How do patients with dysfibrinogenemia present?¶
Answer: Congenital fibrinogen disorders are rare inherited quantitative (afibrinogenemia, hypofibrinogenemia) or qualitative (dysfibrinogenemia, hypodysfibrinogenemia) abnormalities of fibrinogen. They typically present with bleeding complications; however, equally important is the risk of thrombotic disease (both arterial and venous).
Proposed mechanisms include impaired thrombin clearance due to a lack of fibrin formation and structurally abnormal fibrin clots that promote thrombin release into the circulation or hinder fibrinolysis. In afibrinogenemia, the absence of fibrinogen leads to increased circulating free thrombin, while in dysfibrinogenemia, structurally abnormal fibrinogen enhances thrombotic risk.
— The thrombotic paradox in congenital fibrinogen deficiencies: from pathophysiology to practice (RPTH 2025)
Registry data — Congenital fibrinogen disorders: a retrospective clinical and genetic analysis of the Prospective Rare Bleeding Disorders Database (Blood Adv 2024), 123 patients:
| Subtype | Any bleeding | Thrombosis |
|---|---|---|
| Afibrinogenemia (n = 30) | 100% | 11% |
| Hypofibrinogenemia (n = 33) | 66% | 10% |
| Dysfibrinogenemia (n = 55) | 58% | 6% |
| Hypodysfibrinogenemia (n = 5) | 40% | 0% |
| All (n = 123) | 70% | 8% |
- Gynecologic and obstetric complications — Gynecologic and obstetric complications in women with congenital fibrinogen disorders: insights from the Prospective Rare Bleeding Disorders Database (RPTH 2025):
In qualitative CFDs, live birth, PPH, and miscarriage rates were 64%, 23%, and 36%.
- Distinct from fibrinogen amyloidosis: the genetic abnormalities in fibrinogen disorders (typically the thrombin binding site) are distinct from those that cause hereditary fibrinogen Aα-chain amyloidosis (C-terminal region of the fibrinogen Aα chain, most commonly E526V).
Related: 0032 — Dysfibrinogenemia presentation in women covers the gynecologic and obstetric picture from the same registry in detail.
Source: The thrombotic paradox in congenital fibrinogen deficiencies: from pathophysiology to practice