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Contents lists available at ScienceDirect

Injury
journal homepage: www.elsevier.com/locate/injury

Fractures of the femur and blood transfusions

Adam Wertheimera,* , Alexander Olaussenb,c,d , Shanaka Pereraa , Susan Liewa ,
Biswadev Mitrab,c,d
a
Department of Orthopaedic Surgery, The Alfred Hospital, Australia
b
Emergency & Trauma Centre, The Alfred Hospital, Australia
c
Department of Epidemiology & Preventive Medicine, Monash University, Australia
d
National Trauma Research Institute, The Alfred Hospital, Australia

A R T I C L E I N F O A B S T R A C T

Article history: Background: Blood loss estimation after trauma (i.e. physical injury) and early identification of potential
Accepted 7 March 2018 sources of bleeding are important for planning of investigation and management of trauma. Long bone
fractures have been reported to be associated with substantial volumes of blood loss requiring blood
Keywords: transfusion. The aim of this study was to assess rates and amounts of blood transfusion in the setting of
Femoral fractures isolated extra capsular femur fractures and to determine variables associated with the need for
Femur transfusion within the first 48 h of admission.
Hemorrhage
Methods: A retrospective cohort study was conducted of patients in The Alfred Trauma Registry with
Blood transfusion
Shock
isolated extra capsular femur fractures over a 7-year period. We compared patients with a femoral shaft
Hemorrhagic fracture (FSF) to patients with either distal femur or proximal femur fractures (i.e. extremity fracture). We
collected data potentially associated with blood transfusion within 48 h as well as operation details and
patient outcomes.
Results: There were 293 patients included, of which 121 had FSF and 172 extremity fracture. 105 (36%)
patients received a blood transfusion during their admission. Admission haemoglobin (AOR 0.92; 95%CI
0.89–0.94, p < 0.01) was the only independently associated variable with blood transfusion within the
first 48 h of hospital admission.
Conclusion: Volume of blood transfused to patients with extra-capsular femoral fractures was low and
usually in the post-operative period. FSF, compared to femoral extremity fractures, were not more likely
to receive blood transfusion within the first 48 h of admission, and did not receive a higher volume of
blood overall. In the setting of major trauma with haemorrhagic shock, alternate sources of bleeding
should be sought.
© 2018 Elsevier Ltd. All rights reserved.

Background patients and are often treated as an orthopaedic emergency [3].

Blood loss estimation after trauma (i.e. physical injury) and
early identification of potential sources of bleeding are important
for planning of investigation and management of trauma.
Estimation of blood loss helps guide clinical decisions and
resuscitation to avoid ongoing haemorrhagic shock and the lethal
triad of coagulopathy, hypothermia and acidosis in multi-injured
patients [1].
Femoral shaft fractures (FSF) are a frequent injury with a
reported annual incidence ranging from 9.5–18.9 per 100,000 [2].
FSF commonly occur in association with multiple trauma in young
* Corresponding author at: Department of Orthopaedic Surgery, 55 Commercial
Road, Melbourne, Victoria, 3004, Australia.
E-mail address: Adam.Wertheimer@nh.org.au (A. Wertheimer).
They have a bimodal distribution with a first peak in early twenties
and a second peak in older patients with low energy mechanisms,
predominantly women with osteoporosis [4].
Although, long bone fractures have been anecdotally reported
to be associated with substantial volumes of blood loss requiring
blood transfusion, there is little literature to support this position.
Some studies report more than one litre of blood may be lost from
FSF. For instance, Lieurance et al. [5] used haemoglobin and
haematocrit changes to estimate an average blood loss of 1276 ml
from FSF during hospitalization. Clarke et al. [6] used red cell
volume estimates using radioactive 32P red-cell volume method as
well as leg circumference measurements and fluid displacement
measurements of the injured limb compared with the non-injured
limb and concluded an average of 1200 mls of blood loss from FSF
over 4 days. However, in a more recent study by Callahan et al. [7]
adjusting for the presence of solid organ injuries, transfusion rates

