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Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay
Published on: September 9, 2012
Activated protein C resistance as measured by residual factor V after Russell's viper venom and activated protein C
Maurizio Zangari1, Tamara Berno, Fenghuang Zhan
1Myeloma Program, Division of Hematology, University of Utah, Salt Lake City, Utah, USA. maurizio.zangari@hsc.utah.edu
Abstract:
Increased risk of venous thromboembolism (VTE) has been described in multiple myeloma patients, particularly when exposed to immunomodulatory drugs. Epidemiological studies have shown that monoclonal gammopathy of undetermined significance (MGUS) patients also have an increased risk of VTE compared with normal individuals. Acquired activated protein C resistance (APC-R) is an independent risk factor for VTE in hematologic malignancies. We reviewed the records of patients with multiple myeloma and MGUS for APC-R by PEFAKIT APC-R test and compared them to normal individuals. We excluded from the analysis patients with a documented factor V Leiden mutation. The PEFAKIT APC-R is a plasma-based functional prothrombin assay based on ratio of patient clotting time with and without APC. Thirty-three MGUS and 93 multiple myeloma patients were compared with 39 normal individuals. Baseline characteristics from the three groups were similar in terms of age, sex, and performance status. The median APC-R for multiple myeloma, MGUS, and controls were 1, 1.06, and 1.1, respectively. Multiple myeloma patients compared to normal individuals had significantly shorter APC-R (P=0.0012). No significant difference was observed between MGUS and normal individuals (P=0.17). After analyzing APC-R values and multiple coagulation parameters, a significant inverse correlation was found between APC-R and fibrinogen (P=0.0000001) and D-dimer (P=0.045) serum levels and a direct correlation with prothrombin time value (P=0.034). The Pefakit APC-R test measured as continuous variable shows a statistically significant decrease in patients with myeloma compared to normal individuals.
Insights
Multiple myeloma patients show significantly reduced activated protein C resistance (APC-R), a risk factor for venous thromboembolism (VTE). Monoclonal gammopathy of undetermined significance (MGUS) patients did not show a significant difference in APC-R compared to healthy individuals.
Area of Science:
- Hematology
- Thrombosis
- Clinical Coagulation
Background:
- Multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS) are associated with an increased risk of venous thromboembolism (VTE).
- Acquired activated protein C resistance (APC-R) is an established independent risk factor for VTE in hematologic malignancies.
Purpose of the Study:
- To investigate acquired activated protein C resistance (APC-R) in patients with multiple myeloma and MGUS.
- To compare APC-R levels between these patient groups and healthy individuals using the PEFAKIT APC-R test.
Main Methods:
- A comparative study analyzing records of 93 multiple myeloma patients, 33 MGUS patients, and 39 normal individuals.
- The PEFAKIT APC-R test, a plasma-based functional prothrombin assay, was used to measure APC-R.
- Patients with a documented factor V Leiden mutation were excluded.
Main Results:
- Multiple myeloma patients exhibited significantly lower APC-R compared to normal individuals (P=0.0012).
- No significant difference in APC-R was found between MGUS patients and normal individuals (P=0.17).
- APC-R showed significant inverse correlations with fibrinogen and D-dimer levels and a direct correlation with prothrombin time.
Conclusions:
- Multiple myeloma is associated with acquired APC-R, potentially contributing to their increased VTE risk.
- MGUS patients do not appear to have significantly altered APC-R compared to healthy controls.
- The PEFAKIT APC-R test effectively identified reduced APC-R in multiple myeloma.
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