Product REVIEW Alginates as haemostatic agents: worth revisiting?

Patients today present with complex wounds which can cover large surface areas, have undermining, be a mixture of tissue types, be highly exuding and show signs of infection. The goals for the treatment of each individual vary. This increases the demands on dressings, as they need to be absorbent, assist in the debridement process, reduce the bacterial burden and prevent maceration. Alginate dressings are now well- established, being used for their conformability, absorbency and ability to provide a moist wound healing environment (Thomas, 2000), however, alginates are also used extensively in other fields such as dentistry as valuable haemostatic agents (Kaneda et al, 2008).

John Timmons

8 Wounds post debridement (sharp, blood cells. Platelets bind to collagen KEY WORDS surgical or hydrosurgery). which have glycoprotein receptors which Alginate dressings form links with collagen fibrils, thereby Haemostasis Traditional roles of alginate dressings activating the platelets. Activated platelets Alginate products are viewed as become sticky and fuse together. Exudate being biocompatible, hydrophilic Cavity wounds and biodegradable under normal Secondary haemostasis occurs Bleeding wounds physiological conditions (Becker et simultaneously and is recognised by the al, 2001). Once in a gel form, alginate presence of proteins known as clotting dressings will also promote healing and factors, primarily factor VII and factor epidermal regeneration. VIII, collagen and other clotting factors. These are recruited to the injury site by hen alginate dressings were These dressings have been used von Willebrand factor (Furie and Furie, first launched many were also to treat a variety of wound types, in 2005) which exists in the vessel walls. Wpresented as haemostatic particular, wet wounds which also have Prothrombin is altered to form thrombin products. For example, in dental care, a degree of sloughy tissue. The gel which which, in turn, converts fibrinogen to fibrin, alginate products are used extensively to is formed when the product absorbs the basic building block of the haemostatic control bleeding in tooth sockets (Kaneda exudate, prevents the wound from clot. Once the clot forms, a number of et al, 2008). drying out and assists in the process of enzymes are employed to reduce the size debridement. This function precludes of the clot through fibrinolysis and this is Many patients present with wounds alginates from being used in dry or low controlled by plasmin. which are bleeding or prone to bleeding, exuding wounds, as they may adhere to and so cannot be treated with a non- the wound bed. Fibrin strands bind with collagen in the interactive dressing. These wounds include: clot adding strength and stability. Calcium 8 Partial- and full-thickness wounds Haemostasis ions are essential throughout the process, 8 Arterial and venous ulcers Coagulation is an important part of and are of particular importance in the 8 Diabetic foot ulcers haemostasis where there has been formation of fibrin polymers. 8 Pressure ulcers injury to the body. Once a vessel has 8 Fungating lesions been damaged, the lining of the vessel, Beyond the initial clotting response, 8 Post-surgical wounds the endothelium, releases phospholipid a number of growth factors are released 8 Toe nail avulsions components known as tissue by platelets. These are employed in 8 Donor sites thromboplastin, which initiate a chain of wound healing and tissue repair. This 8 Traumatic wounds events to attract platelets to the injury platelet derived growth factor (PDGF) is site, which will form a plug or clot (Furie responsible for angiogenesis. and Furie, 2005). This is known as primary John Timmons is a Tissue Viability Nurse Specialist, haemostasis. In addition to forming the Achieving haemostasis is an essential Department of Tissue Viability, Aberdeen Royal platelet plug, the local vessels contract part of the healing process for both Infirmary, Grampian Health Services, Aberdeen to minimise bleeding. The clot traps red acute and chronic wounds.

