Effectiveness of Preoperative Intravenous Tranexemic Acid on Reduction of Perioperative Blood Loss in Open Intramedullary Nail Fixation of Femoral Shaft Fractures in Mulago
Phase: PHASE4
Conditions: Femoral Fractures, Hemorrhage, Surgical, Tranexamic Acid Use
Sponsor: Masaka Regional Referral Hospital

Official Title:
Effectiveness of Preoperative Intravenous Tranexemic Acid on Reduction of
Perioperative Blood Loss in Open Intramedullary Nail Fixation of Femoral Shaft
Fractures in Mulago
NCT Number:
Document Type:
■Study Protocol
■Statistical Analysis Plan
■Informed Consent Form (English)
Document Date:1st
October 2025
Sponsor-Investigator:
Dr. Paul Kabazzi
Orthopaedic Surgeon
Masaka Regional Referral
Hospital Uganda Ministry
of Health

ii
2018
Contents
ABBREVIATIONS ........................................................................................................................ v
ABSTRACT .................................................................................................................................. vi
OPERATIONAL DEFINITIONS ................................................................................................ vii
CHAPTER ONE ............................................................................................................................ 1
INTRODUCTION .......................................................................................................................... 1
1.1 Background .......................................................................................................................... 1
1.2 Problem Statement ............................................................................................................... 2
1.3 Study Justification ................................................................................................................ 3
1.4 Research Hypothesis ............................................................................................................ 3
1.5 Research Question ................................................................................................................ 3
1.6 Objectives ............................................................................................................................. 3
1.6.1 General Objective .......................................................................................................... 3
1.6.2 Specific Objectives ........................................................................................................ 3
1.7 Conceptual Framework ........................................................................................................ 5
CHAPTER TWO ............................................................................................................................ 6
LITERATUE REVIEW ................................................................................................................. 6
2.1 Introduction .......................................................................................................................... 6
2.2 Tranexemic Acid .................................................................................................................. 6
2.3 Tranexemic Acid in orthopaedic surgery ............................................................................. 7
2.3.1 Tranexemic acid in spine surgeries ............................................................................... 7
2.3.2 Tranexemic acid in Arthroplasty ................................................................................... 8
2.3.3 Tranexemic acid in femoral shaft fractures .................................................................. 8
CHAPTER THREE ...................................................................................................................... 10
METHODOLOGY ....................................................................................................................... 10
3.1 Study design ....................................................................................................................... 10
3.2 Study Site ........................................................................................................................... 10
3.3 Study Population ................................................................................................................ 11
3.3.1 Target Population ........................................................................................................ 11

iii
3.3.2 Accessible Population ................................................................................................. 11
3.4 Study Duration ................................................................................................................... 11
3.5 Selection Criteria ................................................................................................................ 11
3.5.1 Inclusion Criteria ......................................................................................................... 11
3.5.2 Exclusion Criteria ........................................................................................................ 12
3.6 Sample size estimation ....................................................................................................... 12
3.6.1 Sampling Procedure ........................................................................................................ 12
3.6.2 Allocation of intervention ........................................................................................... 13
3.7 Study Procedure ................................................................................................................. 14
3.7.1 Participant recruitment ................................................................................................ 14
3.7.2 Blood collection Procedure for hemoglobin Estimation ............................................ 14
3.7.4 Surgical Time .............................................................................................................. 15
3.7.6 Blood use in the perioperative period ......................................................................... 17
3.7.7 Post-operative care ...................................................................................................... 17
3.7.8 Total blood loss ........................................................................................................... 18
3.8 Study variables ................................................................................................................... 18
3.8.1 Independent Variables ................................................................................................. 18
Surgery18
3.8.2 Outcome Variables ...................................................................................................... 19
3.9 Data Collection ................................................................................................................... 19
3.10 Data Analysis ................................................................................................................... 19
3.11 Data Management ............................................................................................................ 20
3.13 Study Limitations ............................................................................................................. 21
3.14 Ethical Considerations ...................................................................................................... 21
3.15 Dissemination of results ................................................................................................... 21
REFERENCES ............................................................................................................................. 23
APPENDICES .............................................................................................................................. 26
APPENDIX I: ENROLLMENT SCREENING TOOL ............................................................... 26
APPENDIX II: Data Collection Sheet ..................................................................................... 27
APPENDIX III: Transfusion Guidelines for patient’s participating in “EFFECTIVENESS OF
PREOPERATIVE INTRAVENOUS TRANEXEMIC ACID ON REDUCTION OF
PERIOPERATIVE BLOOD LOSS IN OPEN INTRAMEDULLARY NAIL FIXATION OF
FEMORAL SHAFT FRACTURES IN MULAGO” Study ......................................................... 30

iv
APPENDIX IV: Consent Form (English Version) ................................................................... 31

v
ABBREVIATIONS
aPTT
-
ACTIVATED PARTIAL THROMBOPLASTIN TIME
DVT
-
DEEP VEIN THROMBOSIS
EMCA
-
EPISILON-AMINOCAPROIC ACID
ORIF
-
OPEN REDUCTION AND INTERNAL FIXATION
POD
-
POSTOPERATIVE DAY
PT/INR.
-
PROTHROMBIN TIME AND INTERNATIONAL
NORMALIZED RATIO
SAE
-
SERIOUS ADVERSE EVENTS
NDA
-
NATIONAL DRUG AUTHORITY
SOMREC
-
SCHOOL OF MEDICINE RESEARCH AND ETHICS
COMMITTEE
TXA
-
TRANEXEMIC ACID
UBTS
-
UGANDA BLOOD TRANSFUSION SERVICES

vi
ABSTRACT
Background: Major Perioperative blood loos is one of the complications of open femoral shaft
fracture intramedullary nailing surgery with average blood loss estimated at 1500mls. There is
need for strategies to reduce on this blood loss. Antifibrinolytics such as tranexemic acid have
been successfully used to reduce perioperative blood loss in other orthopaedic procedures.
However effectiveness oftranexemic acid use during open femoral shaft fracture intramedullary
nailing surgery has not been studied in our setting.
Aim: To assess the effectiveness of intravenous tranexemic acid in reduction of perioperative
blood loss, transfusion rates in patients undergoing open femoral shaft fracture intramedullary
nailing surgery.
Methods: This will be an open label single arm study. Patients scheduled for open femoral shaft
fracture intramedullary nail fixation surgery will receive preoperative tranexemic acid at
15mg/kg. Blood loss using difference between pre and post-operative hemoglobin, blood
transfusion rates and adverse events in the peri operative period will be measured.
Utility: The results of this study will reveal effectiveness oftranexemic acid in reducing
perioperative blood loss during open femoral shaft fracture surgery in this setting. This
information will be useful in designing protocols for prevention of perioperative blood loss for
femoral shaft fracture surgery.

vii
OPERATIONAL DEFINITIONS
Peri-operative
-
Period from start of surgery to 72 hours after the
Surgery
ORIF
-
Open intramedullary nailing of femoral shaft
fractures.
.

