Tamar Fleischer, BSN, MSN, CNLCP & Mona Yudkoff, RN, MPH, CRRN, CNLCP

BalaCare Solutions

March 2018 St. Peterburg, Florida

How to Write a Life Care Plan for a Child with Hemoglobinopathy

What is Hemoglobinopathy?

• Genetic mutation abnormal hemoglobin blood disorder

• Thalassemia v. structural variant

• Thalassemia: decreased production of hemoglobin parts • Beta Thalassemia • Alpha thalassemia

• Sickel Cell Anemia • (structural variant: abnormally shaped hemoglobin chains)

• Examples: hemoglobin S, C, E etc.

When Does a Child with Hemoglobinopathy Need a

Life Care Plan?

Medical Malpractice

Deviation from standard of care during conception / prenatal period that results in a child born with a significant medical disorder.

Wrongful Birth Lawsuit

Parents or representative of a genetically / congenitally affected child claim their medical provider failed to properly warn of their risk of giving birth to a child with a serious condition.

Wrongful Birth

Elements: • Must be able to demonstrate patient-provider relationship • Provider negligently failed to disclose to prospective

parents risk of having a child with a genetic or congenital disease (deviation from standard of care)

• Plaintiff suffered harm

• Provider’s negligence caused that harm

Prenatal Screening

• Identify & counsel asymptomatic individuals whose offspring are at risk of an inherited blood disorder

• Allow parents to make reproductive choices based on definite information rather than statistical estimate

Methods: • amniocentesis (16 – 18 weeks; 0.5% risk of fetal loss) • chorionic villus sampling (10 – 12 ; <0.05% risk of fetal loss) • fetal cells in maternal circulation (noninvasive; experimental) • pre-implantation screening with in vitro fertilization

• If prenatal testing was warranted, but not offered • OR was improperly administered • OR positive results were not communicated

• AND the child has a hemoglobinopathy

• There may be grounds for a wrongful birth lawsuit

What is Hemoglobin?

• Iron-containing protein in red blood cells that carries oxygen to cells throughout body

• The iron component is called “heme;” the surrounding chains

are called “globins” • Typical hemoglobin is comprised of 2 beta globin and 2 alpha

globin chains around a heme-molecule • Hemoglobinopathy develops when there is an inappropriate

ratio or abnormal structure of these globin chains

Anemia

Most significant feature of hemoglobinopathy is anemia

• Decreased and / or abnormal production of hemoglobin anemia

• Anemia can result from inadequate production and / or increased hemolysis of RBCs

• Signs and symptoms: pallor, jaundice, lethargy, fatigue, poor growth, reduced exercise tolerance

Complications of Chronic Anemia

• Gallbladder disease: cholelithiasis; cholecystitis • RUQ abdominal pain • Cholecystectomy

• Aplastic crisis: acute viral infection (parvovirus)

• Sudden and severe drop in baseline hemoglobin • Blood transfusion

• Poor growth

• Poor linear growth, delayed puberty • Rule out endocrinopathy (growth hormone deficiency) • Consider blood transfusion

• Worsening anemia with pregnancy high risk obstetric care

recommended

Major Hemoglobinopathies Thalassemia (alpha and beta)

Sickle Cell Anemia

Alpha Thalassemia

• A group of hereditary anemias characterized by reduced or absent production of alpha globin chains

• Decreased production of alpha-globins relative excess of beta chains in each hemoglobin tetramer less stable hemoglobin (increased hemolysis)

• Mutation on chromosome 16

• Up to 4 genes can be affected • Alpha thalassemia silent carrier: 1 gene • Alpha thalassemia trait: 2 genes • Hemoglobin H disease: 3 genes • Hydrops fetalis / alpha thalassemia major: 4 genes

Alpha Thalassemia

Types of Alpha Thalassemia

• Hydrops fetalis (usually incompatible with life) • Hemoglobin H Disease • Alpha Thalassemia Trait • Alpha Thalassemia Silent Carrier

