Yuqun Pu,Jingping Zhu,Baihui Zhao,Mengmeng Yang,Qiong Luo

Department of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China

Disseminated intravascular coagulation (DIC)is a clinical syndrome caused by various etiologies and characterized by systemic activation of blood coagulation,leading to vessel thrombosis,organ dysfunction,and severe bleeding.[1]DIC represents a life-threatening condition that is the endpoint of uncontrolled systemic activation of the disease.Once it enters the stage of malignant DIC,the patient’s death becomes unavoidable.DIC always occurs as a secondary disorder and is commonly associated with postpartum hemorrhage,followed by hypertensive disorders,acute fatty liver of pregnancy,sepsis,and amniotic fluid embolism (AFE).[2]In clinical obstetrics,DIC often occurs during delivery or postpartum,while cases of prenatal acute DIC as the first manifestation are uncommon.Patients with DIC have higher rates of multiple organ dysfunction syndrome,including acute renal failure (ARF),respiratory failure,and disturbance of consciousness.

This case report describes the treatment outcomes of a patient who presented with prenatal acute severe DIC as the first symptom,progressing to renal failure.We also analyzed the clinical characteristics,treatment,and prognosis of acute severe DIC in pregnancy.

CASE

At 36+weeks of gestation,a 34-year-old woman (G1P0)was referred to our hospital.She had a fever 3 d prior,with a maximum body temperature of 37.7 °C.Two hours before admission,she experienced chills with no apparent cause,and her temperature was 38.9 °C.She vomited twice and experienced shortness of breath but had no other discomfort.She had no significant medical histories or complicated pregnancy,with normal antenatal investigations.

An ultrasound performed 10 d prior showed an amniotic fluid index (AFI) of 46.5 cm,but upon admission,her AFI was 28.2 cm.Biochemical tests revealed alanine aminotransferase (ALT) 74 U/L,aspartate aminotransferase (AST) 151 U/L,total bilirubin 29.8 μmol/L,direct bilirubin 10.3 μmol/L,indirect bilirubin 19.5 μmol/L,creatinine 87.2 μmol/L,C-reactive protein(CRP) 26.1 mg/L,and blood glucose 3.88 mmol/L.Routine blood results showed a white blood cell (WBC) count 19.5×109/L,neutrophil classification 81.6%,red blood cell (RBC) count 3.44×1012/L,Hb 113.0 g/L,hematocrit 0.330,and platelet (PLT) count 113.0×109/L.

The patient’s initial vital signs were as follows:temperature 38.1 °C,blood pressure (BP) 149/90 mmHg(1 mmHg=0.133 kPa),pulse 116 beats/min,respiratory rate (RR) 35 breaths/min,and SpO296% on room air.The fetal heart rate (FHR) was 136 beats/min,and there were irregular contractions,with low uterine tension and no abdominal tenderness.The patient had wheezing,dizziness,chest tightness,and an inability to lie down.

Active bleeding was observed at the puncture site,and hematuria was detected upon catheterization.The emergency coagulation function results showed 3P positve,prolonged prothrombin time (PT) ＞120 s,activated partial thromboplastin time (APTT) ＞180 s,thrombin time (TT) ＞240 s,fibrin level ＜0.6 g/L,and plasma D-dimer ＞20 mg/L.The patient’s BP increased to 190/119 mmHg and RR to 46 breaths/min.She had a pale complexion.As a result,the obstetric rapid response team was activated,and an emergency exploratory laparotomy and cesarean section under general anesthesia were planned.

During the operation,approximately 1,000 mL of dark red and bloody ascites were seen,with almost no amniotic fluid.The newborn’s Apgar score was 1-8 at 1-5 min,and the birth weight was 1,750 g.The placenta was delivered spontaneously with no signs of placental abruption.However,the patient’s uterine contraction was poor,and the bleeding was significant at 3,000 mL.Therefore,the patient was given carbetocin,carboprost tromethamine,uterine cavity packing with iodoform gauze,methylprednisolone 80 mg,and continuous blood transfusion.An abdominal drainage tube was placed,and the intraoperative urine output was 100 mL.After the operation,the patient was transferred to the intensive care unit (ICU) and received an intravenous infusion of 320 mg of furosemide.In total,the patient received 12 units of RBCs,1,880 mL of plasma,20 units of cryoprecipitate,12 units of platelets,10 g of fibrinogen,2 g of tranexamic acid,and 2,400 U of prothrombin complex.

Despite these measures,the peritoneal drainage fluid was continuously extracted with a small amount of blood,and the patient developed anuria.Considering the possibility of acute renal failure,the patient was urgently transferred to the ICU of a general hospital for hemodialysis.After one week of treatment,the patient’s renal function improved,and she was discharged from the hospital.

