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Hemophilia 101 for the Advanced

Practice Nurse: It’s Easier Than You

Think

Jen Tiller, MSN RN CPNP CPHONPediatric Nurse Practitioner

Children’s Blood and Cancer Center

Dell Children’s Medical Center

Austin, Texas

jltiller@seton.org

Disclosures

• No financial disclosures

• Will discuss off-label use of medications

Objectives

• Describe basic pathophysiology of factor 8 and

factor 9 deficiencies

• Compare and contract basic factor dosing

regimens for factor 8 and factor 9 deficiencies

• Summarize recommendations for acute and

emergent concerns of the child with hemophilia

• Analyze case studies of common outpatient and

inpatient scenarios in the child with hemophilia

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The goal of coagulation: maintain

vascular integrity without

compromising patency.

Hemostasis: Platelets and Coagulation

Factors

• Vasoconstriction at the site of injury

• Platelet aggregation (primary hemostasis)

• Formation of fibrin clot (secondary hemostasis)

Image courtesy of American Heart Association, 2007

Factor 8 and Factor 9 Deficiencies

Factor VIII deficiency

• Hemophilia A –

“classic hemophilia”

• X-linked inheritance

• 80%

• 2/3 have “severe”

disease

Factor IX deficiency

• Hemophilia B –

“Christmas disease”

• X-linked inheritance

• 20%

• 50% have moderate

or mild disease

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http://www.hemophiliafed.org/uploads/hemo

philia_inheritance-father.jpg

http://www.hemophiliafed.org/uploads/hemo

philia_inheritance-both.jpg

Factor 8 and 9 Deficiencies

• Prolonged aPTT, normal PT

• Factor VIII activity assay

• Factor IX activity assay

Normal factor activity level = 50-150%

Mild = 5-24%

Moderate = 1-5%

Severe - < 1%

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Where do they bleed?

• Central nervous system – ICH, intraspinal

• Hemarthrosis – knees, ankles, elbows

• Soft tissue/Skeletal muscle – quadriceps, biceps, iliopsoas, pseudotumor, compartment syndrome

• HEENT – Epistaxis, oral bleeding, posterior pharynx

• Abdominal bleeds – Flank pain, GI tract (melena, hematemesis, intussusception, Meckel’s, AGE), retroperitoneal bleeding, iliopsoas

• GU tract – painless hematuria

Late Complications

• Joint destruction due to hemarthroses

• Transmission of blood-borne infection

• Development of inhibitor antibodies

http://www.kelleycom.com/blog/uploaded

_images/synovitis-784213.jpg

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What do all of those words mean?

• Prophylactic (AKA “prophy”) dosing – Factor replacement given on a routine schedule (i.e., 2-3 times weekly) to prevent spontaneous bleeding symptoms (50-100%)

• On-demand – only receives factor when they need it for bleeding symptoms or to prepare for surgery

• Major dose – factor replacement dose required to bring a patient’s factor 8 or 9 level to 80-100%

• Minor dose – factor replacement dose required to bring a patient’s factor 8 or 9 level to 30-50%

Why do we give factor?

• Prevent bleeding – prophylaxis (“prophy”),

planned/emergent surgery

• Treat bleeding – limit and resolve existing

bleeding symptoms

What are you treating?

• Major dose – joint bleeding, major surgery, oral surgery, intracranial hemorrhage, major trauma, intraabdominal bleeding, face/neck, some GU bleeding

• Minor dose – oral bleeding, minor surgery, some muscle hemorrhages (compartment syndrome)

• Prophy – scheduled replacement to prevent bleeding

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How do you decide how much to give?

Hemophilia A

� Replace factor VIII

� What are you treating?

� What are you trying to

prevent?

� What is baseline factor level?

� Dose calculation:

Weight in kg x desired correction

2

OR:

(Desired correction/2) x wt in kg

Hemophilia B

� Replace factor IX

� What are you treating?

� What are you trying to

prevent?

� What is baseline factor

level?

� Dose calculation:

Weight in kg x desired

correction x 1.4 = factor dose

Dosing Flow

What is your desired correction (what are you treating/preventing)?

Baseline factor level?

Factor VIII or IX deficiency?

Factor Dose

Example 1: Robert

Robert is a 21-month-old with severe factor 8 deficiency who is having major surgery this morning. He weighs 14 kg.

Correct to? � 100%

Baseline factor level?-� <1%

Factor 8 or 9 deficiency? � factor 8

Weight in kg x desired correction

2

14 [kg] x 100[%] = 1400

1400/2 = 700 units of factor 8

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Example 2: Scott

Scott is a 5 year old with mild hemophilia A who twisted his ankle at t-ball practice when he stepped in a hole. It is swollen and painful and he cannot move it. His baseline factor 8 level is 20%. He weighs 18 kg.

