Capstone Project..YF .8.17.2014 (1)

MPH and MD/MPH Degree Program

1

Yendi Fontenard

THE HEMOPHILIA TRIUMPH -‐ THE SOLUTION TO SICKLE CELL DISEASE CHAGRIN

Foundation for Sickle Cell Disease Research

August 2014


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ABSTRACT

Hemophilia and Sickle Cell Disease (SCD), both inherited blood disorders meet the criteria for

rare diseases in the United States with respective prevalence of approximately 20,000 and

100,000. An examination of the infrastructure as well as intangible resources facilitating care

coordination and standardization of care of both diseases shows a skewed reality, in favor of

Hemophilia. For both diseases, care coordination is paramount to ensuring quality of life; yet to

date, this has only come to fruition for Hemophilia through a federally funded nationwide

network of established comprehensive treatment centers. The disconnect among stakeholders

in the SCD community has repeatedly been highlighted as a contributing factor. As a result, the

Foundation for Sickle Cell Disease Research (FSCDR) is striving to address the ineptitude of the

existing SCD climate through their grant proposal to United Health Foundation for support for a

Sickle Cell Care Network (SCCN) -‐ Certification Makes a Difference Program. The goal of this

paper is to make an argument in support of this program by highlighting the unmet needs of

the SCD population as well as the success of Hemophilia Treatment Centers.


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Table of Contents

Summary Statement ..................................................................................................................... 4

Capstone Project Objectives ......................................................................................................... 5

Sickle Cell Disease .......................................................................................................................... 6

Hemophilia .................................................................................................................................. 13

FSCDR’s proposed program ......................................................................................................... 16

Conclusion ................................................................................................................................... 21

Reference List .............................................................................................................................. 22


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SUMMARY STATEMENT

The Foundation for Sickle Cell Disease research (FSCDR) is a non-‐profit organization located in

Florida, committed to sickle cell disease research to confer the highest quality of life possible to

these patients. Their hope is to establish a robust research and funding portfolio for sickle cell

disease but their efforts transcend a typical research organization as their mission also supports

non-‐clinical sickle cell work. Of note, FSCDR serves physicians, allied health professionals,

pharmaceutical companies, biotechnology companies as well as patients. Their work has

inspired me to support one of their recent proposals, a Sickle Cell Care Network (SCCN) -‐

Certification Makes a Difference Program. This paper will add to the body of literature

highlighting the dearth of resources hampering improvements in the quality of life of SCD

patients and will hopefully facilitate a break in the cycle of mediocrity that continues to plague

this population.


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OBJECTIVES

This project will address the following:

1. Highlight the current deficits in care provided to sickle cell patients

2. Compare and contrast the current Sickle Cell Disease climate with that of Hemophilia

3. Examine FSCDR’s proposed solution: “Sickle Cell Advisory Council, the Sickle Cell Care

Network™ (SCCN) – Certification Makes a Difference program”


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SICKLE CELL DISEASE

Sickle Cell Disease (SCD), deemed the most common inherited blood disorder in the

United States (US), is the umbrella term for a group of inherited red blood cell disorders.

Although the exact prevalence in the US is unknown, it affects approximately 90,000-‐100,000

with a predilection for Blacks (Centers for Disease Control and Prevention, CDC 2014). The

incidence of the disease is 1 in every 500 and 1 in 36,000 Black Americans and Hispanic

Americans respectively, with the Sickle Cell Trait occurring 1 in 12 Blacks (CDC, 2014).

Although type and severity of presentation is diverse, SCD is the result of inheritance of

Sickle (S) Hemoglobin (Laurence, George, and Woods, 2006) through a single point mutation in

the sixth position of the Beta Hemoglobin chain (Carroll, Haywood, Hoot, and Lanzkron, 2013).

Sickle Cell Anemia, the most common form of the disease, and more scientifically, SS genotype,

is the result of the inheritance of two abnormal hemoglobin alleles. This lends itself to

significant polymerization of hemoglobin and distortion of red blood cells into sickle-‐shaped

cells under certain conditions. A cascade of events and interactions, including hemolysis, hyper-‐

viscosity and hypo-‐perfusion has the potential to impede the function of every major organ

system (Carroll et al., 2013). Notably, the phenotypic variability of the disease is significant

ranging from relatively mild and asymptomatic to clinically severe with multi-‐organ failure

including; strokes, limb ulcers, acute chest syndrome, infections, avascular necrosis,

retinopathy, priapism, pulmonary embolism renal failure, and untimely death (CDC, 2014;

Sheth, Licursi, & Bhatia, 2013).