https://doi.org/10.1016/j.injury.2018.03.007
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did not differ in patients with various types of long bone fractures
suggesting that blood loss from femurs may be less clinically
significant than previously thought. They showed a transfusion
rate of only 15% in their isolated FSF subgroup.
The proximal femur, distal femur and shaft of the femur have
separate blood supplies (Fig. 1). When fractures of the femur occur,
deformity is created by the muscular attachment. The deformity of
FSF is usually more significant than the deformity at either end of
the bone. It was hypothesized that these differences result in
differing volumes of blood loss.
The aim of this study was to assess rates and amounts of blood
transfusion in the setting of isolated extracapsular femur fractures
and to determine variables associated with the need for transfu-
sion within the first 48 h of admission.
Methods
Setting
The Alfred Hospital is one of two adult trauma centres located in
Melbourne, the capital of Victoria, Australia. The inclusive,
integrated Victorian State Trauma System (VSTS) serves a
population of 6 million. Pre-hospital triage guidelines stipulate
that patients are transported to the highest level of designated
trauma centre within defined transport times bypassing other
hospitals with lower designation [8]. In 2016 The Alfred admitted
1431 major trauma patients. In 2008 a massive transfusion
protocol was introduced at our institution [9]. This guideline
recommended a 2:1 units ratio of Red Blood Cells (RBC) to Fresh
Frozen Plasma (FFP), and 4:1 units of RBCs and leucocyte depleted
platelets. A unit of RBC has an average volume of 260 (SD 19) mL,
FFP an average volume of 280 (14) mL, and each unit of platelets
has an average volume of 326 (14) mL with a platelet count of
284  109 (40) per pool. The use of cryoprecipitate was recom-
mended for fibrinogen levels below 1.0 g/L. Our institution does
Fig. 1. Blood Supply to Femur [21].
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injury.2018.03.007
not have any patient age restrictions on transfusion policies.
Triggers for transfusion according to the American Association of
Blood Banks are 2-tiered, recommending transfusion at either
Hb < 70 g/l for stable patients or <80 g/l for those with pre-existing
diseases placing patients at risk of anaemia. We however do not
have strict transfusion criteria and the amount of transfusion a
patient receives is based on the discretion of the treating surgeon
[10].
Design and methods
A retrospective cohort study was conducted including patients
with isolated extra capsular femur fractures presenting to an adult
Major Trauma Centre over a 7-year period. Electronic medical
records of all patients with the diagnosis of an isolated extra
capsular femur fracture admitted to The Alfred Hospital between
January 2010 and July 2016 were reviewed. These patients were
identified using an international coding data search of the hospital
database. Codes S72.41 Condyle(s), epicondyle(s) NEC, S72.44
intercondylar (T-shaped), S72.40 lower (end), S72.42 epiphysis,
S72.43 supracondylar, S72.3 shaft (lower third) (middle third)
(upper third), S72.43 supracondylar, S72.2 subtrochanteric (re-
gion)(section) were used to identify potential patients. Patients
with associated long bone fractures, head injuries, injuries to the
spine, chest, abdomen, pelvis or vascular injuries were excluded.
Patients with pertrochanteric fractures were excluded as these
patients were predominantly represented by an elderly population
with low energy mechanisms and were deemed to represent a
separate clinical cohort. Patients with haematological malignan-
cies or peri prosthetic fractures were also excluded. Patients were
then divided into two groups according to the anatomical location
of their fracture following review of their admission imaging by
two orthopaedic registrars. One group comprised patients with
FSF, the other group consisted of patients with either distal femur
or subtrochanteric fractures (i.e. extremity). The subtrochanteric
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region was considered to be from the base of the lesser trochanter
to 50 mm distal to the lesser trochanter. The distal femur fracture
group was considered any fracture originating distal to the origin
of the supracondylar ridge. For analysis purposes any fracture that
extended beyond an anatomical region was classified by where the
fracture originated.
Variables
Variables associated with blood transfusion within 48 h that
were assessed included age, sex, open or closed injury, mechanism
of injury, initial haemoglobin (Hb), initial international normalised
ratio (INR), initial platelet count, use of antiplatelet or anti-
coagulation medications, initial systolic blood pressure (SBP) and
initial heart rate (HR), shock index (SI) defined as HR/SBP [11], type
of internal fixation (Intramedullary nail vs plate osteosynthesis)
and time to surgery. The primary outcome variable was the
transfusion of blood products within 48 h of arrival to hospital.
Massive haemorrhage was defined as transfusion of 5 units of
RBC in 4 h [12]. Patient outcomes including mortality at hospital
discharge and length of stay (LOS) in hospital were secondary
outcomes.
Statistical analysis
Data were collated using Microsoft Excel and analysed using
Stata V.13.1 (©StataCorp, Texas, USA). Continuous variables are
summarised using mean (standard deviation), while ordinal
variables are summarised using median (inter-quartile range).
Univariate differences between continuous variables were
assessed using the Student’s t-test, and the chi-squared test or
Fisher’s exact test if number in a cell was <5 were used to assess
categorical variables while the Mann-Whitney U test was used to
assess differences between ordinal variables. Potential confound-
ers that demonstrated any association with the exposure and
comparator variables (p < 0.10) or were considered to be clinically
significant were entered into a multivariable logistic regression
model to determine independent associations of the exposure

