j o u r n a l o f o r t h o p a e d i c s x x x ( 2 0 1 5 ) 1 e5

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Original Article

Compartment syndrome in patients with

haemophilia

James Donaldson*, Nicholas Goddard

Department of Orthopaedics, Royal Free Hospital, Pond St, London, UK

article info abstract

Article history: Background: Acute compartment syndrome (ACS) is an uncommon but potentially devas-
Received 3 February 2015 tating condition.
Accepted 3 May 2015 Methods and results: There are scattered case reports and case series in the literature of ACS
Available online xxx in persons with haemophilia (PWH), and even fewer in PWH and inhibitors. The man-
agement of compartment syndrome in these scenarios is controversial and often anec-
Keywords: dotal. In addition haematological outcomes are frequently quoted but functional outcomes
Compartment syndrome are generally overlooked.
Haemophilia This article aims to provide an overview of ACS and its contemporary management. We
Inhibitors also review the literature and outcomes of patients with haemophilia who develop ACS in
Fasciotomy an effort to assess the best treatment modality.
Conclusion: In the majority of cases ACS settles with normalisation of the clotting cascade.
Specialist haematological input is mandatory before surgical intervention should be
considered, especially in PWH and inhibitors.
Copyright © 2015, Professor P K Surendran Memorial Education Foundation. Publishing
Services by Reed Elsevier India Pvt. Ltd. All rights reserved.

compartment's tissues.3e6 It can occur with any elevation in

1. Introduction interstitial pressure in a closed osseo-fascial compartment.
This causes microvascular compromise and a reduction in the
Richard von Volkmann first described compartment syn- perfusion gradient to below a critical value, leading to
drome in 1881.1 He suggested that paralysis and contracture ischaemia of the tissue within that compartment. ACS is now
came on simultaneously as result of an interruption to the considered a surgical emergency warranting prompt evalua-
blood supply of the affected muscles. The first surgeon to tion and treatment.
reproduce ischaemic contracture in animals was Paul Jepson Any internal or external event that increases intra-
in 19242 whilst working at the Mayo Foundation. He also compartmental pressure can potentially cause a compart-
demonstrated that prompt surgical decompression could ment syndrome. The incidence is thought to be 3.1 per
prevent these contractures. 1,00,000 population, with males ten times more commonly
Acute compartment syndrome (ACS) is defined as a affected than females. By far the commonest cause is trauma,
critical pressure increase within a confined compartmental and in particular tibial shaft fractures (which are more
space causing a decline in the perfusion pressure to that common in men). Bleeding disorders, and in particular

* Corresponding author. 35 Ripplevale Grove, Islington, London, N1 1HS, UK. Tel.: þ44 (0)7931847576.
E-mail address: [email protected] (J. Donaldson).
http://dx.doi.org/10.1016/j.jor.2015.05.007
0972-978X/Copyright © 2015, Professor P K Surendran Memorial Education Foundation. Publishing Services by Reed Elsevier India Pvt.
Ltd. All rights reserved.
Please cite this article in press as: Donaldson J, Goddard N, Compartment syndrome in patients with haemophilia, Journal of
Orthopaedics (2015), http://dx.doi.org/10.1016/j.jor.2015.05.007
2 j o u r n a l o f o r t h o p a e d i c s x x x ( 2 0 1 5 ) 1 e5

haemophilia, are recognised, albeit rarer causes, which put

Table 1 e Common causes of ACS.
these patients uniquely at risk of ACS often with only trivial
trauma. Indeed eighty five percent of bleeding in patients with Fracture Burns
Crush injury Infection
haemophilia occurs within musculoskeletal tissue. In addi-
Injection injury Bleeding disorders
tion a recent systematic review showed that 21% of patients
Penetrating trauma Arterial injury
with acute compartment syndrome of the thigh had coagu- Constrictive dressings Reperfusion
lation defects.7 Casts Extravasation of drugs

