0Haemophilia (2012), 18

DOI: 10.1111/j.1365-2516.2012.02918.x

REVIEW ARTICLE

The effect of cooling on coagulation and haemostasis:

Should Ice be part of treatment of acute haemarthrosis in
haemophilia?
A . L . F O R S Y T H , * N . Z O U R I K IA N , L . A . VALE N T I N O * and G . E . R I VAR D
*RUSH Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, IL USA; and Centre Hospitalier
Universitaire Sainte-Justine, Montre al, Que bec Canada

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

adjunct to medical management in the initial

management of haemarthroses in PWH. In 1970,
Sutor [12] stated that ice, is especially popular for
the treatment of local bleeding in haemophiliacs. Ice
is commonly used to address goals such as reducing:
pain, muscle spasm, tissue metabolism, oedema and
inflammation [13,14].
Repeated haemarthroses and the consequences of
blood in the joint contribute to BIJD in PWH.
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effect of cooling on haemostasis and coagulation. The

literature demonstrates that typical methods of ice
application can cool both the skin and IA space.
Published, general literature studies have also
consistently demonstrated that experimental cooling of
blood and/ or tissue, both in vitro and in vivo in
humans and in animal models, can significantly impair
coagulation and prolong bleeding. In PWH with acute
haemarthrosis, ice application has potential to increase
haemorrhage morbidity
by further
impairing
coagulation and haemostasis. Ice has not been shown to
improve overall outcome, stop bleeding nor swelling
from haemarthrosis. Although ice can help manage
acute, haemarthrosis- related pain, there are other
available interventions that will not impair coagulation
and haemostasis.
Keywords: coagulation, cryotherapy, haemarthrosis, haemophilia, haemostasis, ice

Prevention of bleeding, through medical management,

is the standard of care in developed countries, but is
not universally achievable due to financial and other
barriers. As an adjunct to medical management, the
recommendation to use ice as a part of R.I.C.E. after
acute haemarthrosis is evident in most current
haemophilia publications [1520]. The specific benefits
of ice application following acute haemarthroses in
PWH are thought to be reduction in bleeding, pain,
swelling and inflammation
Correspondence: Angela L. Forsyth, PT, DPT, RUSH Hemophilia and Thrombophilia Center, RUSH University Medical
Center, 1653 West Congress Parkway, Chicago, IL 60612-3833.
Tel.: + 312 942 8114; fax: + 312 942 8975;
e-mail: AngelaForsythPT@yahoo.com
Accepted after revision 28 June 2012

[1519]. However, despite

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A . L . FO R S YTH et al.

these recommendations to treat PWH, there is lack of

evidence within the general literature indicating a
beneficial effect of ice on clinical outcome after acute
soft-tissue injury [21], or on objective measures of
disease in an inflammatory condition such as
rheumatoid arthritis [22]. Furthermore, the evidence
that cooling will stop or even reduce bleeding has not
been confirmed, despite the common recommendations to use cooling for this purpose [12,23].
Therefore, not only is there a lack of evidence of a
beneficial effect of ice after haemarthrosis, the
contrary may be true; The use of ice may pose a risk
in a PWH due to its effects on the coagulation system
and platelet functions, thereby impairing haemostasis.
While this effect might be less relevant in the general
population in whom the haemostatic mechanism is
intact, it may be very important when treating PWH.
There is ample evidence, both in vitro and in vivo
that application of ice locally impairs haemostasis.
This has been demonstrated both in humans and in
animal models showing prolonged bleeding time,
decreased platelet aggregation, increased clotting
time and clot formation time and impairment of
both procoagulant enzyme activity and clot firmness
[12,2331].
Our purpose is to review the biomedical literature
to answer the following questions associated with the
use of ice in the management of acute haemarthrosis
in PWH.
1. To what degree can commonly used clinical methods of local ice application achieve cooling of the
skin and IA space?
2. How does this degree of cooling affect blood coagulation and haemostasis?

Materials and methods

Due to the paucity of evidence on the effect of cold
on haemostasis
and coagulation in PWH, more
specifically, the effect of localized cooling using ice
following acute haemarthrosis in PWH, the general
literature was reviewed for articles in English.
Search terms included: haemophilia, coagulation, haemostasis, cooling, ice, cryotherapy, intra-articular
temperature. Pubmed and Google Scholar were
searched using Boolean logic. The references of
relevant articles were also used for finding additional
publications, as well as general internet search
engines, including searching for literature on acute
care of musculoskeletal soft-tissue injuries. All of the
research articles obtained regarding cold application,
coagulation and
haemostasis, with
the
exception of one article that included just two
subjects with haemophilia [12], were performed on
non-bleeding-disorder subjects. Finally, haemophiliaspecific guidelines and publications from the World

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 .