Fig. 2. Flow diagram of patient selection.

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variable with mortality at hospital discharge. Dichotomous out-
comes based on dichotomous, continuous or categorical variables
were analysed using the Chi squared and Fisher’s exact, logistic or
probit regression tests respectively. Results of this analysis were
presented using adjusted Odds Ratios (ORs) with 95% Confidence
Intervals (CIs). Two-sided p-values of <0.05 were considered to be
statistically significant.
Ethics
Approval for conducting this study was received from Alfred
Health research committee.
Results
There were 23,948 trauma patients in the study period of which
3255 were diagnosed with a femur fracture. Of these, 2076 were
fractures involved the neck of femur, trochanteric region or
intracapsular condylar fractures and were subsequenlty excluded.
Of the 1179 remaining patients with femur fractures, 794 were
associated with polytrauma.
Data from the 385 isolated extra capsular femoral fractures
were reviewed and 92 were excluded for various pre-hoc reasons:
78 were periprosthetic fractures, 5 patients had a concurrent
contralateral femur fracture, 4 patient electronic records had
insufficient details of admission, 4 patients were transferred for
definitive care at an alternative hospital and 1 patient absconded.
The remaining 293 patients were included in the analysis (Fig. 2).
The 293 patients that met inclusion criteria were subdivided
into FSF and extremity (i.e. sub trochanteric and/or distal femoral
fractures including fractures involving the condylar, supracondylar
and intercondylar regions) following review of admission Xrays. 29
of the 121 (24%) subtrochanteric fractures extended in to the shaft
(considered to begin at 50 mm from the lesser trochanter). The
average fracture extension beyond the subtrochanteric region was
52 mm with a median of 42 mm (IQR 30–80 mm) with only 3
fractures extending beyond 100 mm. This was not considered a
significant enough surface area to exclude these fractures from
analysis as subtrochanteric fractures. In 3 cases femoral shaft
fractures extended to within 50 mm of the lesser trochanter. In the
distal femur group only 3 fractures extended in to the shaft
(considered to begin at the proximal tapering of the supracondylar
ridge). The fractures extended 75 mm, 85 mm and 120 mm
respectively and were classified in the distal femur group.
The accuracy of our classification method is supported by
reviewing the surgeons choice of fixation. The subtrochanteric
group all received a form of femoral neck fixation (114 antegrade
femoral nails with femoral neck fixation, 4 plate osteosynthesis
with femoral neck fixation, 3 non op). In the shaft group the
majority of cases were fixed with femoral nails without additional
femoral neck fixation with the surgeon electing to perform femoral
neck fixation in 14 cases, 3 cases were fixed with plate osteosyn-
thesis due to the presence of a hip or knee arthroplasty (95
antegrade femoral nails, 8 retrograde femoral nails, 14 antegrade
femoral nail with femoral neck fixation, 3 Plate osteosynthesis). In
the distal femur group all patients except 2 received either plate
osteosynthesis or supracondylar nail fixation (32 plate osteosyn-
thesis, 8 supracondylar femoral nails, 1 antegrade femoral nails, 1
distal femur replacement, 9 non op).
Table 1 outlines the characteristics of each group with a
univariate analysis of the study population. There were statistically
significant differences in age, male sex, Injury cause, Initial Hb, and
use of antiplatelet medication among the two sub-groups.
There were 105 (36%) patients that received a blood transfusion
during their admission with 20.8% of patients receiving blood
within 48 h. Only 2 patients received blood during the initial
resuscitation (i.e. within 4 h of admission). Amongst those that
received bloods, there was no difference between the 2 cohorts in
terms of amount received with a median of 2 (IQR 2–4) Red Blood
Cell (RBC) units in each cohort (Table 2). Only 14 patients required
5 units of RBC during their admission. (Table 4)
Following multivariable logistic regression analysis, adjusting
for potential confounders only admission Hb (AOR 0.92; 95%CI
0.89–0.94, p < 0.01) was independently associated with blood
transfusion within the first 48 h of hospital admission. Location of
fracture, age, sex, use of antiplatelets, use of anticoagulation, and
cause of injury were not independently associated variables
(Table 3).
Whether patients underwent intramedullary fixation (IMN),
plate osteosynthesis via open reduction internal fixation (ORIF) or
arthoplasty did not correlate with increased risk of blood
transfusion within 48 h of admission to hospital. IMN 50/240
(21%) vs ORIF 8/39 (20.5%) vs arthroplasty 0/1 (0%) (p = 0.26).
When examining the timing of blood in patients relative to time
of surgery there was no differences between the two groups.
(Table 4). The extremity fracture group received blood later than
the FSF group 41 (12.5–64) hours vs 30.5 (17.5–64) hours, (p = 0.32)
however this was not statistically significant. In both groups, blood

