What are the expected lab results in a patient with Afibrinogenemia, including prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and reptilase time?

Laboratory Findings in Afibrinogenemia

The expected laboratory results in afibrinogenemia include elevated PT, elevated aPTT, elevated thrombin time (TT), and elevated reptilase time, corresponding to option D.

Pathophysiology and Laboratory Profile

Afibrinogenemia is a rare bleeding disorder characterized by the absence or severe deficiency of functional fibrinogen in the plasma. This condition has significant implications for both coagulation pathways, resulting in a distinct pattern of laboratory abnormalities:

• Prothrombin Time (PT): Markedly elevated due to the absence of fibrinogen, which is essential for the final common pathway of coagulation 1
• Activated Partial Thromboplastin Time (aPTT): Significantly prolonged as fibrinogen is required for clot formation in both intrinsic and common pathways 1
• Thrombin Time (TT): Extremely prolonged or unmeasurable since this test directly measures the conversion of fibrinogen to fibrin by thrombin 1, 2
• Reptilase Time: Elevated because reptilase, like thrombin, cleaves fibrinogen to form fibrin, and in the absence of fibrinogen, this reaction cannot occur 3

Distinguishing Features from Other Coagulopathies

Afibrinogenemia must be differentiated from other coagulation disorders:

• Disseminated Intravascular Coagulation (DIC): While DIC also shows prolonged PT, aPTT, and TT with low fibrinogen, it typically presents with thrombocytopenia and elevated fibrin degradation products (FDPs) 1
• Liver Disease: Shows prolonged PT and sometimes aPTT, but fibrinogen is often normal or elevated as an acute phase reactant 1
• Heparin Therapy: Prolongs aPTT and TT but typically has minimal effect on reptilase time 1

Diagnostic Approach

When afibrinogenemia is suspected:

1. Initial Screening Tests: Order PT, aPTT, TT, and reptilase time 1
2. Confirmatory Testing: Quantitative fibrinogen assay, which will show either undetectable levels or trace amounts (<10 mg/dL) 3
3. Additional Testing: Fibrinogen antigen assay to differentiate between quantitative deficiency (afibrinogenemia) and qualitative deficiency (dysfibrinogenemia) 1

Clinical Correlation

The severity of bleeding in afibrinogenemia correlates with fibrinogen levels:

• Levels <10% of normal are associated with severe bleeding manifestations
• Even minimal fibrinogen levels (10% of normal) can significantly improve platelet function and hemostasis 2

Common Pitfalls to Avoid

• Misinterpretation of Normal Platelet Count: Despite normal platelet counts, platelet function is impaired due to lack of fibrinogen 2
• Inadequate Treatment Monitoring: Standard PT and aPTT may normalize with minimal fibrinogen replacement while TT remains abnormal 3
• Overlooking Increased Thrombin Generation: Paradoxically, some patients with afibrinogenemia show increased prothrombin activation fragments (F1+2), suggesting compensatory mechanisms 4

Summary

In afibrinogenemia, all four coagulation tests (PT, aPTT, TT, and reptilase time) are prolonged due to the absence of fibrinogen, which is essential for the final common pathway of coagulation. This pattern distinguishes afibrinogenemia from other coagulation disorders and guides appropriate therapeutic interventions.