Prevalence and Risk Factors for Heart Disease Among
Males With Hemophilia
Roshni Kulkarni,1J. Michael Soucie,2*Bruce L. Evatt,2and the Hemophilia
Surveillance System Project Investigators
1Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan
2Division of Hereditary Blood Disorders, National Center on Birth Defects and Developmental Disabilities,
Centers for Disease Control and Prevention, Atlanta, Georgia
There have been conflicting reports in the literature about the protective effect of hemo-
philia on the occurrence of ischemic heart disease (IHD). Circulatory disease has been
reported as the second most common cause of death in persons with hemophilia in the
United States. In addition to diabetes and hypertension, high levels of FVIII, as may occur
during factor concentrate infusions, may increase IHD risk in this population. To estimate
the prevalence of heart disease and examine factors associated with IHD and other heart
diseases among persons with hemophilia, we analyzed data collected from the medical
records of 3,422 males with hemophilia living in six U.S. states from 1993 to 1998. Heart
disease cases were ascertained from among 2,075 persons who were hospitalized at
least once during the 6-year period. Of these, 48 were diagnosed with IHD and 106, with
other types of heart disease. The age-specific prevalence of IHD ranged from 0.05% in
those under 30 years to 15.2% in those 60 years or older. Hospital discharge rates in
males with hemophilia with IHD and other types of heart disease were lower compared to
rates in age-matched U.S. males. In our cohort, as in the general population, IHD was
independently associated with age, hypertension, diabetes, and hyperlipidemia. Other
heart diseases were associated with HIV infection, hypertension, hemophilia B, and
diabetes. In summary, persons with hemophilia have unique risk factors such as infusion
of factor concentrates and infection with HIV that may predispose them to heart disease
as their life expectancy increases. Am. J. Hematol. 79:36–42, 2005.
ª 2005 Wiley-Liss, Inc.
words: hemophilia;coronary heartdisease; acutemyocardialinfarction;
Several European studies [1–3] and one U.S. study
 of cause-specific mortality have found lower rates
of death from ischemic heart disease in persons with
hemophilia compared to the general population.
These findings have been interpreted as providing
evidence that the hypocoagulable state offers protec-
tion from the thrombotic event that precipitates
infarction. An alternative explanation involving
lower prevalence of cardiovascular risk factors
among persons with hemophilia was examined in
a study by Rosendaal et al. who found that the dif-
ference in risk factors could account for only a frac-
tion of the decreased risk observed among Dutch
ª 2005 Wiley-Liss, Inc.
On the other hand, IHD and thrombosis in persons
with hemophilia are thought to be related to factor
VIII levels by some investigators [6,7]. Alsolaiman 
reported coronary artery occlusion during recombi-
nant FVIII infusion in a patient with hemophilia.
Coronary artery disease and myocardial infarction
are well-described complications in patients with
*Correspondence to: J. Michael Soucie, Ph.D., Centers for
Disease Control and Prevention, 1600 Clifton Road, MS E64,
Atlanta, GA 30333. E-mail: firstname.lastname@example.org
Received for publication 27 July 2004; Accepted 25 November
American Journal of Hematology 79:36–42 (2005)
inhibitors and are presumed to be secondary to the
administration of factor concentrates. Persons with
hemophilia who were infected with HIV through
exposure to contaminated factor concentrates receive
treatment with highly active antiretroviral regimens
that may put them at risk for premature atherosclero-
tic disease .
Circulatory disease (including acute myocardial
infarction) was the second most common cause of
death in persons with hemophilia in the United States
during the period 1995–1998 . Moreover, Soucie et
al. found an elevated risk for acute myocardial infarc-
tion (standardized mortality ratio ¼ 3.0; 95% confi-
dence interval ¼ 1.5–5.8) among all persons with
hemophilia living in six U.S. states identified as part
of the Hemophilia Surveillance System (HSS) .
Thus the diagnosis of hemophilia does not preclude
the presence of ischemic heart disease.
The purpose of this study was to determine the
prevalence of and identify risk factors for ischemic
and other types of heart disease in the hemophilia
population. We also examined hospitalization rates
to compare complication rates of heart disease among
males with hemophilia with those of the general male
MATERIALS AND METHODS
The surveillance system, case-finding methods, and
data collection procedures have been described in
detail elsewhere . Briefly, the HSS was a coopera-
tive project between CDC and the health departments
of Colorado, Georgia, Louisiana, Massachusetts,
New York, and Oklahoma, the purpose of which
was to identify and collect information about all per-
sons with hemophilia in these states. Hemophilia
cases were identified through lists obtained from phy-
sicians, clinical laboratories, hospitals, hemophilia
treatment centers (HTCs), and other sources. Demo-
graphic, clinical, treatment, and outcome information
was collected from medical records by trained data
abstractors using a standard data collection form.