Correct to? � 100%

Baseline factor level? � 20% (100-20 = 80%)

Factor 8 or 9 deficiency? � factor 8

(Desired correction/2) x wt in kg

80[%]/2 = 40 [units/kg]

40 [units/kg] x 18 [kg] = 720 units

Example 3: Kyle

Kyle is a 4-year-old with severe hemophilia B who fell and bumped his lip on the curb. He weighs 20 kg.

Correct to? � 30-50%

Baseline factor level? � <1%

Factor 8 or 9 deficiency? � factor 9

Weight in kg x desired correction x 1.4 = factor dose

20 kg x 30 -50 units x 1.4 = 840 – 1400 units factor 9

Factor Products

Factor 8 Deficiency

• Advate*

• Helixate FS*

• Kogenate FS*

• Recombinate*

• Xyntha*

• Koate**

• Alphanate***

• Humate-P***

Factor 9 Deficiency

• BenefIX*

• RIXubis*

• AlphaNine SD**

• Mononine**

FEIBA NF - aPCC

NovoSeven RT - VIIa

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Adjunct Therapies

• Antifibrinolytics – oral, IV– aminocaproic acid 50-100 mg/kg q6h for 3-10 days

(do not exceed 4 gm/day)

– tranexamic acid 25 mg/kg q8h for 3-8 days (black box)

• Desmopressin – mild hemophilia A, after stimulation challenge

• Afrin, Gelfoam

• Analgesia – narcotics, Tylenol. NO ASA. NO IBUPROFEN.

• Ice, rest, EARLY PT for immobilization, crutches, wheelchair

Hemarthrosis

• Early: tingling, pain, limited ROM

• Late: Pain, swelling, decreased ROM

• Early treatment! Within 6 hours of onset

• Factor replacement, RICE, opioids, PT

GU Bleeding

• Painless hematuria: +/- IV factor replacement,

rest, fluids, NO antifibrinolytics

• Scrotal bleeding in toddlers: IV factor

replacement

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Intraabdominal Bleeding

• Large capacity for blood volume

• Peritoneal irritability

• +/- known trauma

• Abdominal pain with inability to flex at the hip

CNS Bleeding

• Spontaneous vs. trauma-induced

• Neonatal presentation

• High index of suspicion

• Bolus infusion (major dose), imaging,

continuous drip, craniotomy, evacuation of

hematoma

Rules for Emergency Care

• Intracranial/spinal

cord bleeds

• HEENT

• Intra-abdominal

• Limb compartments

• Ocular bleeds

FACTOR

FIRST.

Always.

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Rules for Emergency Care

Ask!

• Routine factor dosing?

• Has child had factor today?

• Do they have factor to take to the ER?

• What has worked best in the past?

Indications for Imaging

• Any unwitnessed fall, blow to the head, or fall

from > 3 feet requires emergent evaluation

(head CT, other imaging)

• Unexplained irritability in a pre-verbal child

• Focal neurological deficits, seizures

• Vomiting, +/- blood

• Trauma to the neck, +/- outside bruising

• Abdominal pain with inability to flex at the hip

Sports Participation and Hemophilia

• 60 minutes/day of exercise important for physical, mental, emotional health

• Young children should be encouraged to try a wide range of activities to determine what they enjoy

• Prophylactic factor administration prior to activity, conditioning and strengthening regimens, additional protective equipment

• Coach involvement, major dose at practice/activity site

• NHF: contact sports are not recommended for those with severe factor deficiencies

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http://www.hemophilia.org/NHFWeb/R

esource/StaticPages/menu0/menu2/m

enu35/menu204/PlayingItSafe.pdf

Perioperative Care

Individualized to each patient depending upon factor activity, half life of product used, surgery type, and past history of perioperative hemorrhage

– Continuous drip with timed factor activity levels

– Bolus dosing with timed factor activity levels

– Detailed discharge planning common with daily factor dosing, frequent office visits

What is an inhibitor?

�An inhibitor is an antibody (IgG) produced

against a factor 8 or 9 protein (human-derived

or recombinant) that inhibits the activity of

that clotting factor.

�Factor replacement given in an appropriate

dose not working � suspect an inhibitor

�FEIBA or NovoSeven

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Case Study #1 – Philip

Philip is a 3 year old with severe hemophilia A. His mother calls and says that he fell out of a tree and is crying and conscious. He has had no vomiting, no LOC, but she did not see him fall.