Alpha Thalassemia

Hemoglobin H Disease

• 3 out of 4 genes affected; relative excess of beta globin chains unstable tetramers called “hemoglobin H”

• Hemoglobin H tetramers hemolyze rapidly; primarily a hemolytic anemia

• Anemia (baseline Hb 7 - 10g/dl); poor growth; delayed puberty; splenomegaly; cholelithiasis; worsening anemia with infection and pregnancy

Beta Thalassemia

• Group of inherited blood disorders caused by reduced production of beta chains

• Mutations on HBB gene on chromosome 11

• Inherited in an autosomal recessive pattern

• Prognosis highly variable ranging from asymptomatic to severe

Beta Thalassemia

• Thalassemia Major / Cooley’s Anemia • Thalassemia Intermedia • Thalassemia Minor

Thalassemia Major (Cooley’s Anemia)

• Severe anemia, poor growth, jaundice, pallor, enlarged spleen, liver disease, cardiopulmonary complications, misshapen bones, osteopenia, delayed puberty

• Typically require chronic transfusions to treat severe, symptomatic anemia

• Iron overload hepatic, cardiac and endocrine problems

• Iron chelation therapy

• Splenectomy

• Possible hematopoietic cell transplant

Thalassemia Intermedia

• Mild to moderate anemia

• Possible slow growth and bone abnormalities

• Acute anemia with increased stress infection, periods of rapid growth, surgery, pregnancy

• May require periodic transfusions for management of symptomatic anemia

• Some patients may require chronic transfusions (management similar to Thalassemia Major)

Hemoglobinopathy

Sickle Cell Disease

• Hemoglobin SS, SB0Thal • Hemoglobin SC, SB+Thal

Sickle Cell Disease

• Single point mutation, Hbb gene , chromosome 11

• Sickle cell anemia – HbSS, HbSBeta0Thallassemia

• HbSC, HbSBeta+Thalassemia

• HbSE, HbSBaltimore, HbSD

• Symptoms, management, morbidity and mortality likely to vary depending on genotype

• Significant variation within each genotype for a variety of reasons, much of which we still don’t know

SCD Symptoms / Complications

• Vaso-occlusive crises (acute pain episodes)

• Splenic dysfunction; increased risk of infection

• Acute complications: splenic sequestration, acute chest syndrome, stroke

• Chronic complications: orthopedic (avascular necrosis); renal (papillary necrosis); neurologic (cerebral silent infarct), pulmonary (pulmonary hypertension, nocturnal hypoxemia)

Hemoglobinopathy

General Management

• Regular hematological follow up • Penicillin prophylaxis (SCD) • Vaccination (PPV23, MCV) • Folic acid supplementation • Fever management • Routine serum studies • Periodic imaging • Specialist visits (ophthalmology, cardiology, endocrinology,

audiology, renal, orthopedics, pulmonology) • Hospitalizations (infection, VOC, splenic sequestration, ACS) • Blood transfusions (acute and chronic)

Tips For Drafting a LCP

• Expert hematologist: • Severity • Frequency of follow up • Routine imaging and serum studies • Hospitalizations • Chronic transfusions • Morbidity • Mortality

• History to date

Case Study: S.E.

• 2yo female with Hemoglobin H Disease

• Southeast Asian type, consistent with non-transfusion dependent thalassemia; mild to moderate

• Expert hematologist opined that S.E. will likely require chelation therapy beginning at 40 years of age

Childhood (2 to 21 years old)

Item Frequency Unit Cost Cost Hematology Visit

2 / year

$145

$290 annual

Specialists Visit

1 / year

$145

$145 annual

Venipuncture / Lab Studies (CBC, CMP, ferritin)

2 / year

$183

$366 annual

Folic acid 1mg

1 / day

$0.20

$73 annual

Echocardiogram

5 times

$2,668

$13,340 once

Liver MRI R2

2 times

$3,938

$7,876 once

Counseling Services

75 sessions

$80

$6,000 once

Early Adulthood (21 – 39)

