Plasma Therapy

Plasma has been used as preventive therapy for treatment of failure of passive transfer and therapeutically to raise antibody levels in ill foals less than 2 months of age. The majority of neonatal foals with infectious conditions such as septicemia have failure of passive transfer (IgG < 400 mg/dl). However, some studies indicate that, with good management, healthy foals with serum IgG of 200-400 mg/dl have only slight risk of acquiring illness [1].

I. Indications

Editor's Comment - The controversy of which foals should receive plasma transfusions will continue until more studies on the protective and therapeutic effects of plasma are conducted.

1. Failure of Passive Trans

1. At this time all foals with IgG at 18-24 hours of age < 200 should be treated with plasma
2. Plasma transfusion is optional for healthy, low risk foals with IgG of 400-600 mg/dl at 24 hours and good post birth management.
3. Benefit of raising the serum IgG with a plasma transfusion has limited evidence for healthy, low risk foals with IgG of 400 mg/dl at 24 hours of age and good post birth management.

2. Infectious Conditions

1. Foals with septicemia may benefit from plasma transfusions to raise serum IgG to the 600-800 mg/dl range.
2. When infections are present always check IgG post plasma transfusion after 24 hrs. Levels of serum IgG post transfusion may be quite variable.

3. For High-Risk Foals

1. Some foal conditions result in poor colostrum absorption.

1. Prematurity
2. Decreased gastrointestinal motility (minimal gut sounds) occurs nonspecifically in many stressed, ill foals.

2. Start plasma immediately following birth in premature foals, weak foals with poor gastrointestinal motility, and severely hypothermic and hypoglycemic foals.
3. Additional IgG from plasma transfusion in high-risk foals may be beneficial.

1. Raising levels to 600-800 mg/dl has been suggested.
   Editor's Comment - Higher levels of serum IgG increase the chances of providing specific antibodies to pathogens and may be beneficial.

4. Severe disseminated intravascular coagulopathy (DIC) with life-threatening hemorrhage in conjunction with heparinization.

1. Plasma supplies antithrombin III which is the mechanism whereby heparinization produces a reduction in the hypercoagulable state.
2. Must treat the primary disorder causing the DIC.
3. Plasma administered to patients in DIC may exacerbate organ dysfunction with ongoing thrombin activation. It is important to monitor liver and kidney function and fibrin split products if using plasma in DIC.

II. Types of Plasma

1. Anti-endotoxin (J-5) Plasma

1. Made by vaccination of donors with a modified E. coli (J5).
2. Contains antibodies against the core lipopolysaccharide and should provide cross protection to a variety of Gram negative infections.

2. Anti-endotoxin (Salmonella typhimurium) Plasma

1. Plasma donors vaccinated with mutant S. typhimurium.
2. Protection by similar mechanism as J-5. i.e. cross protection against Gram negative infection with core antibodies.
3. Source - Endoserumtm - IMMVAC, Inc.,
   Columbia, MO 65201.
   Telephone 800-944-7563.
   www.immvac.com/

3. Anti-Rhodococcus equi hyperimmune plasma (See Chapter 29)
4. Botulism - See Infections (Chapter 28)
5. Platelet rich plasma (PRP)

1. This is used in foals with post foaling thrombocytopenia presumed associated with ingestion of antibody to the foal's thrombocytes.
2. Frozen plasma not a source of platelets
3. Fresh harvested plasma is best - Can order from plasma companies for next day delivery

III. Sources of Plasma

1. Commercial availability

1. Use of commercial USDA approved plasma is desirable. Donors may be hyperimmunized, tested for disease conditions and plasma is free of red blood cells.
2. Sources of plasma
   USA

1. Plasmavacc Inc. (formerly: Veterinary Dynamics)
   All types of equine plasma available.
   1535 Templeton Road, Templeton, CA 93465;
   800-654-9743
   805-434-0321
   www.plasvaccusa.com
2. Lake Immunogenics, Inc.,
   348 Berg Road, Ontario, New York, 14519,
   800-648-9990,
   716-265-1973.
   www.lakeimmunogenics.com
3. MgBiologics - Ames, Iowa
   Tel: 515-769-2340.
   www.mgbiologics.com

Europe

1. Veterinary Immunogenics Ltd
   www.veterinaryimmunogenics.com
2. Kraeber GmbH & Co.
   www.kraeber.de

Australia and New Zealand

1. Plasmavacc Inc
   www.plasvacc.com

Canada

1. Centaur Pharmaceuticals,
   503 Imperial Road Unit #3, Guelph, Ontario N1H 6T9,
   Phone 519-824-9570,
   FAX 519-824-3553.
   www.centaurva.com

3. Make your own plasma.
   Editor's Comment - Be careful - Anaphylaxis risk is much higher with untested plasma! Plasma donors need to be tested.

