What are the considerations for using leukocyte-rich versus leukocyte-poor platelet-rich plasma (PRP) in patients with a history of inflammatory conditions?

Leukocyte-Rich vs Leukocyte-Poor PRP in Patients with Inflammatory Conditions

For patients with a history of inflammatory conditions, leukocyte-poor PRP (LP-PRP) should be strongly preferred over leukocyte-rich PRP (LR-PRP) to minimize inflammatory mediator production and synoviocyte toxicity. 1

Critical Evidence on Inflammatory Response

Direct Synovial Toxicity with LR-PRP

• LR-PRP causes significantly greater synoviocyte death (4.9%) compared to LP-PRP (0.72%), representing nearly 7-fold higher cell death in synovial tissue. 1
• Treatment with LR-PRP produces dramatically elevated inflammatory mediators: IL-1β levels reach 1.53 pg/mL (14-fold higher than LP-PRP) and IL-6 levels reach 32,097 pg/mL in synoviocyte cultures. 1
• These findings are particularly critical because fibroblast-like synoviocytes compose 80% of normal human synovium and produce cytokines and matrix metalloproteinases that mediate cartilage catabolism. 1

Paradoxical Anti-inflammatory Profile in OA

• Recent 2023 data from knee osteoarthritis patients shows LR-PRP expresses significantly more IL-1Ra (interleukin-1 receptor antagonist), IL-4, and IL-8 compared to LP-PRP, suggesting potential anti-inflammatory properties in chronic low-grade inflammation. 2
• However, LR-PRP also demonstrates significantly elevated MMP-9 (matrix metalloproteinase 9), indicating potential chondrotoxicity that may outweigh anti-inflammatory benefits. 2

Clinical Decision Algorithm

For Acute Inflammatory Conditions or Intra-articular Use

• Use LP-PRP exclusively to avoid synoviocyte death and inflammatory mediator surge. 1
• Ensure preparation methods minimize leukocyte contamination, as even low-level leukocyte presence triggers inflammatory cascades. 1
• Verify RBC-free formulation, as red blood cell concentrate causes even greater synoviocyte death (12.5%) than LR-PRP. 1

For Chronic Low-Grade Inflammation (e.g., Established OA)

• Consider LR-PRP cautiously in patients with Kellgren-Lawrence grade 2-3 knee OA where chronic inflammation predominates. 2
• However, the elevated MMP-9 expression with LR-PRP creates significant concern for accelerated cartilage degradation, making LP-PRP the safer default choice. 2
• Monitor for progression, as mechanistic clinical trials are still needed to determine long-term effects on OA progression. 2

For Wound Healing Applications

• LR-PRP demonstrates superior outcomes in pressure ulcer healing, with higher wound healing rates on day 7 and more prominent angiogenesis compared to LP-PRP. 3
• For non-articular wound healing in patients with inflammatory conditions, LR-PRP may be preferred as it regulates inflammation more effectively while promoting angiogenesis. 3

Preparation Standardization Requirements

Critical Anticoagulant Selection

• Use trisodium citrate, ACD (acid citrate dextrose), or CPD (citrate phosphate dextrose) as anticoagulants—never use EDTA, which is explicitly contraindicated with a median expert score of 8/9. 4
• Collect blood in plastic tubes to avoid contact activation. 4

Centrifugation Protocol

• Double-spin protocol recommended: first spin at 900 rpm for 5 minutes, second spin at 2000 rpm for 15 minutes. 4
• This protocol has been validated in randomized controlled trials demonstrating significant clinical improvement. 4

Leukocyte Reduction Technique

• For LP-PRP preparation, use gradient centrifugation with Percoll or similar agents to separate granulocytes and mononuclear cells from the platelet layer. 5
• Optional washing step with saline reduces platelet contamination and further purifies the preparation. 5

Common Pitfalls to Avoid

Assuming All PRP is Equivalent

• Different preparation techniques result in significant variations in platelet yields, concentration, purity, viability, and activation status that directly impact clinical efficacy. 6, 7
• The field suffers from severe lack of standardization in preparation methods, terminology, purity, content, and quality control. 6

Ignoring Leukocyte Differential Composition

• Even when systems claim to produce LP-PRP at lowest hematocrit settings, they may still concentrate leukocytes 2-5 times over baseline. 8
• Some systems produce lymphocyte-predominant (>89%) profiles with reduced neutrophils (<11%), which may have different inflammatory effects than neutrophil-rich preparations. 8

Overlooking RBC Contamination

• Red blood cell contamination causes the highest synoviocyte death (12.5%) and significant interferon-γ production (64.34 pg/mL). 1
• Ensure RBC-free formulations for all intra-articular applications. 1

Safety Considerations

• PRP is clinically safe when prepared using sterile autologous technique with minimal immunogenicity risk. 6, 4
• Proper sterile technique is essential during preparation and application to prevent contamination. 7
• The safety concern is not the PRP itself but rather the inflammatory mediator profile and cellular toxicity based on leukocyte content. 1