1
CHAPTER ONE
INTRODUCTION
1.1 Background
Major orthopaedic procedures are often associated with major blood loss.(1, 2) Open Reduction
and Internal Fixation (ORIF) of femoral shaft fractures is one of major orthopaedic procedures
associated with major perioperative blood loss estimated at 1500mls in a developing world
operating theatre.(3)
Worldwide major blood losses cause hemodynamic instability and severe anaemia, hence a need
for allogeneic blood transfusions that are associated with a number of complications such as (e.g.,
mismatched transfusion, allergic reactions, transmission of infections, and acute lung injury).(4-6)
Furthermore, allogeneic transfusions are also associated with increasing costs such as prolonged
hospital stay and the cost of processing, handling, administration ofblood products.
Amount of perioperative blood loss during major orthopaedic procedures can be multifactorial
with patient and institutional factors. Patient factors do include but not limited, inability to
cauterize or coagulate bony surfaces resulting in uncontrollable hemorrhage and increased
fibrinolysis as a result of surgical stress. (2, 7) On the other hand institutional factors include
availability of electro cautery and fluoroscopy guided intramedullary fracture fixation are
believed to reduce intraoperative blood loss.(3)
In the developed and under developed world the need to minimize perioperative blood loss
during orthopaedic procedures has been a focus of multiple strategies addressing both patient and
institutional factors. (e.g. Hypotensive epidural anesthesia (HEA), Platelet rich plasmapheresis,
Acute normovolemic hemodilution (ANH), Cell salvage (scavenging), Anti-fibrinolytics, Fibrin
sealants) (1, 8, 9)
Tranexemic acid (TXA) has been used to achieve hemostasis in a number of orthopaedic and non
orthopaedic procedures. This is because TXA is an antifibrinolytic agent, a synthetic lysine
product that competitively inhibits plasminogen activation to plasmin, and at much higher
concentrations, a noncompetitive inhibitor ofplasmin, i.e., actions similar to aminocaproic acid.
This action prevents dissolution of the fibrin clots stabilizing the clots at the surgical site hence

2
achieving and maintaining hemostasis.(10-12). TXA has a wide therapeutic window and despite
theoretical risk of thromboembolic events has been found to be safe for use in major orthopaedic
procedures.(1, 12, 13)
Despite studies in developed countries showing intravenous administration ofTXA leads to
significant reduction in perioperative blood loss and blood transfusion requirements in
orthopaedic surgeries (Spine, Hip Arthroplasty, Knee Arthroplasty)(12, 14, 15) TXA use can be
further extended to address need for reduction of perioperative blood loss in ORIF.
A study to determine efficacy ofpreoperative intravenous TXA on perioperative blood loss in
patients undergoing Open intramedullary nail fixation of femoral shaft fractures in Mulago
National Referral Hospital.
1.2 Problem Statement
Closed reduction intramedullary nail fixation under guidance of fluoroscopy is the most used
treatment for femoral shaft fractures. However in resource limited settings with lack of standard
theatre facilities, open intramedullary nailing is done with aid ofjig and target arm and this
increases the risk of substantial peri-operative blood loss.(16) Kajja et al(3) in 2009 showed that
ORIF in the resource limited settings leads to a substantial peri-operative blood loss of >1500ml.
This substantial peri-operative blood loss puts a stress on the limited hospital blood bank,
financial and human resources, and limits access of the sparse blood units for others in need of
blood transfusion. The costs to have a unit of safe blood delivered to the hospital have been
estimated to be $45 in Uganda and$150 - $400 elsewhere (17-20).
TXA has been used to achieve hemostasis in number of orthopaedic and non orthopaedic
procedures with significant reduction in peri operative blood loss and blood transfusions (12, 15,
21). In addition, TXA has a wide therapeutic window, is affordable and readily available
compared to other strategies to minimize perioperative blood loss such as fibrin sealants.
However TXA has not been applied in femoral shaft surgeries to reduce blood loss in our
settings.

3
1.3 Study Justification
There is need for an affordable, readily available and safe method ofreducing perioperative
blood loss in ORIF such as TXA.
Use of TXA for this indication has not been assessed and its effect is unknown in our setting.
This study will establish the role of TXA in ORIF in a resource limited theatres. Further
providing clinicians a cheap and readily available option to use in reduction ofblood loss during
open femur shaft fracture Intra Medullary Nailing.
Institutions like hospitals and Ministry of health can use these findings to draw up protocols and
guidelines for prevention of perioperative major blood loss in patients undergoing ORIF.
The study will set a baseline on which further studies on the use ofTranexemic Acid in other
orthopaedic and non orthopaedic surgical procedures may be based.
1.4 Research Hypothesis
Intravenous Tranexemic acid given preoperatively at 15mg/kg before open femoral shaft fracture
intramedullary nailing will reduce average perioperative blood loss of 3.31 g/dl and perioperative
transfusion rates by 30%.
1.5 Research Question
What is the effectiveness of pre-operative intravenous Tranexemic acid in reduction of
perioperative blood loss in open intramedullary nail fixation of femoral shaft fractures in Mulago
Hospital?
1.6 Objectives
1.6.1 General Objective
To determine the effectiveness and safety ofpre-operative intravenous Tranexemic Acid
15mg/kg on reduction ofperioperative blood loss in adult patients undergoing open
intramedullary nail fixation of femoral shaft fractures in Mulago National Referral Hospital.
1.6.2 Specific Objectives
1.6.2.1 Primary Objective
1. To determine the effectiveness ofpre-operative intravenous Tranexemic acid 15mg/kg
reduction of perioperative blood loss as estimated by difference in 72 hour postoperative and
2 hour preoperative Hemoglobin concentration in patients undergoing open intramedullary
nail fixation of femoral shaft fractures in Mulago National Referral Hospital.

4
1.6.2.2 Secondary Objectives
1. To determine effectiveness ofpre-operative intravenous Tranexemic acid 15mg/kg on
reduction of transfusion rates in patients undergoing open intramedullary nail fixation of
femoral shaft fractures in Mulago National Referral Hospital.
2. To determine the safety ofpre-operative intravenous Tranexemic acid 15mg/kg in patients
undergoing open intramedullary nail fixation of femoral shaft fractures in Mulago National
Referral Hospital.

1.7 Conceptual Framework
Demographics
. Age
. Sex
. Weight
Surgery
Intravenous
. General Anaesthesia
. Regional Anaesthesia
. Antegrade Nailing
Technique
. Retrograde Nailing
Adverse Events
Clinical
. Pre-operative
Hemoglobin
. Duration of Injury
.
Fracture Pattern
(AO / OTA)
.
Anaphylaxis
.
Dizziness
.
Hypotension
.
Nausea and Vomiting
.
Diarrhoea
.
Thrombo -embolic
Events
. Others…………………
5
Tranexemic Acid
15mg/kg, 10min
before Skin Incision
. Reduction in
Perioperative
blood loss
. Reduction in
Blood transfusion

