Hemophilia C, caused by Factor XI deficiency, presents a unique diagnostic challenge due to its variable bleeding phenotype. Although often milder than Hemophilia A or B, accurate diagnosis and severity assessment are critical—especially in surgical or trauma settings where bleeding risk must be anticipated. Analytical assays play a vital role by screening for intrinsic pathway abnormalities (via aPTT), confirming the diagnosis with a specific Factor XI activity assay, and evaluating the functional consequences of reduced Factor XI through global assays like Thrombin Generation Assay (TGA) and Thromboelastography (TEG). Together, these tests provide a comprehensive picture of the hemostatic balance, guiding personalized management and treatment strategies for patients with Hemophilia C.

Analytical PK Assays

What it measures:
PK assays in Hemophilia C evaluate the in vivo kinetics of Factor XI, particularly when replacement therapies or novel agents are used.

Why this is important for Hemophilia C:
Given the variable bleeding phenotype in Hemophilia C, precise PK profiling aids in optimizing dosing regimens and ensuring sufficient hemostatic protection during high-risk procedures.

Immunogenicity Assays

What it measures:
These assays monitor the development of anti-Factor XI antibodies, which, although less common than inhibitors in Hemophilia A/B, can still impact treatment outcomes.

Why this is important for Hemophilia C:
Assessing immunogenicity in Hemophilia C helps in identifying patients who may require alternative therapies or immune tolerance induction protocols.

Activated Partial Thromboplastin Time (aPTT)

What it measures:
The time required for plasma to clot via the intrinsic and common coagulation pathways.

Why this is important for Hemophilia C:
Factor XI deficiency typically prolongs aPTT, serving as an essential initial screening tool to identify potential intrinsic pathway abnormalities.

Factor XI Activity Assay

What it measures:
The functional activity of Factor XI in plasma.

Why this is important for Hemophilia C:
This assay is the definitive test for diagnosing Hemophilia C, allowing clinicians to quantify the severity of Factor XI deficiency and tailor treatment accordingly.

Thromboelastography (TEG®)

What it measures:
The viscoelastic properties of whole blood during clot formation, providing parameters such as clot initiation, strength, and stability.

Why this is important for Hemophilia C:
TEG offers a global assessment of clot dynamics, revealing potential impairments in clot stability and formation due to Factor XI deficiency—information that is especially valuable during surgical planning or acute bleeding episodes.

Thrombin Generation Assay (TGA)

What it measures:
The rate and total amount of thrombin generated in plasma following coagulation activation.

Why this is important for Hemophilia C:
The thrombin generation assay (TGA) is a global coagulation test that continuously measures the rate and total amount of thrombin formed in plasma after coagulation is triggered by adding defined concentrations of tissue factor (TF), phospholipids, and calcium. Due to the way that the assay is triggered, it is not inherantly sensitive to intrinsic coagulation factor deficiencies such as  hemophilia A (FVIII) and hemophilia B ( FIX). However, by varying the trigger reagent composition—using low TF (≈0.5 pM), the assay can be directed to maximize sensitivity for bleeding‑related factor deficiencies such as Hemophilia C (FXI deficiency). In Factor XI testing, performing TGA in citrated plasma with a low TF trigger selectively accentuates FXI’s modest contribution to thrombin propagation; under these conditions, endogenous thrombin potential and peak thrombin generation correlate closely with FXI levels and clinical bleeding risk in FXI‑deficient individuals, making TGA a sensitive functional assay for FXI activity and therapeutic monitoring.

Chromogenic Factor XI Assays

What it measures:
These assays determine the functional activity of Factor XI using a two-step enzymatic reaction that produces a colorimetric signal. The chromogenic method quantifies Factor XI activity by measuring the rate of substrate conversion, offering a direct, quantitative readout.

Why this is important for Hemophilia C (Factor XI deficiency):
Chromogenic Factor XI assays provide an alternative to traditional one-stage clot-based assays. They tend to be less affected by plasma inhibitors and interfering substances, which can be particularly beneficial in detecting mild or variant Factor XI deficiencies. This method enhances diagnostic specificity and improves monitoring accuracy in patients with Hemophilia C.