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Role of alginate dressings in haemostasis To provide clinical evidence in support whole human blood. The process of Alginate dressings are fibre dressings of Sorbsan being an affective haemostatic citration removes clotting factor IV which are formed from alginic acids agent when in contact with human blood, (calcium ions) and is commonly used to (mannuronic and guluronic), extracted two in vitro studies were conducted. These prevent clotting during blood screening from seaweed species (Timmons, studies also tested two other dressing tests. The scope of this test was to 1999). The fibrous dressings form a gel products: Kaltostat® (ConvaTec), a sodium- evaluate the degree of ‘ability’ of the red when in contact with wound exudate calcium alginate and ActivHeal AquaFiber® blood cells from the citrated blood to through an ion exchange process (AMS Medlogic), a CMC-alginate mix as clot when in contact with a selection of (Heenan, 1998). both have claimed haemostatic properties. wound dressings. A non-alginate control material was The ratio of mannuronic to guluronic also used. The test criteria were to acid within the dressing will determine demonstrate the ability for human the clinical properties of the product, In vitro study I — haemolysis test blood to coagulate when in contact such as speed to gelling, the strength and This test was to evaluate the dressings’ with the selected alginate dressings, the amorphous nature of the gel. The ‘inability’ to break the red blood cells, i.e. Sorbsan, Sorbsan Plus , Kaltostat, compound within the alginate dressing is therefore demonstrating each dressing’s and ActivHeal AquaFiber. The amount calcium alginate which, when in contact compatibility with human blood and of coagulation achieved in contact with exudate, will form sodium alginate potential for haemolytic activity (Wright, with each test sample is quantified by and calcium ions. The sodium ions are 2008a). The ‘inability’ to release the measuring the amount of unclotted present within exudate and plasma. The haemoglobin from the red blood cell is blood, expressed as a percentage of availability of calcium ions at the injury measured as a percentage. The test criteria total citrated blood applied. site helps to support the normal clotting for non-haemolytic was set at <5%. process, and this has been shown to Results and interpretation significantly reduce clotting times, in Results and interpretation A statistical evaluation was conducted some cases up to 54% compared with The results identified Sorbsan Plus using the spectrophotometer data, based controls (Kaneda et al, 2008). and Kaltostat to have non-haemolytic upon the Mann-Whitney Test. The efficacy properties with results falling within the of Sorbsan Plus to promote haemostasis Sorbsan® calcium alginate dressing <5% threshold, thus demonstrating their (clotting) was significantly superior when Sorbsan® calcium alginate dressing ‘inability’ to release haemoglobin when in compared with the other alginate dressings (Aspen Medical Europe) is prepared as contact with human red blood cells. within this study: Kaltostat when compared a textile fibre, and presented as a loose with Sorbsan Plus (p=0.02); ActivHeal ‘rope’ or packing for cavities, a ribbon The results for Sorbsan Flat were AquaFiber when compared with Sorbsan for narrow wounds or sinuses, and a flat marginally above the 5% threshold at Plus (p=0.03). The efficacy of Sorbsan non-woven pad for application to larger 6.8%, demonstrating weak haemolytic (flat, ribbon and packaging) to promote open wounds. properties, while those for the ActivHeal haemostasis was statistically equivalent AquaFiber appeared to have stronger to Kaltostat and significantly greater than Sorbsan is of particular use in haemolytic properties with a result ActivHeal AquaFiber (p=0.02). cavity wounds, and has been used in of 21.5%. However, when compared pilonidal sinus wounds as a dressing against a gauze control which provided Discussion which conforms to the wound bed, is a haemolytic response of 100%, all the The results of these tests support the easily rinsed out and reduces the pain alginate-containing dressings within the earlier work of Beldon (2004) and experienced by patients with pilonidal study provided results of acceptable O’Donohue et al (1997), where calcium sinus wounds (Figure 1) (Timmons, biocompatibility properties. alginate dressings were used to manage 2007). As a flat sheet dressing, Sorbsan bleeding in split-thickness skin grafts. is also used to treat venous leg ulcers. In vitro study II — haemostasis test (bespoke method) Both of these studies highlighted the Sorbsan Plus, which consists of a sterile, This study was undertaken to investigate value of alginates as haemostatic agents. calcium alginate wound contact layer, not only Sorbsan’s compatibility in contact O’Donohue carried out a trial of calcium bonded to a secondary absorbent with blood, but also whether the sodium- alginates compared with paraffin gauze viscose layer, provides added absorbency calcium ion exchange in alginates has a on donor sites, with 21 out of 30 patients and can be used under compression. positive effect on primary haemostasis in the alginate group healing in ten days, (Wright, 2008b). compared with only seven of 21 in the The moist wound healing paraffin gauze group. environment which alginates create This bespoke haemostatic test promotes the formation of granulation using spectrophotometer techniques In a study of forty patients with donor tissue. As said, the gel is easily rinsed out was developed by Robert Duward of site wounds, Beldon (2004) compared of a wound, thereby ensuring that the Safepharm Laboratories, and the statistical alginate dressing with paraffin gauze, dressing does not inhibit the formation evaluations of the results were performed with or without film dressings, and of new tissue (Heenan, 1998). (Wright, 2008b). The test uses citrated demonstrated that alginate with film

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Activated platelet Platelet Sorbsan dressing Key points Red blood cell

Na+ 8 Alginates have an important role Na+ to play in wound care due to their ability to absorb, conform and provide moist wound healing properties.