The case definition was a person with physician-
diagnosed hemophilia A or B or a baseline clotting
factor VIII or IX activity of ?30%. Severity level was
categorized as mild if the activity was 6–30%, mod-
erate if 1–5%, and severe if<1% of normal. Persons
with acquired inhibitors of factor VIII in the absence
of congenital factor deficiency and carriers of the
hemophilia gene were excluded.
From January 1995 through December 1999, data
were abstracted from the medical records of persons
with hemophilia identified among residents of the six
states during the period January 1993 through
December 1998. Information collected during the
first year of follow-up was used to determine date of
birth and race.
Because persons often received medical care in
more than one setting during a year, information
collected from the records of care received in all set-
tings was aggregated prior to entry into a computer-
ized database. The results of inhibitor titer assays
were used to determine whether an inhibitor (anti-
body) to factor VIII or IX was present. Persons
with a peak inhibitor titer during the first year of
follow-up of ?1.0 Bethesda unit were classified as
having an inhibitor at baseline.
The results of all laboratory tests for hepatitis were
abstracted from medical records. A person was con-
sidered infected with hepatitis C virus (HCV) based
on a positive result from any antibody (anti-HCV)
tests performed during the surveillance period. Per-
sons were considered to be seropositive for HIV if
evidence in their medical records indicated they had
ever tested positive for HIV-1 antibody.
Information about all hospitalizations during the
study period, including dates of admission and dis-
charge, up to 5 admitting diagnoses, and as many as
10 discharge diagnoses was obtained from medical
records. Data were collected and categorized accord-
ing to the ninth revision of the International Classifi-
cation of Diseases, Clinical Modification (ICD-9)
. Discharge diagnoses for all hospitalizations dur-
ing the 6-year period were used to determine for each
person the presence of (a) ischemic heart disease
(ICD-9 codes 410–414), (b) other heart disease (420–
429), (c) hyperlipidemia (272–272.4), (d) hypertension
(401–405), and (e) diabetes (250–250.9).
The prevalence of IHD and separately of other
heart diseases was calculated by using the total num-
ber of identified prevalent cases from hospitalization
data as the numerator and the entire cohort as the
Differences in the distribution of ischemic or other
heart diseases across levels of patient characteristics
were examined in univariate analyses using chi-square
tests. Factors independently associated with ischemic
and other forms of heart disease were identified in sepa-
rate multivariate analyses using logistic regression .
We calculated an average rate of ischemic and
other heart disease discharges by dividing the total
number of discharges for each category by the num-
ber of persons in the surveillance during the 6-year
period and multiplying by 1,000 (discharges per 1,000
Heart Disease and Hemophilia 37
population). Because heart disease is closely linked to
age, we calculated rates separately for men who were
45–64 years old and for those who were 65 years and
older. For comparison, we calculated corresponding
rates among U.S. males using data from the National
Hospital Discharge Survey . All hypothesis testing
was two-tailed, with a significance level of 0.05 and all
analyses were performed using SAS statistical soft-
A total of 3,422 males with hemophilia were iden-
tified in the six states over the 6-year period of study.
Of these, 2,075 (61%) had been hospitalized at least
once during follow-up. Figures 1 and 2 show the
subclassification of ischemic and other heart diseases
listed at discharge for hospitalized patients. Of the 79
IHD listed discharges in 48 patients, 56% were
related to acute ischemic events that included acute
myocardial infarction, acute/subacute ischemic dis-
ease, and angina pectoris (Fig. 1). Of the 136 other
heart disease diagnoses in 106 patients, 28% were
related to heart failure (Fig. 2).
The age-specific prevalence of IHD in persons with
hemophilia ranged from 0.05% in those under 30
years of age to 15.2% in those 60 years or older
(Table I). Persons diagnosed with ischemic heart dis-
ease were more likely to be older, white, have hemo-
philia B, have mild disease, diabetes, hypertension,
hyperlipidemia, and be uninfected with either hepati-
tis C or HIV than those without this diagnosis. The
prevalence of other heart disease ranged from 1.3% in
those under 30 years old to 19.6% in those ?60 years
listed at discharge from among 48 persons with hemophilia
hospitalized in six U.S. states, 1993–1998 (MI, myocardial
Distribution of ischemic heart disease diagnoses
at discharge from among 106 persons with hemophilia
hospitalized in six U.S. states, 1993–1998.