Fig. 1. Schematic depiction of a synovial joint.

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Table 1.

Baseli ne Tempe rature of the Skin.

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to 29.5C after 15 min, to 28.5C after 30 min and to

Haemophilia (2012), 1--8

Baseline Temperature C

Location

27.9
28.8
29.5
29.6

Anterior knee
Ankle
Anterior knee
Ankle

Oosterveld 1992 [33]

Kennet 2007 [34]
Warren 2004 [13]
Palmer 1996 [35]

Table 2. Baseline Temperature of the IA Space.

Baseline Tempe rature
publication

31.9
32.2
33.5

Location
Knee
Knee
Knee

26.9C after 1 h [36].

Author and year of publication

Author

and year of

Oosterveld 1992 [33]

Sanchez-Inchausti 2005 [36]
Warren 2004 [13]

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.

Application of ice to the skin surface can also cool

the deeper IA space. Knight summarized that: IA
temperatures decrease more than in adjacent muscle,
and the longer the application, the greater the IA
temperature decrease. Similar to other deep tissues, the
minimum IA temperature is reached after the ice pack
is removed; consequently, IA re-warming back to
baseline temperatures can be delayed for up to an
hour or more . Ice chips applied for 30 min to the
anterior of the knee reduced the IA temperature from
31.5C to 22.5C. As was the case for skin
temperature, 2 h after ice removal, the IA
temperature still remained below baseline at 27.5C
. Application of ice chips in a plastic bag, to the
anterior knee, reduced the IA temperature from 33.5
C to 30.4C after 30 min and to 20.9C after 60 min .
Similarly, as already noted , IA knee temper- atures
remained significantly decreased, at 5.7C below
baseline (33.5C), even at 60 min following removal
of the ice pack . After arthroscopy and upon
returning to their hospital rooms, a bag of ice was
applied to the knees of 23 patients,
which
resulted in a decrease in IA temperature from 32.2C

Effect of cooling on coagulation and haemostasis

It is commonly known that the biochemical reactions
associated with haemostasis and coagulation function
most efficiently at basal body temperature. The haemostatic mechanism involves the complex interplay of
platelets with the vessel wall, mediated at least in part
by von Willebrand factor (VWF). VWF serves an
adhesive function, bridging platelets to subendothelial
collagen and with coagulation proteins which dock to
phospholipid sites on the surface of platelets, resulting
in fibrin-generating concentrations of thrombin.
Although the activity of platelets can be assessed by
light transmission aggregometry, impedance testing or
flow cytometry, and more recently by one of several
whole blood methodologies, primary haemostasis, the
interaction of platelets with damaged tissue can only
be assessed by the bleeding time, performed by one of
several techniques. Several methods exist to estimate
the potential of the haemostatic mechanisms to
generate thrombin including the classic prothrombin
time (PT) and the partial thromboplastin time (PTT).

Table 3. Temperature of the skin following ice application.

Mode

Duration Applied (min)

Crushed ice, plastic bag

Ice pack
Crushed ice, plastic bag
Crushed ice
Crushed ice
Ice chips, 3kg, plastic bag

60
20
30
20
26
30

Location
Anterior knee
Lateral ankle
Anterior knee
Ankle
Ankle
Anterior knee

Temperature (C )

Author and year of publication

3.2
5.9
8
9.2
10
11.5

Warren 2004 [13]

Palmer 1996 [35]
Warren 2004 [13]
Kennet 2007[34]
Algafly 2007 [37]
Oosterveld 1992 [33]

Table 4. Temperature of the IA space following ice application.

Mode

Duration Applied (min)

Crushed ice, plastic bag

Ice chips, 3kg
Ice bag, 2 kg
Ice bag, 2 kg
Ice bag, 2 kg
Crushed ice, plastic bag

60
30
60
30
15
30

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Location
Anterior knee
Anterior knee
Knee
Knee
Knee
Anterior knee

Temperature (C)

Author and year of publication

20.9
22.5
26.9
28.5
29.5
30.4

Warren 2004 [13]

Oosterveld 1992 [33]
Sanchez-Inchausti 2005 [36]
Sanchez-Inchausti 2005 [36]
Sanchez-Inchausti 2005 [36]
Warren 2004 [13]

Haemophilia (2012), 1--8

A . L . FO R S YTH et al.

