Guidelines for the management of

daughters) of a person with hemophilia should 

have their clotting factor level checked, especially 

prior to any invasive intervention, childbirth, or 

if any symptoms occur. (Level 3) [3,5]

2

SPECIAL MANAGEMENT 

ISSUES

GUIDELINES FOR THE MANAGEMENT OF HEMOPHILIA

22

2.2  Genetic testing/counselling and prenatal diagnosis 

1.  Where available and possible, genetic testing for 

carrier status should be offered to at-risk female 

family members of people with hemophilia to 

facilitate genetic counselling, and if desired 

by the family, prenatal diagnosis. (Level 4) [6]

2.  DNA-based mutation analysis to identify the 

specific mutation responsible for hemophilia in 

a particular family is becoming technically easier 

and more widely available. This facilitates iden-

tification of carriers and prenatal diagnosis for 

male fetuses. 

3.  Genetic counselling is key to helping people with 

hemophilia, carriers, and their families make 

more informed choices. 

4.  Prenatal diagnosis is usually offered when termi-

nation of the pregnancy would be considered if 

an affected fetus was identified. However, it may 

also be done to help the family prepare and to 

plan delivery. Assisted delivery is best avoided 

in an affected fetus. 

5.  Fetal gender can be determined using Y chromo-

some-specific PCR in maternal plasma/serum 

after 7-9 weeks of gestation [7,8] or by ultraso-

nography beginning week 11 of gestation [9]. 

6.  Chorionic villus sampling (CVS), or biopsy, 

is the main method of prenatal diagnosis and 

is best done between 9-14 weeks of gestation. 

Biopsy carried out earlier may be associated 

with increased complications including fetal 

limb abnormalities. (Level 1) [10-13]

7.  Amniocentesis can be done at 15-17 weeks of 

gestation [11]. 

8.  It is important to be aware of and to follow the 

relevant laws governing such procedures in the 

country where the service is being provided. 

9.  For carriers with low factor levels (< 50 IU/dl), 

hemostatic support may be required to prevent 

maternal bleeding during prenatal diagnosis 

procedures. 

10. All invasive methods used for prenatal diag-

nosis may cause feto-maternal hemorrhage. 

Anti-D immunoglobulin should be given if the 

mother is RhD negative. (Level 3) [14]

11. Pre-implantation genetic diagnosis allows selec-

tion of embryos without specific mutation to be 

implanted into the uterus [15]. 

2.3  Delivery of infants with known or suspected hemophilia 

1.  FVIII levels usually rise into the normal range 

during the second and third trimesters and 

should therefore be measured in carriers during 

the third trimester of pregnancy to inform 

decisions for factor coverage during delivery. 

(Level 3) [4]

2.  In carriers with significantly low factor levels 

(< 50 IU/dl), clotting factor replacement is 

necessary for surgical or invasive procedures 

including delivery. (Level 3) [4]

3.  The need for clotting factor replacement should 

be planned in the prenatal period.

4.  Route of delivery in carriers with a normal fetus 

should be as per obstetric indications.

5.  Delivery of infants with known or suspected 

hemophilia should be atraumatic, regardless 

of whether it is vaginal or cesarean, to decrease 

the risk of bleeding. (Level 3) [4] 

6.  Forceps and vacuum extraction should be avoided 

in vaginal delivery, as well as invasive procedures 

to the fetus such as fetal scalp blood sampling and 

internal fetal scalp electrodes [16]. 

SPECIAL MANAGEMENT ISSUES

23

2.4  Vaccinations

1.  Persons with bleeding disorders should be 

vaccinated, but should preferably receive the 

vaccine subcutaneously rather than intra-

muscularly or intradermally, unless covered 

by infusion of clotting factor concentrates. 

(Level 4) [17]

2.  If intramuscular injection is to be given:

 ■ It is best done soon after a dose of factor 

replacement therapy.

 ■ An ice pack can be applied to the injection area 

for five minutes before injection. 

 ■ The smallest gauge needle available (usually 

25-27 gauge) should be used. 

 ■ Pressure should be applied to the injection site 

for at least five minutes [18]. 

3.  Live virus vaccines (such as oral polio vaccine, 

MMR) may be contraindicated in those with 

HIV infection. 

4.  People with hemophilia who have HIV should 

be given pneumococcal and annual influenza 

vaccines. 

