Guidelines for the management of

possible, preferably within two hours. If in 

doubt, treat. (Level 4) [2]

5.  Patients usually recognize early symptoms of 

bleeding even before the manifestation of phys-

ical signs. This is often described as a tingling 

sensation or “aura”. 

6.  During an episode of acute bleeding, an assess-

ment should be performed to identify the site of 

bleeding (if not clinically obvious) and appro-

priate clotting factor should be administered.

7.  In severe bleeding episodes that are potentially 

life-threatening, especially in the head, neck, 

chest, and gastrointestinal tract, treatment with 

factor should be initiated immediately, even 

before diagnostic assessment is completed. 

8.  To facilitate appropriate management in emer-

gency situations, all patients should carry 

easily accessible identification indicating the 

diagnosis, severity of the bleeding disorder, 

inhibitor status, type of treatment product used, 

initial dosage for treatment of severe, moderate, 

and mild bleeding, and contact information of 

the treating physician/clinic. (Level 5) [3]

9.  Administration of desmopressin (DDAVP) can 

raise FVIII level adequately (three to six times 

baseline levels) to control bleeding in patients 

with mild, and possibly moderate, hemophilia 

A. Testing for DDAVP response in individual 

patients is appropriate. (Level 3) [4-6]

TABLE 1-1: RELATIONSHIP OF BLEEDING SEVERITY TO CLOTTING FACTOR LEVEL [62]

SEVERITY

CLOTTING FACTOR LEVEL

BLEEDING EPISODES

Severe

< 1 IU/dl (< 0.01 IU/ml) or 

< 1 % of normal

Spontaneous bleeding into joints or muscles, 

predominantly in the absence of identifiable hemostatic 

challenge

Moderate

1-5 IU/dl (0.01-0.05 IU/ml) or 

1-5% of normal

Occasional spontaneous bleeding; prolonged bleeding 

with minor trauma or surgery

Mild

5-40 IU/dl (0.05-0.40 IU/ml) or

5-<40% of normal

Severe bleeding with major trauma or surgery. 

Spontaneous bleeding is rare.

TABLE 1-2: SITES OF BLEEDING IN HEMOPHILIA [63]

Serious

Joints (hemarthrosis)

Muscles, especially deep compartments 

(iliopsoas, calf, and forearm)

Mucous membranes in the mouth, 

gums, nose, and genitourinary tract

Life-

threatening

Intracranial

Neck/throat 

Gastrointestinal

TABLE 1-3: APPROXIMATE FREQUENCY OF BLEEDING AT 

DIFFERENT SITES 

SITE OF BLEEDING

APPROXIMATE 

FREQUENCY

Hemarthrosis

 

■ more common into hinged joints: 

ankles, knees, and elbows

 

■ less common into multi-axial joints: 

shoulders, wrists, hips

70%–80%

Muscle

10%–20%

Other major bleeds

5%–10%

Central nervous system (CNS)

<5%

GENERAL CARE AND MANAGEMENT OF HEMOPHILIA 

9

10. Veins must be treated with care. They are the life-

lines for a person with hemophilia.

 ■ 23- or 25-gauge butterfly needles are recom-

mended.

 ■ Never cut down into a vein, except in an 

emergency.

 ■ Apply pressure for three to five minutes after 

venipuncture.

 ■ Venous access devices should be avoided 

whenever possible but may be required in 

some children.

11. Adjunctive therapies can be used to control 

bleeding, particularly in the absence of clotting 

factor concentrates, and may decrease the need for 

them (see ‘Adjunctive management’ on page 12).

12. If bleeding does not resolve despite adequate treat-

ment, clotting factor levels should be measured. 

Inhibitor testing should be performed if the level 

is unexpectedly low (see ‘Inhibitor testing’, on 

page 32 and ‘Inhibitors’, on page 59). 

13. Prevention of bleeding can be achieved by 

prophylactic factor replacement (see ‘Prophylactic 

factor replacement therapy’, on page 12).

14. Home therapy can be used to manage mild/

moderate bleeding episodes (see ‘Home therapy’, 

on page 13).

15. Regular exercise and other measures to stimu-

late normal psychomotor development should be 

encouraged to promote strong muscles, develop 

balance and coordination, and improve fitness 

(see ‘Fitness and physical activity’, on page 11).

16. Patients should avoid activities likely to cause 

trauma (see ‘Fitness and physical activity’, on 

page 11).

17. Regular monitoring of health status and assess-

ment of outcomes are key components of care 

(see ‘Monitoring health status and outcome’, on 

page 14).

18. Drugs that affect platelet function, particularly 

acetylsalicylic acid (ASA) and non-steroidal 

anti-inflammatory drugs (NSAIDs), except 

certain COX-2 inhibitors, should be avoided. 

