Congenital dysfibrinogenemia misdiagnosed and inappropriately treated as acute fatty liver in pregnancy: A case report and review of literature

Table 1 Review of congenital dysfibrinogenemia in pregnancy

Ref.	Age (yr)	Symptoms	BCF	GT	Treatments	Clinical outcomes
Bouvier et al[1], 2018	21	Placental abruption	1. Fibrinogen plasma level (Clauss): 0.6 g/L ↓; 2. A normal immunological level: 1.91 g/L	FGA exon 5: c.1415_1416 ins C	Fibrinogen substitution with heparin and aspirin	(1) First pregnancy: A low-birth-weight baby by cesarean delivery followed by postpartum hemorrhage; (2) Second pregnancy: Cesarean delivery due to decreased fetal movements; (3) Third pregnancy: Fetal death; and (4) Fourth pregnancy: Pregnancy was normal with a programmed cesarean delivery
Edwards and Rijhsinghani[3], 2000	24	(1) Vaginal bleeding; and (2) Placental abruption	Fibrinogen level: 84 mg/dL ↓; thrombin time: 67 s ↑	-	Operation	-
Langer et al[6], 2021	28	Heavy vaginal bleeding after her first sexual intercourse	Fibrinogen activity level: < 60 mg/dL ↓	-	(1) Fibrinogen replacement therapy; and (2) Prophylactic anticoagulation	Uneventful delivery
Takala et al[17], 1991	-	Thrombotic	-	-	Heparin	Fetal loss
Yamanaka et al[18], 2003	38	(1) Vaginal bleeding; and (2) Three times repeated abortions due to placental abruption	(1) Clottable fibrinogen: 66 mg/dL↓; and (2) Immunologic fibrinogen: 225 mg/dL (normal)	-	(1) Cesarean section; and (2) Before and during the operation 6 g of fibrinogen was infused	(1) No findings of placental abruption at the time of surgery; and (2) The newborn developed normally
Franchini et al[19], 2007	30	Miscarriage at 9 wk of gestation 2 yr previously	(1) Functional fibrinogen: 161 mg/dL ↓; and (2) Immunologic fibrinogen: 466 mg/dL	Prothrombin G20210A mutation	LMWH	The woman delivered a healthy female baby
Franchini et al[19], 2007	36	Idiopathic thrombocytopenic purpura	(1) Functional fibrinogen: 85 mg/dL ↓; and (2) Immunologic fibrinogen: 221 mg/dL	-	-	The woman delivered a healthy male baby
Franchini et al[19], 2007	25	No	(1) Functional fibrinogen: 56 mg/dL ↓; and (2) Immunologic fibrinogen: 268 mg/dL	-	LMWH	The woman delivered a male baby
Franchini et al[19], 2007	33	No	(1) Functional fibrinogen: 63 mg/dL ↓; and (2) Immunologic fibrinogen:180 mg/dL	-	LMWH	A normal male baby was delivered
Kotlín et al[20], 2011	36	(1) Bleeding; and (2) Spontaneous abortions	(1) Functional fibrinogen level: 0.85 g/L ↓; and (2) Thrombin time: 39.3 s ↑	A heterozygous G4864A transition in exon 2 of the FGA (GenBankaccess number M64982)	Curettage	-
Yan et al[15], 2015	26	(1) Viral cold and Mycoplasma genitaliuminfection; and (2) No other clinical signs.	(1) Fibrinogen concentration: 0.56 g/L ↓; and (2) Immunoturbidimetry: 3.82 g/L	-	Operation	Artificial abortion
Yan et al[21], 2018	30	No	Function fibrinogen level: 0.55 g/L ↓	FGA exon 2: 1233C→A	No specific intervention in this case because the patient had no previous episodes of abnormal bleeding or thrombosis	Uneventful delivery

The normal level of functional fibrinogen (Clauss) was 150-450 mg/dL; the normal thrombin time was 12.5-16.5 s; the normal reptilase time was 12–22 s. BCF: Blood coagulation function; GT: Genetic testing; LMWH: Low-molecular-heparin; FGA: Fibrinogen alpha chain gene; ↓: Decreased values; ↑: Prolonged values.

Table 2 Review of gene mutation sites

Ref.	cDNA	Gene	Exon	CM	Clinical symptoms
Yoshida et al[5], 2017	-	FGB	-	Ala68Thr	Superior sagittal sinus thrombosis, pulmonary embolism, DVT
Qiao et al[16], 2020	c.92G>A	FGA	-	p.Gly31Glu	No symptoms so far
Kotlín et al[22], 2012	-	FGA	-	Gly13Glu and Ser314Cys	Easy bruising, excessive bleeding during pregnancy and delivery, menorrhagia
Kotlín et al[22], 2022	-	FGA	-	Gly13Glu	Epistaxis, bleeding from gums, prolonged bleeding after venipuncture
Luo et al[23], 2016	c.104G>A	FGA	2	Arg16His	Mostly asymptomatic, sometimes severe bleeding and postpartum DIC
Cai et al[24], 2018	c.103C>A	FGA	2	Arg38Thr	No symptoms so far
Shlebak et al[25], 2017	c.221G> T	FGB	2	p.Arg74Leu	Venous and arterial thrombosis
Casini et al[26], 2017	c.284 G>C	FGB	2	p.Cys95Ser	One miscarriage followed by metrorrhagia lasting nearly 2 mo
Undas et al[27], 2009	c.1052A>T	FGG	8	Asn325Ile	DVT after appendectomy
Luo et al[28], 2020	c.1178T>C	FGG	9	p.IIe367Thr	Menorrhagia
Yan et al[29], 2016	g.5877G>A	FGG	8	Arg275His	No symptoms so far
Imafuku et al[30], 2002	γ chain from Arg 275 to Cys (gR275C)	FGG	8	γ R275C	No symptoms so far

CM: Causative mutations; cDNA: Complementary DNA; FGA: Fibrinogen alpha chain; FGB: Fibrinogen beta chain; FGG: Fibrinogen gamma chain; DIC: Disseminated intravascular coagulation; DVT: Deep venous thrombosis.