1.1. Overview of compartment syndrome

ACS is a clinical diagnosis; the most important determi-
nant of outcome is early recognition and expeditious surgical
ACS is characterised by a critical pressure increase within a
intervention. Where doubt remains the intra-compartmental
confined compartmental space causing a decline in the
pressures can be measured. Marginal pressure readings
perfusion pressure to the compartment tissue.3e6 It can occur
should be repeated with further compartment pressure
with any elevation in interstitial pressure in a closed osseo-
readings and repeat physical exam. A compartment pressure
fascial compartment. This causes microvascular compro-
of 30 mmHg less than the diastolic blood pressure is often
mise and a reduction in the perfusion gradient to below a
quoted beyond this capillary pressure is insufficient to main-
critical value, leading to ischaemia of the tissue within that
tain muscle blood flow and the fascia has reached its
compartment. Fig. 1 below displays the cycle of events and the
maximum limitation of stretch.19
development of acute compartment syndrome.
The treatment of ACS is immediate removal of all
Approximately 40% of all ACSs occur after fractures of the
circumferential dressings down to the skin, usually followed
tibial shaft8 with an incidence in the range of 1%e10%.9 The
by open fasciotomy. The limb should be kept at the level of the
next commonest location is in the forearm, but almost any
heart and not be elevated in the interim (or if the diagnosis is
compartment can be affected: arm,10 thigh,11 foot,12 buttock,13
in doubt), as this decreases arterial flow and narrows the
hand,14 and abdomen.15 Any internal or external event that
arterial-venous pressure gradient.20
increases intra-compartmental pressure can cause a
compartment syndrome. Table 1 below shows some of the
more common causes.
Rorabeck reported almost complete recovery of limb
2. Compartment syndrome in haemophilia
function if fasciotomy was performed within six hours.16
Compartment syndrome is well described in persons with
When fasciotomy was performed within twelve hours
haemophilia (PWH) and remains a significant challenge for
normal limb function was regained in only 68% of patients;
the haematologist and the orthopaedic surgeon. The lack of a
after twelve hours only 8% regained normal function.17
clear aetiology or conspicuous traumatic event can contribute
With late diagnosis irreversible tissue ischaemia develops
to the diagnostic difficulty, whilst the possibility of cata-
causing potentially disastrous neurological deficits, muscle
strophic bleeding makes fasciotomy potentially disastrous.
necrosis, ischaemic contracture, infection, chronic pain,
Haemorrhages located within the calf and anterior forearm
delayed fracture union,18 rhabdomyolysis,17 amputation and
represent the highest risk for the development of compart-
even death.
ment syndrome.21 In patients without bleeding disorders the
treatment of choice is fasciotomy, even when in doubt to
prevent the establishment of motor and sensory loss,
contracture and severe extremity impairment. The role of
fasciotomy in haemophilia has been downplayed and care
largely focuses on haemostatic manoeuvres.22
The first step in the management of a suspected
compartment syndrome should be sufficient substitution of
clotting factors, which may help lower the compartment
pressure.23 Bleeding will typically tamponade before the pa-
tient experiences a substantial drop in haemoglobin. Howev-
er, raised compartment pressures can cause significant
morbidity in the extremities. Given the short window between
symptomatic onset and tissue necrosis, early intervention is
crucial and may prove to be not only limb-saving but also life-
saving.
If manoeuvres to normalise the clotting derangement fail,
fasciotomy is often performed to prevent muscle necrosis,
joint contracture and long-term sequelae.
There are no specific pre-operative guidelines for factor
Fig. 1 e Pathophysiology of compartment syndrome. replacement levels during fasciotomy, but the authors
Reproduced with permission: Prasarn M, Oulette E. J Am Acad recommend 100% of normal. Infection is a significant
Orthop Surg 2011; 19:49e58. complication usually related to persistent bleeding.

Please cite this article in press as: Donaldson J, Goddard N, Compartment syndrome in patients with haemophilia, Journal of
Orthopaedics (2015), http://dx.doi.org/10.1016/j.jor.2015.05.007
 j o u r n a l o f o r t h o p a e d i c s x x x ( 2 0 1 5 ) 1 e5 3

Haematological outcomes including blood loss, trans-

Successful split skin graft later

fusion requirement, and clotting correction are usually re-
ported in the literature in PWH and surgical intervention, but

Bled/oozed until day 15

little is published regarding the functional or orthopaedic

Table 2 e Details of the cases. FEIBA (Factor eight inhibitor bypass activity), SSG (split skin graft), AKA (above knee amputation), rFIIa (recombinant factor VIIa).
Outcome

4 week hospital stay

outcomes. Indeed clinicians often under report poor out-
comes, and much of the known data and treatment policies in

Bled until day 3

SSG 24d later

large haemophilia units is anecdotal.