6
CHAPTER TWO
LITERATUE REVIEW
2.1 Introduction
The orthopaedic surgeon is faced with numerous perioperative complications arising from
modern day orthopaedic surgery. Excessive intraoperative and postoperative blood loss, is a
common occurrence attributed orthopaedic surgeries, being more invasive procedures as
compared to other surgical specialties. Amongst the many strategies attempted to reduce
perioperative blood loss in modern day orthopaedic procedures is use of antifibrinolytic agents
such as Tranexemic Acid. (8)
2.2 Tranexemic Acid
Okamoto et al discovered trans-4-Aminomethyl-Cyclohexanecarboxylic Acid (Tranexamic acid)
as a potent antifibrinolytic superior to the previously used antifibrinolytic lysine analogue
Episilon-Aminocaproic Acid (EMCA).(22) TXA is an Antifibrinolytic Agent. TXA is a synthetic
derivative of the amino acid lysine with antifibrinolytic activity. With strong affinity for the five
lysine-binding sites of plasminogen, TXA competitively inhibits the activation ofplasminogen to
plasmin, resulting in inhibition of fibrinolysis ensuring stabilization of clot: at higher
concentrations, this agent noncompetitively inhibits plasmin. This agent has a longer half-life, is
approximately ten times more potent, and is less toxic than aminocaproic acid, which possesses
similar mechanisms of action.(10)
Tranexemic acid has two formulations i.e. Oral tablet and injectable solution, however in surgery
Injectable solutions have been mostly used due to the rapid distribution in intracellular and
extracellular compartments. Despite several clinical studies proving the efficacy ofTXA with
single or multiple boluses of different sizes with or without subsequent infusions, no consensus
has been reached regarding the optimal regimen for intravenous TXA administration. Previous
studies have established the need for a therapeutic plasma concentration of 10 ng/ mL and an
80% reduction in the activity of plasminogen activator for adequate suppression of fibrinolysis in

7
tissues, the dosage of 10-15mg/kg has been found to achieve this concentration within 10 mins of
administration in the knee Arthroplasty surgeries. (23) (24) (25)
TXA has been reported to be a safe drug with a large therapeutic window and adverse effects
mostly documented at high doses >20mg/kg. Some of the common adverse effects of intravenous
TXA reported are.
-
Hypotension, this is associated with rapid infusion, infusion rate of at most 1 mL per
minute is recommended.
-
Gastrointestinal disturbances (nausea, vomiting, diarrhea)
-
Allergic dermatitis, giddiness
-
The risk of thromboembolism among patients receiving TXA has been shown not to be
different from those not receiving TXA (10, 23, 26)
2.3 Tranexemic Acid in orthopaedic surgery
2.3.1 Tranexemic acid in spine surgeries
Both intravenous and topical Tranexemic acid have been employed in spine surgery. Meta-
analysis data analysis showed TXA reduced intraoperative, postoperative, and total blood loss by
averages of 219, 119 (-141, - 98; p<00001), and 319 mL, respectively. 33% reductions in blood
transfusion (0.54, 0.83; p<000001) and no apparent increase in Deep Venous Thrombosis (DVT)
nor myocardial infarctions.(27)
Pradeep et al used intravenous TXA 10mg/kg versus placebo preoperatively in stabilization
surgeries noted a significant decrease in intraoperative blood loss 1042ml in cases and 1149 in
controls (p<0.033), thereby decreasing intraoperative transfusions however they noted that there
was no major impact on postoperative blood loss 318ml in cases and 354 in controls. In their
study they did not observe any thromboembolic events nor adverse effects.(15)
Ho Yong Choi et al also used intravenous loading dose ofTXA 10mg/kg in spinal deformity
correction and noted use ofTXA can provide beneficial effects not only on reducing surgical
bleeding (case 841 vs. controls 1336 mL, p=0.002), but also on decreasing transfusion
requirements both intra- and postoperatively (cases 544 vs. control 812 mL, p=0.012; cases 193
vs. control 359 mL, p=0.034). They further noted no difference in the Incidence of

8
thromboembolic event and other complications did not show any differences between TXA and
non-TXA groups.(28)
2.3.2 Tranexemic acid in Arthroplasty
In orthopaedics, TXA use has been explored most in field of hip and knee arthroplasty with both
topical and intravenous routes of administration used however the most common route remains
intravenous. However Topical administration ofTXA at an intra-articular and/or peri-articular
soft tissue level is growing in popularity. With one of the advantages of topical use of TXA is the
minimal systemic absorption hypothesizing less systemic adverse effects.(23, 29)
In hemi and total hip arthroplasty, most randomized placebo controlled trials clinical trial found
that TXA administration safely reduced blood loss (TXA group was 242 mL lower on
Postoperative Day (POD) 1 (731 vs. 973 mL, P = 0.01), 294 mL lower on POD 2 (830 vs. 1124
mL, P = 0.0002), and 305 mL lower on POD 3 (902 vs. 1205 mL, P = 0.0005) with a tendency
for decreased transfusion rate (cases 17% vs. controls 26%) and total blood product consumption
with no significant increase in the risk ofthromboembolic event. This showing an 11% decrease
in transfusion rates.(4, 12, 30)
In knee arthroplasty, study comparing routes of administration showed all routes had significant
reduction of perioperative blood loss and transfusion needs with no superior route of
administration.(4) (31)
Study comparing intravenous and topical TXA versus tourniquet showed intravenous TXA use
without a tourniquet had less hidden blood loss, a lower ratio ofpostoperative knee swelling, less
postoperative knee pain, lower levels of inflammatory biomarkers, better early knee function,
and even better early satisfaction than those treated with a tourniquet.(32)
2.3.3 Tranexemic acid in femoral shaft fractures.
There is a paucity of literature on TXA use in femoral shaft fracture. Two literatures were
addressing TXA use in femoral shaft fractures.
90 patient study in India looked at preoperative TXA 10mg/kg in femoral and hip surgeries,
looked at postoperative drain volume (39.33± as compared to 91.11± in placebo) 56.8% less than
placebo, postoperative heamoglobin on days 0 (2.99±3.457 in the study group as compared to
7.70±6.05 in the placebo a 61.1% difference that has P value 0.01) and 2 (0.3578±0.744 and in

9
the placebo was 2.7122±2.70, P value 0.000) a difference of 86.6% Results showed preoperative
TXA caused a highly significant reduction in the blood loss in the first 24 hours in patients
undergoing surgeries for hip and femoral fractures as well it caused a significant reduction in
postoperative anemia and need for transfusion among these patients. In this study out of 45
patients, 18 patients (40%)who fell in the placebo group required blood transfusion and while 7
patients out of 45 (15%) in the study group needed a transfusion (P=0.01) a 25% difference in
transfusion rates. This study recommended further investigation to determine the effectiveness of
TXA in these surgeries.(33)
In Iran, double blinded randomized controlled clinical trial on role ofpreoperative TXA 15mg/kg
versus placebo in intramedullary nailing ofproximal femoral fracture shaft was done. With total
of 40 patients, each study group was allocated 20 patients. Hemoglobin concentration was used
to estimate blood loss, hemoglobin level was measured four hours before and after the surgeries.
Blood transfusions observed and integrated into the blood estimation formula. Results showed
No significant difference was observed between the groups in drain blood volume four hours
after surgery. Mean fall in hemoglobin concentration in placebo group was higher than the TXA
group, however, the difference was not statistically significant. (P= 0.570) A difference in
transfusion rate between the placebo group (30%) and TXA group (5.6%) was also not
statistically significant (P=0.06) a difference of 25%. Surgeon satisfaction level was also
observed and noted to higher in the TXA group (94.4%) compared to the placebo group (80%),
however the difference was not statistically significant. The study concluded that intravenous
TXA before skin incision in patient undergoing proximal femoral shaft fractures surgery, may
reduce intraoperative blood loss and hemoglobin fall however without significant reduction in
postoperative anemia. This study recommended further investigations.(34)