DISCUSSION

DIC etiology during pregnancy

Several pregnancy complications are associated with DIC.The typical presentation of AFE includes sudden hypoxia,hypotension,cardiac arrest,and coagulopathy.[3]In this case,the patient’s condition rapidly progressed,and severe DIC was the first presentation.With no symptoms of ruptured membranes,it was supposed that the patient’s polyhydramnios caused spontaneous rupture of the membrane close to the uterine horn.The amniotic fluid flowed out and entered the abdominal cavity,and AFE was caused by the rupture of tiny veins,which then perfused into the peripheral blood circulation.However,ascites was not retained for further examination to clarify the nature of the ascites,and venous blood sample was not collected to conf irm the amniotic f luid composition.Nevertheless,the clinical manifestations of refractory DIC and ARF were highly consistent with AFE.

Infection and sepsis are also common causes of DIC,which can cause vascular endothelial injury,leukocyte aggregation,and inflammatory factor release,resulting in platelet aggregation and microintravascular thrombosis.[4]The inflammatory cytokine interleukin 6 (IL-6) is one of the mediators involved in coagulation activation in sepsis.[5]The patient had a transient fever on admission,accompanied by nasal congestion,runny nose,and chills,with a body temperature of 38.9 °C.The CRP was 26.1 mg/L,and the WBC count was 19.5×109/L,suggesting that infection factors should be considered.However,no obvious infection lesions were found,the postoperative body temperature was normal,and there were no signs of organ infection.It is unfortunate that no etiological examination was performed during the operation,and cytokine detection might provide more details about this case.

Although the patient had increased blood pressure and abnormal hepatic enzymes,serum lactate dehydrogenase (LDH) was not detected,and platelets were 113×109/L,which did not support the diagnosis of HELLP syndrome (hemolysis,elevated liver enzymes,low platelets).The majority of women developing acute fatty liver of pregnancy (AFLP) complain of nausea/vomiting and abdominal pain.Rapid separation of bile enzymes and negative urinary bilirubin are the characteristic manifestations.[6]The patient vomited twice,and coagulation dysfunction appeared rapidly and seriously.However,as there was no bile-enzyme dissociation performance,AFLP was not the first diagnosis.In some severe cases of placental abruption,shock and DIC may occur.Although the patient had highrisk factors such as hypertension and polyhydramnios,there were no typical manifestations,and nothing abnormal was found in the placenta during the operation.

DIC diagnosis

Early and accurate recognition is crucial to the successful treatment of DIC.The clinical manifestations of DIC are complex and diverse.Embolism is an early symptom of DIC and can manifest as dyspnea and cyanosis when a pulmonary embolism occurs.Bleeding is a common manifestation,with multiple bleeding tendencies,extensive subcutaneous petechiae,and submucosal hemorrhage.DIC can often present as diffuse hemorrhage and hypovolemic shock in some cases,especially when vessels are destroyed.This patient presented with acute severe DIC clinical manifestations,such as shortness of breath,orthopnea,active bleeding at the venipuncture site,and hematuria before delivery.

There is no laboratory or clinical test that is sensitive and specific enough to diagnose DIC.Abnormal findings mainly include thrombocytopenia,coagulation factor consumption,and activation of the fibrinolytic system.In this case,the patient’s coagulation function was consistent with DIC.However,most diagnostic criteria for DIC are applicable to non-pregnant patients,and DIC progresses rapidly,requiring dynamic observation.In this case,the timely evaluation of clinical manifestations was more important than positive test results in making a diagnosis.

DIC treatment

The treatment principles for obstetric DIC include managing the underlying condition that predisposes patients to DIC,providing supportive care with blood products and related measures,conducting regular clinical and laboratory surveillance,and seeking assistance from relevant specialists as early as possible.[7]The most critical principles are managing the underlying condition causing DIC and prompt delivery or termination of pregnancy.[8]Although the final diagnosis of this case may not be completely conf irmed,rapid correction of abnormal coagulation function and immediate termination of pregnancy through cesarean section are the most critical treatment methods.

CONCLUSIONS

DIC is a life-threatening condition that can arise from various causes,often with an insidious onset,making it difficult to diagnose.In pregnant patients,DIC can lead to severe obstetric hemorrhage and its sequelae.Prompt diagnosis and understanding of the underlying mechanisms are crucial for a favorable outcome,and termination of pregnancy via cesarean section should be performed as soon as possible.

Funding:This work was supported by a grant from Scientific Research Foundation of the National Health Commission (WKJZJ-2126).

Ethical approval:The study was approved by the Ethics Committee of the hospital.

Conflicts of interest:The authors declare that they have no competing interests.

Contributors:All authors contributed substantially to the writing and revision of this manuscript and approved of its contents.