hormone levels, hypercoagulable state, increased cardiac output, and increased intra-abdominal and intracranial pressure, which can induce ICH [10]. In addition, aspirin is widely used for cardiovascular disease prevention, but daily use of low-dose aspirin can significantly increase the risk of ICH [11,12]. In our patient, ICH may have been caused by a combination of factors, including pregnancy status, dyslipidemia, hypercoagulopathy, and aspirin use. This poses a significant challenge to treatment decision-making and treatment planning. Individual treatment plans were tailored to the condition of the mother and fetus. The primary concern is the safety of the mother, and a fetus in the third trimester has a high chance of surviving timely cesarean delivery.

The clinical manifestations of ICH are decreased consciousness, vomiting, headache, seizures, and very high blood pressure. ICH needs to be differentiated from ischemic stroke and eclampsia. The diagnosis of ICH must always rely on neuroim-aging. Conventional CT or MRI is safe during pregnancy [13]. CT is faster, easier to obtain, and more sensitive in identifying acute bleeding and is considered the criterion standard imaging method. CT angiography, MRI, or magnetic resonance angiography (MRA) are helpful in ruling out cerebrovascular malformations. Patients diagnosed with ICH should be quickly admitted to the stroke ward or neurological intensive care unit, and multidisciplinary discussion should be conducted among obstetrics, neurosurgery, pediatrics, and critical care medicine departments. When the fetus is in the third trimester of pregnancy and the mother’s neurological disease is critical, emergency cesarean section should be performed to protect the safety of the mother and fetus. Life support, prevention of secondary brain injury, and treatment of complications are given. The timely delivery of bundled therapy including immediate anticoagulation reversal, simultaneous blood pressure reduction, and a prespecified stroke unit protocol can improve clinical outcomes [14]. Surgical treatment is related to the location of the ICH site. For patients with infratentorial intracerebral hemorrhage who have clinical deterioration due to hydrocephalus or brain stem compression, surgery can reduce secondary brain injury and perihematoma edema, and reduce mortality [15].

Conclusions

The occurrence of cerebral hemorrhage and intraventricular hemorrhage in pregnant women who take aspirin daily is very rare and seriously threatens the life and safety of mother and child. Computed tomography helps with diagnosis, and such patients require multidisciplinary team support, timely cesarean section to save the fetus, and individualized treatment of intracranial hemorrhage.