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Regardless of phenotypic expression, SCD is typically progressive with irreversible organ

damage (Sheth et al., 2013). Often, chronic anemia, impaired growth, episodic pain crises, renal

dysfunction, neuro-‐psychiatric abnormalities and life threatening complications (acute chest

syndrome, splenic sequestration, infarctive strokes) present themselves in infancy and

childhood. Thereafter, adolescence and adulthood are plagued with a myriad of complications

including chronic pain, leg ulcers, pulmonary embolism, hemorrhagic strokes and organ failure

(Sheth et al., 2013). Figure (1) below, puts the scope of clinical manifestations from childhood

through adulthood into further perspective.

Figure 1. Complications of SCD: childhood and adulthood. Reprinted from “Management of sickle cell disease

from childhood through adulthood by J. Kanter & R. Kruse-‐Jarres 2013, Blood Reviews, 27(2013) 279-‐287:

Copyright (2013) by Elsevier. Reprinted with permission.


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A hallmark of SCD is pain (Kanter & Kruse-‐Jarres 2013); medically described as vaso-‐

occlusive crises (VOCs), its unpredictability and potentially crippling nature has made it the best

described phenomenon associated with the disease (Carroll et al.,2013). Further, it is

undisputed that high utilization of emergency rooms and significant morbidity are attributed to

these painful phenomena (Okam, Shaykevich, Ebert, Zaslavsky, and Ayanian, 2014). Some

patients have expressed these crises as a daily battle; one that many have difficulty

comprehending which leads to them being branded as fabulists and drug-‐addicts (Weisberg,

Balf-‐Soran, Becker, Brown, and Sledge, 2013). Needless to say, patients and providers have an

onerous task managing this disease. The clinical course notably diverse, calls for comprehensive

care that is ongoing, patient-‐centered and delivered by a multidisciplinary team (Raphael &

Oyeku 2013).

Improvement in Life expectancy is a matter of utmost concern for any chronic disease,

SCD being no exception. Hassell (2010) demonstrated in Figure (2) below, that due to progress

made in treatment of the disease, a comparison of mortality rates in individuals with SCD

between 1979 vs. 2006 shows: 1) a shift in the mortality curve to the right and 2) that the shape

of the curve has remained the same.


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Figure 2. Age at death for individuals with SCD in 1979 and 2006. Reprinted from “Population estimates of sickle

cell disease in the U.S. by K.L.Hassell,2010, American Journal of Preventive Medicine, 38(4 Suppl):S512-‐21.

Copyright (2010) by Elsevier. Reprinted with permission.

Due to increased infection prophylaxis (penicillin antibiotics) against opportunistic infections

(e.g. streptococcus pneumonia) in childhood, mortality rates in early childhood have improved.

Of note, the dramatic rise in mortality rates previously occurring in infancy and the second

decade of life has merely shifted to the third decade. While over 90% of children are

progressing to adulthood, this elucidates health care providers’ incompetence and or neglect in

ensuring seamless pediatric to adulthood transition and care (Sheth et al., 2013). Does rarity of

the disease have anything to do with it or has ignorance allowed an exploitation of a subset of

our population?


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Aside from ensuring longevity, ensuring a high quality of life is imperative. A review of

this metric utilizing 39 studies was quite alarming, concluding that “adults and children with

sickle cell disease have significantly impaired health-‐related quality of life that is comparable to

or worse than other chronic diseases…even in their baseline state of health (Panepinto &

Bonner, 2012).” Many echo that compared to their unaffected peers, their physical, social and

school functioning is significantly lower; one study stating that functionality is lower by 58%,

70% and 48% respectively (Roth, Krystal, Manwani , Driscoll, and Ricafort 2012).

Additionally, to date, there is one curative therapy, namely Hematopoietic Stem Cell

Transplantation (HSCT) (Kanter & Kruse-‐Jarres 2013). Why then is there not 100% cure rate?