5.  Immunization to hepatitis A and B is important 

for all persons with hemophilia. These immu-

nizations may not be as effective in those with 

HIV infection. (Level 4) [19,20]

2.5  Psychosocial issues 

1.  Patients and their families should be provided 

with psychological and social support [21,22]. 

2.  Hemophilia is also a financial burden that places 

restrictions on several aspects of normal living 

[23]. 

3.  The social worker and/or other members of the 

comprehensive care team should:

 ■ provide as much information as possible about 

the physical, psychological, emotional, and 

economic dimensions of hemophilia, in terms 

the patient/parents can understand.

 ■ be open and honest about all aspects of care. 

 ■ allow the patient/parents to work through their 

emotions and ask questions. Provide care and 

support patiently.

 ■ talk to affected children, not just their parents. 

Children can often understand a good deal 

about their illness and can work with the physi-

cian if properly informed and educated. 

 ■ remind parents not to ignore siblings that are 

healthy.

 ■ be able to recognize warning signs of burnout 

and depression, which are common with 

chronic illness, and provide suggestions for 

coping.

 ■ recognize that cultural background may affect 

patients’ views of illness.

 ■ encourage patients to engage in productive and 

leisure activities at home and in the workplace. 

 ■ work in partnership with the patient organi-

zation to advocate for hemophilia care and to 

provide education to families and members 

of the community.

 ■ enlist the assistance of local groups and orga-

nizations where social workers are unavailable.

2.6  Sexuality 

1.  Patients with hemophilia can have normal sexual 

intercourse [24]. 

2.  Muscle bleedings (for e.g. iliopsoas) may some-

times be the result of sexual activity. 

3.  Complications of hemophilia can be accompa-

nied by sexual dysfunction, which may include 

lack of libido or impotence. 

4.  Pain or fear of pain may affect sexual desire, and 

hemophilic arthropathy may place limitations on 

sexual intercourse. 

GUIDELINES FOR THE MANAGEMENT OF HEMOPHILIA

24

5.  Sexuality is also affected by chronic HCV and 

HIV infection, age-related diseases like hyper-

tension and diabetes mellitus, and certain 

medications.

6.  In some cases, oral phosphodiesterase-5 inhib-

itors (sildenafil, tadalafil) may be helpful. These 

medications mildly inhibit platelet aggregation 

in vitro, and may cause epistaxis due to nasal 

congestion. 

2.7  Ageing hemophilia patients 

1.  Ageing patients with hemophilia will inevitably 

suffer from age-related diseases [24,25]. 

2.  Comorbidities in ageing hemophilia patients 

should be managed appropriately as they may 

accentuate problems associated with hemophilia 

and impact the patient’s physical and psychoso-

cial health, and thus their quality of life. 

Osteoporosis

1.  Bone mineral density (BMD) is decreased in 

people with hemophilia [26,27]. 

2.  An increased number of arthropathic joints, loss 

of joint movement, and muscle atrophy leading to 

inactivity are associated with a lower BMD [27]. 

3.  Weight-bearing activities (suitable sports) that 

promote development and maintenance of good 

bone density should be encouraged if joint health 

permits. 

4.  Calcium and vitamin D supplementation are 

also important and bisphosphonate therapy 

may be required. A dental evaluation is advis-

able before initiating long-term bisphosphonate 

therapy [28,29]. 

Obesity

1.  The prevalence of overweight (BMI 25-30 kg/m

2

) 

and obesity (BMI > 30kg/m

2

) is increasing [30]. 

2.  Lack of activity may contribute to an increase in 

BMI and increased body weight.

3.  A high BMI has been associated with:

 ■ a significant limitation in range of motion 

(ROM) [31] 

 ■ increased arthropathic pain 

 ■ increased risk of developing target joints [32]

 ■ increased risk of diabetes mellitus, atheroscle-

rosis, and cardiovascular disease, which may 

further damage arthropathic joints. 

4.  Regular physical activity should be advised.

5.  If functional limitations restrict daily activities, 

a physiotherapist familiar with hemophilia may 

be able to suggest appropriate alternatives.

6.  In some cases referral to a dietician may be 

indicated. 

Hypertension

1.  Hemophilia patients have a higher mean blood 

pressure, are twice as likely to have hyperten-

sion, and use more anti-hypertensive medication 

compared to the general population [33,34]. 

2.  In view of increased risk of bleeding, hyperten-

sive patients with hemophilia should be treated 

adequately and have their blood pressure checked 

regularly.

