Guidelines for the management of



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GUIDELINES FOR THE 

MANAGEMENT OF 

HEMOPHILIA 

2

nd



 edition

These guidelines were originally published by Blackwell Publishing in Haemophilia; Epub 6 JUL 2012. 

DOI: 10.1111/j.1365-2516.2012.02909.x. They are reprinted with their permission.  

© Blackwell Publishing Ltd., 2012

The WFH encourages redistribution of its publications for educational purposes by not-for-profit 

hemophilia organizations. For permission to reproduce or translate this document, please contact the 

Communications Department at the address below.

This publication is accessible from the World Federation of Hemophilia’s website at www.wfh.org. 

Additional copies are also available from the WFH at: 

World Federation of Hemophilia

1425, boul. René-Lévesque O., bureau 1010

Montréal, Québec 

H3G 1T7 Canada

Tel.: (514) 875-7944

Fax: (514) 875-8916

E-mail: wfh@wfh.org

www.wfh.org



GUIDELINES FOR THE 

MANAGEMENT OF HEMOPHILIA 

2

nd

 edition



Prepared by the Treatment Guidelines Working Group, on behalf of the World 

Federation of Hemophilia (WFH) 



Dr. Alok Srivastava (Chair)

Department of Hematology, Christian Medical 

College, Vellore, Tamil Nadu, India

Dr. Andrew K. Brewer

Department of Oral Surgery, The Royal Infirmary

Glasgow, Scotland

Dr. Eveline P. Mauser-Bunschoten, 

Van Creveldkliniek and Department of 

Hematology, University Medical Center Utrecht, 

Utrecht, the Netherlands



Dr. Nigel S. Key 

Department of Medicine, University of North 

Carolina, Chapel Hill, NC, U.S.A.

Dr. Steve Kitchen

Sheffield Haemophilia and Thrombosis Centre, 

Royal Hallamshire Hospital, Sheffield, UK

Dr. Adolfo Llinas

Department of Orthopaedics and Traumatology, 

Fundación Santa Fe University Hospital Fundación 

Cosme y Damián and Universidad de los Andes 

and Universidad del Rosario, Bogotá, Colombia

Dr. Christopher A. Ludlam

Comprehensive Care Haemophilia and 

Thrombosis Centre, Royal Infirmary

Edinburgh, U.K.



Dr. Johnny N. Mahlangu

Haemophiia Comprehensive Care Centre, 

Johannesburg Hospital and Department of 

Molecular Medicine and Haematology, Faculty of 

Health Sciences, National Health Laboratory 

Services and University of the Witwatersrand, 

Johannesburg, South Africa 

Kathy Mulder

Bleeding Disorders Clinic, Health Sciences Center 

Winnipeg, Canada

Dr. Man-Chiu Poon

Departments of Medicine, Pediatrics and 

Oncology, and Southern Alberta Rare Blood and 

Bleeding Disorders Comprehensive Care Program, 

University of Calgary, Foothills Hospital and 

Calgary Health Region, Alberta, Canada



Dr. Alison Street

Department of Haematology, Alfred Hospital

Melbourne, Australia


Acknowledgements

A professional agency was engaged to assist with the literature search and to grade the evidence. In 

addition, given the fact that many recommendations are based on expert opinion, a draft version of these 

guidelines was circulated to many others involved in hemophilia care outside of the writing group. The 

authors are grateful to those who provided detailed comments. Finally, we would like to acknowledge the 

extraordinary effort from WFH staff, Jennifer Laliberté, and also Elizabeth Myles, in completing this work. 



Disclaimer

The World Federation of Hemophilia (WFH) does not endorse particular treatment products or manu-

facturers; any reference to a product name is not an endorsement by the WFH. The WFH does not engage 

in the practice of medicine and under no circumstances recommends particular treatment for specific 

individuals. Dose schedules and other treatment regimens are continually revised and new side-effects 

recognized. These guidelines are intended to help develop basic standards of care for the management of 

hemophilia and do not replace the advice of a medical advisor and/or product insert information. Any 

treatment must be designed according to the needs of the individual and the resources available.



Summary and introduction

 .................................