Paracetamol/acetaminophen is a safe alternative 

for analgesia (see ‘Pain management’, on page 15).

19. Factor levels should be raised to appropriate levels 

prior to any invasive procedure (see ‘Surgery and 

invasive procedures’, on page 16).

20. Good oral hygiene is essential to prevent peri-

odontal disease and dental caries, which 

predispose to gum bleeding (see ‘Dental care 

and management’ on page 17).

1.3  Comprehensive care 

1.  Comprehensive care promotes physical and 

psychosocial health and quality of life while 

decreasing morbidity and mortality. (Level 3) 

[7-9]

2.  Hemophilia is a rare disorder that is complex to 

diagnose and to manage. Optimal care of these 

patients, especially those with severe forms of 

the disease, requires more than the treatment of 

acute bleeding. 

3.  Priorities in the improvement of health and 

quality of life of people with hemophilia include:

 ■ prevention of bleeding and joint damage

 ■ prompt management of bleeding

 ■ management of complications including: 

 ■

joint and muscle damage and other sequelae 

of bleeding

 ■

inhibitor development 

 ■

viral infection(s) transmitted through blood 

products 

 ■ attention to psychosocial health

Comprehensive care team

1.  The wide-ranging needs of people with hemo-

philia and their families are best met through 

the coordinated delivery of comprehensive 

care by a multidisciplinary team of health-

care professionals, in accordance with accepted 

protocols that are practical and national treat-

ment guidelines, if available. (Level 5) [10-12]

GUIDELINES FOR THE MANAGEMENT OF HEMOPHILIA

10

2.  The comprehensive care team should be multidis-

ciplinary in nature, with expertise and experience 

to attend to the physical and psychosocial health 

of patients and their families. 

3.  The core team should consist of the following 

members:

 ■ a medical director (preferably a pediatric and/

or adult hematologist, or a physician with 

interest and expertise in hemostasis)

 ■ a nurse coordinator who

 ■

coordinates the provision of care

 ■

educates patients and their families

 ■

acts as the first contact for patients with an 

acute problem or who require follow-up 

 ■

is able to assess patients and institute initial 

care where appropriate

 ■ a musculoskeletal expert (physiotherapist, 

occupational therapist, physiatrist, orthopedist, 

rheumatologist) who can address prevention 

as well as treatment 

 ■ a laboratory specialist

 ■ a psychosocial expert (preferably a social 

worker, or a psychologist) familiar with avail-

able community resources

4.  The roles assumed by core team members may 

differ, depending on the availability and expertise 

of trained staff and the organization of services 

within the centre.

5.  All members of the core team should have exper-

tise and experience in treating bleeding disorders 

and should be accessible to patients in a timely 

and convenient manner. Adequate emergency 

care should be available at all times. 

6.  The following support resources are necessary:

 ■ Access to a coagulation laboratory capable of 

performing accurate and precise clotting factor 

assays and inhibitor testing.

 ■ Provision of appropriate clotting factor concen-

trates, either plasma-derived or recombinant, 

as well as other adjunct hemostatic agents such 

as desmopressin (DDAVP) and tranexamic 

acid where possible.

 ■ Where clotting factor concentrates are not 

available, access to safe blood components 

such as fresh frozen plasma (FFP) and cryo-

precipitate.

 ■ Access to casting and/or splinting for immobi-

lization and mobility/support aids, as needed. 

7.  The comprehensive care team should also include 

or have access to, among others: 

 ■ chronic pain specialist

 ■ dentist 

 ■ geneticist 

 ■ hepatologist

 ■ infectious disease specialist

 ■ immunologist

 ■ gynecologist/obstetrician

 ■ vocational counsellor

8.  Written management protocols are required to 

ensure continuity of care despite changes in clinic 

personnel.

9.  The comprehensive care team should have the 

resources to support family members. This may 

include identifying resources and strategies to 

help cope with:

 ■ risks and problems of everyday living, partic-

ularly with management of bleeding

 ■ changes associated with different stages of the 

patient’s growth and development (especially 

adolescence and aging)

 ■ issues regarding schooling and employment

 ■ risk of having another affected child and the 

options available

10. Establishing a long-term relationship between 

patients/families and members of the compre-

hensive care team promotes compliance. 

Functions of a comprehensive care program

1.  To provide or coordinate inpatient (i.e. during 

hospital stays) and outpatient (clinic and other 

visits) care and services to patients and their 

family.

 ■ Patients should be seen by all core team 

members at least yearly (children every six 

months) for a complete hematologic, muscu-

loskeletal, and psychosocial assessment and 

to develop, audit, and refine an individual’s 

comprehensive management plan. Referrals 

for other services can also be given during 

these visits. (Level 5) [13,14]

GENERAL CARE AND MANAGEMENT OF HEMOPHILIA 

11

 ■ The management plan should be developed 

with the patient and communicated to all 

treaters and care facilities. Communication 

among treaters is important.

