Topical Autologous Blood Clot Therapy

An Introduction and Development of Consensus Panel to Guide Use in the Treatment of Complex Wound Types

Robert J. Snyder, DPM, MBA, MSc, CWSP, FFPM RCPS (Glasgow); Vickie Driver, DPM, MS; Windy Cole, DPM, CWSP; Warren S. Joseph, DPM; Alez Reyzelman, DPM; John C. Lantis II, MD; Jarrod Kaufman, MD; Thomas Wild, MD

Disclosures

Wounds. 2022;34(9):223-228. 

In This Article

Abstract and Introduction

Abstract

Complex or hard-to-heal wounds can be acute or chronic; the complexity is based on patient-specific local, systemic, and psychosocial factors. Use of autologous tissue can be a significant adjunct to wound closure. Grafts and flaps are the most common autologous tissue used in wound reconstruction. However, patient factors, wound size, and exposed structures may preclude using these methods as primary or even secondary closure techniques. Alternative autologous tissue therapies include those derived from adipose, epidermis or dermis, bone marrow, and blood. Limitations of these treatment modalities include access-related difficulty, cost, creation of a secondary donor site, use of singular or limited cell types, and sparse or contradictory evidence basis of their efficacy of use. A panel of providers experienced in wound care and surgical wound management was convened to create a series of publications on the use of topical autologous blood clot therapy (TABCT) in the treatment of complex wounds. This publication, the first in a series, provides an evidence basis of the gap between definition and treatment of complex wounds, an overview of the use of autologous therapies in these wounds, and the science behind TABCT. The development of a consensus panel for decision pathways and recommendations for TABCT use in specific complex wound types are also discussed. Subsequent articles will provide consensus recommendations on the use of TABCT in full-thickness wounds with exposed tendon and/or bone and undermining or tunneling wounds, in wounds in patients who are nonsurgical candidates, in those who cannot undergo sharp debridement, in patients with arterial wounds who have been maximally revascularized, and in those with transsphincteric anal fistula. This article provides a foundation of knowledge and describes the plan for consensus panel decision pathways and recommendation development of use of TABCT in the treatment of specific complex wound types.

Introduction

The term complex wound is often used in the wound care literature, but defining this term is difficult. Although multiple studies cite contributing factors to and treatments for complex wounds, the complex or head-to-heal wound is difficult to define beyond one that does not follow the orderly and timely course of wound healing—that is, a chronic wound.[1–7] Defining these wounds and optimizing management of them must move beyond the belief that chronicity is the only deciding factor in the definition of a complex or hard-to-heal wound. Acute and chronic wound types that can be complex or hard to heal include, but are not limited to, those with exposed tendon or bone, undermining or tunneling ulcerations, fistulous wounds in patients with Crohn disease, venous leg ulcerations, wounds in patients who are nonsurgical candidates or who cannot undergo sharp debridement, arterial wounds in patients who have been maximally revascularized, and rheumatologic and hematologic ulcers.[8,9] These wound types are often excluded in randomized controlled trials.

The common factor in the management of the above wound types is optimization of the patient and wound bed itself.[10] Patient optimization involves assessing the physical, psychological, and social aspects that can hinder wound healing. Wound bed optimization involves removal of nonviable tissue and senescent cells, reduction of bacterial load, reduction of exudate while maintaining a moist environment, creation of a well-vascularized wound bed, and restoration of dynamic reciprocity to promote wound resolution.

Autologous Therapies for Complex Wounds

Assessment of the entire patient rather than only the wound is necessary to improve outcomes. For example, the patient with a DFU is treated with appropriate offloading, management of hyperglycemia, maximization of perfusion, and assessment and management of the bacterial burden of the wound. In the patient with a venous stasis ulcer, treatment includes assessment of the venous anatomy and intervening, if necessary; application of adequate compression; and assessment and management of the bacterial burden of the wound. Holistic care can optimize treatment pathways for expeditious outcomes. Generally, management of these wounds should focus on patient- and provider-specific contributors to delayed healing, including patient age, comorbidities, pain, psychosocial factors, wound size and location, and microbial presence, as well as provider skill, knowledge, and access to available treatment options.[11,12] Such a treatment approach can have a dramatic effect on the patient's psyche in addition to increased expenditure for care.