More recently, testing of ex vivo and in vitro samples

using thrombin generation assays or using thromboelastography has been employed.
Coagulation is typically triggered after the exposure
of tissue factor (TF) found in the subendothelium
binds circulating activated factor (F) VII (FVIIa). This
enzyme complex (TF-FVIIa) activates zymogen FVII,
FIX and FX to FVIIa, FIXa and FXa, respectively.
FXa converts prothrombin (FII) to thrombin (FIIa).
The low quantities of FIIa generated releases FVIII
from its carrier protein, VWF, and activates it to
FVIIIa. Thrombin also activates platelets exposing a
negatively charged phospholipid-rich surface capable
of binding coagulation proteins including FIXa, which
was generated on TF-bearing cell surface. FIXa along
with cofactor FVIIIa, calcium and phospholipids
forms the tenase complex, recruits FX to the complex
and activates it to FXa. Activated FX along with
calcium and phospholipids forms the prothrombinase
complex, which in turn converts large quantities of
prothrombin to thrombin capable of cleaving fibrinogen to form fibrin monomers. Thrombin activates
FXIII which cross-links the fibrin monomers to stabilize the clot and thrombin-activatable fibrinolysis
inhibitor (TAFI) which prevents clot breakdown, both
improving clot firmness.
Biochemical reactions involved in multiple aspects
of these coagulation processes are adversely affected
by cooling, as shown both in humans and in animal
models, completed mainly in subjects without
coagulation disorders . As early as 1942, the adverse
Subjects

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

Haemophilia (2012), 1--8

Author and year

of publication
Copley
1942 [26]
Sutor
1970 [12]
Niemczura
1979 [29]
Bahn
1980 [23]

Valeri
1995 [28]

Romlin
2007 [30]
Rundgren
2008 [27]

Kattlove
1970 [24]
Wolberg
2004 [25]

Johnston
1994 [31]

effects of cold on haemostasis were recognized by

studying the effect of cold on bleeding times.
Following creation of a standardized, 6 mm deep
wound on the finger of 13 healthy volunteers, the
finger was cooled in an isotonic saline bath. The
bleeding times were prolonged at temperatures below
36.5C . The landmark study of Sutor, Bowie and
Owen in 1970 demonstrated the same phenomenon in
two patients with severe haemophilia A. This was the
sole study in our review that included subjects with
a coagulation disorder. An automatic lancet was used
to produce a wound, over which warmed (37C) or
chilled water (1617C) was passed. Bleeding time
was increased approximately three-fold and blood loss
was approximately 610-fold greater after the bleeding site and the surrounding skin were exposed to the
chilled water. The effect of cold on a standardized
bleeding time in rabbits generated similar conclusions
. Incisions were made on the abdomen down to deep
fascia and 2 9 2 gauze sponges moistened in sal- ine
at 4, 15, 25, 37 or 49C were immediately placed on
the wounds using gentle manual compression. At all
compress temperatures below 37C, approximately 1
2C below the rabbits basal temperature, bleeding
times were increased. In another study using a rabbit
model, in vitro coagulation times and in vivo bleeding
times were measured after the ear temperature of the
rabbits was reduced . Both in vitro coagulation
times and in vivo bleeding times were proportionately prolonged as the temperature of the rabbit ear
skin progressively decreased from about 30C to 1C.
The authors noted that they could not find a
temperature below that of the body that could
enhance haemostasis without freezing cells. Template bleeding time was assessed in healthy volunteers by placing wet ice in a plastic overwrap on
the anterior forearm [28]. Cooling resulted in progressive
bleeding
time
prolongation
from
6.3 2 min at basal skin temperature of 32C, to
10.3 3 min at 28C, and to 22.5 10 min at 22
C, which represented 1.6- and 3.6-fold increases
from baseline respectively. Blood was also obtained
from the antecubital vein to test for clotting time at
similar temperatures and found to be similarly prolonged:
From
3.6 1.2 min
at
37C,
to
4.3 1.2 min at 32C, to 6.1 2.5 min at 28C
and finally to 12.1 10.0 min at 22C. In another
study [30], a water bath was used to cool the forearm of healthy volunteers and bleeding times measured using the Ivy technique. Cooling the forearm
skin temperature from the baseline of 32 degrees C,
down to 30 degrees C significantly prolonged bleeding times more than to almost double, bleeding time
doubled compared with baseline.
Cooling also adversely affects platelet aggregation
and adhesion. Platelet rich plasma, harvested from