10
CHAPTER THREE
METHODOLOGY
3.1 Study design
This will be an open label single arm trial involving adult patients undergoing open
intramedullary femoral shaft nail fixation at Mulago National Referral Hospital.
3.2 Study Site
This study will be carried out in the Orthopaedic Department of Mulago National Referral
Hospital.
Mulago National Referral Hospital is located on upper Mulago hill road, Kampala, the capital
city of Uganda, in Kawempe Division, Mulago Parish. It is about 6 kilometers from city center.
It has a bed capacity of about 1500 beds with an annual in-patient turnover in excess of 140,000
patients. It also serves as the teaching hospital for Makerere University, College of Health
Sciences.
The Orthopaedic Department of Mulago National Referral Hospital is located in Old Mulago
part of the Mulago Hospital Complex, it admits nearly 2000 patients with fractures annually.
There are 3 in patient wards including spine ward (manages patients with spine deformities,
fractures, infection and tumors), ward 7 (manages closed fractures, musculoskeletal deformities
and tumors) and trauma ward (manages closed and open fractures, bone infections, ulcerative
tumours) and 3 operating theatres including, spine theatre handles spine surgeries, Ward 7
theatre handles closed fractures, deformities, tumours arthroscopic and arthroplasty surgery,
Trauma theatre handles open fractures, bone infections and ulcerative tumor surgery.
The study will be specifically carried out on ward 7, trauma ward and the ward 7 theatre. Patients
scheduled for Femoral shaft fracture surgery pre operatively are assessed for their suitability to
undergo surgery, Lab tests such as Complete Blood Count to assess hemoglobin levels are done,
patients with Hemoglobin levels ≥10g/dl are considered fit for surgery other patients are
optimized with blood transfusions. All patients preoperatively do have blood Grouping and

11
Cross matching done before surgery. Intraoperatively, excessive blood loss is prevented,
however not always by use of intravenous Tranexemic acid, tourniquet, diathermy, intraoperative
hypotension techniques, and occasionally topical / intramuscular adrenaline concoctions. Blood
loss intraoperatively is estimated by anaesthesiologist and surgeon who use visual estimation
assessing amount ofbleeding at surgical site, blood volume in suction drain containers, soaking
of the surgical mops, patient’s vitals, level of consciousness and mucous membrane pallor.
Intraoperatively blood transfusions are sanctioned by anaesthesiologist depending on visual
estimation ofblood loss, and patient’s hemodynamic stability. Postoperatively patients receive
intravenous fluids antibiotics, analgesia and are mobilized in and out ofbed 12hours. Patients
who are clinically aneamic and hemodynamically unstable have a complete blood count done
and transfusions sanctioned by attending physician if necessary. DVT investigation and
prophylaxis are not routinely done on patients post operatively however at the discretion ofthe
primary surgeon and attending physician for patients at risk this is done.
3.3 Study Population
3.3.1 Target Population
All adult patients with femoral shaft fractures in Mulago National Referral Hospital Orthopaedic
Department.
3.3.2 Accessible Population
Adult patients with isolated femoral shaft fractures scheduled for open intramedullary nail
fixation at Mulago National Referral Hospital during the study period.
3.4 Study Duration
The study will be conducted over a period of 3 months from the date of ethical approval.
3.5 Selection Criteria
3.5.1 Inclusion Criteria
.
All adult (≥18yrs) patients with isolated closed femoral shaft fractures scheduled for
open intramedullary nail fixation in Mulago National Referral Hospital.
.
Patients who will give informed consent to participate in the study

12
3.5.2 Exclusion Criteria
Patients presenting with
.
More than one month after the injury
.
Repeat surgery for a fractured femur
.
Pathological fractures ofthe femur
.
Undergoing Open Reduction and Internal Fixation of more than one fracture in peri
operative period
.
Known allergy to Tranexemic Acid
.
History of a bleeding disorder
.
Medical comorbidities (Diabetes Mellitus, Deep Venous Thrombosis, Pulmonary
Thromboembolism)
.
Patients already receiving anticoagulants.
3.6 Sample size estimation
3.6.1 Sampling Procedure
Comparison of Two Means (Minn M. Soe and Kevin M. Sullivan, Emory University)
(u1– u2)2
n = Sample size in each group
Z1= 1.96 for 95% confidence level
Z2 = 0.84 for 80% power
S = Standard Deviation of Outcome in Control Group
u2– u1= minimum meaningful difference between means
In study done in Mulago by Kajja et al estimated blood loss in 93 patient who underwent open
femur shaft fracture intramedullary nailing estimated 72 hours postoperative mean total blood
loss at 3.31g/dl, (SD 1.56).
Tranexemic Acid is expected to give 30% reduction in Blood Loss
i.e.
u1– u2 = 0.3

13
u1
3.31 – u2 = 0.3
3.31
u1 – u2 = 0.993
n = (1.96 + 0.84)2 2x 1.562
0.9932
= 38.7
n = 39
Adjust for non-response = 39 /0.9
= 43.3 =43
N= 43
3.6.2 Allocation of intervention
Orthopaedic patients with
closed unilateral femur
shaft fracture undergoing
ORIF
Screening for
Eligibility &
Consent
Study participants receive
Intervention (Pre OP TXA)
N =43

14
3.7 Study Procedure
3.7.1 Participant recruitment
Participants who meet criteria for inclusion and exclusion will be recruited from two wards i.e.
ward 7 and Trauma ward. Principle investigator and research assistant shall access patient’s file
and use screening tool to assess patient’s eligibility for enrollment into the study. If patient is
eligible participants will be educated on the study procedure and informed consent will be
achieved. Participants will be clinically assessed for the Risk ofthromboembolic events and have
hematological screening for thromboembolic events or bleeding dyscrasia with Prothrombin
Time and International Normalized Ratio (PT-INR) and activated Partial Thromboplastin Time
(aPTT) done prior to enrollment. Pre tested data collection tool will then be used by the principal
investigator and his research assistants to collect participants demographics and clinical data.
3.7.2 Blood collection Procedure for hemoglobin Estimation.
The principal investigator or his research assistants will draw 2.0 mls of blood under aseptic
conditions from the cubital vein of the participant, using a Becton Dickinson vacutainer® system
containing EDTA-K3. The tube will be shaken to allow proper mixing of blood with the
anticoagulant, legibly labeled with first and given name, age, sex and hospital number of the
patient. A laboratory request form for hemoglobin determination will be filled by principal
investigator or his research assistants and both the sample and the form delivered to the hospital
central laboratory. Upon receiving the result the Hemoglobin concentration will be entered into
the data collection tool as Preoperative Hemoglobin in g/dl.
Blood for hemoglobin concentration estimation will be collected 2 hours prior to surgery and 72
hours after surgery. Optimal timing for post-operative heamoglobin concentration monitoring
still remains a challenge, however studies in orthopaedic surgeries have noted major variation in
hemoglobin concentration estimations from day 0 to day 2 which is attributed to hemodilution
with colloids and crystalloids together with ongoing hidden blood losses into the joint cavity and
within soft tissue planes. From day 3 onwards minimal changes are noted and this is attributed to
heamostabilistion. (35-37)