In the appropriate patient and wound, autologous therapies may be ideal for wound closure. Examples include myocutaneous flap closure for a DFU, or split-thickness skin graft closure for venous stasis ulceration after optimal wound bed preparation. Use of autologous tissue negates the potential for patient rejection and accelerates healing compared with use of nonautologous products such as xenografts, allografts, and synthetic grafts.[13,14] However, autologous flap and graft closure creates other possible morbidities, including a secondary donor site, increased pain, and potential delays in return to function.[13,15,16] Other autologous tissue types, including tissue and cells derived from adipose, epidermis, dermis, bone marrow, and blood, have the same advantages as these more complex autologous tissue closure techniques without the associated disadvantages.[17–20] Limitations of these other autologous tissue therapies include procedural pain, limited or contradictory evidence on their efficacy, the skill level required to perform the procedure, the potential need for an operating room, the creation of a secondary donor site, and the exclusion of patients who are not surgical candidates.[17–26]

Of these autologous tissue types, those originating from blood may be the most sensible because it is an unlimited resource, easy to access, and has limited associated complications and procedural pain.[27] A systematic review and meta-analysis of randomized controlled trials found that use of stem cells from peripheral blood resulted in similar outcomes on the healing of lower extremity ulcers compared with bone marrow aspirate (relative risk, 2.20 and 2.13, respectively).[19] Rather than focusing on only a few specific blood cell types, such as platelets, endothelial progenitor cells, or granulocyte colony-stimulating factor–mobilized peripheral blood mononuclear cells, TABCT incorporates all of the essential factors present in blood and has been shown to reduce wound size, increase local tissue oxygenation saturation and angiogenesis, adjust local pH levels, and expedite wound healing[7,28–32] (Figure 1). Also, TABCT has been shown to be cost-effective in chronic wound management compared with other commercially available advanced wound care products; it has the lowest cost per cm2 with the highest healing efficacy at 12 weeks.[27] The weighted average treatment cost for TABCT ranged from $2504 to $6278, compared with $5505 to $11 783 for other synthetic and allograft-based advanced wound care products studied (Apligraf, Organogenesis; Dermagraft, Organogenesis; GRAFIX Core, Smith + Nephew; EpiFix, MiMedx).

Figure 1.

Topical autologous blood clot therapy applied to a plantar heel ulcer in a patient with diabetes.

Science Behind TABCT

The application of topical blood supports nutrient and waste exchange, regulation of pH levels, and infection prevention.[27] Topical autologous blood clot therapy—which includes the entire array of proteins, enzymes, cells, clotting factors, minerals, electrolytes, and dissolved gases—is theorized to assist in healing by acting as a barrier to bacterial ingress; providing a temporary extracellular matrix that serves as a scaffold for cellular infiltration, migration, and interaction; modulating pain and inflammation; maintaining an optimal moist environment for healing; assisting in autolytic debridement; and increasing oxygenated hemoglobin within the wound.

Hemostasis, the first phase in the healing cascade, begins with activated platelets forming an initial platelet plug that contains red blood cells and fibrin.[27,33,34] This clot matrix prevents further blood loss and serves as a barrier to bacterial invasion.[34] Fibrin is organized in a sheet-like fashion at the air-clot interface to prevent further clot growth. This physical barrier has been shown to prevent bacterial ingress into the area of injury for the first 12 to 27 hours.[34] This delay in bacterial ingress allows time for the patient's own immune system to recruit the essential cells of the inflammatory phase of healing to begin removal of damaged tissues and further prevent the potential for infection. One cell type that is critical in the inflammatory phase is the macrophage.[7] Macrophages are unique in that they possess 2 phenotypes critical to the wound healing cascade.[35] The M1 classically activated macrophage phenotype is responsible for host defense in the inflammatory phase of the wound healing cascade. Within the deeper aspect of the blood clot, fibrin is organized in a more fibrous-like fashion. This configuration mimics the structure of the extracellular matrix, allowing for cellular infiltration, propagation, and interaction with the temporary scaffold structure of the clot to propagate the wound to the proliferative phase of healing.[7,27,34,36]

In the proliferative phase, the M2 alternatively activated macrophage phenotype aids in granulation tissue formation and tissue repair. Transition between the M1 and M2 macrophage phenotypes is mediated by the macrophages themselves and the local wound environment.[27,34] Topical autologous blood clot therapy delivers macrophages to the wound and provides the necessary environment to assist in wound resolution.[7] The presence and interaction of the various components within blood results in fibroblast proliferation and angiogenesis, signifying the transition to the proliferative phase of healing.[7,27,33,37] Interaction with the components in TABCT may also aid in wound bed preparation and modulation of inflammatory and pain signaling pathways, in addition to propagation to the proliferative phase of healing.[37,38] Alteration of the pH of the local wound environment with TABCT may also have positive effects on wound healing progression.[27,36,39–41] Although autolytic debridement can take longer than other methods of debridement, it is less invasive, is highly selective, has a lower risk for infection, is associated with relatively low levels of pain, and is available in all care settings; additionally, it may be the only debridement option for some patients.[42] Through the presence of proteolytic enzymes within the TABCT and its ability to maintain a moist wound healing environment, TABCT can assist in autolytic debridement. A small case series of 3 patients demonstrated increased oxygenated hemoglobin within the wound bed, as measured with near-infrared spectroscopy, as well as associated reduction in wound size with serial application of TABCT.[28]

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