6

1.  General care and management 

of hemophilia 

 .................................................

7

1.1  What is hemophilia?



 ...............................

7

Bleeding manifestations



 ...........................

7

1.2  Principles of care



 .....................................

8

1.3  Comprehensive care 



 ...............................

9

Comprehensive care team



 ........................

9

Functions of a comprehensive care 



program

 .................................................

10

1.4  Fitness and physical activity



 .................

11

1.5  Adjunctive management 



 ......................

12

1.6  Prophylactic factor replacement therapy



 ..

12

Administration and dosing schedules



 .....

13

1.7  Home therapy 



 ......................................

13

1.8  Monitoring health status and outcome 



 

14

1.9  Pain management 



 ................................

15

Pain caused by venous access



 .................

15

Pain caused by joint or muscle bleeding



 ..

15

Post-operative pain



 ................................

15

Pain due to chronic hemophilic 



arthropathy

 ............................................

15

1.10  Surgery and invasive procedures



 ..........

16

1.11  Dental care and management 



 ..............

17

References 



 .....................................................

18

2.  Special management issues

 ..........................

21

2.1 Carriers



 .................................................

21

2.2  Genetic testing/counselling and 



prenatal diagnosis 

 ................................

22

2.3  Delivery of infants with known or 



suspected hemophilia 

 ..........................

22

2.4 Vaccinations



 ..........................................

23

2.5  Psychosocial issues 



 ...............................

23

2.6 Sexuality 



 ...............................................

23

2.7  Ageing hemophilia patients 



 .................

24

Osteoporosis



 ...........................................

24

Obesity



 ...................................................

24

Hypertension



 .........................................

24

Diabetes mellitus (DM)



 ..........................

24

Hypercholesterolemia



 .............................

25

Cardiovascular disease 



 .........................

25

Psychosocial impact 



 ..............................

25

2.8  Von Willebrand disease and rare 



bleeding disorders

 .................................

25

References



 ......................................................

26

3.  Laboratory diagnosis

 ...................................

29

3.1  Knowledge and expertise in 



coagulation laboratory testing 

 .............

29

Principles of diagnosis 



 ...........................

29

Technical aspects 



 ...................................

29

Trained personnel



 ..................................

32

3.2  Use of the correct equipment and 



reagents

 .................................................

32

Equipment 



 ............................................

32

Reagents 



 ................................................

33

3.3  Quality assurance 



 .................................

34

Internal quality control (IQC)



 ...............

34

External quality assessment (EQA) 



.......

34

References



 ......................................................

34

CONTENTS



4.  Hemostatic agents

 ........................................

37

4.1  Clotting factor concentrates



 .................

37

Product selection



 ....................................

37

FVIII concentrates



 .................................

38

FIX concentrates 



 ...................................

39

4.2  Other plasma products



 .........................

40

Fresh frozen plasma (FFP)



 .....................

40

Cryoprecipitate



 ......................................

41

4.3  Other pharmacological options 



 ...........

41

Desmopressin (DDAVP)



 ........................

41

Tranexamic acid



 ....................................

42

Epsilon aminocaproic acid



 .....................

43

References



 ......................................................

43

5.  Treatment of specific hemorrhages

 .............

47

5.1  Joint hemorrhage (hemarthrosis)



 .........

47

Arthrocentesis



 ........................................

48

5.2  Muscle hemorrhage 



 .............................

49

Iliopsoas hemorrhage 



 ............................

50

5.3  Central nervous system  



hemorrhage/head trauma 

 ....................

50

5.4  Throat and neck hemorrhage



 ...............

51

5.5  Acute gastrointestinal (GI)  



hemorrhage

 ...........................................

51

5.6  Acute abdominal hemorrhage 



 .............

51

5.7  Ophthalmic hemorrhage



 ......................

51

5.8  Renal hemorrhage



 .................................

52

5.9  Oral hemorrhage



 ...................................

52

5.10 Epistaxis 



 ...............................................

52

5.11  Soft tissue hemorrhage 



 .........................

53

5.12  Lacerations and abrasions



 .....................

53

References



 ......................................................