15
3.7.3 Tranexemic Acid other preoperative drugs.
Tranexemic Acid (Kapron, Egypt) 500mg / 5ml ampoule will be used. Drug will be prepared at
15mg/kg by the anaesthetist who will administer it for over 10mins to prevent drug induced
hypotension, dizziness vomiting and nausea. 10mins before skin incision so as to achieve
optimal plasma and interstitial concentrations.
All patients will receive pre-operative antibiotics, before the surgery.
3.7.4 Surgical Time
Time of skin incision and last skin suture will be documented to determine surgical time. It will
be presented in minutes.
3.7.5 Surgical Technique
Qualified Orthopaedic surgeons will perform the surgeries and the surgical technique shall be as
below:
The choice of ante grade or retrograde nailing can also be influenced by a number of factors
including the patient’s body habitus, the condition of the soft tissues, and concerns regarding
positioning of the patient during anesthesia.
Ante grade Technique
This technique will be preferred for fractures ofthe proximal or middle third of the femur shaft
as the centered starting point helps to ensure that the nail will be centered within the distal
fracture fragment. Antegrade nailing will be performed with the patient in the lateral position.
Open reduction of the fracture will be used. The length of the skin incision will depend primarily
on the duration since the injury, the more the time the longer the incision as wider dissections are
required to release the use a periosteal elevator to longitudinally separate the muscle fibers of the
vastus lateralis down to the fracture site. Free up the callus and soft tissues with aid ofperiosteal
elevators and osteotomes until each fracture fragment is free. Surgeon will preserve immature
callus to fill the dead space. Once fragments are free, hand reaming will` performed through the
fracture site until the full length of the isthmus had been reamed. Any bone retrieved from the
flutes ofthe reamer will be saved for placement in the fracture site at the end of the procedure.
Then the surgeon with aid of assistants and manual maneuvers will reduce the fracture ensuring

16
to line up the linea aspera on both sides of the fracture to accomplish rotational alignment.
Accurate rotational alignment ofthe fracture site is an advantage of open reduction over closed
reduction. Reduction will be held by bone holding clamps.
The proximal incision will be made and the proximal aspect of the femur was entered with use of
a curved awl positioned at the tip of the greater trochanter or piriformis fossa between the
posterior and middle thirds ofthe femur. Hand reamers will then be used to ream the segment of
bone between the osseous entrance and the femur shaft. The reaming will also be used to
determine the proper nail diameter, which is 2 mm less than the diameter of the reamer that will
elicits ‘‘chatter’’ for a distance of approximately 6 cm.
The target arm will then be attached to the nail, and the longitudinal positions ofthe proximal
and distal interlocking screws noted. The target arm will then be removed and the nail inserted,
with rotation allowed during placement of the nail. After the nail is inserted, the target arm will
be reattached to guide the placement of the interlocking screws. Two, three or four interlocking
screws will be used. A window will be drilled in the near cortex at the position indicated by the
target arm, and a specially designed cannulated slot finder will be placed through this cortical
window into the slot of the nail. The hole in the far cortex will then be drilled through the
cannulated slot finder, the length of the screw will be measured, and the interlocking screw will
be placed. The proximal interlocking screws will be placed from lateral to medial or from
anterior to posterior, with the direction depending on how the nail will be rotated during insertion,
as the two orientations provide equal stability.
Retrograde Technique
This technique will be preferred for fractures ofthe distal third of the femur. Nailing will be
performed with the patient in the supine position. As in the antegrade technique, the fracture site
will be opened to allow for reduction as well as reaming through the fracture site. After the knee
incision will be made, the femoral canal will be opened distally with use of an awl, and hand
reaming will be performed. The nail will be inserted in a retrograde direction and the target arm
will be used to place the interlocking screws with use of a technique similar to that described for
antegrade technique.
Electro cautery will be used for all patients undergoing ORIF.

17
3.7.6 Blood use in the perioperative period
The decision to transfuse patients in the intraoperative period will be taken by the
anaesthesiologist in concert with the primary surgeon, Basing on:
.
Visual assessment of the extent of soaking of the surgical mops with blood.
.
Extent ofpallor of the finger nail beds, palms and mucous membranes.
.
Patient with features of severe hemodynamic instability, tachycardia, hypotension,
dizziness etc.
.
Post op hemoglobin results of severe anaemia (≤6g/dl)
The decision to transfuse patients in the postoperative period will be taken by the primary
surgeon or the residents on the wards basing on:
.
Patient with features of severe hemodynamic instability, tachycardia, hypotension,
dizziness, palpitations etc.
.
Extent ofpallor of the finger nail beds, palms and mucous membranes.
.
Post op hemoglobin results of severe anaemia (≤6g/dl)
Intraoperative and postoperative transfusion guidelines shall be availed to the teams to guide on
when to transfuse patients to reduce on bias.
Whole blood and packed red blood cell units will be used. 450mls ofwhole blood and 200mls of
packed red blood cells will be estimated to be equivalent to 1g/dl rise in hemoglobin level.
3.7.7 Post-operative care
Patients in the immediate post-operative period will be monitored by the nurses on their primary
wards noting vitals (Blood Pressure, Pulse Rate, Respiratory Rates and observe blood soiling of
the surgical site dressing). Adequate analgesia will be given to the patients and mobilization in or
out of bed will be instituted 12 hours following surgery with guidance of the physiotherapist as
per patient tolerability.
Principal investigator together with the surgeons and residents on the primary wards will
clinically review the patients daily as part of routine post-operative follow-up with emphasis on
identifying and addressing post-operative complications such as thromboembolic phenomena e.g.
DVT. Patients with features ofthromboembolic phenomena or develop other Serious Adverse

18
Events will be investigated thoroughly with blood work up PT-INR, aPTT and Doppler Studies
for the lower limbs. They will receive treatment as per guidance of qualified physician.
Serious Adverse Events (SAE) shall be reported within 24hours of occurrence to Department Of
Orthopaedics, SOMREC, and National Drug Authority (NDA) using National SAE reporting
tools.
Patients shall be followed up for a period of 2 weeks post operatively.
3.7.8 Total blood loss
Total blood loss due to the surgical procedure will be represented by total hemoglobin loss in the
perioperative period.
Pre-operative hemoglobin (Pre-opHb) will be taken off 2 hours prior to surgery. Post-operative
(Post-opHb) hemoglobin will be done 72 hours after surgery, it will be assumed hemodynamic
stability is restored at that time.
Total Blood Loss = Pre-opHb – (Post-opHb + Blood Units g/dl)
3.8 Study variables
3.8.1 Independent Variables
Demographics
.
Age
.
Sex
.
Weight
Clinical
.
Pre-operative Hemoglobin
Fracture
.
Duration of Injury
.
Fracture Pattern (AO / OTA)
Surgery
.
General Anaesthesia
.
Regional Anaesthesia
.
Antegrade Nailing Technique

