Platelet-Rich Plasma (PRP) & Orthobiologics

Orthobiologics are biologically active preparations used to augment musculoskeletal healing, and platelet-rich plasma (PRP) is the most widely used and best-studied of them. The appeal is simple: take a small volume of the patient's own blood, concentrate the platelets, and deliver their growth-factor payload to a degenerate or injured tissue to nudge it towards repair.

Why examiners like it. Because it is autologous and office-based, PRP has spread rapidly into sports medicine and arthroplasty practice, ahead of robust evidence. That makes it a favourite viva theme, and the examiner is testing judgement: can you separate the genuine level-1 signal in knee osteoarthritis from the hype and the heterogeneity?

What is examinable. The science is concrete: the growth factors, their platelet source, and the leukocyte axis. The evidence is uneven, strong for knee OA, mixed for tendinopathy and weak or low-level for most other uses, and lack of standardisation is the recurring criticism.

What it is. PRP is an autologous preparation in which the patient's own blood is centrifuged to concentrate platelets, commonly several-fold above the whole-blood baseline, into a small plasma volume.

What it delivers. Platelets store growth factors in their alpha-granules, not their dense granules, and release them on activation: PDGF, TGF-β, VEGF, IGF-1, EGF and bFGF, among others. The rationale is that a bolus of these factors, delivered to an injured or degenerate tissue, promotes cell proliferation, matrix synthesis, angiogenesis and modulation of inflammation, augmenting the local healing environment.

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At the point of care. Anticoagulated whole blood is centrifuged and separates by density into plasma on top, a thin buffy coat of platelets and leukocytes in the middle, and red cells at the bottom. PRP preparation harvests and concentrates the platelet-rich plasma and buffy-coat fraction, and the proportion of leukocytes captured defines whether the product is leukocyte-rich or leukocyte-poor.

One spin or two. A single soft spin concentrates platelets in plasma while keeping some red and white cells. A double spin starts with a soft spin that separates plasma from red cells, then adds a harder second spin that achieves a higher platelet concentration and allows selective pipette harvest at the buffy-coat interface. The operator can then include or exclude the leukocyte layer, and how much buffy coat is retained changes the final product.

Liquid or matrix. The product may be used as a liquid, often activated with calcium chloride or thrombin to trigger granule release, or as a fibrin matrix, platelet-rich fibrin (PRF).

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"PRP" is not one product. Platelet dose, leukocyte content, activation method and spin protocol all vary, so two PRP injections can be biologically very different. This is the single most examined caveat: always specify the preparation, and cite the leukocyte content when you quote a trial.

Leukocyte-poor PRP (LP-PRP). Low white-cell content, sometimes called 'pure' PRP. It is generally preferred for intra-articular use, as in knee OA, because leukocytes and their catabolic enzymes and cytokines can provoke a more inflammatory flare in a joint. Level-1 data favour LP-PRP over LR-PRP for knee OA.

Leukocyte-rich PRP (LR-PRP). Higher white-cell content, and more pro-inflammatory. It has been advocated for some tendinopathies, where a controlled inflammatory and anabolic stimulus may help, though comparative evidence is limited.

Platelet dose. Alongside the leukocyte axis, the absolute number of platelets delivered, the 'P' of PAW, is increasingly recognised as a key determinant of efficacy. Clinically effective PRP generally needs a meaningful concentration above whole-blood baseline: a commonly cited target is around a five-fold concentration, or an absolute dose on the order of ~10 billion platelets for knee OA. There is an apparent dose-response, and too low a dose under-treats.

More is not always better. The relationship may be bell-shaped: very high platelet concentrations can paradoxically be inhibitory in laboratory studies. This is why two leukocyte-poor PRPs from different systems can still behave differently, and why reporting the platelet dose, and not only LP versus LR, matters when trials are compared.

Reporting systems. Because products vary so much, classification systems exist to standardise reporting. The headline distinction for the exam is LP versus LR, but know the systems by name:

• PAW (DeLong): Platelets, Activation, White cells
• Mishra
• PLRA: Platelet, Leukocyte, Red cell, Activation

PRP is autologous and very safe, but examiners expect the practical caveats.

Contraindications. Anticoagulation is a relative contraindication. Relative or absolute contraindications include:

• Active infection, local or systemic
• Active malignancy, especially at the injection site
• Critical thrombocytopenia or platelet-function disorders
• Significant anaemia

The NSAID rule. NSAIDs and aspirin inhibit platelet COX and granule release, so they are usually withheld around the procedure, commonly for about a week before and one to several weeks after. A recent intra-articular corticosteroid may blunt the anabolic response, so the two are spaced apart.

Adverse effects. The main one is a self-limiting post-injection pain or inflammatory flare, more common with leukocyte-rich PRP; serious complications such as infection are rare. Counsel about the transient flare, the need to pause anti-inflammatories, and the out-of-pocket cost.

Stem cells. MSC therapy is largely investigational and regulated; do not overstate it in a viva.

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The honest caveat. Across all orthobiologics the limiting issue is lack of standardisation and regulation. Dose, cell or platelet content, processing and activation vary between systems and studies, outcomes are heterogeneous, and many indications rest on low-level evidence.

The mature position. Use the best-supported indications, such as LP-PRP for knee OA; specify the preparation; counsel honestly about uncertainty and cost; and avoid overselling unproven uses.

Knee osteoarthritis. This is where the evidence is strongest. Two level-1 meta-analyses show that intra-articular PRP gives better pain relief and function than hyaluronic acid at 6 and 12 months, with IKDC and WOMAC scores improved and no increase in adverse events, and that leukocyte-poor PRP is associated with better outcomes than leukocyte-rich. In Belk et al. (18 level-1 RCTs) the mean WOMAC improvement was 44.7%PRP versus 12.6%HA.

Where it fits in OA. PRP is a non-operative option, used particularly in mild-to-moderate OA for symptomatic relief and to potentially delay surgery.

Tendinopathy. The evidence is more mixed. PRP is used for recalcitrant lateral epicondylitis and other tendinopathies where conservative measures have failed; some trials show benefit over corticosteroid at longer follow-up, but heterogeneity and variable preparations limit firm conclusions. Rotator cuff repair augmentation and many other tendon and ligament indications have inconsistent evidence.

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Other indications. PRP and related biologics have been trialled in muscle injury, cartilage and osteochondral lesions, bone healing and nonunion, and surgical augmentation, with variable and often low-quality evidence. Use should be evidence-guided, and the patient counselled honestly about uncertainty and out-of-pocket cost.