8 Some patients present with Na+ wounds which have minor Na+ bleeding, such as donor sites which would benefit from the use of alginate products.

8 In tests, Sorbsan Plus proved to be an effective haemostat with Blood clot excellent biocompatibility. Sorbsan dressing (formation of fibrin Ca2+ strands) Ca2+ Ca2+ Ca2+ References Becker TA, Kipke DR, Brandon TA (2001) Calcium alginate gel: a biocompatible and mechanically stable polymer for endovascular embolization. J Biomed Res 54: 76–86 Beldon P (2004) Comparison of four different dressings on donor site wounds. Br. J Nurs 13(6): S38–S45 Heenan A (1998) Frequently asked questions, Alginate dressings. World Wide Wounds. Available online at: www.worldwidewounds. com/1998/june/Alginates-FAQ/alginates- Figure 1. These images demonstrate the sodium calcium exchange that occurs when Sorbsan dressing is questions.html# [accessed October 2009] applied to a bleeding wound and the calcium ions provided by the dressing to the damaged area assist in the Furie B, Furie BC (2005) Thrombus formation coagulation cascade, or primary haemostasis. in vivo. J Clin Invest 115(12): 3355–62 Kaneda K, Kuroda S, Goto N, Sato D, Ohya achieved healing faster and was much less The calcium sodium ion exchange K, Kasugai S (2008) Is sodium alginate an traumatic for the patient than the other which takes place when the dressing is alternative haemostatic material in the tooth groups in the study. in contact with wound exudate allows extraction socket? J Oral Tissue Engineering 5(3): 127–33 calcium ions to be released into the Therefore, in wounds with minor O’Donoghue JM, O’Sullivan ST, Beausang ES, et wound. As calcium is a normal part of al (1997) Calcium alginate dressings promote bleeding, in vivo and in vitro data the coagulation response, this release of healing of split skin graft donor sites. Acta Chir demonstrates that alginate dressings have calcium assists in haemostasis. Plast 39(2): 53–5 proven effective. Thomas S (2000) Alginate dressings in surgery Although alginates have been and wound management — Part 1. J Wound Conclusion promoted as haemostats in the past, there Care 9(2): 56–60 Alginate dressings are indicated for the is now more evidence to suggest that they Timmons JP (1999) Alginates and hydrofibre treatment of a number of wound types, are clinically beneficial (O’Donoghue et al, dressings. Prof Nurse 14(7): 496–9, 501, 503 and are particularly useful in managing 1997; Beldon, 2004). In particular, Sorbsan Timmons J (2007) Diagnosis, treatment and sloughy wounds with moderate to Plus has been identified by the bespoke nursing management of patients with pilonidal heavy levels of exudate. Alginates are test and backed up by the haemolysis test sinus disease. Nurs Standard 21(52): 48–56 also ideal for treating cavity wounds and, as having good haemostatic properties, Wright R (2008a) Blood Compatibility — as Sorbsan forms a soft conformable Haemolysis Test, Direct Contact Method (ISO which may increase the indications for its 10993-4). Pharm Labs. Technical File # 1& 2, gel, it can be used to treat non-uniform use in clinical practice. Sorbsan Flat, Ribbon, Aspen Medical Europe Ltd. Data on File cavities. In addition to the wound healing Packing and Plus are proven to be suitable Wright R (2008b) Haemostatic Activity Test function, alginate dressings can be used to for the management of minor bleeding Report. Safepharm Laboratory. Technical File # promote haemostasis in bleeding wounds. in wounds. Wuk 1& 2, Aspen Medical Europe Ltd. Data on File

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