19
.
Retrograde Nailing Technique
.
Duration of Surgery
3.8.2 Outcome Variables
.
Primary Outcome: Perioperative blood loss –Will be represented as difference in the 2
hour pre-operative and 72 hour post-operative hemoglobin concentration in g/dl.
.
Secondary Outcome: Blood Transfusion – will be represented as the number ofblood
units. 450mls of whole blood will equate to 1 unit ofwhole blood. 200mls ofpacked cells
will equate to 1 unit ofwhole blood.
.
Secondary Outcome: Safety – Will be described as adverse events secondary to
administration of Tranexemic Acid observed in patients in the study during the
perioperative period.
o
Anaphylaxis
o
Dizziness
o
Hypotension
o
Nausea and Vomiting
o
Diarrhoea
o
Thrombo -embolic Events
o
Others…………………………..
3.9 Data Collection
In this study, the principal investigator and research assistant will obtain data using a standardly
developed data-collection tool.
3.10 Data Analysis
3.10.1 Interim analysis
This study will conduct two interim analysis and will be done at the midpoint of data collection
and at 90% data collection by the DSMB which will be independent from the day to day staff
working on the study which will meet at the midpoint of the study for Interim analysis and study
progress review.
3.10.2 Data Safety Monitoring Board (DSMB)

20
A data safety monitoring board will be identified and they will ensure quality, subject safety and
provide independent advice to the study team regarding progress and appropriateness of study
continuation. It will be composed of 3 members: 1 Orthopaedic Surgeon 1 Pharmacologist, 1
Clinical Epidemiologist, and 1 Ethicist and will meet when 50% data collection completed and
90% completed to perform an interim analysis.
A Bonferroni approximation will be applied during the planned interim analysis for efficacy. For
the interim analysis, the critical value for the 2-degree-of-freedom omnibus test will be set to
have α = 0.0001
3.10.3 Stoppage rules / discontinuation
These shall include the following
.
Serious Adverse Events and toxicity data compromising participant safety.
.
When noted a large efficacy effect.
The DSMB may recommend stopping the study based on their reviews. Because the DSMB
could stop the trial for safety concerns as well as for a large efficacy benefit, there could be
multiple opportunities to reject the null hypothesis.
3.11 Data Management
The data collected by the tool will be checked daily and edited for completeness. The data will
be entered into the computerized system particularly in Epi Data version 3.1. Following entry,
range and consistency checks will be run for each variable to identify inadmissible values. In
some cases in which it is impossible to correct errors in the data, a missing value code will be
assigned.
3.12 Statistical analysis
Data will then be exported into a SPSS version 19 system which will be used for analysis. We
will summarise the study population. We will use descriptive statistics such as means (standard
deviations) or median and interquartile range (IQR) for continuous variables and proportions for
categorized variables. We will also conduct appropriate statistical tests such as chi square or
Fischer’s test for categorical variables and a one sample independent T-test or wilcoxon sum
rank test for continuous variables.

21
Objective 1: To determine the efectiveness of pre-operative intravenous Tranexemic acid
15mg/kg on reduction of perioperative blood loss as estimated by difference in 72 hour
postoperative and 2 hour preoperative Hemoglobin concentration in patients undergoing open
intramedullary nailfixation offemoral shaftfractures in Mulago National Referral Hospital.
We will assess for the hypothesis that TXA reduces perioperative blood loss by at least 30%
using one sample independent T-test
Objective 2: To determine efectiveness ofpre-operative intravenous Tranexemic acid 15mg/kg
on reduction oftransfusion rates by 30% inpatients undergoing open intramedullary nail
fixation offemoral shaftfractures in Mulago National Referral Hospital.
We will conduct univariate analysis and adjust for effect modification and confounding.
Objective 3: To determine the safety ofpre-operative intravenous Tranexemic acid 15mg/kg in
patients undergoing open intramedullary nailfixation offemoral shaftfractures in Mulago
National Referral Hospital.
We will assess for safety using descriptive statistics showing proportions of adverse events in
the study group.
3.13 Study Limitations
Ward 7 theatre currently being used together with the spine team and hence reduced numbers of
patients being worked on.
3.14 Ethical Considerations
The permission to carry out the study will be sought from the department of Orthopaedics,
Makerere University and ethical Approval will be sought from the School of Medicine Research
and Ethics Committee, Mulago Research Ethics Committee.
During the data collection, study identification numbers will be used on all study related
documents to maintain confidentiality and privacy. Informed consent will be sought from all
study participants before enrollment into the study.
3.15 Dissemination of results
Results from this study will be compiled into a dissertation and availed to the following:

22
.
Department of Orthopaedic surgery, Makerere University.
.
Sir Albert Cook Library, Makerere University.
.
School of Post Graduate Studies, Makerere University.
.
School of Medicine Research and Ethics Committee.
.
A manuscript will be written for publication in peer reviewed journals.

23
REFERENCES
1.
Mannucci PM, Levi M. Prevention and treatment of major blood loss. The New England journal
of medicine. 2007;356(22):2301-11.
2.
Sculco TP. Global blood management in orthopaedic surgery. Clinical orthopaedics and
related research. (357).
3.
Kajja I, Bimenya GS, Eindhoven B, Jan ten Duis H, Sibinga CTS. Blood loss and contributing
factors in femoral fracture surgery. African Health Sciences. 2010;10(1):18-25.
4.
Carling MS, Jeppsson A, Eriksson BI, Brisby H. Transfusions and blood loss in total hip and
knee arthroplasty: a prospective observational study. Journal of Orthopaedic Surgery and Research.
2015;10:48.
5.
Soleimanha M, Haghighi M, Mirbolook A, Sedighinejad A, Mardani-Kivi M, Naderi-Nabi B, et
al. A Survey on Transfusion Status in Orthopedic Surgery at a Trauma Center. Archives of Bone and
Joint
Surgery. 2016;4(1):70-4.
6.
Goodnough LT, Maniatis A, Earnshaw P, Benoni G, Beris P, Bisbe E, et al. Detection,
evaluation,
and management of preoperative anaemia in the elective orthopaedic surgical patient:
NATA guidelines. BJA: British Journal of Anaesthesia. 2011;106(1):13-22.
7.
Kambayashi J, Kim TD, Yokota M, Tsujinaka T, Sakon M, Mori T, editors.
ACTIVATION OF COAGULATION AND FIBRINOLYSIS DURING SURGERY,
ANALYZED BY MOLECULAR MARKERS1989; STUTTGART: F K SCHATTAUER
VERLAG GMBH.
8.
Sambandam B, Batra S, Gupta R, Agrawal N. Blood conservation strategies in
orthopedic surgeries: A review. Journal of clinical orthopaedics and trauma. 2013;4(4):164-70.
9.
Keating EM. Preoperative Evaluation and Methods to Reduce Blood Use in Orthopedic
Surgery. Anesthesiology Clinics of North America. 2005;23(2):305-13.
10.
Tranexamic Acid [Internet]. 2005 [cited Mar. 27, 2018]. Available
from: https://pubchem.ncbi.nlm.nih.gov/compound/5526.
11.
Samson AL, Samson AL, Alwis I, Maclean JAA, Priyananda P. Endogenous fibrinolysis
facilitates clot retraction in vivo. Blood.130(23):2453-62.
12.
Watts CD, Watts CD, Houdek MT, Sems SA, Cross WW. Tranexamic Acid Safely Reduced
Blood Loss in Hemi- and Total Hip Arthroplasty for Acute Femoral Neck Fracture: A Randomized
Clinical Trial. Journal of orthopaedic trauma.31(7):345-51.
13.
Henry DA, Carless PA, Moxey AJ, O'Connell D. Anti-fibrinolytic use for minimising
perioperative allogeneic blood transfusion. Cochrane database of systematic reviews. 2011(3).
14.
O. MD, P. AHA, L. O, J. M, K. WR, E. BD. Comparison of topical fibrin spray and
tranexamic acid on blood loss after total knee replacement. The Journal of bone and joint surgery
British volume.
2007;89-B(3):306-9.
15.
S P, M B J, Ali L. DOES TRANEXEMIC ACID REDUCE BLO O D TRANSFUSION
REQUIREMENTS PERIOPERATIVELY IN PATIENTS UNDERGOING SPINE
STABILIZATION SURGERIES? A PROSPECTIVE
RANDOMIZED DOUBLE BLINDED
CONTROLLED STUDY. Journal of evolution of medical and dental sciences.3(66):14314-22.
16.
Sekimpi P, Okike K, Zirkle L, Jawa A. Femoral fracture fixation in developing countries: an
evaluation of the Surgical Implant Generation Network (SIGN) intramedullary nail. The Journal of
bone and joint surgery American volume. 2011;93(19):1811-8.
17.
Services UBT. Uganda Blood Transfusion Services Strategic Plan 2010 - 2015. 2009.
18.
Blanchette CM, Wang PF, Joshi AV, Kruse P, Asmussen M, Saunders W. Resource utilization
and costs of blood management services associated with knee and hip surgeries in US hospitals.
Advances in Therapy. 2006;23(1):54-67.