No details
There are scattered case reports and case series in the

SSG later
published literature of ACS in PWH, and even less in PWH who
have inhibitors. The largest series published was by Lancourt
et al.24 The authors found 34 cases of bleeding into the hand
and forearm in 200 PWH from 1969 to 1976. In six cases
bleeding into the anterior muscles of the forearm was

rFVIIa and tranexamic acid needed

complicated by contracture, neuropathy, or both. Early diag-
nosis, replacement of the missing clotting factor, and immo-

FVIII and platelets for 2/52

bilization were deemed essential. Fasciotomy was not

Management
performed in any of them.

FEIBA and then rFVIIa

Dumontier et al.25 described 12 cases of ACS in the upper
limb. They again confirmed the importance of clotting factor

FEIBA 14 days
32 days FEIBA
replacement as first line therapy. Two of the twelve patients

No details
required fasciotomy. Two patients had sequelae and incom-
plete recovery, and both of these were associated with late

rFVIIa
diagnosis and treatment.
Rodriguez-Merchan26 reported on three patients who
developed ACS. None of them required fasciotomy. In two the
condition reversed with factor replacement and in the third

Intubated/paralysed to control bleeding

the patient's condition was irreversible with an ulnar claw on
presentation. The ACS had likely started 4 days prior to
seeking medical attention. In the two treated successfully
with replacement clotting factors one had a forearm contu-

‘Good’ haemostatic control

Blood loss

sion, the other a distal radius fracture as the initiating insult.

2.1. Compartment syndrome in persons with

haemophilia and inhibitors
7U, took 2 hrs
Significant

No details

No details
The development of inhibitors against replacement clotting
factor is a rare but serious complication of haemophilia.27
Inhibitors may develop in around 30% of patients with se-
vere or moderately-severe haemophilia A and in 1e6% of pa-
tients with haemophilia B. A number of risk factors have been
Fasciotomies x2 in same patient

identified including duration of exposure to clotting factor,

2 forearm fasciotomies cases

ethnicity and type of gene mutation. Patients with severe

haemophilia and inhibitors generally have more orthopaedic
complications and worse quality of life than those without
Forearm amputation

Forearm amputation
Surgery
Forearm fasciotomy

Forearm fasciotomy

inhibitors.28 The presence of inhibitors has also been

3 limb fasciotomy
Leg fasciotomy

demonstrated to be associated with increased morbidity and

mortality from all causes.
In patients with inhibitors compartment syndrome is just
AKA

as likely but the management is more controversial and

specialized. Where there are low titre antibodies, therapeutic
choices to normalise clotting include higher does of factor VIII
or factor IX as well as inhibitor bypassing agents. In high titre
DiMichele and Negrier32

antibody patients, options are limited to inhibitor bypassing

agents, either activated prothrombin concentrated compound
(FEIBA) and recombinant factor.
VIIa (NovoSeven).
Rangarajan34

There are scattered case reports and a few studies

Lauroua33
Negrier31

Moraca36
Author

Berdel37
Watts29

assessing factor bypassing agents in surgical patients, within

Rajic30

Lak35

which compartment syndrome is mentioned. Details of the

cases are shown in Table 2 below. It is interesting to note that

Please cite this article in press as: Donaldson J, Goddard N, Compartment syndrome in patients with haemophilia, Journal of
Orthopaedics (2015), http://dx.doi.org/10.1016/j.jor.2015.05.007
4 j o u r n a l o f o r t h o p a e d i c s x x x ( 2 0 1 5 ) 1 e5

prolonged bleeding was associated with lower doses of

bypassing agents. Little detail is however given on the timing Conflicts of interest
of surgery or the initiation of bypassing agents.
Seven had a fasciotomy and where details were given All authors have none to declare.
(three of the seven) all had significant blood loss. In the three
amputation cases, details of only two of the patients were
references
given and they bled post-operatively for fifteen and thirty-two
days.
Lauroua in 200933 described major and minor surgery using
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Orthopaedics (2015), http://dx.doi.org/10.1016/j.jor.2015.05.007
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Please cite this article in press as: Donaldson J, Goddard N, Compartment syndrome in patients with haemophilia, Journal of
Orthopaedics (2015), http://dx.doi.org/10.1016/j.jor.2015.05.007