Table 1
Characteristics of extra capsular femoral fractures by anatomical location.

FSF (n = 121) Extremity (n = 172) P-value

Age (years) Median (IQR) 47 (28–79) 76.5 (60–87) <0.01
Male sex (%) 66(54.5) 56 (32.6) <0.01
Open fracture (%) 5 (4.1) 5 (2.9) 0.57
Injury cause (%) <0.01
Ped v Car 28 (23.1) 13 (7.6)
Fall 79 (65.3) 150(87.2)
Horse related 4 (3.3) 0 (0)
Other 10 (8.3) 9 (5.2)
Antiplatelets (%) 23 (19) 57 (33.1) <0.01
Anticoagulants (%) 7 (5.8) 18 (10.5) 0.20
Initial SBP (mmHg) Mean (SD) 144.8 (21.7) 146.6 (52.1) 0.47
Initial HR (bpm) Mean (SD) 83.2 (16.3) 81.9 (15.5) 0.72
Initial SI*, Mean (SD) 0.6 (0.1) 0.6 (0.2) 0.85
Initial SI 3 1 (%) 1 (0.8%) 2 (1.2%) 0.99
Initial haemoglobin (g/L) Mean (SD) 131.6 (18) 123.6 (17.2) <0.01
INR Mean (SD) 1.1 (0.4) 1.1 (0.4) 0.55
Platelet count (10^9/L) Mean (SD) 226.9 (57.1) 228 (71.0) 0.89

IQR = Interquartile range; SD = standard deviation; Ped v Car = Pedestrian versus Motor Vehicle; SD = Standard Deviation; SBP = Systolic Blood Pressure; HR = Heart Rate;
*SI = Shock Index, available for 295pts.

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Table 2
Amount of blood received in FSF and extremity.

Transfusion Incidence During Admission FSF (n = 121) Extremity (n = 172) Total (n = 293) P-Value
Received RBC (%) 36 (29.8) 69 (40.1) 105 (36.0) 0.08
Received RBC in 4 h (%) 0 (0) 2 (1.2) 2 (0.6) 0.51
Received RBC in 48 h (%) 22 (18.2) 38 (22.1) 61 (20.8) 0.46
Median Total RBC transfused per patienta 2 (2–4) 2 (2–4) 2 (2–4) 0.21
Required  5 units RBCa 6 (17) 8 (11) 14 (13.3) 0.36
a
Amongst those that received blood.

Table 3
Multivariable logistic regression analysis for independent associations of PRBC
transfusion in 48 h.