24
19.
Forbes JM, Anderson MD, Anderson GF, Bleecker GC. Blood transfusion costs: a
multicenter study. Transfusion (Philadelphia, Pa).31(4).
20.
Toner RW, Pizzi L, Leas B, Ballas SK, Quigley A, Goldfarb NI. Costs to hospitals of
acquiring and processing blood in the US. Applied Health Economics and Health Policy. 2011;9(1):29
-37.
21.
Danninger T, Memtsoudis SG. Tranexamic acid and orthopedic surgery-the search for the
holy grail of blood conservation. Annals of translational medicine.3(6).
22.
Okamoto S, Okamoto U. AMINO-METHYL-CYCLOHEXANE-CARBOXYLIC ACID:
AMCHA
A NEW POTENT INHIBITOR OF THE FIBRINOLYSIS. The Keio Journal of Medicine.
1962;11(3):105-15.
23.
Nilsson IM. Clinical pharmacology of aminocaproic and tranexamic acids. Journal of
Clinical Pathology Supplement (Royal College of Pathologists). 1980;14:41-7.
24.
Reed MR, Woolley LT. Uses of tranexamic acid. Continuing Education in Anaesthesia Critical
Care & Pain. 2015;15(1):32-7.
25.
Maniar RN, Kumar G, Singhi T, Nayak RM, Maniar PR. Most Effective Regimen of
Tranexamic Acid in Knee Arthroplasty: A Prospective Randomized Controlled Study in 240 Patients.
Clinical
Orthopaedics and Related Research®. 2012;470(9):2605-12.
26.
Åstedt B, Åstedt B. Clinical Pharmacology of Tranexamic Acid. Scandinavian
journal of gastroenterology. 1987;22(s137):22-5.
27.
Cheriyan T, Maier SP, Bianco K, Slobodyanyuk K, Rattenni RN, Lafage V, et al.
Efficacy of tranexamic acid on surgical bleeding in spine surgery: a meta-analysis. The Spine
Journal.
2015;15(4):752-61.
28.
Choi HY, Hyun S-J, Kim K-J, Jahng T-A, Kim H-J. Effectiveness and Safety of Tranexamic
Acid in Spinal Deformity Surgery. Journal of Korean Neurosurgical Society. 2017;60(1):75-81.
29.
Kim C, Park SS-H, Davey JR. Tranexamic acid for the prevention and management of
orthopedic surgical hemorrhage: current evidence. Journal of Blood Medicine. 2015;6:239-44.
30.
Zhu J, Zhu JX, Zhu Y, Lei PF, Zeng M. Efficacy and safety of tranexamic acid in total
hip replacement: A PRISMA-compliant meta-analysis of 25 randomized controlled trials.
Medicine (Baltimore).96(52).
31.
Marra F, Rosso F, Bruzzone M, Bonasia DE, Dettoni F, Rossi R. Use of tranexamic acid in
total knee arthroplasty. Joints. 2016;4(4):202-13.
32.
Huang Z, Huang ZY, Xie XW, Li LL, Huang Q. Intravenous and Topical Tranexamic Acid
Alone Are Superior to Tourniquet Use for Primary Total Knee Arthroplasty A Prospective, Randomized
Controlled Trial. Journal of bone and joint surgery American volume.99(24):2053-61.
33.
Vijay B, Bedi V, Mitra S, Das B. Role of tranexamic acid in reducing postoperative blood loss
and transfusion requirement in patients undergoing hip and femoral surgeries. Saudi Journal of
Anaesthesia. 2013;7(1):29-32.
34.
Haghighi M, Ettehad H, Mardani-Kivi M, Mirbolook A, Nabi BN, Moghaddam R, et al.
Does Tranexamic Acid Reduce Bleeding during Femoral Fracture Operation? Archives of Bone
and Joint Surgery. 2017;5(2):103-8.
35.
Director Mavis N. Schorn Cnm P. Measurement of Blood Loss: Review of the Literature2010.
20- 7 p.
36.
Khalfaoui MY, Godavitarne C, Wilkinson MCP. Optimal Timing for Hemoglobin
Concentration Determination after Total Knee Arthroplasty: Day 1 versus Day 2. Knee Surgery &
Related Research. 2017;29(1):52-6.
37.
Chen Z-Y, Wu H-Z, Zhu P, Feng X-B. Postoperative Changes in Hemoglobin and
Hematocrit in Patients Undergoing Primary Total Hip and Knee Arthroplasty. Chinese Medical
Journal.
2015;128(14):1977-9.

26
APPENDICES
APPENDIX I: ENROLLMENT SCREENING TOOL
Information to be picked from file of patient’s with femoral shaft fractures awaiting
surgery
Patient Initials: …………….
Ward: ……………………………..
Inclusion Criteria: Individual should meet all criteria to qualify for enrollment.
Circle what
applies
Duration of Injury ≤30 days
YES / NO
Isolated Femoral Shaft Fracture
YES / NO
Patient Age ≥18yr
YES / NO
Patient scheduled for Intramedullary Nail
Fixation
YES / NO
Exclusion Criteria: Presence of any below excludes individual from enrollment.
Circle what
applies
Known Allergy to Tranexemic Acid
YES / NO
History ofbleeding disorder
YES / NO
Has received or is currently on Anticoagulant
therapy
YES / NO
Deep Vein Thrombosis
YES / NO
Pulmonary Embolism
YES / NO
Myocardial Infarction
YES / NO
Diabetes Mellitus
YES / NO
Pathological fracture
YES / NO
Above individual is FIT / NOT FIT FOR ENROLLMENT
Name of Investigator ………………………………………
Signature of Investigator ………………………………….

