Antithrombin in the treatment of burn trauma

Abstract

Antithrombin (AT) is a natural anticoagulant with anti-inflammatory properties that has demonstrated value in sepsis, disseminated intravascular coagulation and in burn and inhalation injury. With high doses, AT may decrease blood loss during eschar excision, reducing blood transfusion requirements. There are no human randomized, placebo-controlled studies, which have tested the true benefit of this agent in these conditions. Two main forms of AT are either plasma-derived AT (phAT) and recombinant AT (rhAT). Major ovine studies in burn and smoke inhalation injury have utilized rhAT. There have been no studies which have either translated the basic rhAT research in burn trauma, or determined the tolerance and pharmacokinetics of rhAT concentrate infusions in burn patients. Advantages of rhAT infusions are no risk of blood borne diseases and lower cost. However, the majority of human burn patient studies have been conducted utilizing phAT. Recent Japanese clinical trials have started using phAT in abdominal sepsis successfully. This review examines the properties of both phAT and rhAT, and analyzes studies in which they have been utilized. We believe that it is time to embark on a randomized placebo-controlled multi-center trial to establish the role of AT in both civilian and military patients with burn trauma.

Keywords: Antithrombin; Burn injury; Burn trauma; Inhalation injury; Recombinant antithrombin.

Figure 1

AT levels after calculations for bolus single infusions to attain > 175% plasma antithrombin levels (personal file AKV). AT: Antithrombin.

Figure 2

A 72 h depiction of q 8 h dosage coefficient of variations for the antithrombin-treated burn patients (black dots) compared to control plasma antithrombin levels (white squares) (personal file AKV). AT: Antithrombin.

Figure 3

The severity of injury requiring an escharotomy in a burn patient with 80% total body surface area (personal file AKV).

Figure 4

The “peeling off” of the eschar, not requiring knife excision with exposed viable subcutaneous tissue and minimal bleeding (personal file AKV).

Figure 5

A representation of the pathology in third degree burnt skin from a patient treated with plasma-derived antithrombin and in patient without plasma-derived antithrombin treatment. Whereas the skin beneath the control eschar is dead and non-viable with clotted and coagulated blood vessels, the skin and subcutaneous tissue beneath the phAT-treated skin is more viable in comparison with fewer thrombi (personal file AKV). phAT: Plasma-derived antithrombin.

Figure 6

The thrombi, sludge and necrotic debris in burnt skin subcutaneous tissue blood vessels. A: Illustrates a blood vessel with sludge and fibrin debris; B: Depicts a small vessel with fibrin debris; C: Shows a clotted vessel; D: A larger vessel occluded with amorphous material. Magnification 40-100 ×, PTAH staining (personal file AKV).