Case report

Fracture blisters and sodium valproate: two case reports

Simon Scott

Orthopaedic Department, Whiston Hospital, Merseyside L35, UK

Accepted 20 January 2000

1. Introduction

It is now well recognised that fracture blisters mostlyform following fractures caused by signi®cant trauma,or torsional-type injuries [1], but there are times whentheir occurrence and severity are not so easy to pre-dict. This short article presents the case histories oftwo patients who presented to our department, within4 days of each other, with severe fracture blisters, anda possible theory as to why they should have devel-oped such complications.

2. Case reports

G.C., a 26 year old male, who had been on Epilim(sodium valproate) for seizures over a 10 year period,following a hypoxic brain injury, presented to the acci-dent and emergency department within 1 h of sustain-ing a fracture-subluxation of his right ankle. It wasinitially described by the casualty doctor as being mini-mally swollen, but within half an hour he noted it``blew up like a balloon''. It was reduced in the depart-ment within 2 h, and when inspected, within 3 h hoursof the injury occurring, was already noted to have sig-ni®cant fracture blister formation and bruising overthe medial aspect of the ankle such that surgery couldnot be contemplated. Despite strict elevation and iceovernight, the ankle went on to develop such extremelysevere circumferential blistering that internal ®xationcould not be considered, and the patient requiredexternal ®xation and several debridements (Fig. 1).

J.C., a 54 year old female, also on long-term Epilimfor seizures, presented 12 h after sustaining a low-energy, minimally displaced bimalleolar fracture,which she initially thought was ``only a sprain''. Onexamination, she already had considerable bruising

and fracture blister formation around the ankle suchthat open reduction and internal ®xation could not beconsidered. These worsened so that manipulation,accepting a less than ideal reduction, had to beaccepted as de®nitive treatment.

Both patients had normal prothrombin times, ®bri-nogen levels and other standard coagulation par-ameters, as well as normal platelet counts and liverfunction tests. On qualitative testing of platelet func-tion, it was found, in both patients, that there wassome functional abnormality, in that the plateletsshowed a reduced activation response to stimulationby collagen.

3. Discussion

The incidence of fracture blisters has been reportedin 2.9% of all acute fractures requiring hospitalisation,and in 5.2% of ankle fractures [2]. They most com-monly occur around the ankle, tibia, foot, or elbow. Ithas been noted that they can occur as early as 6 h fol-lowing injury [1]. The pathophysiology of fracture blis-ters is multifactorial. It is known that they form in thedermo±epidermal layer, and are due to the separationof these two layers. Strains created in the skin duringinitial fracture deformation, coupled with the di�eringelastic and visco±elastic properties of the dermis andepidermis, cause these two layers to separate [3]. Thesecond insult, acting via a combination of Starlingsforces, and the in¯ammatory cascade, then causes ¯uidto pass into the potential space between the dermisand epidermis. Further insult from surgery can exacer-bate the situation. Other factors suggested to be impli-cated in fracture blister formation are alcohol abuse,hypertension, smoking, peripheral vascular disease,lymphatic obstruction, and diabetes [1].

Injury, Int. J. Care Injured 31 (2000) 541±542

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Sodium valproate is well recognised to be bene®cialin decreasing the frequency of seizures in variousforms of epilepsy [4], but it is not without side-e�ects.The side-e�ects of prolonged bleeding time and throm-bocytopaenia have been well documented, and it is rec-ommended, in pharmocological texts [5], that patientstaking sodium valproate should have both their bleed-ing time and platelet count measured prior to majorsurgery to minimise potential bleeding complications.More interestingly, it has also been demonstrated thatplatelet function can be a�ected. The secondary phaseof platelet aggregation, following normal primaryaggregation with adenosine di-phosphonate, was inhib-ited in six out of 23 patients taking sodium valproate[6]. All subjects had normal bleeding time and plateletcounts.

4. Conclusion

Sodium valproate has never been reported in the lit-erature as being associated with fracture blisters. Itmay simply have been a coincidence, but both thesepatients developed severe skin problems, that compro-

mised their management, and both had altered plateletfunction probably as a side-e�ect of taking sodiumvalproate. It might be advised that a full and precisedrug history be taken in all patients sustaining frac-tures, and any patient found to be on sodium valpro-ate should perhaps be regarded as being at increasedrisk of fracture blister formation.

References

[1] McCann S, Gruen G. Fracture blisters: A review of the litera-

ture. Orthopaedic Nursing 1997;16(2):17±22.

[2] Varela C, Vaughan T, Carr B, Slemmons B. Fracture blisters:

Clinical and pathological aspects. Journal of Orthopaedic

Trauma 1993;7(5):417±27.

[3] Giordano CP, Scott D, Koval KJ, Kummer F, Atik T, Desai P.

Fracture blister formation: a laboratory study. The Journal of

Trauma: Injury, Infection, and Critical Care 1995;38(6):907±9.

[4] Jeavons PM, Clark JE. Sodium valproate and seizure control.

British Medical Journal 1974;2:584.

[5] ABPI Compendium of Datasheets and Summaries of Product

Characteristics 1998±99. Datapharm Publications Ltd.

[6] Richardson SGN, Fletcher DJ, Jeavons PM, Stuart J. Sodium

valproate and platelet function (Letter). British Medical Journal

1976;1:221±2 24 Jan 1976.

Fig. 1. Clinical photograph showing severe circumferential fracture blister formation in patient 1.

S. Scott / Injury, Int. J. Care Injured 31 (2000) 541±542542