3.  In the absence of other cardiovascular risk factors, a 

systolic blood pressure ≤140 mmHg and a diastolic 

pressure ≤90 mmHg should be maintained.

Diabetes mellitus (DM)

1.  The prevalence of DM in hemophilia is not well 

documented, but was observed to be higher in 

a cohort of mild hemophilia [35]. 

2.  In ageing hemophilia patients, especially among 

those who are overweight, glucose levels should 

be checked annually. 

3.  If treatment with insulin is indicated, subcuta-

neous injections can be administered without 

bleeding complications. (Level 5) [24]

SPECIAL MANAGEMENT ISSUES

25

Hypercholesterolemia

1.  Mean cholesterol levels in patients with hemo-

philia have been reported to be lower than in the 

general population [36]. 

2.  Cholesterol levels (total cholesterol, HDL, and 

LDL fraction) should be measured in ageing 

hemophilia patients at risk of cardiovascular 

disease.

3.  Treatment is indicated if cholesterol levels are 

high. As a general rule, the total cholesterol/HDL 

ratio should not be higher than 8. 

Cardiovascular disease 

1.  Hemophilia patients appear to have a reduced 

risk of mortality from ischemic cardiovascular 

disease, but the number of deaths from this cause 

is increasing [34,37,38]. 

2.  A possible association between the occurrence 

of myocardial infarction and previous adminis-

tration of clotting factor concentrates has been 

described [39,40]. 

3.  Hemophilia patients with cardiovascular disease 

should receive routine care adapted to the indi-

vidual situation, in discussion with a cardiologist 

[41,42].

4.  For acute coronary syndromes requiring percu-

taneous cardiac intervention (PCI):

 ■ Adequate correction with clotting factor 

concentrates before PCI and until 48 hours 

after PCI is required. (Level 4) [40,41,43] 

 ■ High factor levels should be avoided in order 

to prevent occlusive thrombi. During complete 

correction: 

 ■

Heparin can be administered according to 

standard cardiologic treatment protocols.

 ■

Glycoprotein IIb/IIIa inhibitors (abcix-

imab, tirofiban) used in PCI with stenting 

can be administered. 

 ■ Radial artery access site, if technically 

possible, is preferred over femoral, in order 

to minimize retroperitoneal or groin bleeds. 

(Level 4) [40,41,43] 

 ■ Factor concentrates should be given for the 

duration of dual antiplatelet therapy, usually 

about two weeks, aiming at trough levels of 

30 IU/dl [41]. 

 ■ Prolonged use of aspirin is not recommended 

in severe hemophilia. Its use in patients on 

regular intensive prophylaxis is possible, 

though the data available is inadequate [41]. 

Psychosocial impact 

1.  In the ageing patient, the presence of crippling, 

painful arthropathy can affect quality of life and 

may lead to loss of independence [44].

2.  Patients may be confronted with unexpected 

emotional problems due to memories of nega-

tive experiences related to hemophilia (such as 

hospitalization) during their youth.

3.  Adaptations at home or at work and an adequate 

pain schedule are indicated to improve quality 

of life and preserve independence. 

4.  Active psychosocial support should be provided 

by a social worker, hemophilia nurse, physician 

and/or psychologist.

2.8  Von Willebrand disease and rare bleeding disorders

1.  The WFH is committed to providing support 

and information to patients, families, and clini-

cians on other hereditary bleeding disorders and 

many such patients are cared for in hemophilia 

treatment centres. 

2.  These guidelines are intended for the treatment 

of hemophilia. Recent publications that address 

the principles of diagnosis and treatment of von 

Willebrand disease (VWD) and rare bleeding 

disorders include:

 ■ Management of von Willebrand disease: 

a guideline from the UK Haemophilia 

Centre Doctors’ Organization. Haemophilia 

2004;10(3):218.231.

GUIDELINES FOR THE MANAGEMENT OF HEMOPHILIA

26

 ■ The Diagnosis, Evaluation and Management 

of von Willebrand Disease. US Dept of Health 

and Human Services, National Heart, Lung and 

Blood Institute NIH Publication no. 08-5832, 

December 2007. www.nhlbi.nih.gov

 ■ Von Willebrand Disease: An Introduc-

tion for the Primary Care Physician. David 

Lillicrap and Paula James, World Federation of 

Hemophilia Treatment of Hemophilia mono-

graph No 47, January 2009. www.wfh.org 

 ■ Rare Bleeding Disorders. Peyvandi F, Kaufman 

R, Selighson U et al. Haemophilia 2006 Jul; 12 

Suppl: 137-42.