PRBC in 48 h Adjusted Odds Ratio (95% CI) P-Value

FSF 1.69 (0.78–3.66) 0.18
Age (years) 1.02 (0.99–1.04) 0.21
Hb (g/dL) 0.92 (0.89–0.95) <0.01
Antiplatelets 0.88 (0.36–1.99) 0.77
Anticoagulation 2.27 (0.79–6.5) 0.12
Male sex 2.13 (0.91–5.0) 0.08 Fig. 3. Number of patients who received blood in the pre, peri and post operative
Injury Cause period.
Fall 5.70 (0.54–59.5) 0.15
Ped v Car 3.70 (0.21–64.83) 0.37

PRBC = Packed Red Blood Cells; CI = Confidence Interval; Hb = Haemoglobin; Ped v
Car = Pedestrian versus Motor Vehicle; FSF = Femoral Shaft Fracture.
was given predominantly in the post-operative period with only
15% of blood given pre-operatively (Fig. 3).
When examining time to the operating theatre the FSF cohort
had shorter median time to theatre of 15.5 (10.9–21.1) hours
compared to 21 h (15.1–34.2) for the extremity fracture group
(p < 0.01). 50% of all patients underwent surgery within 18 h.
Overall unadjusted inpatient mortality was at 3% (n = 9/293),
but higher in the extremity fracture group (n = 8/172) compared to
FSF (n = 1/121) but this was not statistically significant (p = 0.06).
The overall LOS was 6 (4–7) days in the FSF group compared to 7
(5–9) days in the extremity group (p = 0.002).
Discussion
Only a third (36%) of isolated femur fractures in our cohort
required a blood transfusion during their admission and when
transfused, it was not as part of emergency resuscitation.
Transfusion volumes were low, with a median volume of 2 units
of RBC transfused to those patients receiving blood. The majority
(n = 97, 92%) of those that received blood did so in the post-
operative period, and only 14 (15%) received pre-operative
transfusion. Only 14 patients (4.8%) required  5 units of RBC.
Only admission haemoglobin was independently associated with
increased transfusion incidence within in the first 48 h.
Previous work has estimated blood loss from closed FSF to be
between 400ml–2200 ml. It would require 5 units of RBC to replace
the red cell volume lost in 2000 ml of haemorrhage and if lost
acutely would put a 70 kg man into the class 3 shock as per the
ATLS guidelines [13]. The transfusion incidence in our study cohort
was not in keeping with what would be expected from this volume
of blood loss. These findings are consisted with those of Callahan
et al. [7] and reinforces the hypothesis that blood loss from FSF may
not be as clinically significant as previously thought, especially in
the immediate period following injury.
The blood supply and variation in deformity of fracture type are
potential reasons for differing volumes of blood loss in FSF
compared to fractures at the extremity of the femur. The blood
supply to the subtrochanteric region of the femur is from the
trochanteric and cruciate arterial anastomoses with vessels
penetrating the proximal femur. The femoral shaft has periosteal
and endosteal blood supply. Endosteal circulation provides blood
to the inner two thirds to three quarters of the cortex of the femoral
diaphysis. Endosteal supply is from the nutrient artery, a branch
which usually comes from the first perforating branch of profunda
femoris. It enters the shaft posteriorly at the linea aspera and
branches both proximally and distally. Rarely a second nutrient
artery contributes more distally but no major artery enters the
distal thirds of the femoral diaphysis [14]. The periosteal supply
comes from perforating branches of profunda femoris which wrap
circumferentially around the femoral shaft. The distal metaphysis
has many vascular foraminae, with the arterial supply coming from
the geniculate arteries, branches of the popliteal artery.
When the proximal third of the femur is fractured the proximal
fragment is usually abducted by the gluteus medius and gluteus
minimus muscles which attach to the greater trochanter of the
femur. The proximal part is also flexed and externally rotated by the
iliopsoas which attaches to the lesser trochanter. The adductors and
hamstring muscles pull the distal fragment upwards and medially. In
fractures of the middle third of the femur the proximal fragment is
frequently adducted by the adductor muscles and flexed due to
iliopsoas. The distal fragment is externally rotated by the weight of

Table 4
Timing of blood for those who received RBC.

