Understanding What do they replace plasma with? A Guide to Plasma Substitutes

October 9, 2025 •

4 min read

According to the American Red Cross, about 55% of your blood is plasma, and in cases of severe trauma, infection, or specific autoimmune diseases, medical teams may need to replace it. When considering what do they replace plasma with, clinicians primarily turn to either crystalloid or colloid solutions, depending on the patient’s specific needs.

Quick Summary

Medical treatments for replacing plasma use a variety of solutions, categorized as crystalloids or colloids. These fluids serve different purposes, from simple volume expansion to replenishing vital proteins. The choice of fluid depends on the medical condition, such as severe bleeding, infection, or the targeted removal of harmful substances in the plasma. Albumin and Fresh Frozen Plasma are key options, along with other synthetic alternatives.

Key Points

Two Primary Categories: Plasma is replaced with either crystalloids (salt and water solutions) or colloids (large molecule solutions like albumin).
Crystalloids for Volume : Crystalloids like Normal Saline are primarily used for rapid fluid resuscitation to address overall blood volume loss, though they do not stay in the intravascular space for long.
Colloids for Sustained Expansion: Colloids such as human albumin provide longer-lasting plasma volume expansion and can help replace specific plasma proteins.
Fresh Frozen Plasma (FFP): For patients with deficiencies in clotting factors or other plasma proteins, Fresh Frozen Plasma from donors is the most physiological replacement.
Therapeutic Plasma Exchange: In procedures like plasmapheresis, harmful components are removed from a patient’s plasma and replaced with a healthy fluid, most commonly human albumin.
Synthetic Options Have Declined: Older synthetic colloids like hydroxyethyl starches and dextrans are now used less frequently due to documented side effects like renal dysfunction and coagulopathy.
Selection is Condition-Dependent: The choice of replacement fluid is a complex medical decision based on the underlying condition, balancing immediate stabilization needs with the restoration of specific blood functions.

The Role of Plasma and the Need for Replacement

Blood plasma is the liquid component of blood, carrying essential water, salts, enzymes, hormones, and proteins throughout the body. It is a critical component for maintaining blood pressure, volume, and clotting factors. Medical interventions become necessary when a patient's plasma volume or composition is compromised. The most common reasons include severe blood loss from trauma, burns, shock, or life-threatening infections like sepsis. Additionally, in a procedure known as therapeutic plasma exchange (TPE) or plasmapheresis, a patient’s plasma, which may contain harmful antibodies or proteins, is removed and replaced with a healthier fluid.

The Two Main Categories of Plasma Replacements

Medical professionals primarily replace plasma using two main classes of intravenous fluids: crystalloids and colloids. The choice between them hinges on the clinical scenario, weighing factors like cost, efficacy, and potential side effects.

Crystalloid Solutions

Crystalloids are aqueous solutions containing mineral salts or other water-soluble molecules that can easily pass through capillary membranes. They are the most common fluids used for volume replacement and are readily available and inexpensive.

Normal Saline (0.9% Sodium Chloride): A standard isotonic solution often used for immediate fluid resuscitation. It expands both the intravascular and interstitial fluid spaces.
Lactated Ringer's (LR): A balanced electrolyte solution containing sodium, potassium, calcium, and lactate. The lactate is metabolized to bicarbonate, which can help correct metabolic acidosis.

While effective for initial volume expansion, crystalloids require large volumes to achieve a sustained plasma-expanding effect because they do not remain in the intravascular space for long.

Colloid Solutions

Colloids are solutions containing larger molecules, like proteins or starches, that do not easily cross capillary membranes. This allows them to stay in the intravascular space for a longer period, exerting a higher colloid osmotic pressure to draw fluid from the interstitial space and sustain blood volume.

Specific Types of Colloidal Replacements

Human Albumin: A naturally occurring protein, human albumin solution is derived from pooled human plasma. It is considered a safe and effective replacement fluid, particularly for conditions causing low albumin levels (hypoalbuminemia). It is also the most common replacement fluid in therapeutic plasma exchange.
Fresh Frozen Plasma (FFP): This is donor plasma that is frozen shortly after collection to preserve its valuable clotting factors, immunoglobulins, and other proteins. It is thawed before use and must be matched to the patient's blood type. FFP is the most physiological replacement fluid, as it contains all the proteins found in natural plasma, and is used when a patient has a specific clotting factor deficiency.
Synthetic Colloids: Other colloidal solutions are made from synthetic polymers. Historically, these included dextrans and hydroxyethyl starches (HES), used for their ability to expand plasma volume. However, due to concerns over adverse effects like coagulopathy, renal dysfunction, and allergic reactions, their use has declined, particularly in critically ill patients.

