Abstract
Background: Neonatal hypofibrinogenemia is often asymptomatic but can manifest as hemorrhage.Objective: This study was conducted to characterize clinical characteristics of neonates with hypofibrinogenemia and identify factors associated with hemorrhage.Methods: This was a retrospective study of neonates with plasma fibrinogen level (FIB) ≤1.0 g/L who were hospitalized at the Neonatology Department, People's Hospital, Chongqing, China, from January 2012 to December 2017. Based on severity, patients were grouped into severe, moderate, and mild hypofibrinogenemia (FIB < 0.5 g/L, 0.5 g/L ≤ FIB < 0.7 g/L, and 0.7 g/L ≤ FIB ≤ 1.0 g/L, respectively). Clinical characteristics associated with hemorrhage were analyzed.Results: Among 330 neonates, 52.7% showed mild hypofibrinogenemia, 25.5% had moderate hypofibrinogenemia, and 21.8% had severe hypofibrinogenemia. Severe hypofibrinogenemia was not associated with gestational age, but the mild form was frequent in neonates with low/normal birthweight (P = 0.018). Approximately 80.6% of neonates presented hypofibrinogenemia as variable combinations of thrombocytopenia or coagulopathies. Hemorrhage occurred in 38.8% of the cases, 60.9% of which were mild. Hemorrhage manifested as puncture site bleeding (47.7%) or spontaneous skin/mucous membrane bleeding (34.2%). The degree of hypofibrinogenemia was not associated with the severity or occurrence of hemorrhage. Among patients with hypofibrinogenemia and bleeding, 53.4% of the cases with coagulopathies showed mild hemorrhage, 85.7% of the cases with thrombocytopenia had moderate bleeding, while 53.8% of the cases with coagulopathy and thrombocytopenia showed severe hemorrhage.Conclusion: Neonatal hypofibrinogenemia is often comorbid and occurs with thrombocytopenia and/or coagulopathies. Although hemorrhage is not associated with the degree of hypofibrinogenemia, it may be severe when hypofibrinogenemia co-occurs with coagulopathies and/or thrombocytopenia.
Highlights
Fibrinogenis a 340 kDa hexameric protein composed of alpha, beta, and gamma chains [1]
Following injury to tissue and blood vessels, fibrinogen is cleaved by thrombin to fibrin, which leads to the formation of a blood clot composed of cross-linked fibrin and incorporated blood cells [5]
Levels were found to be significantly higher after treatment with fresh frozen plasma or cryoprecipitate than those observed prior to therapy (1.18 ± 0.49 and 0.61 ± 0.28 g/L, respectively; t = −8.157; P = 0.001). This retrospective cohort provides novel insights into the clinical characteristics of hypofibrinogenemia in neonates and further reveals comorbid coagulopathies and/or thrombocytopenia to be predictive factors that may influence the risk of hemorrhage
Summary
Fibrinogen (coagulation factor I, FIB)is a 340 kDa hexameric protein composed of alpha, beta, and gamma chains [1]. Fibrinogen is synthesized by the liver [2] and circulates in the blood as one of the most abundant plasma proteins, with a normal concentration range of 1.5–3.5 g/dl [3]. This glycoprotein is an important component of the coagulation system involved in hemostasis [4]. The most common causes of hypofibrinogenemia include reduced synthesis (especially in liver diseases), increased consumption of clotting factors (e.g., in patients with cancer or sepsis with disseminated intravascular coagulation (DIC), or during treatments with tissue plasminogen activator), and hemodilution (e.g., during massive transfusion) [7]. Neonatal hypofibrinogenemia is often asymptomatic but can manifest as hemorrhage
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