53

6.  Complications of hemophilia 

 .....................

55

6.1  Musculoskeletal complications



 .............

55

Synovitis



 ................................................

55

Chronic hemophilic arthropathy



 ............

56

Principles of physiotherapy/physical 



medicine in hemophilia

..........................

57

Pseudotumours



 ......................................

58

Fractures



 ................................................

58

Principles of orthopedic surgery in 



hemophilia

 .............................................

58

6.2 Inhibitors



 ...............................................

59

Management of bleeding 



 .......................

60

Allergic reactions in patients with 



hemophilia B

 ..........................................

61

Immune tolerance induction 



 .................

61

Patients switching to new concentrates



 ..

61

6.3  Transfusion-transmitted and other 



infection-related complications 

 ...........

61

Principles of management of HIV 



infection in hemophilia

 ..........................

62

Principles of management of HCV 



infection in hemophilia

 ..........................

62

Principles of management of HBV 



infection in hemophilia

 ..........................

62

Principles of management of bacterial 



infection in hemophilia

 ..........................

63

References



 ......................................................

63

7.  Plasma factor level and duration of 



administration

 ..............................................

69

7.1  Choice of factor replacement therapy 



protocols

 ...............................................

69

References



 ......................................................

73

Appendix I 

Oxford Centre for Evidence-Based 

Medicine, 2011 Levels of Evidence

 .......

74


TABLES AND FIGURES

Table 1-1:   Relationship of bleeding severity to clotting factor level 

 ..........................................................

8

Table 1-2:   Sites of bleeding in hemophilia 



 .................................................................................................

8

Table 1-3:   Approximate frequency of bleeding at different sites 



 ...............................................................

8

Table 1-4:   Definitions of factor replacement therapy protocols



 ...............................................................

12

Table 1-5:   Strategies for pain management in patients with hemophilia



 .................................................

15

Table 1-6:   Definition of adequacy of hemostasis for surgical procedures



 ...............................................

16

Table 3-1:   Interpretation of screening tests



 ..............................................................................................

31

Table 5-1:   Definition of response to treatment of acute hemarthrosis 



 ...................................................

48

Table 7-1:   Suggested plasma factor peak level and duration of administration  



(when there is no significant resource constraint)

 ..................................................................

71

Table 7-2:   Plasma factor peak level and duration of administration  



(when there is significant resource constraint)

 .......................................................................

72

Figure 7-1:  Strategies for clotting factor replacement at different ages and impact on outcomes 



 ............

69


GUIDELINES FOR THE MANAGEMENT OF HEMOPHILIA

6

The first edition of these guidelines, published in 



2005 by the WFH, served its purpose of being a 

useful document for those looking for basic infor-

mation on the comprehensive management of 

hemophilia. The need for revision has arisen for 

several reasons. The most significant of these was 

to incorporate the best existing evidence on which 

recommendations were based. There is recent high 

quality data from randomized controlled trials estab-

lishing the efficacy and superiority of prophylactic 

factor replacement over episodic treatment – though 

the optimal dose and schedule for prophylaxis 

continue to be subjects of further research. There 

is also greater recognition of the need for better 

assessment of outcomes of hemophilia care using 

newly developed, validated, disease-specific clini-

metric instruments. This revised version addresses 

these issues in addition to updating all sections. 

These guidelines contain several recommenda-

tions regarding the clinical management of people 

with hemophilia (practice statements, in bold). All 

such statements are supported by the best available 

evidence in the literature, which were graded as per 

the 2011 Oxford Centre for Evidence-Based Medicine 

(see Appendix I). Where possible, references for 

recommendations that fell outside the selection for 

practice statements were also included. These refer-

ences have not been graded.

A question often raised when developing a guide-

line document such as this is its universal applicability 

given the diversity of health services and economic 

systems around the world. Our strongly held view 

is that the principles of management of hemophilia 

are the same all over the world. The differences are 

mainly in the doses of clotting factor concentrates 

(CFC) used to treat or prevent bleeding, given that 

the costs of replacement products comprise the major 

expense of hemophilia care programs. Recognizing 

this reality, these guidelines continue to include a dual 

set of dose recommendations for CFC replacement 

therapy. These are based on published literature and 

practices in major centres around the world. It should 

be appreciated, however, that the lower doses recom-

mended may not achieve the best results possible and 

should serve as the starting point for care to be initi-

ated in resource-limited situations, with the aim of 

gradually moving towards more optimal doses, based 

on data and greater availability of CFC. 