What is the first thing you should tell Reece’s mother to do?

a) Go to the ER

b) Watch for signs of ICH/ICP and call if she sees them

c) Give a prophy dose of factor

d) Give a major dose of factor

Philip

• Philip weighs 16 kg and uses Advate. How

much should his mother give him?

Case Study #2 - Tim

Tim is an 18 year old with mild hemophilia B who is in his freshman year at college in a small town. He calls you because he has had some stomach pain for the last several days and now he cannot flex his right hip. He does not remember any injury. What is your best first advice you should give Chandler?

a) Go to the ER

b) Bed rest for the next 24 hours to see if there is improvement

c) Give a prophy dose of factor

d) Give a major dose of factor

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Tim

You call ahead to the Emergency Room and

speak with the attending MD, who has never

seen a person with hemophilia. What

information do you need to have available to

give to him?

Case Study #3 - Jackson

Jackson is a 7 year old with severe hemophilia A

who had his tonsils out 24 hours ago. You are

rounding inservice today and have been assigned to

see him. He weighs 19 kg. Which of these would

you not expect to see on his orders?

a) Ibuprofen 10 mg/kg PRN pain

b) Timed factor level 30 minutes after next bolus

dose

c) Advate 350 units q 12 h with timed levels prior

to bolus dose

d) Ambulate as tolerated

Jackson

Jackson has a peak factor level drawn 30

minutes after a bolus dose with factor 8 activity

= 12%. Which of these could be the cause?

a) Aliens

b) He received the wrong dose of factor

c) He has an inhibitor

d) He is bleeding

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Case Study #4 - Dillon

Dillon is a 15 month old with severe hemophilia A who just started walking. His father calls in a panic because Dillon stumbled, hit his head on the coffee table, and now has a 2 cm gooseegg that seems to be growing bigger by the minute. He cried for a few minutes and now is eating a snack and watching a movie. What should your first advice to Dad be?

a) Put some ice on it

b) Give him a major dose of factor

c) Go to the ER

d) Wrap him in bubble wrap until he’s 18

Golden Rules of Hemophilia Care

• No ibuprofen or ASA

• Factor first, imaging/eval second

• Excessive irritability in a preverbal child –factor first, imaging second

• If you don’t know the level, presume it is ZERO

• Parents are experts!

• Nevereverever waste or throw away factor

• Treat them like a normal kid ☺

Image courtesy of National Hemophilia Foundation

www.hemophilia.org

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Image courtesy of Indiana Hemophilia & Thrombosis Center

https://www.partnersprn.org/

www.hemophilia.org

Image courtesy of Region VI Hemophilia Nursing Group

http://www.hemophilia.ca/files/Emergency%20Care.pdf

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guide to bleeding disorders (1st ed., pp. 1-8).

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[Brochure]. Quebec, Canada.

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Haemophilia in children. Accessed July 16, 2013 at

http://www.kkh.com.sg/HealthPedia/Pages/ChildhoodIllnessesHaemophilia.aspx

Hoots, W.K & Shapiro, A.D. (2013). Treatment of hemophilia. Accessed July 16, 2013 at

http://www.uptodate.com/contents/treatment-of-hemophilia

Hoots, W.K. & Shapiro, A.D. (2012). Clinical manifestations and diagnosis of hemophilia. Accessed

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of-hemophilia

National Hemophilia Foundation (2001). MASAC recommendation #112: MASAC

recommendations on improved access to emergency care for persons with inherited bleeding

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http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=57&contentid=298

National Hemophilia Foundation (2002). MASAC recommendation #132: Standards and criteris

for the care of persons with congenital bleeding disorders. Accessed July 18, 2013 at

http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=57&contentid=220

National Hemophilia Foundation (2006). MASAC recommendation #175: Guidelines for

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at

http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=57&contentid=691

National Hemophilia Foundation (2011). MASAC recommendation #204: MASAC recommendations regarding physical therapy guidelines in patients with bleeding disorders. Accessed July 19, 2013 at http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=57&contentid=1724

Osip, J., White, E., Christie, B. (2002). Prophylaxis and venous access devices. In National hemophilia foundation nurses’ guide to bleeding disorders (1st ed., pp. 1-8).

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Sharma, N.K., Sherker, A.H. (2009). Epidemiology, risk factors, and natural history of chronic hepatitis C. In

University of Illinois. The clotting process (hemostasis). Accessed July 16, 2013 at http://www.med.illinois.edu/hematology/PDF%20Files/Hemostasis.pdf

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