DOI: 10.1111/j.1365-2516.2012.02918.x
REVIEW ARTICLE
Summary. Repeated haemarthroses and the consequences of blood in the joint contribute to blood
induced joint disease (BIJD) in people with haemophilia
(PWH). Prevention of bleeding, through medical
management, is the standard of care in developed
countries, but is not universally available due to
financial and other barriers. Ice application, as part of
R.I.C.E. (Rest, Ice, Compression, Elevation) or alone, is
commonly recommended as an adjunct treatment to
decrease bleeding, pain, tissue metabolism, oedema,
and inflammation. This article will review evidence
regarding local cooling by commonly used ice
application methods, to decrease the temperature of the
skin and intra-articular (IA) joint space and the
resultant effects on haemostasis and coagulation. The
general literature was reviewed for articles in English
describing temperatures achievable in the skin and IA
space using clinically relevant ice protocols, and the
Introduction
The use of ice to alleviate pain and suffering can be
traced back to ancient times and was recommended
by Hippocrates, who suggested that Cold should be
used in the following cases: When there is, or is likely
to be hemorrhage [1]. R.I.C.E. is a widely
accepted initial treatment for acute musculoskeletal
injury believed to carry minimal risk. Commonly
described in the sports medicine and first aid literature
[210] beginning in the 1970s [11], this intervention
was incorporated into the standard of care as an
A . L . FO R S YTH et al.
Federation of Hemophilia, Canadian Hemophilia Society and the National Hemophilia Foundation were
also included.
Results
The synovial membrane, haemarthrosis and the
effect of ice on tissue temperature
Haemarthrosis, or IA bleeding, is possible in
any synovial joint. The synovial membrane is a
relatively superficial structure, located just
below the skin, between the joint capsule and
IA space (Fig. 1) and contains a rich network
of capillaries. In PWH, damage to these
capillaries [32] caused by trauma or even the
stress of ordinary movement may cause
haemarthrosis, as blood is expelled into the
joint space, leading to acute joint swelling. This is
followed by inflammatory and biochemical
changes evoked by the presence of blood within
the IA space [32].
Many authors have used surface and IA probes to
demonstrate that superficial ice application over a
joint has the ability to achieve cooling at both the skin
and IA levels. The baseline temperature of the skin is
27.929.6C and that of the IA
space is 31.933.5C
Common methods of ice application to the skin
over the knee or ankle, decreases the skin and IA
temperature. For example, application of ice chips
over the anterior knee for 30 min reduced the mean
skin temperature from 27.9 C to 11.5C. This effect
persisted even after the ice was removed, such that
after 2 h the skin tempera- ture was still decreased at
25.2C. Similarly, application of an ice pack to the
lateral
aspect
of the ankle decreased
skin
temperature from 29.6C to 5.9C after 20 min .
The same magnitude of temperature reduction was
achieved following application of crushed ice in a
plastic bag to the skin over the knee; from 29.5C to
8C after 30 min and to 3.2C after 60 min .
Baseline Temperature C
Location
27.9
28.8
29.5
29.6
Anterior knee
Ankle
Anterior knee
Ankle
31.9
32.2
33.5
Location
Knee
Knee
Knee
Author
and year of
measure
IA temperature
a canine
The
only animal
study, in was
our performed
review, to in
directly
model by Bocobos group [38]. A cold compress consisting of crushed ice wrapped in a cloth was applied
to the knees of dogs for 5, 15 or 30 min and IA
temperature directly measured. The IA temperature
decreased by 4.1C after 15 min and by 6.5C after
30 min. As clearly depicted in their article in Fig. 2B ,
the temperature of the synovial membrane clearly
lies at a point between the temperature of the skin
and the IA space. The authors noted in their
results: The superficial tissues of the knee such as
skin and synovium demonstrate the most rapid and
profound cooling effect.
60
20
30
20
26
30
Location
Anterior knee
Lateral ankle
Anterior knee
Ankle
Ankle
Anterior knee
Temperature (C )
3.2
5.9
8
9.2
10
11.5
60
30
60
30
15
30
Location
Anterior knee
Anterior knee
Knee
Knee
Knee
Anterior knee
Temperature (C)
20.9
22.5
26.9
28.5
29.5
30.4
A . L . FO R S YTH et al.