Distribution of other heart disease diagnoses listed
TABLE I. Characteristics and Associations With Ischemic and
Other Heart Disease Among 3,422 Persons With Hemophilia
in the U.S.*
3.1 3,13746 97
3.0 3,40843 102
2.7 2,594 47
*Total columns do not all sum to 100% due to missing data.
38 Kulkarni et al.
(Table I). Compared to persons without a heart
disease diagnosis, those with other forms of heart
disease were more likely to be older, black, HIV
infected, have hemophilia B, diabetes, hypertension,
and hyperlipidemia. Unlike with ischemic disease,
neither hemophilia severity nor hepatitis C serostatus
was associated with other heart disease diagnoses.
Several factors were independently associated with
IHD in multivariate analyses including increasing
age, diagnosed hypertension, and diabetes (Table II).
Although the odds of having hyperlipidemia was
nearly 4 times greater for persons with hemophilia
who were diagnosed with IHD than for those with-
out this diagnosis, the relationship was of borderline
statistical significance. Compared to persons with no
other heart disease diagnoses, those with other types
of heart disease were older, more likely to have
hypertension, be infected with HIV and to have
hemophilia B rather than A. An increased likelihood
to have diabetes was of borderline statistical signifi-
The rate of ischemic heart disease discharges among
45- to 64-year-old hemophilic men was one-half that of
U.S. males (Table III). In addition, for men of age 65
years and older, IHD discharge rates for hemophilic
men were nearly 30% lower than that of U.S. males. In
contrast, rates of discharges with other heart disease
diagnoses were similar among 45- to 64-year-old men
with and without hemophilia. Lastly, discharge rates
for other heart diseases among the oldest men were
approximately 25% lower for hemophilic than for
Studies of mortality that rely on cause of death
information recorded in death records may come to
wrong conclusions. Problems with death certificate
information, including form completion errors and
lack of understanding of the definitions of both
cause and underlying cause of death, result in accu-
racy rates of about 50% . In addition, certain
causes of death have been shown to be more likely
to be incorrect. According to data from the Framing-
ham study, over a 20-year-period death records over-
estimated coronary heart disease rates by 24% overall
and may be more than double the actual rate among
those over the age of 85 . An additional complica-
tion when using death records to study mortality in
persons with hemophilia is that hemophilia must be
listed among the causes of death in order to identify
deaths that occur among this population. Persons
who die from causes unrelated to their bleeding dis-
order may be more likely to be missed because hemo-
philia may not listed as an underlying cause of death.
Finally, death from IHD in a person with hemophilia
may go unrecognized, especially if it is considered a
IHD prevalence among living populations would
be a more informative measure of occurrence, but
such data in persons with hemophilia are scarce.
None of the hemophilia patients in the Dutch
study of heart disease risk factors had overt evi-
dence of IHD, but the number of persons studied
was small . De Paz and co-workers  reported
TABLE II. Patient Characteristics Independently Associated
With Ischemic and Other Heart Disease Among 3,422 Persons
Odds ratio (95% CI)P value
Ischemic heart disease
Age (per 10-year increase)
Other heart disease
Age (per 10-year increase)
Hemophilia B (vs. A)
aFactors included in both logistic regression models are age, race
(white vs. other), hemophilia type, severity (severe vs. mild/moderate),
inhibitor, diabetes, hypertension, hyperlipidemia, and HIV and HCV
TABLE III. Hospital Discharges Among Persons With Hemophilia Living in Six U.S. States, 1993–1998, and Among U.S. Males, 2000
Ischemic heart disease discharges Other heart disease discharges
Total no. of personsAge 45–64 Age 65+Age 45–64Age 65+
Year Age 45–64 Age 65+No.Ratea
Hemophilic males (1993–1998)
U.S. males (2000)
aRate ¼ discharges per 1,000 population.
bProjected based on 1990 Census data.
Heart Disease and Hemophilia39
that 9 of 371 moderate and severe hemophilia
patients in Spain had IHD, a prevalence of 2.4%.
However, no information was provided about the
age distribution of this population. We found that
the prevalence of IHD varied from under 1%
among persons less than 40 years old to over 15%
among PWH who were 60 years and older in our
cohort. A large population-based study in a pri-
mary-care setting reported coronary heart disease
in 8% of British men over the age of 44 years .
