What are the indications for plasma donation and for the clinical use of donor plasma?

Indications for Plasma Donation and Clinical Use of Donor Plasma

Donor Eligibility and Selection Criteria

Plasma donors must be healthy adults meeting specific eligibility requirements, with particular attention to infection risk reduction and donor safety.

General Donor Requirements

• Donors must meet FDA and Plasma Protein Therapeutics Association requirements for source plasma donor eligibility, including health screening and testing to exclude viral contamination 1
• Each plasma donation undergoes individual screening for viral markers (direct antigens and indirect antibodies) to exclude contaminated units 2
• Donors should be selected from populations at lower risk of carrying infectious agents, with careful exclusion of high-risk individuals 2

Special Considerations for Convalescent Plasma Donors (COVID-19 Context)

• Optimal timing for convalescent plasma donation is ≥28 days after symptom onset, particularly in donors who experienced fever >38.5°C or fever lasting >3 days 3
• Donors must have complete resolution of symptoms for at least 14-28 days before donation, with negative COVID-19 tests 4
• Donors must test negative for human leukocyte antigen (HLA) antibodies 4
• Required neutralizing antibody titers should be >1:80 (FDA criteria) or >1:640 (optimal criteria), with S-RBD-specific IgG titer ≥1:160 4, 3

Donor Safety Parameters

• Donation volume should not exceed 8 mL/kg body weight or 600 mL to minimize adverse events 5
• Pre-donation systolic blood pressure should be ≥100 mmHg 5
• Donors should wait at least 28 days from symptom onset to reduce vasovagal reactions 5
• Adverse event rate is approximately 5.2%, consisting primarily of mild vasovagal reactions without loss of consciousness 5

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Clinical Indications for Fresh Frozen Plasma (FFP) Use

FFP should be used only for active bleeding with documented coagulopathy or massive hemorrhage, not for prophylactic correction of laboratory abnormalities in non-bleeding patients.

Definitive Indications for FFP Transfusion

Massive Hemorrhage

• Administer FFP in massive bleeding (>10 units RBC in 24 hours or >6 units in 6 hours) using high-ratio transfusion strategies of at least 1:2 FFP:RBC, ideally approaching 1:1 6
• Initial dose: 10-15 mL/kg (approximately 2-4 units or 500-1000 mL for a 70 kg adult) 6
• FFP is indicated when PT >1.5 times normal or INR >2.0, or aPTT >2 times normal with microvascular bleeding 6

Specific Coagulopathy with Active Bleeding

• FFP is indicated for patients with active bleeding and INR >1.5 6
• Use FFP for coagulation intravascular dissemination (DIC) with active bleeding 6
• FFP is appropriate for replacement of coagulation factors during major hemorrhage, particularly in trauma and obstetrics 6

Urgent Warfarin Reversal

• For urgent warfarin reversal with bleeding, doses of 5-8 mL/kg FFP (approximately 1-2 units) are usually sufficient 6
• Prothrombin complex concentrate (PCC) should be preferred over FFP for emergency reversal of oral anticoagulants when available 6

Absolute Contraindications and Inappropriate Uses

The Surviving Sepsis Campaign guidelines recommend against using FFP to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures (weak recommendation, very low quality of evidence) 4

• Do NOT use FFP for volume expansion or albumin replacement 6
• Do NOT use FFP for prophylactic correction of abnormal coagulation tests prior to low-risk invasive procedures in hemodynamically stable patients 6
• Do NOT use FFP to correct coagulopathy in cirrhotic patients without bleeding, as it may increase portal pressure 6
• Do NOT use FFP for mild-moderate coagulation abnormalities in non-bleeding critically ill patients before invasive procedures 6

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Dosing and Administration Guidelines

Standard FFP Dosing

• Initial dose: 10-15 mL/kg body weight, typically 2-4 units (500-1000 mL) for a 70 kg adult 6
• Each unit of FFP contains approximately 250-300 mL 6
• Four units of FFP contain approximately 2 g of fibrinogen 6

Administration Technique

• FFP should be infused as rapidly as clinically tolerated in acute bleeding situations 6
• Use ABO-compatible plasma (group AB if blood type unknown) 6
• FFP can be thawed using dry oven (10 minutes), microwave (2-3 minutes), or water bath (20 minutes) 6
• Once thawed, FFP must be used within 24 hours if stored at 4°C, or within 30 minutes if removed from refrigeration 6

Monitoring and Repeat Dosing

• Recheck coagulation parameters after transfusion to determine need for additional doses 6
• Higher doses (8 mL/kg vs 4 mL/kg) show better response in correcting coagulopathy 6
• Doses below 10 mL/kg are unlikely to achieve the 30% factor concentration threshold needed for hemostasis 6

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Alternative to FFP: Cryoprecipitate for Hypofibrinogenemia

For isolated hypofibrinogenemia, cryoprecipitate is more effective and efficient than FFP.

Cryoprecipitate Indications

• Use cryoprecipitate when fibrinogen <1.5 g/L in major hemorrhage/trauma 7
• Use cryoprecipitate when fibrinogen <2.0 g/L in obstetric hemorrhage 7
• Cryoprecipitate is preferred over FFP because FFP has relatively low fibrinogen content (four units contain only ~2 g fibrinogen) 6

Cryoprecipitate Dosing

• Standard adult dose: two pools (10 units total), providing approximately 4 g of fibrinogen 7
• Alternative weight-based dosing: 50 mg/kg (approximately 15-20 units in a 70 kg adult) for major trauma 7
• Each pool contains 5 units with at least 2 g of fibrinogen 7

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Convalescent Plasma for COVID-19 (Historical Context)

Clinical Use Criteria

• Convalescent plasma was listed by FDA as emergency investigational therapy for serious or life-threatening COVID-19 4
• Severe disease defined as: dyspnea, respiratory rate ≥30/min, SpO2 ≤93%, PaO2/FiO2 <300, and/or lung infiltrates >50% within 24-48 hours 4
• Life-threatening disease defined as: respiratory failure, septic shock, and/or multiple organ dysfunction 4

Dosing for Convalescent Plasma

• Typical dose: 200-250 mL of ABO-compatible convalescent plasma, with some protocols using two consecutive transfusions 4
• Donors required neutralizing antibody titer >40 and ELISA antibody titer >1:1000 4

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Critical Safety Warnings

Transfusion-Related Risks

• Transfusion-related acute lung injury (TRALI) is the most serious complication, with FFP being one of the most frequently implicated products 6
• Other risks include: transfusion-associated circulatory overload (TACO), allergic reactions, pathogen transmission, ABO incompatibility 4, 6
• Monitor for signs of circulatory overload, TRALI, and metabolic derangements during massive transfusion 6

Viral Safety Measures

• All plasma undergoes nucleic acid amplification testing (NAT/PCR) for viral genomes, with mandatory HCV RNA testing in Europe 2
• Plasma products undergo viral inactivation through solvent-detergent treatment and pasteurization 2
• Additional viral reduction includes nanofiltration and specific dry-heat treatments 2