Child with bleeding problems edited

Child with bleeding problems

Dr Neoh Hui Pheng Hospital Seberang Jaya

Normal Hemostasis

Def : consequence of tightly regulated processes that maintain blood in a fluid, clot-free state in normal vessels while introducing the rapid formation of a localized hemostatic plug at the site of vascular injury.

Mechanism vasocontriction formation of platelet plug coagulation cascade fibrinolysis

The coagulation cascade

Classification of bleeding disorder

Coagulation Vs Platelet defects

Comparing coagulation factor and platelet defects

  Coagulation factor defects Platelet disorders and von Willebrand's disease

Bruising on trunk and limbs Large bruises Small bruises

Bleeding from cuts Relatively slight Profuse

Nosebleeds Uncommon Common, frequently profuse and of long duration

Gastrointestinal bleeding Uncommon Common

Haematuria Common Rare

Haemarthrosis In severe haemophilia Very rare

Bleeding after surgery or dental extraction

Up to a day's delay before bleeding occurs Immediate bleeding

Hemophilia

Hemophilia

Defect in clotting mechanism Hemophilia A : Deficiency of Factor

VIII ( 85%) Hemophilia B : Deficiency of Factor IX ( 15%)

70 % X linked recessive. 30 % spontaneous mutation with no family hx.

Presentation:

Rarely,bleeding symptoms may present from birth ( Factor 8 and 9 do not cross placenta)

- Intracranial hemorrhage /prolonged oozing from heel stick/venepuncture sites.

- Most children present with easy bruising when crawling and walking ( ard 9-12 months)

- Hemarthrosis – characteristic. - large joints ( ankle, knee, elbow ) – swollen

and painful ( ankle joint : often the earliest joint involved. )

Presentations

Other bleeding tendencies: Epitaxis, gum bleeding , hematuria.

Bleeding can be spontaneously, after trauma , operation or dental procedures.

Lungs/ CVS / PA : unremarkable

Investigations

FBC Coagulation screen : PT/ APTT RP / LFT Specific factor assay : Factor 8 or factor 9 Von willebrand screen even if APTT

normal .Others : - Infective screen ( at diagnosis and yearly) :

Hep B/ Hep C /HIV - Platelet aggregation if highly suspicious of

platelet defect.

Classification

Classification Clinical manifestation

Severe(<1% of normal)

•Manifest in infancy when child reaches toddler stage• Spontaneous bleeding – in muscles or joints (haemarthroses)• Excessive bleeding after minor trauma, postoperatively, or after intramuscular childhood vaccinations

Moderate( 1-5% of normal)

•Manifest after 2 years of life• Moderate trauma causes bleeding episodes• Occasionally spontaneous bleeding occurs

Mild ( >5 % - < 40% of normal)

• Often diagnosed in teenagers and adults• Significant trauma/surgery or dental procedures to induce bleeding• No spontaneous bleeding

Management

First Aid ( PRICE) : Pressure, Rest, Ice, Elevation

Factor VIII /IX replacement Infuse factor 8 by slow IV push at the rate not

exceeding 100U/ min in young children. FFP and cryoprecipitate should not be

used as there is higher risk of viral transmission.

Management

Type of bleed Factor VIII dose Factor IX dose

Hemarthrosis 20U/kg 40 U /kg

Soft tissue or muscle bleeds

30-40U/kg 60-80 U /kg

Intracranial hemorrhage or Surgery

50U /kg 100 U /kg

Management ( contd)

Calculate the required dose:- Factor VIII : ( % rise reqd) x ( wt in

kg) x 0.5- Factor IX : (% rise reqd) x ( wt in kg)

x 1.4Type of bleed % rise required

duration

Haemarthroses 30-40% 2-3 days

Soft tissue /Muscle bleed( Risk of compression/compartment syndrome)

40-50% 4-5 days

Intracranial bleed /operation

100% 7-10days

management

Analgesic often not required ( as there is rapid pain relief after missing factor concentrate is infused)

- AVOID I.M injection - Don’t use Aspirin/NSAIDs – affect

platelet fx - Acetaminophen with or without

opioids can provide adequate pain control

management

Dental care is required as dental caries are a regular source of bleeding.

In severe cases, dental clearance with factor replacement will be required.

Medic alert bracelet Register with hemophilia society.

Complications

1) Joint destruction : Recurrent hemarthrosis into the same joint osteoarthritis and joint deformity.

Preventable by prompt and adequate factor 8 replacement.

2) Infection : Hep B/Hep C and HIV - All hemophiliacs must be immunised

with Hep B

Complications

3) Inhibitors: Antibodies directed against the exogeneous Factor VIII and IX neutralising the clotting activity.