The comparable rate in our cohort was 8.5%,
suggesting that, in fact, IHD may not be less fre-
quent in persons with hemophilia.
Importantly, despite the similar prevalence of IHD
that we found, hospital discharge rates in persons
with hemophilia with IHD were substantially lower
compared to age-matched U.S. males. This suggests
that perhaps IHD in persons with hemophilia is
accompanied by fewer complications requiring hospi-
talization than in the general population. Heart dis-
ease-related deaths in persons with hemophilia who
have never experienced symptoms of cardiac disease
while living may go undetected, especially because
suspicion may be low and autopsies are rare.
Rosendaal found no relationship between cardiovas-
cular risk factors, such as hypertension and elevated
triglycerides, and IHD in the Dutch hemophilic popu-
lation and used these data to support the hypothesis
that the low incidence of IHD in this population was
directly attributable to the coagulation defect . In
our study, persons with hemophilia with IHD were
more likely to be hypertensive, have hyperlipidemia
and were more likely to be diabetic than those without
IHD. These risk factors are the same as those identi-
fied for the general population .
abnormalities that play a major role in venous throm-
bosis have either weak or no effect in arterial disease.
This is because of the dominant role of atherosclero-
sis in arterial disease. The degree of atherogenesis
among PWH has been shown to be similar to that
in unaffected males [22,23]. In a recent review of the
role of elevated FVIII levels and the risk of thrombo-
sis, Kamphuisen et al.  concluded that high levels
of FVIII are indeed a risk factor for thrombosis,
levels of FVIII ? 150% accounted for 16% of all
venous thrombosis and levels of ?123% explained
4% of arterial thrombosis. While the role that high
levels of FVIII might play in thrombosis among per-
sons with hemophilia cannot be defined at this point,
such levels can potentially be achieved during factor
Acute coronary disease has been reported in mild
hemophilia ; whether the higher levels of FVIII
compared to severe hemophilia plays a role in the
etiology of IHD is unknown. Von Willebrand factor
levels may also play an important modifying role .
It is well known that individuals with blood group O
have lower levels of von Willebrand factor than those
with other blood types and, in patients with hemophi-
lia A, a shorter half-life of infused FVIII has been
observed in patients with type-O blood . Future
studies are needed to define the role of prothrombotic
risk factors, particularly in mild hemophilia with IHD.
We found that HIV infection and hemophilia type
were significantly associated with other forms of
heart disease. In our population, cardiac dysrhyth-
mias, cardiomyopathy, and heart failure were the
most common of these other heart disease diagnoses.
HIV-associated cardiac complications may occur
either as a result of the disease or its treatment or
due to secondary opportunistic infections. Cardiac
diseases such as dilated cardiomyopathy have been
described in 3.6% of HIV-infected patients, and
arrhythmias are a common complication of infecting
endocarditis, myocarditis, or as a side effect of anti-
retroviral drugs . High levels of FIX have been
shown to be a risk factor for thrombogenesis. In the
body, FIX is activated to FIXa by tissue factor/FVIIa
complex. High levels of FIXa, as found in prothrom-
bin complex concentrates, have been associated with
arterial and venous thromboses and accounted for the
majority of hemophilia B cases with thromboses .
Although the currently available high-purity FIX
products (including recombinant FIX) have not
been associated with an increased risk of thrombotic
events, there have been anecdotal reports of paradox-
ical venous thrombosis. Because our patient popula-
tion with IHD was older, it is possible that they may
have received non-high-purity products as a part of
their treatment. There have been excess reports of
IHD in hemophilia B, some in very young patients,
and the causes have been multifactorial . They
include under-diagnosis due to reduced life expec-
tancy, lack of exercise due to arthropathy, and possi-
ble thrombogenicity of replacement therapy.
Several limitations of the study warrant discussion.
First, we relied on hospital-discharge diagnosis infor-
mation to determine the presence of heart disease,
diabetes, and hypertension in our cohort. However,
nearly 40% of the cohort had no hospitalization dur-
ing the 6-year follow-up period. This methodology
introduced a diagnostic bias that probably had a
variable influence on our prevalence estimates,
depending on the condition. Persons with hemophilia
with either IHD or other heart disease were likely to
have had a hospitalization during the 6-year follow-
up period and also were likely to have this diagnosis
indicated in their hospitalization records. On the
other hand, those with angina, hypercholesterolemia,
40Kulkarni et al.
and other risk factors such as hypertension were
probably less likely to have been admitted and, there-
fore, more likely to have been missed by our
surveillance. In fact, at least one study has reported
a higher prevalence of hypertension in a hemophilia
cohort compared to a control population .