Item Frequency Unit Cost Cost Hematology Visit

2 / year

$145

$290 annual

Specialists Visit

1 / year

$145

$145 annual

Venipuncture / Lab studies (CBC, CMP, ferritin)

2 / year

$183

$366 annual

Folic acid 1mg

1 / day

$0.20

$73 annual

Echocardiogram

1 / 4 years

$2,668

$13,340 once

Liver MRI R2

1 / 4 years

$3,938

$7,876 once

Counseling Services

30 sessions

$80

$2,400 once

Later Adulthood (40 – 82)

Item Frequency Unit Cost Cost

Hematology Visit

4 / year

$145

$290 annual

Specialists Visit

2 / year

$145

$145 annual

Venipuncture / Lab Studies (CBC, CMP, ferritin)

4/ year

$183

$366 annual

Folic acid 1mg

1 / day

$0.20

$73 annual

Echocardiogram

1 / year

$2,668

$13,340 once

Liver MRI R2

1 / year

$3,938

$7,876 once

Counseling Services

30 sessions

$80

$2,400 once

Chelation Therapy (Deferasirox)

1 / day

$160

$58,400 annual

Costing Sources

• Treating providers; local hospitals • Office visits • Laboratory studies / Venipuncture • Imaging studies

• National websites • Medications (Goodrx.com)

• Local agencies • Counseling services

Case Study: J.A.

• 6 yo male with HbSS

• Baseline hemoglobin 8 – 9g/dL

• Hospitalizations: 8 to date; 7 for fever; 1 for pain

• ED visits: 4 to date; 1 for broken arm; 3 for pain

• Prescribed Hydroxyurea

Childhood (6 to 21 years old)

Item Frequency Unit Cost Cost Hematology Visit 4 / year $161 $644 annual Specialist Visit 2 / year $161 $322 Venipuncture / Lab studies (CBC, CMP, U/A, fetal Hb)

4 / year

$208

$832

Hospitalizations 5 days / year $7,428 $37,140 Echocardiogram 1 / 2 year $2,341 $1,171 Transcranial doppler 1 / year $1,334 $1,334 Counseling Services 75 sessions $130 $9,750 once Penicillin VK, 250mg 2 / day $0.32 $239 Folic acid, 1mg 1 / day $0.10 $36 Hydroxyurea, 400mg 1 / day $84 / 90 caps $336 Specialty vaccinations (PPV23, MCV, Bexsero)

6

$85

$510

Adulthood

Item Frequency Unit Cost Total Cost

Hematology Visit 4 / year $149 $596 annual

Specialist Visit 2 / year $149 $596 annual

Venipuncture / Lab studies (CBC, CMP, U/A, fetal Hb)

4 / year

$208

$832 annual

Hospitalization, day 5 / year $7,428 $37,140 annual

Hydroxyurea, 1,500mg 1 / day $1.42 $1,551 annual

Folic acid, 1mg 1 / day $0.10 $36 annual

Echocardiogram 1 year $2,341 $2,341 annual

Counseling Services 75 sessions $130 $9,750 annual

Genetic Counseling once $450 $450 once

High Risk Pregnancy twice $6,500 $13,000 once

Costing Sources

• Treating providers; local hospitals; billing records • Office visits • Laboratory studies / Venipuncture • Imaging studies

• National websites • Medications (Goodrx.com)

• Local agencies • Counseling services

References

• Benz, E. (2018, January 8). Clinical manifestations and diagnosis of the thalassemias. https://www.uptodate.com/index.html

• Galanello, R. (2010). Beta-thalassemia. Orphanet Journal of Rare

Diseases. 5:11 • Schrier, S. (2017, July 19). Pathophysiology of alpha

thalassemia. https://www.uptodate.com/index.html • Yates, A. (2018, January 8). Prenatal screening and testing for

hemoglobinopathy. https://www.uptodate.com/index.html • National Institute of Health (2014) Evidence based management of

sickle cell disease: expert panel report 2014. https://www.nhlbi.nih.gov/health-topics/evidence-based-management-sickle-cell-disease