Can develop at ANY age, but usually 10-20 exposure days.

Suspected when there is lack of response to replacement therapy instead of higher doses.

2 agents – “bypassing” the deficient clotting factor : i) Recombinant activated Factor VII ( rfVII or

Novoseven) ii) FEIBA ( Factor Eight Inhibitor Bypass Activity) Immune tolerance induction Refer to hematologist in specialised centres.

Immune thrombocytopenic purpura ( ITP)

Thrombocytopenia

neonatal alloimmune thrombocytopenia- Thrombocytopenia in < 6 months Sepsis and infections ( eg HIV ) Drug induced thrombocytopenia Hematological Malignancy -eg : Acute leukemia Congenital marrow failure syndromes -eg : Fanconi anemia , thrombocytopenia with absent radius Autoimmune disorders- Eg : SLE , Evan syndrome Primary immunodeficiency syndromes- Wiskott-aldrich syndrome

Immune thrombocytopenic purpura

ITP

Isolated thrombocytopenia with NORMAL blood counts in a patient, with no clinically apparent alternative cause of thrombocytopenia .

In children, ITP is an acute but self limiting that resolves spontaneously.

Autoantibodies bind to platelet membrane antigen

Increased platelet destruction Subtypes : 1) Acute ITP

2) Chronic ITP

Presentations

Usually acute onset. Majority will have h/o viral

infection in the preceding 2-4 weeks.

Can be present as mild cutaneous bleed like petechiae , to mucosal bleeds like gum bleeding or epitaxis , to life threathening bleeds like Intracranial hemorrhage.

Diagnosis

Based on history, examination and investigation.

Physical examination : Absence of hepatosplenomegaly or lymphadenopathy.

FBC : Isolated low platelet, normal Hb and TWBC

FBP : Normal, apart from reduced larger platelet, no abnormal cells.

Coagulation profile : prolonged BT, normal PT and APTT.

When to do BMA ?

Usually not require BMA, unless child present with Atypical features ( eg : Organomegaly, significant lymphadenopathy, abnormal blood counts or suspicious FBP. )

Before starting steroid therapy ( to avoid partially inducing an undiagnosed acute leukemia)

If there is failure to respond to Immunoglobulin therapy

When there is persistent thrombocytopenia more than 6 months.

Thrombocytopenia recurs after initial response to treatment.

Atypical presentations

Antinuclear factor and DNA antibodies

Coomb’s test CMV serology ( < 1 yr old ) Coagulation profile ( suspected NAI

and inherited bleeding disorder) HIV testing for those at risk ( eg

parents RVD + or IVDU ) Immunoglobulin factor for those with

recurrent infection

Management( treat the child, not the platelet count )

Most children remit spontaneously - 70% achieve platelet count > 50x 109/L by the

end of 3rd week. Careful observation with monitoring of platelet

count , without specific treatment is appropriate for patient with :

- Platelet count > 20x 109/L without bleeding - Platelet count > 30x 109/L with only cutaneous

purpura- repeat FBC within 7-10 days to ensure there is

no evidence of serious evolving marrow condition.

Advise precautions with physical activities , avoidance of contact sports and seeking immediate medical attention if bleeding occurs should be advised.

When to hospitalise?

Hospitalise the child if - Severe life threathening bleding eg

ICH regardless of platelet count - Platelet count < 20x 109/L with

evidence of bleeding - Platelet count < 20x 109/L without

bleeding but inaccessible to health care. - Parents request due to lack of confidence

in home care.

Management ( contd)

Treatment indicated if - Life threathening bleeding like ICH- Platelet count < 20x 109/L with

mucosal bleeding - Platelet count < 10x 109/L with any

bleedingChoices of treatment: i) Oral prednisolone 2mg/kg/day for

14 days then taper offii) Oral prednisolone 4mg/kg/day for 4

daysiii) IVIG 0.8mg/kg/dose for a single

dose.

Management

Note that the above mentioned regimes do not help to reduce bleeding complications or mortality or influence progression to chronic ITP.

S/E of IVIG ( 15-75%) : - fever, flushing, headache, nausea, aseptic

meningitis, transmission of Hep C ( older preparation )

Steroid should not be continued if there is no response or if there is a rapid relapse after withdrawal.

Treatment should not be directed at increasing the platelet count above a preset level but rather on the clinical status of the patient.