One of the reasons for the wide acceptance of the 

first edition of these guidelines was its easy reading 

format. While enhancing the content and scope of 

the document, we have ensured that the format has 

remained the same. We hope that it will continue to be 

useful to those initiating and maintaining hemophilia 

care programs. Furthermore, the extensive review of 

the literature and the wide consensus on which practice 

statements have been made may encourage practice 

harmonization around the world. More importantly, in 

areas where practice recommendations lack adequate 

evidence, we hope that this document will stimulate 

appropriate studies. 

Introduction

Summary 


Hemophilia is a rare disorder that is complex to 

diagnose and to manage. These evidence-based 

guidelines offer practical recommendations on 

the diagnosis and general management of hemo-

philia, as well as the management of complications 

including musculo skeletal issues, inhibitors, and 

transfusion-transmitted infections. By compiling 

these guidelines, the World Federation of Hemophilia 

(WFH) aims to assist healthcare providers seeking to 

initiate and/or maintain hemophilia care programs, 

encourage practice harmonization around the 

world and, where recommendations lack adequate 

evidence, stimulate appropriate studies.


7

1.1  What is hemophilia?

1.  Hemophilia is an X-linked congenital bleeding 

disorder caused by a deficiency of coagulation 

factor VIII (FVIII) (in hemophilia A) or factor 

IX (FIX) (in hemophilia B). The deficiency is 

the result of mutations of the respective clotting 

factor genes. 

2.  Hemophilia has an estimated frequency of 

approximately one in 10,000 births.

3.  Estimations based on the WFH’s annual global 

surveys indicate that the number of people with 

hemophilia in the world is approximately 400,000 [1]. 

4.  Hemophilia A is more common than hemophilia 

B, representing 80-85% of the total hemophilia 

population. 

5.  Hemophilia generally affects males on the 

maternal side. However, both F8 and F9 genes 

are prone to new mutations, and as many as 1/3 

of all cases are the result of spontaneous muta-

tion where there is no prior family history. 

6.  Accurate diagnosis of hemophilia is essential to 

inform appropriate management. Hemophilia 

should be suspected in patients presenting with 

a history of: 

 ■ easy bruising in early childhood

 ■ “spontaneous” bleeding (bleeding for no 

apparent/known reason), particularly into the 

joints, muscles, and soft tissues

 ■ excessive bleeding following trauma or surgery 

7.  A family history of bleeding is obtained in about 

two-thirds of all patients.

8.  A definitive diagnosis depends on factor assay to 

demonstrate deficiency of FVIII or FIX.



Bleeding manifestations

1.  The characteristic phenotype in hemophilia is 

the bleeding tendency.

2.  While the history of bleeding is usually life-long, 

some children with severe hemophilia may not 

have bleeding symptoms until later when they 

begin walking or running. 

3.  Patients with mild hemophilia may not bleed 

excessively until they experience trauma or 

surgery.


4.  The severity of bleeding in hemophilia is gener-

ally correlated with the clotting factor level, as 

shown in Table 1-1. 

5.  Most bleeding occurs internally, into the joints 

or muscles (see Table 1-2 and Table 1-3). 

6.  Some bleeds can be life-threatening and require 

immediate treatment (see Section 5).

1

GENERAL CARE AND MANAGEMENT 



OF HEMOPHILIA 

GUIDELINES FOR THE MANAGEMENT OF HEMOPHILIA

8

1.2  Principles of care



1.  The primary aim of care is to prevent and treat 

bleeding with the deficient clotting factor.

2.  Whenever possible, specific factor deficiency 

should be treated with specific factor concentrate.

3.  People with hemophilia are best managed in a 

comprehensive care setting (see ‘Comprehensive 

care’, on page 9).

4.  Acute bleeds should be treated as quickly as 


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