 ■ Smaller centres and personal physicians can 

provide primary care and management of some 

complications, in frequent consultation with 

the comprehensive care centre (particularly 

for patients who live a long distance from the 

nearest hemophilia treatment centre). 

2.  To initiate, provide training for, and supervise 

home therapy with clotting factor concentrates 

where available.

3.  To educate patients, family members and other 

caregivers to ensure that the needs of the patient 

are met.

4.  To collect data on sites of bleeds, types and doses 

of treatment given, assessment of long-term 

outcomes (particularly with reference to musculo-

skeletal function), complications from treatment, 

and surgical procedures. This information is best 

recorded in a computerized registry and should 

be updated regularly by a designated person and 

maintained in accordance with confidentiality 

laws and other national regulations. Systematic 

data collection will: 

 ■ facilitate the auditing of services provided by 

the hemophilia treatment centre and support 

improvements to care delivery.

 ■ help inform allocation of resources.

 ■ promote collaboration between centres in 

sharing and publishing data.

5.  Where possible, to conduct basic and clinical 

research. Since the number of patients in each 

centre may be limited, clinical research is best 

conducted in collaboration with other hemo-

philia centres.

1.4  Fitness and physical activity

1.  Physical activity should be encouraged to 

promote physical fitness and normal neuro-

muscular development, with attention paid to 

muscle strengthening, coordination, general 

fitness, physical functioning, healthy body 

weight, and self-esteem. (Level 2) [15]

2.  Bone density may be decreased in people with 

hemophilia [16, 17]. 

3.  For patients with significant musculoskeletal 

dysfunction, weight-bearing activities that 

promote development and maintenance of 

good bone density should be encouraged, to the 

extent their joint health permits. (Level 3) [16]

4.  The choice of activities should reflect an indi-

vidual’s preference/interests, ability, physical 

condition, local customs, and resources.

5.  Non-contact sports such as swimming, walking, 

golf, badminton, archery, cycling, rowing, sailing, 

and table tennis should be encouraged. 

6.  High contact and collision sports such as soccer, 

hockey, rugby, boxing, and wrestling, as well 

as high-velocity activities such as motocross 

racing and skiing, are best avoided because of 

the potential for life-threatening injuries, unless 

the individual is on good prophylaxis to cover 

such activities. 

7.  Organized sports programs should be encour-

aged as opposed to unstructured activities, where 

protective equipment and supervision may be 

lacking. 

8.  The patient should consult with a musculoskeletal 

professional before engaging in physical activi-

ties to discuss their appropriateness, protective 

gear, prophylaxis (factor and other measures), 

and physical skills required prior to beginning 

the activity. This is particularly important if the 

patient has any problem/target joints [18]. 

9.  Target joints can be protected with braces or 

splints during activity, especially when there 

is no clotting factor coverage. (Level 4) [19,20]

10. Activities should be re-initiated gradually after a 

bleed to minimize the chance of a re-bleed. 

GUIDELINES FOR THE MANAGEMENT OF HEMOPHILIA

12

1.5  Adjunctive management 

1.  Adjunctive therapies are important, particularly 

where clotting factor concentrates are limited or 

not available, and may lessen the amount of treat-

ment product required. 

2.  First aid measures: In addition to increasing factor 

level with clotting factor concentrates (or desmo-

pressin in mild hemophilia A), protection (splint), 

rest, ice, compression, and elevation (PRICE) may 

be used as adjunctive management for bleeding 

in muscles and joints. 

3.  Physiotherapy/rehabilitation is particularly 

important for functional improvement and 

recovery after musculoskeletal bleeds and for 

those with established hemophilic arthrop-

athy (see ‘Principles of physiotherapy/Physical 

medicine in hemophilia’, on page 57).

4.  Antifibrinolytic drugs (e.g. tranexamic acid, 

epsilon aminocaproic acid) are effective as 

adjunctive treatment for mucosal bleeds and 

dental extractions (see ‘Tranexamic acid’, on page 

42 and ‘‘Epsilon aminocaproic acid’, on page 43).

5.  Certain COX-2 inhibitors may be used judiciously 

for joint inflammation after an acute bleed and 

in chronic arthritis (see ‘Pain management’, on 

page 15).

1.6  Prophylactic factor replacement therapy

1.  Prophylaxis is the treatment by intravenous injec-

tion of factor concentrate in order to prevent 

anticipated bleeding (see Table 1-4).

