Table 2.
Description of clinical studies and fibrinogen mutations in congenital hypofibrinogenemia associated with bleeding and thrombotic manifestations [2,22,34,35,36,37,38,39,40,41].
| Name/Origin | Mature Protein Variation | Native Protein Variation | cDNA | Gene Status | e–i | Numbers of Studied Patients/Numbers of Patients with Thrombosis | Bleeding Complications | Numbers of Thrombotic Complications and Obstetrical Problems | Localization of Thrombosis | Other Thrombophilic States |
|---|---|---|---|---|---|---|---|---|---|---|
| Fibrinogen Aα Chain Mutations Associated with Hypofibrinogenemia and Bleeding and Thrombosis | ||||||||||
| MARSEILLES II | Aα(45)Cys˃Tyr | p.Cys64Tyr | c.191G˃A | Heterozyg. | e–3 | 2/1 | Spontaneous digestive tract bleeding Metrorrhagia |
1x External iliac VT, common femoral, popliteal | External iliac VT, common femoral, popliteal | Protein S deficiency |
| ITALY P16 | Aα(110)Arg˃Pro | p.Arg129Pro | g.3076G˃C | Heterozyg. | e–4 | 1 | Colon bleeding | Repetitive DVT | DVT | No other thrombophilic state |
| GDANSK | Aα(112)Ser˃Pro | p.Ser131Pro | c.391T˃C | Heterozyg. | e–4 | 4/1 | Easy bruising, bleeding after surgery | 1x Left popliteal and calf veins | Left popliteal and calf veins | No other thrombophilic state |
| Fibrinogen Bβ Chain Mutations Associated with Hypofibrinogenemia and Bleeding and Thrombosis | ||||||||||
| CHRISTCHURCH V | Bβ(58)Lys˃frameshift–stop | p.Lys88Frameshift Stop | 3404delA | Heterozyg. | e–2 | 3/1 | Easy bruising | 1x IS | IS | No other thrombophilic state |
| ITALIAN | Bβ(172)Leu˃Gly | p.Leu202Gly | 3282C˃T | Compound | e–2 | 1 | Bleeding after dental care | 6x Miscar., 1x tibial artery thrombosis | Tibial artery thrombosis | Heterozygous Factor V Leiden |
| LYON | Bβ(118)Met˃Lys | p.Met148Lys | 4075T˃G | Heterozyg. | e–3 | 2/1 | Easy bruising, bleeding after dental care, post—partum bleeding | 3x Miscar. | Miscar. | x |
| PARIS IX | Bβ(236)Tyr˃Cys | p.Tyr266Cys | 5909A˃G IVS7+1G˃C |
Compound Compound |
e–5 i–7 |
1 | Easy bruising, epistaxis, menorrhagia | 1x Miscar., 1x DiVT | Miscar, DiVT | x |
| Fibrinogen γ Chain Mutations Associated with Hypofibrinogenemia and Bleeding and Thrombosis | ||||||||||
| BEJA | IVS6+23T˃A (c.666+23T˃A) | Homozyg. | i–6 | 1 | Bleeding after dental care | 1x MI | MI | No other thrombophilic state | ||
| DARLINGHURST | γ(253)Trp˃Gly | p.Trp279Gly | c.835T˃G | Homozyg. | e–7 | 2/1 | Bleeding after dental care | CHTED, repetitive miscar. | CHTED, miscra. | No other thrombophilic state |
| COLUMBUS | γ(200)Gly˃Val | p.Gly226Val | c.677G˃T | Heterozyg. | e–7 | 2/2 | x | 1x DVT | DVT | Heterozygous Factor V Leiden, MTHFR C677T mutations |
| FINLAND P21 | γ(277)Thr˃Pro γ(301)Asp˃His |
p.Thr303Pro p.Asp327His |
g.7481A˃C g.7553G˃C |
Compound Compound |
e–8 e–8 |
4 | x | x | x | x |
| CHINESE | γ(314)Thr˃IIe | p.Thr340Ile | c.1019C˃T | Heterozyg. | e–8 | 5/1 | Metrorrhagia | 1x CVT | CVT | x |
| AGUADILLA | γ(375)Arg˃Trp | p.Arg401Trp | c.1201C˃T | Heterozyg. | e–9 | 1/1 | x | x | x | x |
FVT—femoral vein thrombosis; PE—pulmonary embolism; Miscar.—miscarriages; LI—leg ischemia; IS—ischemic stroke; DVT—deep vein thrombosis; DiVT—distal vein thrombosis; VT—vein thrombosis; CVT—cerebral venous thrombosis; MI—myocardial infarction; CHTED—chronic thromboembolic disease.