Effect Shown
with Cooling
Humans
Prolonged bleeding
time
Humans
(severe haemophilia A)
Rabbits
Prolonged bleeding
time
Prolonged bleeding
time
Prolonged bleeding
time
Prolonged coagulation
time
Prolonged bleeding
time
Prolonged clotting
time
Prolonged bleeding
time
Prolonged clotting
time
Impaired clot
firmness
Decreased platelet
aggregation
Decreased platelet aggregate
size and adhesion
Decreased coagulation
enzyme activity
Decreased FVIII and
FIX activity
Rabbits
Humans
Humans
Humans
Humans
Humans
Humans
Valeri
1995 [28]
Romlin
2007 [30]
Rundgren
2008 [27]
Kattlove
1970 [24]
Wolberg
2004 [25]
Johnston
1994 [31]
blood of healthy volunteers, was used to test ADPinduced platelet aggregation using light transmission
aggregometry [24]. After 8 min at 6C, minimal
platelet aggregation was observed and at 24C no
aggregation was observed. Upon re-warming the samples to 37C, platelet responsiveness was restored to
normal levels. Assessment of whole blood samples
from healthy volunteers were tested using thromboelastography [27]. As blood samples were cooled from
the basal 37C to 34, 31, 28 or 25C, clotting times
were progressively prolonged and maximum clot
firmness was significantly impaired at 28 and 25C
respectively.
The average size of platelet aggregates induced by
stirring platelet rich plasma from healthy volunteers in
the presence of low concentration of thrombin was
measured using phase microscopy [25]. Cooling the
plasma resulted in a linear decrease in the aggregate
size, reaching 40% at 33C, compared with aggregates
formed at 37C. Furthermore, platelet adhesion
decreased by 33% at 33C. In addition, at temperatures below 33C, the enzyme activity of coagulation
proteins was also reduced, compounding the defect in
platelet function.
Cooling also impairs haemostasis, affecting the
activity of the various clotting factors [31]. Blood
samples, obtained from healthy volunteers, were
cooled to 2535C and compared in an activated PPT
(aPPT) assay to results from testing performed at 37
C. Testing at 31C resulted in the equivalent of 16%
FVIII activity and 7% FIX activity. At 29C, there
was only 3% FVIII and FIX activity. Upon further
cooling to 27C and 25C, neither FVIII nor FIX
activity could be measured. Cooling of the blood samples clearly produced the functional equivalent of a
clotting factor deficient state.
Discussion
As noted in a 2002 book entitled, Evidence-based
Sports Medicine, Ice is the most often applied therapeutic modality yet little is known of the physiological
effects on soft tissue and how it is best used. Little
attention is given to the physiological effect of ice at
various tissue depths or of potential adverse side
effects .It is common
knowledge that the
recommended treatment and standard of care for
haemarthrosis in PWH is medical
management,
which is often combined with adjunct measures
such
as
R.I.C.E. Medical
management is
accomplished by either intra- venous infusion of the
deficient clotting factor or in the case of non-severe
FVIII deficiency, through the use of desmopressin
acetate. In PWH with inhibitors, a bypassing agent
is often necessary, although the efficacy of bypassing
agents does not approach that of factor replacement in
PWH without inhibitors. Under optimal conditions,
PWH will infuse factor concen- trate or a bypassing
agent within minutes to hours of haemarthrosis and
bleeding will promptly
be halted. Unfortunately,
Haemophilia (2012), 1--8
Conclusion
Local cooling impairs haemostasis and coagulation in
people without bleeding disorders, and presumably in
PWH. In people with an intact haemostatic system and
normal procoagulant factor levels, who typically do
not experience repeated haemarthroses, using ice may
not be a concern, or, however, have any added benefit
according to the literature. In PWH, with haemarthrosis, the use of ice appears to have a greater risk than
benefit. Therefore, ice application in the treatment of
acute haemarthrosis should be questioned. Additional
studies are needed - specifically in the field of bleeding
disorders to provide high-quality evidence surrounding
the potential risks associated with ice in PWH with
haemarthrosis, whether there exists any net, beneficial
effect of ice, and to better define the role of ice in clinical outcomes for this population.
Acknowledgements
Angela Forsyth, Nichan Zourikian, Leonard Valentino and Georges-E tienne Rivard contributed to the conceptualization, content and composition of this manuscript.
Disclosures
The authors stated that they had no interests which might be perceived as
posing a conflict or bias.
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