What is the difference in clotting factors between plasma and serum?

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Clotting Factors in Plasma vs. Serum

Plasma contains all clotting factors, while serum contains none of the consumed clotting factors (I, II, V, VIII) because they are depleted during the coagulation process that forms the clot. 1

Key Differences in Clotting Factor Content

Plasma Composition

  • Plasma contains approximately 70% of normal levels of all clotting factors when prepared as fresh frozen plasma (FFP), including factors I (fibrinogen), II (prothrombin), V, VII, VIII, IX, X, XI, XII, and XIII 2
  • All pro- and anticoagulant factors remain intact in plasma because anticoagulants (citrate, EDTA, or heparin) prevent the coagulation cascade from proceeding 2
  • Factor levels remain stable when plasma is properly stored, though Factor VIII may decline by 13-23% after 24 hours at room temperature 3

Serum Composition

  • Serum is the fluid remaining after blood has clotted, meaning all clotting factors involved in fibrin formation have been consumed or removed 1
  • Factors I (fibrinogen), II, V, and VIII are significantly depleted or absent because they are consumed during clot formation 1
  • Some residual factors may remain (VII, IX, X, XI, XII) but at unpredictable and clinically insignificant levels 1

Clinical Implications

When Plasma is Required

  • For coagulation factor replacement in bleeding patients, only plasma (or concentrated factor products) can provide functional clotting factors 2
  • FFP requires PT or APTT >1.5 times normal to justify transfusion in bleeding patients 2
  • Plasma must be given at minimum 10-15 mL/kg to achieve clinically significant increases in clotting factor levels 2

Laboratory Testing Considerations

  • Coagulation studies (PT, APTT, fibrinogen) require plasma samples with anticoagulant, never serum 1
  • Serum causes artifactual changes in some analytes due to the coagulation process itself, making plasma preferable for many assays 1
  • The choice between serum and plasma affects turnaround time, with plasma available immediately while serum requires 30-60 minutes for clot formation 1

Important Caveats

A critical pitfall: FFP contains only ~70% of normal clotting factor levels, not 100%, meaning large volumes are required for adequate replacement 2. This is why prothrombin complex concentrates (containing 25 times the concentration of vitamin K-dependent factors) are often preferred over FFP for rapid reversal 2, 4.

Another common misconception: Plasma and serum are not interchangeable for any clinical purpose—plasma is for coagulation support and specific laboratory tests, while serum is primarily for chemistry and immunology testing where clotting factors would interfere 1.

References

Research

Serum or plasma? An old question looking for new answers.

Clinical chemistry and laboratory medicine, 2020

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Reversal of Anticoagulation with 4-Factor Prothrombin Complex Concentrate

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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