HSCT, requires transplantation of bone marrow of a patient with SCD with healthy bone

marrow from a donor, largely limited to individuals with a matched sibling donor (MSD)

(Shenoy, 2011), with only 14-‐20% of individuals with SCD have a matched sibling donor. First

performed in a patient with both SCD and leukaemia, its widespread use has been hindered

understandably so by the lack of a suitable donor and the risk of transplant associated

morbidity and mortality (Sheth et al., 2013). While there is no unanimity regarding indications

for HCST, it has historically been administered to patients with debilitating symptomology with

children being favored. The rationale is that they have less end-‐stage organ damage and lower

risk for transplant-‐related morbidity (Sheth et al., 2013). As a result, a mere 600 individuals

have undergone HSCT despite a marked reduction in transplant related infections, graft failure,

graft-‐versus host disease, long-‐term organ toxicity and death (Sheth et al., 2013).


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With the possibility of a cure improbable for the majority, the approach to SCD patients

involves precautionary, supportive and reactionary management (Sheth et al, 2013). The

mainstay of treatment involves relief of pain, prevention of likely infections, organ damage,

strokes and the control of any complications (Kanter & Kruse-‐Jarres 2013). Complicating

management further is the fact that there is no conclusive way to predict the clinical trajectory

in any one patient (Sheth et al., 2013).From infancy and childhood, prophylaxis generally

involves routine vaccinations, antibiotics, monitoring of growth and their academic

achievement (Kanter & Kruse-‐Jarres 2013).

Pain, an often recurring event as highlighted earlier, may require care in an urgent care

setting, as an in-‐patient, or if mild enough, at-‐home or as an outpatient. Pharmacological and

non-‐pharmacological modalities of treatment are often utilized; Severe pain requires parenteral

infusions of opioid analgesics (morphine) in tandem with non-‐opioids such as non-‐steroidal

anti-‐inflammatory drugs (NSAIDS), acetaminophen and psychotropic drugs (tranquilizers,

stimulants) (Raphael & Oyeku 2013). Warm compresses and relaxation techniques may also be

used (Kanter & Kruse-‐Jarres 2013).

If the complexity of the disease was not realized prior to reading this brief, there is no

question that by now it is. What then is the status quo of provision of care and utilization of

care in the United States? Available data suggests that SCD-‐related complaints account for

approximately 113,000 admissions per year with an estimated cost of approximately 488

million in-‐patient costs alone, in the United States (Steiner & Miller, 2006). Further, the disease

has resulted in 30% of individuals on disability and a startling 50% unemployment rate


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(Ballas, Bauserman, McCarthy, Waclawiw; Multicenter Study of Hydroxyurea in Sickle Cell

Anemia, 2010). If an accurate numerical value could be given for loss of productivity secondary

to hospitalizations and morbidity, it would surely surpass the aforementioned millions (Sheth et

al., 2013). Additionally, analysis of data from the National Hospital Ambulatory Medical Care

Survey (NHAMCS) from 1999-‐2007 stated approximately 197,333 emergency room (ER) visits

with SCD listed as a diagnosis occurred each year. This pales in comparison to the total number

of ER visits per year but yet still, Lanzkron, Carroll, and Haywood (2010) demonstrated that

“charges for hospital admissions from emergency departments for SCD are on a similar order of

magnitude to conditions over 100 times more common.” This is a significant contribution for a

“rare disease” and makes this a matter of utmost public health concern.

To avert these high hospitalization patterns for SCD and many other chronic illness, a

push for patient-‐centered medical homes (PCMH) are at the forefront of health care reform

(Raphael & Oyeku 2013). As described by Raphael & Oyeku (2013), “the PCMH can be

envisioned as a multidisciplinary team of providers focused on the patient’s needs, with care

functions and team processes coordinated through integrated health information technology.”

While this may not be a panacea for decreasing the burden SCD has on the health care system,

its adoption and implementation nationwide are sin qua non. If the cited facts throughout this

paper aren’t cause for heightened efforts to improve the status of SCD nationwide, a glimpse

into the success of hemophilia will surely do so.