Chronic ITP

Persistent thrombocytopenia after 6 months of onset ( in 20% )

Wide spectrum of manifestation: - Mild asymptomatic low platelet

count -> intermittent relapsing symptomatic thrombocytopenia -> rare stubborn and persistent symptomatic and hemorrhagic disease.

Acute Vs Chronic ITP

Feature Acute ITP Chronic ITP

Peak age Children (2-6 yrs) Adults (20-40 yrs)

Female:male 1:1 3:1

Antecedent Infection Common Rare

Onset of symptoms Abrupt Insidious

Platelet count at presentation

<20 000 <50 000

Duration 2-6 weeks Long term

Spontaneous remission

Common Uncommon

management

Try to give enough time for the disease to remit spontaneously.

EXCLUDE other causes of thrombocytopenia. Asymptomatic child – Observe and conservative +

precaution in physical activity Symptomatic- short course of treatment like acute

ITP Counselling to parents- natural history of disease

and detecting symptoms and complications. Parents should be confident in taking care of child

with persistent low platelet count at home. Must know when and how to seek early medical

attention.

2nd line therapy?

For child with persistent bleeding. MUST d/w paediatric hematologist before

initiating. Pulses of steroid : - Oral dexamethasone 1mg/kg given on 4

consecutive days every 4 weeks for 4 months.

Intermittent anti-RhD Immunoglobulin treatment for Rh +ve : 45-50mcg/kg – May cause drop in Hb level.

Splenectomy is rarely indicated.

Platelet count

PT APTT Bleeding time

Thrombin time

Additional test

Hemophilia A

N N Prolonged

N Factor 8 low

Hemophilia B

N N Prolonged

N Factor 9 low

Von Willebrand’s disease

N N Prolonged or Normal

N VWF / Factor 8 low- Impaired ristocetin impaired platelet aggregation

Liver disease

Low Prolonged

prolonged

N (Rarely prolonged)

DIC Low Prolonged

prolonged

Grossly prolonged

Oral anticoagulant

N Grossly Prolonged

Prolonged

N

Heparin Normal( rarely low)

Mildly Prolonged

Prolonged

Prolonged

Case

April 2013 10 yrs old , Chinese , boy, BW : 30kgp/w : 1) pain, swelling and reduced movement for

both elbows X 2/7 2) Bruises over bilateral knee

Denies history of recent contact sports. Denies history of trauma Denies history of fall. No other bleeding tendency like epitaxis, gum

bleeding, hemetemesis, hemoptysis, hematuria, malena, petechiae or bruises at other body part.

He has had multiple previous admissions since young for joint swellings or soft tissue injury like calf swelling and bruises.

Child was previously followed up in Hospital Sultanah Aminah since 1 yr old of age.

Blood investigation during 1 yr old: - PT 11.9 - APTT 106.6 - Factor VIII <1.0% - Von Willebrand factor 103.1%

What do you think ?

Past history

He was diagnosed with Hemophilia A since 1 yr old. In 2012, he was referred to HSJ for follow up due to

logistic reason . May 2012 : right thigh swelling after a fall- Factor VIII 750U ( 30U/kg ) x 3 doses August 2012:right elbow swelling and bruises after

falling down in basketball court.- Factor VIII 750U x 15 doses September 2012 : bilateral knee bruises after

playing with a friend. - Factor VIII 750 U x 7 doses November 2012: Swelling over elbow . Admitted to

HSAH in SP. Factor VIII given, child was not admitted.

Development history: standard 4 student with average performance. ( frequent absence from school due to frequent admissions)

Family & Social history:Father is single parent. Mother is

cambodian, was told to be carrier of hemophilia. Parents already divorced. He is the only son.

o/e : Alert, pink , active and comfortable. Not dyspneic, not tachypneic. Good perfusion , good pulse volume, CRT < 2 secs. No petechiae over body. No gum bleeding/nose

bleeding.Lungs : A/E equal, clearCVS : DRNM PA : soft, not distended, no liver / spleen palpable.Local findings :both elbows slightly swollen and warm

on touch. Restricted ROM : 75-135 degrees bilaterally. Bruises over both knees. However, bilateral knee has

full ROM.

Ix : - FBC : Hb 12.8 , TWC 8.4 , Plt 414 - PT 12.6, APTT 85.5 , INR 1.0Management:- Given Factor VIII 750 U BD ( 25mg/kg/dose)

for 2 days, followed by 750U OD for 3 days. A total of 7 doses given.

- Subsequently, child had full ROM in right elbow, however, his left elbow still slightly restricted to 15-145 degrees.

TCA stat if hemarthrosis/ soft tissue bleeding / bleeding tendency.

Advise child not to take part in contact sports.

Thank you !