BLEEDING DISORDERS

By: Siti and Nurul

OBJECTIVES

1) Classify causes of bleeding disorders
2) Clinical approach in making a diagnosis
3) Review of certain bleeding conditions
4) Discuss the current treatment strategies



BLEEDING
DISORDER
S
Platelet
disorder
Reduced
count
Normal
count
Coagulatio
n factor
disorder
Inherited
Acquired
CAUSES OF BLEEDING DISORDERS
PLATELET
DISORDER
Reduced platelet count Normal platelet count
Increased
platelet
destruction
or
consumptio
n
Impaired
platelet
production
Platelet
dysfunctio
n
Vascular
disorders
INCREASED PLATELET DESTRUCTION OR CONSUMPTION
Immune Immune thrombocytopenia purpura
Systemic lupus erythematosus
Alloimmune neonatal thrombocytopenia

Non-
immune
Haemolytic uremic syndrome
Disseminated intravascular coagulation
Thrombotic thrombocytopenic purpura
Congenital heart dz
Giant haemangiomas (Kasabach-Merritt syndrome)
Hypersplenism
i) Platelet count reduced
Neonatal Alloimmune Thrombocytopenia
a disease that affects fetuses and newborns.
Genetic differences between the fetus and mother may result in
the expression of certain antigens by fetal platelets, not
expressed by the mother.
Fetomaternal transfusions result in the recognition of these
antigens by the mother's immune system as non-self, with the
subsequent generation of allo-reactive antibodies which cross the
placenta.
NAIT, hence, is caused by transplacental passage of maternal
platelet-specific alloantibody and rarely human leukocyte antigen
(HLA) allo-antibodies (which are expressed by platelets) to
fetuses whose platelets express the corresponding antigens.
Thrombotic thrombocytopenic purpura (TTP)
a blood disorder that causes blood clots to form in small blood vessels
around the body and leads to a low platelet count
D/t problems with a certain enzyme (ADAMTS13 aka von Willebrand
factor-cleaving protease) that involved in blood clotting cause clotting to
occur in an abnormal way.
As the platelets clump together in these clots, fewer platelets are
available in the blood in other parts of the body to help with clotting
lead to bleeding under the skin and purpura.
In some cases, the disorder is inherited and patients are born with
naturally low levels of this enzyme.
This condition also may be related to:
Bone marrow transplantation
Cancer
Chemotherapy
Hematopoietic stem cell transplantation
HIV infection
Hormone replacement therapy and estrogens
Medications (including ticlopidine, clopidogrel, guinine, and cyclosporine A)
KasabachMerritt syndrome (KMS)
aka Hemangioma with thrombocytopenia
is a rare disease, usually of infants, in which a vascular tumor leads
to decreased platelet counts and sometimes other bleeding
problems which can be life-threatening
When these tumors are large or are growing rapidly, sometimes
they can trap platelets, causing severe thrombocytopenia.
The combination of vascular tumor and consumptive
thrombocytopenia defines KMS.
Tumors can be found in the trunk, upper and lower extremities,
retroperitoneum, and in the cervical and facial areas.
This consumptive coagulopathy also uses up clotting factors, such
as fibrinogen which may worsen bleeding DIC
Hemolytic anemia secondary to microangiopathic destruction
(physical damage) of the RBCs can be expressed as mild,
moderate, or severe

Hypersplenism
an overactive spleen.
The spleen helps filter old and damaged cells from
bloodstream. If it is overactive, it removes the blood cells too
early and too quickly.
The spleen plays an important role in helping body fight
infections.
Problems with the spleen can make one more likely to
develop infections.
Causes:-
Thalassemia
Cirrhosis
Lymphoma
Malaria
Tuberculosis
Various connective tissue and inflammatory diseases

IMPAIRED PLATELET PRODUCTION
Congenital Fanconi Anaemia
Wiskott-Aldrich syndrome
Bernard-Soulier syndrome

Acquired Aplastic anaemia
Marrow infiltration e.g. leukaemia
Drug-induced

i) Platelet count reduced <cont>
Aplastic anemia
is a syndrome of bone marrow failure characterized by
peripheral pancytopenia and marrow hypoplasia.