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HEMOPHILIA

Hemophilia is the umbrella term for a group of rare inherited bleeding disorders due to

a mutation in the genes responsible for the production of blood clotting factor proteins

(Franchini and Mannucci, 2012). Hemophiliacs have lower than normal levels of either Factor

VIII (Hemophilia A) or Factor IX (Hemophilia B), both integral for blood clotting. Like SCD, the

clinical manifestations of Hemophilia are varied, and more specifically classified as mild,

moderate and severe. (Franchini and Mannucci 2012). The inheritance mechanisms, causes the

disease to have a predilection for males with the prevalence in females much lower (CDC,

2013). In the United States, the disease prevalence is estimated at 20,000 (significantly lower

than SCD) with an incidence of 1 in 5,000 male births and approximately 400 afflicted births per

year (CDC, 2013).

Hemophiliacs are at risk for spontaneous bleeding or bleeding at a site of injury with the

potential for marked disability and mortality if left unchecked (Soucie, Nuss, Evatt, Abdelhak,

Cowan, Hill, Kolakoski, and Wilber, 2000). Similar to SCD is the potential for multi-‐organ

involvement with bleeding sites including the nose, the skin, the mouth, joints and internal

organs (CDC, 2013). Ironically, complications may arise from the disease itself as well as its

treatment (infusions of replacement factor concentrates and other clotting agents) (Soucie et

al., 2000). Advancements in care over the years have led to increased longevity but with

concomitant complications including: joint damage from recurrent hemarthroses, transfusion-‐

transmitted infections, increased risk of development of inhibitors secondary to transfusions,


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adverse reactions from clotting factor treatments, and brain damage secondary to intracranial

bleeding (Philipp, 2010).

The complexity and chronicity of the disease requires comprehensive treatment with a

multidisciplinary approach (CDC, 2013). Advocacy for this disease resulted in the initiation of

the national Hemophilia Treatment Center (HTC) program in 1975. And today, there is a

network of over 100 HTCs throughout the United States and its territories, providing a host of

services including: diagnosis, clinical management, individual treatment plans, orthopedic care,

dental care, patient education and counseling (Soucie et al., 2000). Figure (3) below shows the

distribution of these centers.

Figure 3.Distribution of Hemophilia Treatment Centers. Reprinted from Hemophilia Management: Collaborating

in a new era to optimize by the National Hemophilia Foundation,2006. Retrieved from

http://www.managedcarehemo.com/resources.html#2. Reprinted with permission.


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Figure (3) reminds us that rarity of a disease is not synonymous with lack of awareness

and lack of advancement. The success of these programs is laudable as the socioeconomic

benefits to hemophiliacs utilizing their services are substantive (Smith and Levine, 1984; Soucie

et al., 2000). Longevity has been afforded to many through improvements in care as evident by

the proportion of hemophilia A and B patients recently surveyed at HTCs that are 65 years and

older (2%) and 45 years and older (15%) (Philipp, 2010). Further, hemophiliacs who utilize an

HTC have a 40% reduction in risk of death compared to those who do not, which is “even more

remarkable because HTCs provide health care services to a higher proportion of severely

affected patients as well as to a disproportionate share of patients with severe liver disease,

HIV infection, and AIDS-‐the primary risk factors for mortality in this population (Soucie et al.,

2000).”

Healthcare is very costly for any Hemophiliac and even further for those with certain

nuances to the typical disease manifestation. In 2008, mean health care expenditures for all

males averaged US $155,136 and costs for individuals with Hemophilia A with an inhibitor (to

the blood clotting factor) were 4.8 times higher than that for non-‐inhibitor patients ($696,279

versus $144,306) (Guh, Grosse, McAlister, Kessler, and Soucie, 2012). In light of this, HTCs

individualize treatment plans for their patients and place a premium on preventive medicine

service (Soucie et al., 2000). Improvement in mortality has also been attributed more

specifically to HTCs’ emphasis on prevention, through their promotion and facilitation of “home

factor-‐infusion” as prophylaxis and early treatment of bleeding episodes. Home factor-‐infusions


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have also been recognized for their role in reducing hemophilia-‐related musculoskeletal

damage, pain, school absenteeism and under-‐treatment associated with hospital care. This

practice is pervasive among patients who receive care at HTCs (61%) compared to those who do

not (25%) (Soucie et al., 2000).