2.  Prophylaxis was conceived from the observation 

that moderate hemophilia patients with clotting 

factor level >1 IU/dl seldom experience sponta-

neous bleeding and have much better preservation 

of joint function [21-24].

3.  Prophylaxis prevents bleeding and joint 

destruction and should be the goal of therapy 

to preserve normal musculoskeletal function. 

(Level 2) [24-29]

4.  Prophylactic replacement of clotting factor has 

been shown to be useful even when factor levels 

are not maintained above 1 IU/dl at all times. 

[26,29,30] 

TABLE 1-4: DEFINITIONS OF FACTOR REPLACEMENT THERAPY PROTOCOLS [64]

PROTOCOL

DEFINITION

Episodic (“on demand”) treatment

Treatment given at the time of clinically evident bleeding

Continuous prophylaxis 

Primary prophylaxis

Regular continuous* treatment initiated in the absence of documented 

osteochondral joint disease, determined by physical examination and/or imaging 

studies, and started before the second clinically evident large joint bleed and 

age 3 years** 

Secondary prophylaxis 

Regular continuous* treatment started after 2 or more bleeds into large joints** 

and before the onset of joint disease documented by physical examination and 

imaging studies

Tertiary prophylaxis 

Regular continuous* treatment started after the onset of joint disease 

documented by physical examination and plain radiographs of the affected 

joints

Intermittent (“periodic”) prophylaxis 

Treatment given to prevent bleeding for periods not exceeding 45 weeks in a year 

* continuous is defined as the intent of treating for 52 weeks/year and receiving a minimum of an a priori defined frequency of infusions 

for at least 45 weeks (85%) of the year under consideration. 

 **large joints = ankles, knees, hips, elbows and shoulders

GENERAL CARE AND MANAGEMENT OF HEMOPHILIA 

13

5.  It is unclear whether all patients should remain 

on prophylaxis indefinitely as they transition 

into adulthood. Although some data suggest 

that a proportion of young adults can do well 

off prophylaxis [31], more studies are needed 

before a clear recommendation can be made [32].

6.  In patients with repeated bleeding, particu-

larly into target joints, short-term prophylaxis 

for four to eight weeks can be used to inter-

rupt the bleeding cycle. This may be combined 

with intensive physiotherapy or synoviorthesis. 

(Level 3) [33,34]

7.  Prophylaxis does not reverse established joint 

damage; however, it decreases frequency of 

bleeding and may slow progression of joint 

disease and improve quality of life.

8.  Prophylaxis as currently practiced in coun-

tries where there are no significant resource 

constraints is an expensive treatment and is only 

possible if significant resources are allocated to 

hemophilia care. However, it is cost-effective 

in the long-term because it eliminates the high 

cost associated with subsequent management 

of damaged joints and improves quality of life. 

9.  In countries with significant resource constraints, 

lower doses of prophylaxis given more frequently 

may be an effective option.

10. Cost-efficacy studies designed to identify 

minimum dosage are necessary to allow access 

to prophylaxis in more of the world.

Administration and dosing schedules

1.  There are two prophylaxis protocols currently in 

use for which there is long-term data: 

 ■ The Malmö protocol: 25-40 IU/kg per dose 

administered three times a week for those with 

hemophilia A, and twice a week for those with 

hemophilia B. 

 ■ The Utrecht protocol: 15-30 IU/kg per dose 

administered three times a week for those with 

hemophilia A, and twice a week for those with 

hemophilia B. 

2.  However, many different protocols are followed 

for prophylaxis, even within the same country, 

and the optimal regimen remains to be defined. 

3.  The protocol should be individualized as much 

as possible, based on age, venous access, bleeding 

phenotype, activity, and availability of clotting 

factor concentrates.

4.  One option for the treatment of very young 

children is to start prophylaxis once a week and 

escalate depending on bleeding and venous 

access. 

5.  Prophylaxis is best given in the morning to cover 

periods of activity. 

6.  Prophylactic administration of clotting factor 

concentrates is advisable prior to engaging in 

activities with higher risk of injury. (Level 4) 

[18,34,35]

1.7  Home therapy 

1.  Where appropriate and possible, persons with 

hemophilia should be managed in a home therapy 

setting.

2.  Home therapy allows immediate access to clot-

ting factor and hence optimal early treatment, 

resulting in decreased pain, dysfunction, and long-

term disability and significantly decreased hospital 

admissions for complications. (Level 3) [36,37]

3.  Further improvements in quality of life include 

greater freedom to travel and participate in 

physical activities, less absenteeism, and greater 

employment stability [38]. 

4.  Home therapy is ideally achieved with clotting 

factor concentrates or other lyophilized products 

that are safe, can be stored in a domestic fridge, 

and are reconstituted easily. 

5.  Home treatment must be supervised closely