Fanconi anemia
is the most common inherited form of aplastic anemia
due to an abnormal gene that damages cells, which keeps
them from repairing damaged DNA.
To inherit Fanconi's anemia, a person must get one copy
of the abnormal gene from each parent (autosomal
recessive)
The condition is usually diagnosed in children between 2
and 15 years old.

Wiskott-Aldrich syndrome (WAS)
is a condition with variable expression, but commonly
includes immunoglobulin M (IgM) deficiency.
an X-linked recessive genetic condition; therefore, this
disorder is found almost exclusively in boys.
always causes persistent thrombocytopenia and, in its
complete form, also causes:-
small platelets,
Atopy (eczema)
cellular and humoral immunodeficiency
increased risk of autoimmune disease and hematologic
malignancy.
Congenital platelet function defects
Congenital platelet function defects are bleeding disorders
that cause reduced platelet function, even though there are
normal platelet counts.
People with these disorders usually have a family history of a
bleeding disorder that causes prolonged bleeding after minor
cuts or surgery, or easy bruising.
Bernard-Soulier syndrome occurs when platelets lack a
substance that sticks to the walls of blood vessels. This
disorder may cause severe bleeding.
Glanzmann's thrombasthenia is a condition caused by the
lack of a protein needed for platelets to clump together. This
disorder may also cause severe bleeding.
Platelet storage pool disorder (aka platelet secretion
disorder) is due to one of several defects that cause easy
bleeding or bruising. It is caused by the faulty storage of
substances inside platelets. These substances are usually
released to help platelets function properly.
ii) Platelet count normal
PLATELET DYSFUNCTION
Congenital Rare disorders e.g. Glanzmann thromboasthenia

Acquired Uraemia
Cardiopulmonary bypass

Uremia
a clinical syndrome associated with fluid, electrolyte, and
hormone imbalances and metabolic abnormalities, which
develop in parallel with deterioration of renal function.
Uremia more commonly develops with chronic renal
failure (CRF) or the later stages of chronic kidney
disease (CKD), but it also may occur with acute renal
failure (ARF) if loss of renal function is rapid.
Toxins, such as parathyroid hormone (PTH), beta2
microglobulin, polyamines, advanced glycosylation end
products, and other middle molecules, are thought to
contribute to the clinical syndrome.
Severe complications of untreated uremia include seizure,
coma, cardiac arrest and death.
Spontaneous bleeding can occur with severe uremia and
may include gastrointestinal (GI) bleeding, spontaneous
subdural hematomas, increased bleeding from any
underlying disorder, or bleeding associated with trauma.

Cardiopulmonary bypass
Over the past 2 decades, postoperative thrombocytopenia
a/w CABG has been brought to the attention of cardiac
surgeons and hematologists because this complication is not
uncommon and can seriously undermine the recovery of
patients.
Among several causes of postoperative thrombocytopenia,
heparin-induced thrombocytopenia with thrombosis
(HITT) and thrombotic thrombocytopenic purpura (TTP) have
been identified as 2 pathologic conditions that can result in
high morbidity and mortality.
These complications are often associated with various life-
threatening thrombotic syndromes and their diagnoses may
be difficult at the onset of signs and symptoms.
Clinical presentations of these 2 diseases are almost
identical, although their treatments should be different.
In both, thrombocytopenia occurs within a few days after
CABG, and thrombotic syndromes (ie, gangrene of the toes
and fingers) develop in association with progressive
thrombocytopenia.

ii) Platelet count normal <cont>
VASCULAR DISORDERS
Congenital Rare disorders e.g. Ehlers-Danlos, Marfan
syndrome, hereditary haemorrhagic telangiectasia

Acquired Meningococcal & other severe infections
Vasculitis e.g. Henoch-Schonlein purpura, systemic
lupus erythematosus
Scurvy

COAGULATION FACTOR
DISORDER
INHERITED ACQUIRED
Hemophilia A and B Disseminated
intravascular
coagulation
Von Willebrand disease

Liver disease
Other factor deficiencies Vitamin K deficiency /
warfarin overdose
CLINICAL
APPROACH TO A
BLEEDING CHILD
History Taking
Age of onset (first episode?)