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Haemophilia (2012), 1--8

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

medical management is not consistently available

worldwide. In situations where factor replacement or
bypassing agents are unavailable, infu- sion is delayed,
or treatment inefficient or suboptimal, bleeding may
persist for an extended period of time. When the
underlying
coagulopathy has not been improved
with medical management during haemarth- rosis, the
resulting increased volume of blood in the IA space
results in catastrophic consequences for both the
articular cartilage and synovial membrane , eventually
resulting in arthropathy from BIJD. Joint bleeds
should be prevented or limited, employing both medical
management and conservative measures (i.e. activity
modification and education). Minimizing the presence
of blood in the joint is vital to limiting BIJD.
In the reviewed studies investigating cold application, both the times (15 or 20 min) and methods (such
as ice chips, cold packs or compresses) are clinically
relevant to current practice in PWH. Cooling, by all
methods, results in reductions in IA temperature that
can interfere with coagulation and haemostasis. Several studies cited here also described increased cooling
effects with longer durations of chilling, including 26 ,
30 and 60 min , which cannot be discounted as it is
known that many patients do keep ice packs on for
extended time periods. Indeed, one author who has
published extensively on the use of cryotherapy in
sports
medicine
now
recommends longer ice
application durations ice application of at least 30
45 min and in some cases 60 min In addition, ice
is often used in combination with com- pression as
part of R.I.C.E. It should be noted that tissue
cooling depth, degree and duration are signifi- cantly
amplified when ice is applied with compression .
Therefore, with potentially colder tempera- tures
achieved by combining ice with compression, it can
be surmised that coagulation and haemostasis can also
be more negatively affected.
The application of ice clearly decreases skin and IA
temperatures , well into the zones which interfere
with coagulation, as is demonstrated in the reviewed
studies. Therefore, it is reasonable to assume that there
is a concomitant decrease in temper- ature of the
synovial membrane, which lies anatomi- cally at a
point between the skin and IA space . Clinically
relevant methods of topical cold application in PWH
during
haemarthoses could impair haemostasis,
potentially by a number of mechanisms including:
reductions
in platelet and vessel wall function
reflected by prolongation of bleeding times, reductions
in platelet
adhesion
and
aggregation, impaired
procoagulant enzyme activity, increased clotting times
and clot formation times and impaired clot firmness .
It is important to reiterate that with the exception
of two subjects reported in one study [12], all of the
studies reviewed and data presented herein, were
performed in animal and human subjects with normal
haemostasis. They have all provided ample evidence that
cold impairs coagulation and haemostasis in animal
and human subjects with normal haemostasis. There
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is no reason to believe that cold impairs haemostasis

in normal subjects, while simultaneously improving
the
already compromised haemostasis
in PWH.
Similarly, local ice treatment
in
PWH
during
acute
haemarthroses, whether applied before or
immediately following med- ical management, will still
impair haemostasis and coagulation in the lesioned
synovial membrane. This impairment can result in
prolonged bleeding, which in PWH can lead to
potentially
increased
amounts of IA blood
accumulation during an acute haemarthrosis. As a
key, common goal in the management of PWH is to
prevent or limit joint bleeding, treaters should
ensure that their recommended interventions do not
subsequently increase blood in the joint.
Haemarthrosis can be a very painful condition,
requiring pain control via additional treatment
through pharmacological or other means. In PWH
with immediate and adequate access to medical management, haemarthosis is likely to cease prior to the
joint capsule undergoing extreme distension. In PWH
without access to medical management, blood can
continue to collect in the IA space, and a tamponade
effect may slow and halt bleeding. As described by
Ribbans , there is clearly a limit to the amount of
fluid within a joint before a tamponade effect prevents additional accumulation. The pain from haemarthrosis is believed to be a result of the richly
innervated joint capsule undergoing rapid distension
as the IA space fills with blood . It stands to reason
that PWH who do not receive medical manage- ment
may experience even more pain, due to the con- tinued
distension of the joint capsule from prolonged
bleeding. Ice application, which is more readily available than medical management in many world areas,
can be an effective, temporary pain reliever. In fact,
when local tissue temperatures are cooled, nerve
conduction velocity (NCV) is decreased and the result
is a reduction in pain. When ankle skin temperature
was decreased to 10C, with 26 min of ice application
, Algafly used EMG on the tibial nerve and reported
a 33% decrease in NCV, associated with an
89% increase in pain threshold and a 76% increase in
pain tolerance . Kennet reported that ice applica- tion
for 20 min on ankles led to skin surface tempera- tures
of 9.2C, which was enough to promote local
analgesia . However, it is important to mention that
the anaesthetic effect achieved with cooling is
merely a temporary measure that will disappear after
ice is removed, as the local tissue re-warms and NCV