1. Pre-selection of suitable blood/plasma donors on a large breeding farm or in a large practice is possible using blood typing procedures.
2. The preferred donor is negative for A, Q, and C erythrocyte antigens and contains high level of antibody to indigenous pathogens.

1. Contains no common anti-erythrocyte antibodies (universal donor).
2. Alternately, blood from the dam, a Shetland pony, or unrelated gelding with no history of transfusion, may be used if the situation warrants.

3. Collection

1. Plasma collected by plasmapheresis is preferred.
2. Centrifugation can be used but plasma may not be RBC free.

4. Plasma can be administered immediately after collection or frozen and subsequently thawed at the time of administration. Frozen storage should not exceed 3 years.

1. Quantitate immunoglobulin content of plasma if possible.
2. Assess for anti-RBC alloantibodies which could produce neonatal isoerythrolysis.

5. Storage of non-frozen plasma increases the risk of contamination - Use immediately after collection or thawing. Do not refrigerate non-commercial harvested plasma longer than 12-24 hours.

IV. How Much Plasma to Administer

Editor's Comment - It is difficult to determine exactly how much plasma is needed to raise IgG by a specific amount in an individual foal. In general, septic foals need to have more plasma administered (2-3 times the amount) to raise the IgG by 200 mg/dl compared to a healthy foal being treated for FPT.

1. Volume Determination (1 liter/45 Kg foal)

1. A dose of 20 ml/Kg of average IgG concentration plasma results in an increase of 50-200 mg/dl serum IgG. Consequently, always check the serum IgG of the foal post treatment.
2. Greater than 2 (4-6) liters of plasma may be needed to elevate IgG to 600-800 mg/dl in septicemic foals.

2. Milligram Amount Determination [2].

1. A dose of 200 mg/kg of IgG in normal foals raised the serum IgG by 450 mg IgG/dl.
2. A dose of 400 mg/Kg of IgG in normal foals raised the serum IgG by 575 mg/dl.
3. Serum IgG decreased by 30% from day 1 to day 7 of age, post plasma transfusion.
4. A dose of 500 mg/kg IgG has been recommended for infected patients.

3. Administration (I.V.)

1. Experience suggests 1 liter/45 Kg healthy foal can be administered over a 15-minute period; slower if giving other fluids (maximum 2 L/hr).
2. In sick foals or when giving greater than 2 liters, rate should not exceed 2 liters/hour.

1. 20 ml/kg/hr delivers 1 liter/hour.

3. Warm plasma to body temperature before administration.
   Editor's Comment - Must protect plasma by placing the plasma bag in a protective-sterile bag to thaw. Otherwise contamination at ports may occur.

1. Do not thaw in very hot water or in a microwave oven; use tepid water.
2. Use within 12-24 hours of thawing.

4. Oral administration of plasma

1. In foals still capable of absorbing IgG (less than 16 hours of age).
   Editor's Comment - This is very inefficient - Better to give intravenously.
2. In foals with severe gastroenteritis may protect the bowel.

V. Complications

1. Plasma transfusion is believed to be generally safe. Infrequent complications include:

1. Mild reactions of tachypnea and trembling.
2. Anaphylaxis.
3. RBC destruction if the plasma has sufficient amount of antibodies to foal's erythrocytes.
4. Volume overload with subsequent hypertension

2. If a transfusion reaction develops, i.e., tachypnea, dyspnea, shaking, sweating:

1. Slow the rate of administration or stop for 5-10 minutes and restart.
2. Discontinue the administration of plasma if signs persist.
3. Epinephrine IV - 1 cc/45 kg foal of the 1:1000 for severe reactions and shock.
4. Antihistamine - IV (May produce anaphylaxis itself).
5. Prednisolone sodium succinate - 100 mg - 200 mg IV

3. Sensitization of the foal with red blood cell contamination using non-commercial plasma is a potential concern although no documentation of it developing has been reported to date.
4. Serum hepatitis has not occurred in horses less than 18 months of age and does not appear to be a risk of plasma therapy in neonatal foals.