Additionally, it is well documented that insurance is a predictor of health outcomes for

individuals with special healthcare needs. Of note, higher levels of insurance coverage have

been documented among Hemophilia patients seen at HTCs (Baker, Riske, Voutsis, Cutter,

and Presley, 2011). And the provision of social services as part of HTCs’ multidisciplinary team

surely plays an integral role here.

FSCDR’s PROPOSED PROGRAM

HTCs have undoubtedly been crucial in the progress made with Hemophilia and FSCDR

recognizes the potential to achieve similar successes with SCD through a similar concept. The

foundation is seeking funding for the development of a Sickle Cell Advisory Council, Sickle Cell

Care Network™ (SCCN) – Certification Makes a Difference Program. The foundation’s rationale

is that presently there is no single organization with regulatory power in the United States

overseeing the many private and hospital affiliated treatment centers in individual states.

Comprehensive care is a model of health care facilitating the coordinated interaction of medical

and non-‐medical services with patients. FSCDR believes that an agency providing oversight is

indispensable for any comprehensive program especially one involving geographically dispersed

centers. The goal of this project, if funded, is to improve the current delivery of care for

patients, and address the disadvantages accompanying “a rare disease” namely: 1) lack of


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standardized care, 2) national data rigged with inconsistencies that lack external validity and 3)

funding shortage.

The goal of Sickle Cell Care Network™ (SCCN) – Certification Makes a Difference

Program is to create a national sickle cell disease comprehensive care network of certified

programs for the entire East coast of the US including 3 Florida centers, as this coast accounts

for the majority of the SCD population. Figure (4) below illustrates the estimated distribution of

SCD in the United States with clear indication of its heightened prevalence along the East Coast.

Figure 4. Estimated number of individuals with SCD, based on state-‐specific African-‐American and Hispanic birth-‐

cohort disease prevalence and 2008 U.S. Census population, corrected for early mortality. Reprinted from

“Population Estimates of Sickle Cell Disease in the U.S.,” by K.L. Hassell, 2010, American Journal of Preventive

Medicine, 38(4), S512–S521. Copyright 2010 by Elsevier Inc. Reprinted with permission.


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The outcomes that this program hopes to fulfill are a reflection of the current SCD climate in

the United States, one in which patients are disadvantaged by a highly fragmented system and

include: 1) evaluation, improvement and standardization of sickle cell treatment facilities, 2)

establishment of a Sickle Cell Disease Registry, 3) development of a relevant education program

for patients, health care professionals and the public to create informed participation and

support treatment centers and, 4) establishment of a healthcare expected value analysis model

to follow Sickle Cell Disease throughout the lifespan.

A decision is as good as the information that informs it, and without a national registry

in particular, progress with sickle cell disease will remain stagnant. How do we truly make

strides with prevention and control of the disease, if nationally we lack accurate health

statistics (disease prevalence, morbidity, mortality)? Recognized nationally as an issue

perpetuating health disparities among individuals with Sickle Cell Disease the US Department of

Health and Human Services, outlined a number of objectives in “Healthy People 2020” related

to this. The result was a collaborative effort among the CDC, NIH and 7 states (California,

Florida, Georgia, North Carolina, New York, Michigan and Pennsylvania) called “Registry and

Surveillance System for Hemoglobinopathies (RuSH)” project launched in 2010 (CDC, 2014).

RuSH was designed to collect prevalence, morbidity and mortality data for SCD and

Thalassemia. (CDC, 2014). FSCDR was the designated Florida organization so continuing this

effort beyond RuSH seems logical.


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FSCDR hopes that the registry will capture additional information including; patient

distribution, social assimilation of patients, availability of treatment and other patient services,

qualification and availability of appropriate human resources and payment mechanisms. The

data collected will allow the foundation to serve as an advisory council to establish protocol for

standardization of sickle cell centers. This protocol will include metrics such as: 1) numbers of

patients to be served, 2) types of treatments available, 3) professional staff required 4)

reciprocal relationships with multiple disciplines-‐ hospitals, social services, employment, and

insurers.

This may seem insurmountable, but the foundation has all intent on seeking external

expertise. For instance, one consulting institution would be the Florida Institute for Health

Innovation’s (FIHI) Center for Collective Impact. They will provide FSCDR with the planning,

implementation strategy, facilitation and technical assistance for the different states. FSCDR’s

call for action has been endorsed by a number of stakeholders and Table (1) below gives insight

into the location and target population of potential participants of the proposed program.