Haemophilia (2012), 1--8

returns to baseline. Unfortunately, the levels of

cooling needed to realize this temporary reduction in
NCV and pain are well within the temperature range
where interference with coagulation and haemostasis
has been demonstrated [12,2331].
Control of distension of the joint capsule by managing swelling is another goal in the adjunct treatment of
haemarthrosis, which can influence the pain and recovery from bleeding. Indeed, many treatment variations
exist in the practise of R.I.C.E., where these elements
are combined to address swelling. The use of ice is not
an effective method to achieve control of haemarthrosis-related swelling [56]. In a systematic review of controlled trials of ice in soft-tissue injury, Bleakley et al.
[59] found, little evidence to suggest that the addition
of ice to compression had any significant effect.
Knight [2] also concluded that cryotherapy does not
reduce swelling originating from haemarthrosis. Compression is known to help to limit IA blood volume
and joint swelling, by increasing external pressure, limiting joint capsule distensibility, thereby leading to a
halt in bleeding by achieving tamponade sooner [57].
In addition, compression may play a greater role in
acute haemarthrosis treatment when medical management is not available. In a study of non-PWH following knee replacement, firm bandaging was employed
(without ice), which resulted in reduction in postoperative swelling and bleeding, as well as speedier recovery
times, a shorter hospital stay and a greater range of
flexion on discharge [57]. The authors suggested compression reduced postoperative joint bleeding by
decreasing the IA pressure at which tamponade normally occurs (i.e. from 5262 mm Hg) to 28
32 mm Hg. Another component of R.I.C.E., elevation,
is also an effective method to reduce swelling due to
haemarthrosis. Positioning of the swollen area above
the level of the heart helps by reducing tissue capillary
hydrostatic pressure [2] and using gravity to help with
fluid return. Ong [58] documented a 25% reduction in
blood loss following knee replacement in patients who
were supine positioned, with the knee elevated 35.
Other benefits of ice as a treatment modality have
also been questioned. Sutor [12] stated Despite the
almost universal use of cold to stop bleeding, we
were unable to find experimental evidence which
would support this practice. Similarly, Bahn [23]
reiterated Despite these almost universal recommendations for the use of cold to stop bleeding, experimental evidence to support this practice has been
contradictory. In the 2004 systematic review on
the use of ice in the treatment of acute soft-tissue
injury, Bleakley [59] summarized: Few studies
assessed the effectiveness of ice on closed soft-tissue
injury, and there was no evidence of an optimal
mode or duration of treatment. Most recently, a
2008 review by Collins [21] concluded that There
is insufficient evidence to suggest that cryotherapy
improves clinical outcome in the management of
soft tissue injuries.
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Notwithstanding the lack of evidence regarding

improved overall clinical outcome or objective measures
with respect to ice application in people with normal
haemostasis, and considering the poten- tial deleterious
effects of ice in bleeding-disorder pop- ulations, this
treatment remains a cornerstone in the standard of
care of PWH. Ice application in a PWH potentially
leads to prolonged bleeding, which was clearly
described by Sutor, Bowie and Owen who reported
increased time and intensity of bleeding when exposed
to cold, was most obvious in patients with congential
coagulation factor deficiencies. Prolonged bleeding
leads to larger quantities of blood in the joint, is
detrimental to the cartilage and synovium, eventually
resulting in BIJD.
Haemophilia care providers should decide on a caseby-case basis (including consideration of factor replacement and pain management medication availability),
whether the transient benefits of ice application to temporarily decrease pain during treatment of an acute
haemarthrosis, outweigh the potential risks of bleeding. Other effective treatment choices, such as compression and elevation along with pharmacological
management as appropriate, are available to address
both pain and swelling, without the risk for
interference with coagulation and haemostasis.

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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