27
APPENDIX II: Data Collection Sheet
Study Number.........................................................................
Date of Surgery
Study Arm
A
B
A. Patient information
1) Inpatient number
2) Age (yrs)
3) Sex:
M
F
4) Weight (kg)
B. Pre-operative Data
1) Duration of Injury (Days)
2) Fracture Pattern (AO / OTA)
………………………………
A
B
C
3) Preoperative Hemoglobin (g/dl)
4) Platelet Count
5) aPTT
6) PT-INR
C. Procedure Data
1) Type ofAnaesthesia
2) Time : Start of Surgery
GA
Regional
………………………………..
3) Time : End of Surgery
4) Duration of Surgery (hrs)
5) Nailing Approach
6) Whole Blood Units Transfused
Ante grade / Retrograde
……………………………………………
7) Adverse Event/s Y
N (Describe Event/s)
………………………………………………………………………………………………....
..............................................................................................................................................
D. Postoperative Data
1) Whole Blood Units Transfused
2) 72hr Post-operative Hemoglobin (g/dl)

28
3) aPTT
4) PT-INR
Peri-operative Blood Loss (g/dl)
=
Pre-opHb
– (
Post-opHb +
Blood Units )
= ……………………. - (………………………..…...+ ……………….……………)
= ………………………………. (g/dl)
Intraoperative and Post-operative Adverse Events and complications
Pre /
Intraoperative
Period
Comments
DVT / TEE
Nausea
Vomiting
Diarhoea
Anaphylaxis
Dermatitis
Hypotension
Others
Day 1
Comments
DVT / TEE
Nausea
Vomiting
Diarhoea
Anaphylaxis
Dermatitis
Hypotension
Others
Day 2
Comments
DVT / TEE
Nausea
Vomiting
Diarhoea
Anaphylaxis
Dermatitis
Hypotension

29
Others
Day 3
Comments
DVT / TEE
Nausea
Vomiting
Diarhoea
Anaphylaxis
Dermatitis
Hypotension
Dizziness
Others
Day 3-14
Comments
DVT / TEE
Nausea
Vomiting
Diarhoea
Anaphylaxis
Dermatitis
Hypotension
Dizziness
Others

30
APPENDIX III: Transfusion Guidelines for patient’s participating in
“EFFECTIVENESS OF PREOPERATIVE INTRAVENOUS TRANEXEMIC
ACID ON REDUCTION OF PERIOPERATIVE BLOOD LOSS IN OPEN
INTRAMEDULLARY NAIL FIXATION OF FEMORAL SHAFT FRACTURES
IN MULAGO” Study
Category 1
Circle
Transfusion Criteria
Intraoperative Hemoglobin
Concentration of< 7g/dl
YES / NO
Transfuse with 1 Unit ofWB or
PRBC if 1 Criteria in category 1 is met
Category 2
Intraoperative Hemoglobin
Concentration of < 10g/dl
YES / NO
Transfuse with 1 Unit ofWB or
PRBC if 1 criteria in Category 2 is
met together with 3 criteria in Category
3
Category 3
Severe bleeding at the surgical site
and soiling of surgical drapes and
mops
YES / NO
Transfuse with 1 Unit ofWB or
PRBC if ≥4 criteria in Category 3 are
met
Tachycardia
YES / NO
Oxygen Saturation < 90%
YES / NO
Hypotension
YES / NO
Severe pallor of the Mucous
Membranes
YES / NO
Decreasing Levels of Consciousness
YES / NO
Dyspnoea
YES / NO
Angina
YES / NO
Severe active bleeding from surgical
site soiling of wound dressings with
blood
YES / NO
Re-transfusion: Reassess patient using above guidelines before next transfusion.
KEY
WB – Whole Blood
PRBC – Packed Red Blood Cells

31
APPENDIX IV: Consent Form (English Version)
EFFECTIVENESS OF PREOPERATIVE INTRAVENOUS TRANEXEMIC ACID ON
REPUCTION OF PERIOPERATIVE BLOOD LOSS IN OPEN INTRAMEDULLARY
NAIL FIXATION OF FEMORAL SHAFT FRACTURES IN MULAGO
Investigator: Dr Kabazzi Kaweesa Paul, Department of Orthopaedics Makerere University,
Tel:+256701047424, email: kabazzip@gmail.com
Introduction:
I am conducting a study to assess the efficectiveness of intravenous Tranexemic Acid in
reduction of perioperative blood loss in open intramedullary nail fixation of femoral shaft
fractures Mulago Hospital. Tranexemic acid is a drug used to prevent and reduce blood loss. As a
result of major blood loss, patients become severly anaemic increasing risk of post operative
complications and sometimes may blood transfusions. Resources blood tranfusion are scarce
and transfusions can result in complications. This will increase costs for treatment,lengthening
hospital stay and sometimes even death.
Purpose:
This study will help Orthopaedic surgeons at Mulago hospital to formulate evidence based
method of preventing major perioperative blood loss. This, will inturn help to improve measures
of preventing major perioperative blood loss in patients ungergoing femoral shaft fracture
surgery.
Procedure:
A data collection form will be filled with your information. Blood Samples will be safely drawn
from you before and after Surgery. You will be recieve Tranexemic Acid at 15mg/kg. This will
be done by the principal investigator or research assistant after you have consented to participate
in the study.
Risk of study
There is no identified risk associated with you being a participant of this study

32
Benefits
There is no direct benefits with you being a participant of this study, however knowledge that
will be obtained from study will help to improve care of patients.
Confidentiality
Information related to you will be treated with strict confidence as provided by law. Your
identity will be coded and will not be associated with any published results.
Cost of being a participant
You will incur no cost to participate in this study.
Compensation/Reimbursement for participation in the study:
There will be no any compensation/reimbursement to a participant but from this study many
patients will benefit in future since the study will set the basis of development of protocal of
Prevention if major perioperative blood loss in Femoral Shaft fracture surgery.
Incase of Serious Adverse Events the principal investigator together with the study team will
ensure the you / participant gets timely and adequate intervention within the resources of the
Hospital till full recovery.
Rights of Participant
Participation in this study is voluntary. Participant is at liberty to exit the study at any point in
time. Refusal to participate in the study shall not have any effect on your care and management
in Mulago National Referral Hospital nor your relations with Makerere University College of
Health Sciences.
Question about the study

33
If you have any question about the study you may contact one of the following:
Dr Kabazzi Kaweesa Paul
Principar investigator
0701047424
Dr Sekimpi Patrick
Supervisor
0772470060
Dr Kironde Edward
Supervisor
0772517273
In case you have queries or questions in regard to your personal rights, you may contact the
Chairman of Ethics Committee:
Assoc. Prof Ponsiano Ocama
Chairperson School of Medicine Research and Ethics Committtee (SOMREC)
P.O Box 7072, Kampala.
Mobile number: 0772421190

STATEMENT OF CONSENT
..............................has described to me what is going to be done, the risks, the benefits involved
and my rights regarding this study. I understand that my decision to participate in this study will
not alter my usual medical care.In the use of information my identity will be concealed. I am
aware that I may withdraw at any time.I undrestand that by signing this form, I do not waive any
of my legal rights but merely indicate that I have been informed about the research study in
which I am voluntarily agreeng to participate. A copy of this form will be provided to me.
Signature ofparticipant
Signature of Interviewer
Signature of Witness
Date
.
.
.
.
Date
Date
Name
Name
Name