 ■ The Rare Coagulation Disorders. Paula Bolton-

Maggs, World Federation of Hemophilia 

Treatment of Hemophilia No 39, April 2006. 

www.wfh.org

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3.  Plug I, Mauser-Bunschoten EP, Brocker-Vriends 

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4.  Chi C, Lee CA, Shiltagh N, Khan A, Pollard D, Kadir 

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5.  Ljung R, Tedgård U. Genetic counseling of hemophilia 

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6.  Dunn NF, Miller R, Griffioen A, Lee CA. Carrier 

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8.  Rijnders RJ, van der Luijt RB, Peters ED, Goeree JK, 

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9.  Chi C, Hyett JA, Finning KM, Lee CA, Kadir RA. 

Non-invasive first trimester determination of fetal 

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15.  Lavery S. Preimplantation genetic diagnosis of 

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16.  Kletzel M, Miller CH, Becton DL, Chadduck WM, 

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17.  Kulkarni R, Lusher J. Perinatal management of 

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18.  Evans DI, Shaw A. Safety of intramuscular injection 

of hepatitis B vaccine in haemophiliacs. BMJ 

1990;300:1694–95.

19.  Miller EJ, Lee CA, Karayiannis P, Holmes S, Thomas 

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virus infection. J Med Virol 1989;28:96–100.

20.  Steele M, Cochrane A, Wakefield C, et al. Hepatitis A 

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21.  Cassis F. Psychosocial care for people with hemophilia. 

Treatment of Hemophilia monograph no 44. Montreal: 

World Federation of Hemophilia, 2007.

22.  Miller R. Counselling about diagnosis and inheritance 

of genetic bleeding disorders: haemophilia A and B. 

Haemophilia 1999;5(2):77-83.

23.  Bullinger M, von Mackensen S. Psychosocial 

determinants of quality of life in children and 

adolescents with haemophilia: a cross-cultural approach. 

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24.  Mauser-Bunschoten EP, Fransen Van De Putte DE, 

Schutgens RE. Co-morbidity in the ageing haemophilia 

patient: the down side of increased life expectancy. 

Haemophilia 2009 Jul;15(4):853-63.

25.  Siboni SM, Mannucci PM, Gringeri A, et al. Health 

status and quality of life of elderly persons with 

severe haemophilia born before the advent of modern 

replacement therapy. J Thromb Haemost 2009;7(5):780-6.

26.  Iorio A, Fabbriciani G, Marcucci M, Brozzetti M, 

Filipponi P. Bone mineral density in haemophilia 

patients: A meta-analysis. Thromb Haemost 2010 

Mar;103(3):596-603.

27.  Wallny TA, Scholz DT, Oldenburg J, et al. Osteoporosis 

in haemophilia - an underestimated comorbidity? 

Haemophilia 2007;13(1):79-84. 

28.  Kovacs CS. Hemophilia, low bone mass, and osteopenia/

osteoporosis. Transfus Apher Sci 2008;38(1):33-40.

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2011.

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PW, Rosendaal FR, Peters M. Obesity: a new disaster 

for haemophilic patients? A nationwide survey. 

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hemophilia: prevalence and risk factors. Blood 

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Kraaijenhagen RA, Den Heijer M, Büller HR, 

Kamphuisen PW. Cardiovascular risk assessment 

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M, Scully MF. Health-related quality of life in a cohort 

of adult patients with mild hemophilia A. J Thromb 

Haemost 2008;6(5):755-61.

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SH, Mauser-Bunschoten EP. Treatment of ischaemic 

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8-12.

29

1.  A correct diagnosis is essential to ensure that a 

patient gets the appropriate treatment. Different 

bleeding disorders may have very similar 

symptoms.

2.  Accurate diagnosis can only be made with the 

support of a comprehensive and accurate labora-

tory service. This is dependent on the laboratory 

following strict protocols and procedures, which 

require: 

 ■ knowledge and expertise in coagulation labo-

ratory testing

 ■ use of the correct equipment and reagents

 ■ quality assurance

3.  For detailed information on technical aspects 

and specific instructions on screening tests and 

factor assays, please consult the WFH’s Diagnosis 

of Hemophilia and Other Bleeding Disorders: A 

Laboratory Manual, Second edition [1]. 

3.1  Knowledge and expertise in coagulation laboratory testing