Comparison: Crystalloids vs. Colloids


Feature	Crystalloids	Colloids
Composition	Aqueous solution with small mineral salts and water-soluble molecules (e.g., Normal Saline)	Solution with large, insoluble molecules (e.g., Albumin, Dextran)
Cost	Less expensive	More expensive (especially human-derived products)
Retention	Short duration in the intravascular space	Longer duration in the intravascular space
Mechanism	Replenishes overall fluid volume (intravascular and interstitial)	Primarily expands intravascular volume by increasing osmotic pressure
Key Use	Initial fluid resuscitation, dehydration, electrolyte imbalances	Sustained volume expansion, replacing specific proteins, therapeutic plasma exchange
Risks	Fluid overload, pulmonary edema, electrolyte imbalances	Allergic reactions, coagulopathy, renal issues (especially synthetic)

The Role of Therapeutic Plasma Exchange (TPE)

In conditions where a patient's plasma contains harmful substances, such as autoimmune antibodies in myasthenia gravis or inflammatory proteins in sepsis, TPE is performed. A machine separates the plasma from the blood cells. The unhealthy plasma is removed and discarded, and the blood cells are returned to the patient along with a replacement fluid, such as albumin or FFP, effectively flushing out the harmful components.

Innovations and Considerations

Ongoing research explores newer blood and plasma substitutes, including hemoglobin-based oxygen carriers (HBOCs) and modifications to existing colloids. However, challenges remain, such as achieving stability, avoiding toxicity, and ensuring broad compatibility. The decision to use a specific fluid is a complex medical judgment, balancing the speed of action, duration of effect, potential risks, and cost. Ultimately, for conditions requiring specific protein replacement, human-derived products like albumin and FFP remain gold standards, while for general fluid resuscitation, crystalloids are often the first-line choice.

In emergency situations, particularly with significant blood loss, the immediate goal is to stabilize blood volume and pressure, which crystalloids can achieve quickly and affordably. Subsequent treatment is tailored to address specific deficits, using targeted replacements to restore the proper function of the circulatory system. The appropriate replacement fluid is a critical pharmacological decision impacting patient outcomes.

Conclusion

What do they replace plasma with? The answer is not a single substance but a careful selection from a spectrum of solutions. Depending on the patient's medical condition and the specific components needing replacement, healthcare providers use either inexpensive and readily available crystalloids for general volume expansion or more targeted and costly colloids, like human albumin and Fresh Frozen Plasma. Therapeutic plasma exchange provides a method to remove and replace harmful plasma components with healthy substitutes. These pharmacological decisions are vital for stabilizing critically ill patients and treating a wide range of complex medical issues.

Frequently Asked Questions

Crystalloids are solutions of small molecules that move freely across capillary walls and are primarily used for immediate volume resuscitation. Colloids are solutions of larger molecules that remain in the intravascular space longer, providing more sustained volume expansion.

Human albumin solution is one of the most commonly used colloid fluids for plasma replacement, particularly during therapeutic plasma exchange. For routine fluid resuscitation in emergency situations, crystalloids like normal saline are most often used.

FFP is used when a patient has a deficiency of specific clotting factors, as it contains all the plasma proteins necessary for blood clotting. It is a more complex replacement than albumin and must be matched by blood type.

Yes, synthetic colloids like dextrans and hydroxyethyl starches have been used as plasma expanders. However, due to concerns over adverse effects like renal injury and blood clotting problems, their use has been largely superseded by safer alternatives.

Therapeutic plasma exchange is a procedure where a machine removes a patient's plasma to eliminate harmful substances like autoimmune antibodies. The removed plasma is replaced with a substitute fluid, most often 5% human albumin, to restore volume.

The risks vary by the fluid used. Colloids carry risks of allergic reactions and can interfere with blood clotting. Synthetic colloids have been linked to potential renal damage. Crystalloids carry a risk of fluid overload and electrolyte imbalances.

Plasma replacement is necessary in cases of severe blood loss from trauma or surgery, severe burns, conditions causing critically low protein levels (hypoalbuminemia), shock, sepsis, and autoimmune disorders where harmful antibodies need to be removed via plasma exchange.