Second, our prevalence estimates for heart disease
were based on diagnoses that were unaccompanied
by laboratory values or other objective measures of
heart function. Without these additional data, it is
neither possible to determine the criteria used to
assign the diagnosis nor to evaluate its validity.
Therefore, our prevalence figures should be viewed
Third, the associations that we found between HIV
infection and heart disease do not necessarily imply
causality. Cardiovascular complications in HIV are
often a late manifestation and may be due to the
infection, its complications, or treatment. In the
absence of detailed data, it cannot be known with
certainty that the heart disease in HIV-infected
patients resulted from the infection.
Our data suggests that while IHD may be just as
common among persons with hemophilia as in the
general population, the rate of complications from
heart disease might be less. Physicians should be
aware that risk factors unique to the hemophilia
population, such as administration of factor concen-
trates and infection with HIV, may play a role in
the occurrence of heart disease in this population.
Future studies are needed to define the role of pro-
thrombotic risk factors, particularly in mild hemo-
philia with IHD.
The authors thank Jean Kozak, Ph.D., in the Divi-
sion of Health Care Statistics for providing additional
analysis results of the National Hospital Discharge
data. The Hemophilia Surveillance System comprises
the following institutions and persons: Centers for Dis-
ease Control and Prevention (B. Cicatello, B. Evatt,
M.D., and D. Jackson, J.M. Soucie, Ph.D.); Colorado
Department of Health (R. Hoffman, M.D., S. Michael,
R.N., and F. Nocera); Mountain States Regional
Hemophilia Center (M. Manco-Johnson, M.D., R.
Nuss, M.D., B. Riske, R.N., M.S.N, M.B.A., and J.
Stultz, M.P.H.); Georgia Division of Public Health (N.
Stroup, Ph.D.); Emory University School of Public
Health (E. Brockman, M.P.H., H. Hill, M.D., Ph.D.,
B. McDowell, T. Poindexter, M.P.H., K. Smith,
M.P.H., and S. Stein, M.D.); Louisiana State Depart-
ment of Health (C. Myers); Louisiana Comprehensive
Hemophilia Care Center (B. Bates, M.P.H., J. Bunting,
M.P.H., C. Leissinger, M.D., V. Shea, R.N., and K.
Wulff, R.N.); Massachusetts Department of Public
Health (L. Livens, J. Su, D. Walker, Ed.D., and N.
Wilber, Ed.D.); Boston Hemophilia Center (B. Ewen-
stein, M.D., Ph.D., and F. Ross); New England Hemo-
philia Center (D. Brettler, M.D., A. Forsberg, M.A.,
M.P.H., P. Geary, L.S.W., and D. Thibeault); New
York State Department of Health (M. Arrington, J.
Bartholomew, B.S.N., R.N., B. Connelly, L.P.N., B.
Cushman, R.N., B. Kearney, R.N., M. Kolakoski,
M.S., J. Lima, and J. Linden, M.D., M.P.H.); Mt.
Sinai Medical Center (E. Aulov and S. Gaynor, R.N.,
M.B.A., Dr.P.H.); Oklahoma State Department of
Health (S. Kinney, R.N., M.S.); Oklahoma Hemophi-
lia Treatment Center (H. Huszti, Ph.D., F. Kiplinger,
and C. Sexauer, M.D.); and University of Oklahoma
Health Sciences Center (N. Asal, Ph.D., L. Cowan,
Ph.D., B. Erickson, M.P.H., L. Hudson, Ph.D., C.
Smith-Edwards, M.A., S. Warner, and M. Young).
1. Rosendaal FR, Varekamp I, Smit C, et al. Mortality and causes of
death in Dutch haemophiliacs, 1973–86. Br J Hematol 1989;71:
2. Koumbarelis E, Rosendaal FR, Gialeraki A, et al. Epidemiology
of haemophilia in Greece: an overview. Thromb Haemostasis
3. Darby SC, Ewart DW, Giangrande PL, Dolin PJ, Spooner RJ,
Rizza CR. Mortality before and after HIV infection in the
complete UK population of haemophiliacs [letter]. Nature
4. Aronson DL. Cause of death in hemophilia A patients in the
United States from 1968 to 1979. Am J Hematol 1988;27:7–12.