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Table 1. Sickle Cell Programs to participate in FSCDR’s

INSTITUTION SCD POPULATION

Georgia Regents University (Georgia) 650 children

adolescents-‐adults

St. Jude Children’s Research Hospital (Tennessee) 900 children

University of Alabama Division of Pediatric Hematology and

Oncology (Alabama)

>1300 patients

University of Miami Miller School of Medicine Sickle Cell Center

(Miami, Florida)

500 children

400 adults

Jawan Ayer-‐Cole Private Practice (Tampa, Florida) Not indicated

Diggs Kraus Sickle Cell Center (Tennessee) 650 patients

Bronx-‐Lebanon Hospital Center (New York) primarily pediatric, small

adult component

University of Louisville Division of Hematology/Oncology and

Sickle Cell Transplantation (Kentucky)

250 children

Carolinas Healthcare System (North Carolina) not indicated

Medical University of South Carolina (MUSC)

(South Carolina)

children

Children’s Healthcare of Mississippi (Mississippi) 1000 children, 600 adults


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Support of Sickle Cell Care Network™ (SCCN) – Certification Makes a Difference

Program needs to go beyond the aforementioned institutions and be nationwide. The

cooperation of stakeholders as well as sustainable funding is necessary to catapult progress

with the management of SCD. We cannot attribute the dearth of successes to rarity of the

disease, as success with Hemophilia dispels this. Let us not allow this disease to be another

prime example of health disparities experienced by U.S census defined racial minority groups. It

is irrefutable that social constructs (race, socio-‐economic status) form part of the web of

causation of health disparities, but this FSCDR endorsed program gives an opportunity to

dampen its influence.

CONCLUSION

Improved well-‐being of SCD patients on the population level will ultimately be a

reflection of successful implementation of Sickle Cell Care Network™ (SCCN) – Certification

Makes a Difference Program. Previously unmeasurable and/or inaccurate, the program

components will allow measurement of this indicator. As I see it, support for this program

would be mutually beneficial. My advice to anyone who frowns upon this proposal is to first

have a conversation with those individuals who inadvertently inherit the disease and those

passionate about its eradication. The public health costs of the disease outlined are nothing

short of alarming and refusal to support this proposed program will allow crippling of

potentially able-‐bodied individuals in our society.


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REFERENCE LIST

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prophylaxis in U.S. youth with severe hemophilia. American Journal of Preventive Medicine,

41(6 Suppl 4), S338-‐45. doi:10.1016/j.amepre.2011.09.002.

Ballas, S. K., Bauserman, R. L., McCarthy, W. F., Waclawiw, M. A., & Multicenter Study of

Hydroxyurea in Sickle Cell Anemia. (2010). The impact of hydroxyurea on career and

employment of patients with sickle cell anemia. Journal of the National Medical

Association, 102(11), 993-‐999.

Carroll, P. C., Haywood, C. J., Hoot, M. R., & Lanzkron, S. (2013). A preliminary study of

psychiatric, familial, and medical characteristics of high-‐utilizing sickle cell disease

patients. The Clinical Journal of Pain, 29(4),317-‐23. doi:10.1097/AJP.0b013e3182579b87.

Centers for Disease Control Prevention. (2011). Sickle cell disease: Data & statistics. Retrieved,

2014, Retrieved from http://www.cdc.gov/ncbddd/sicklecell/data.html

Centers for Disease Control Prevention. (2013). Hemophilia: Data & statistics. Retrieved, 2014,

Retrieved from http://www.cdc.gov/ncbddd/hemophilia/data.html

Centers for Disease Control Prevention. (2014). Hemophilia treatment centers. Retrieved, 2014,

Retrieved from http://www.cdc.gov/ncbddd/hemophilia/HTC.html

Centers for Disease Control Prevention. (2014). Registry and surveillance system for

hemoglobinopathies (RuSH). Retrieved, 2014, Retrieved from

http://www.cdc.gov/ncbddd/hemoglobinopathies/rush.html


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Guh, S., Grosse, S. D., McAlister, S., Kessler, C. M., & Soucie, J. M. (2012). Healthcare

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Lanzkron, S., Carroll, C. P., & Haywood, C.,Jr. (2010). The burden of emergency department use

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