FSF (n = 36) Extremity (n = 69) Total (n = 105) p

Received RBC within 4 h (%) 0 (0) 2 (3) 2 (1.9) 0.55
Received RBC within 48 h (%) 22 (61) 38 (55) 60 (57) 0.68
Received pre-op (%) 4 (11) 12 (17) 16 (15) 0.57
Received peri-op (%) 10 (28) 8 (12) 18 (17.1) 0.06
Received post-op (%) 34 (94) 63 (91) 97 (92) 0.71
Median time to 1st PRBC (hours) 30.5 (17.5–64) 41 (19–79.8) 41 (18–72) 0.32

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the foot and displaced upwards and posterior due to the adductors
and hamstring muscles. This deformity results in a more spherical
shape of the femur and coupled with the loose fascial envelope of the
thigh may allow a significant volume of blood to accumulate. In
supracondylar fractures the distal fragment is usually flexed
posteriorly as a result of the pull of the gastrocnemius muscle.
The proximal fragment is pulled into flexion and adduction by
iliopsoas and the adductors. Although fractures at the ends of the
femur can create deformity it is generally less pronounced than the
shaft. The anatomical and physiological differences remain theoreti-
cal. We did not find a difference in the incidence of transfusion within
the first 48 h and identical amounts of RBC units were transfused in
the 2 groups. Previous studies have demonstrated that transfusion
decision during trauma resuscitation can have varied indications and
often based on clinician gestalt, rather than a true physiological
derangement [10], despite the numerous transfusion prediction
models that exist [16]. This is supported by the observation that the
only two patients in our cohort that required blood within four hours
of arrival were later shown to have chronic anaemia and not acute
haemoglobin loss related to their injuries. Bleeding from femur
fractures may not be a significant source to consider in the initial
periods following injury and overall blood loss may be over-
estimated. There was a significant difference in age demographic
between the two groups. The extremity group was on average 18
years older than the FSF group (median age 76.5 (60–87) vs 57(30–
80)). This difference was also reflected in the mechanism of injury
with FSF group more likely to be involved in higher energy
mechanisms such as Pedestrian versus Car. It is likely that the age
of the patient, as well as their comorbidities would play a part in a
clinician’s decision to transfuse a patient or not. Advancing age may
restrict a liberal transfusion strategy, however our institution does
not support restrictive resuscitation or transfusion on the basis of age
alone [17]. Furthermore, advancing age carries co-morbidities,
which may dictate the aims of transfusion treatment (e.g. a lower
threshold may exist for transfusing a patient with known ischaemic
heart disease and a higher threshold for a patient with congestive
cardiac failure). However, our multivariate analysis was based on the
binary outcome of blood transfusion or not, which makes this
confounding factor less likely to impact our findings.
There was no independent association with the use of antiplatelet
or anticoagulation medications and the increased incidence of blood
transfusion within the first 48 h of admission. This is in contrast to
recent research by Takao et al. [18] that looked at the effect of pre
injury anticoagulant and antiplatelet agents on blood loss in elderly
patients with severe trauma and showed that the use of warfarin was
independently associated with increased incidence of blood
transfusion and was independently associated with increased rate
of massive transfusion. Yusuke et al. [19] showed antiplatelet and
anticoagulation medications to be independently associated with
increased perioperative blood loss in proximal femur fractures
however did not look specifically at transfusion incidence.
Our findings must be interpreted in light of its limitations, given
its retrospective design at a single centre institution. Potential
unknown confounders limit confidence in the association of
transfusion requirement. In addition, indications of blood transfu-
sion after injury remain varied, and blood transfused may not
always reflect clinical need [20].
Conclusions
Volume of blood transfused to patients with extra-capsular
femoral fractures was low and usually in the post-operative period.
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Femoral shaft fractures, compared to femoral extremity fractures,
are not more likely to receive blood transfusion within the first 48 h
of admission and receive the same volume of blood overall. Initial
haemoglobin was independently associated with transfusion in the
first 48 h of admission. No cases of femoral fractures were shown to
be associated with massive haemorrhage. These findings suggest
that in the setting of haemodynamic instability and extra-capsular
femur fractures, alternative sources of blood loss or causes of shock
should be sought.
Conflict of interest
None.
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based on similar schemas from Moore's Essential Clinical Anatomy (3rd
edition) and Netter's Atlas of Human Anatomy (5th edition): Wikimedia
Commons Distributed under a CC-BY 3.0 license 2010 [cited 2017 31st Oct].
Available from: https://commons.wikimedia.org/wiki/File:
Thigh_arteries_schema.svg#.