5. Rosendaal FR, Briet E, Stibbe J, et al. Haemophilia protects
against ischaemic heart disease: a study of risk factors. Br J
6. Rice GI, Grant PJ. FVIII coagulant activity and antigen in
subjects with ischaemic heart disease. Thromb Haemost 1998;
7. Alsolaiman MM, Chang K, Arjomand H, Oza R, Costacurta G.
Acute left anterior descending artery occlusion in a hemophiliac
A patient during recombinant factor VIII infusion: treatment
with coronary angioplasty. Catheter Cardiovasc Interv 2000;
8. Sklar P, Masur H. HIV infection and cardiovascular disease—is
there really a link? (Comment) N Engl J Med 2003;349:2065–2067.
9. Chorba TL, Holman RC, Clarke MJ, Evatt BL. Effects of HIV
infection on age and cause of death for persons with hemophilia A
in the United States. Am J Hematol 2000;66:229–240.
10. Soucie JM, Nuss R, Evatt B, et al. Mortality among males with
hemophilia: relations with source of medical care. The Hemophilia
Surveillance System Project Investigators. Blood 2000;96:437–442.
11. Soucie JM, Evatt B, Jackson D. Occurrence of hemophilia in the
United States. The Hemophilia Surveillance System Project Inves-
tigators. Am J Hematol 1998;59:288–294.
12. World Health Organization. Manual of the international statisti-
cal classification of diseases, injuries, and causes of death. Based
Heart Disease and Hemophilia41
on recommendations of the 9threvision conference, 1975, and
adopted by the 29thWorld Health Assembly. Geneva, Switzerland:
World Health Organization; 1977.
13. Kleinbaum DG, Kupper LL, Muller KE. Applied regression ana-
lysis and other multivariate methods. Boston: PWS-Kent Publish-
ing Co.; 1988.
14. Kozak LJ, Hall MJ, Owings MF. National Hospital Discharge
Survey: 2000 Annual Summary with detailed diagnosis and pro-
cedure data. National Center for Health Statistics. Vital Health
15. SAS/STAT User’s Guide, Version 6. Cary, NC: SAS Institute,
16. Sehdev AES, Hutchins GM. Problems with proper completion
and accuracy of the cause-of-death statement. Arch Intern Med
17. Lloyd-Jones DM, Martin DO, Larson MG, Levy D. Accuracy of
death certificates for coding coronary heart disease as the cause of
death. Ann Intern Med 1998;129:1020–1026.
18. De Paz R, Cobo T, Garcia S, et al. Ischemic heart disease in
patients with hemophilia. [Abstract] Blood 2003;102:103b.
19. Carroll K, Majeed A, Firth C, Gray J. Prevalence and manage-
ment of coronary heart disease in primary care: population-based
cross-sectional study using a disease register. J Publ Health Med
20. Greenland P, Knoll MD, Stamler J, et al. Major risk factors as
antecedents of fatal and nonfatal coronary heart disease events. J
Am Med Assoc 2003;290:891–897.
21. Rosendaal FR. Clotting and myocardial infarction: a cycle of
insights. J Thromb Haemost 2003;1:640–642.
22. Sramek A, Reiber JHC, Gerrits WBJ, Rosendaal FR. Decreased
coagulability has no clinically relevant effect on atherogenesis:
observations in individuals with a hereditary bleeding tendency.
23. Dalldorf FG, Taylor RE, Blatt PM. Arteriosclerosis in severe hemo-
philia:a postmortem study.Arch Pathol Lab Med 1981;105:652–654.
24. Kamphuisen PW, Eikenboom JCJ, Bertian RM. Elevated factor
VIII levels and the risk of thrombosis. Arterioscler Thromb Vasc
25. Paolini R, Viero M, Pietrogrande F, Girolami A. Mild haemophi-
lia A fails to protect from coronary artery disease: the report of
two cases. Haematologia (Budapest) 1993;25:179–184.
26. Bilora F, Dei Rossi C, Girolami B, et al. Do hemophilia A and
von Willebrand disease protect against carotid atherosclerosis? A
comparative study between coagulopathics and normal subjects by
means of carotid echo–color Doppler scan. Clin Appl Thromb
27. Barbaro G, Fisher SD, Giancaspro G, Lipshultz SE. HIV-asso-
ciated cardiovascular complications: a new challenge for emer-
gency physicians. Am J Emerg Med 2001;19:566–574.
28. Au WY, Jim MH. Unusual case of coronary artery disease
in a patient with severe hemophilia B. Am J Hematol 2002;69:
29. Lowe GDO. Factor IX and thrombosis. Br J Haematol 2001;
42 Kulkarni et al.