Neonate - in 20% of haemophilias, bleeding occurs in
the neonatal period, usually with intracranial
haemorrhage or bleeding after circumcision
Toddler - haemophilias may present when starting to
walk
Adolescent - von Willebrand disease may present with
menorrhagia


Location / pattern of bleeding

Muscle & joint : coagulation defect
(characteristic of haemophillia)
Mucosa (gum, nose) & skin : epistaxis
poorly controlled? Unilateral?
Scarring and delayed haemorrhage -
suggestive of disorders of connective tissue,
e.g. Marfan syndrome, osteogenesis
imperfecta or factor XIII deficiency.

Type of bleeding
Purpura, prolonged bleeding from superficial cuts,
epistaxis, GI bleeding, menorrhagia : platelet
disorder, thrombocytopenia or von Willebrand dz

Precipitating cause
If spontaneous: severe defect
Crawling / walking?
Cuts? Trauma?
Surgery?


History Taking - rationale
Bruising and bleeding disproportionate to injury?
Large or palpable bruising?
Frequency & duration of bleeding
Quantify bleeding
Associated symptoms
Infection URTI
Menorrhagia pad changes <2h, menses >7days,
>1 menstrual period/month
Recent medications? NSAID (aspirin), cytotoxic,
anticoagulant (Heparin, Warfarin)
Nutritional status? scurvy, decrease hepatic
synthesis
Medical hx (underlying dz)
Presence of chronic dz e.g. liver / renal dz?
Connective tissue dz e.g. Ehlers danlos

Surgical hx
Dental extraction, tonsillectomy, circumcision excess
bleeding?
Bleeding immediately after surgery indicate defective
platelet plug formation
Bleeding after some hours indicate failure of platelet plug
stabilisation by fibrin dt coagulation defect
Family hx
Detailed family tree required history of bleeding disorder?
Gender of affected relatives (if all boys, suggests haemophilia)

1. Sex-linked recessive (hemophilia A, B)
2. Autosomal recessive (clotting factors deficiency 2, 5, 7, 10,
11, 13)
3. Autosomal dominant (von Willebrand, qualitative platelet
disorders)

Negative hx does not exclude a hereditary cause e.g. about
1/3 of hemophilia cases have negative family hx (mutations)
Petechiae
-a small (1-2mm) red or purple
spot on the body, caused by a
minor hemorrhage (broken
capillary blood vessels)
Purpura
-red or purple discolorations on
the skin that do not blanch on applying
pressure
-measure 310 mm
-caused by bleeding underneath the skin
Petechiae and purpura
INFECTION
Meningococcemia

Group A strep

Atypical measles

Rocky mountain spotted
fever

Echovirus 9, 4, 7

Epstein-Barr virus

Coxsackie virus A 9

NON-INFECTIOUS
Normal platelets
- Henoch Scholein purpura
- Coagulation disorders
- Trauma

Low platelets
- Immune
thrombocytopenic
purpura
- Leukemia

Physical Examination
General stability, vital signs
Look for:
Anaemia: BM failure, leukemia
Telangiectasia of lips: hereditary haemorrhagic
telangiectasia (HHT)
Significant lymphadenopathy: leukemia, viral (ITP)
Stigmata of chronic liver dz: jaundice, clubbing,
palmar erythema, spider naevi

Detailed mucocutaneous exam
Skin stigmata: petechiae, purpura, ecchymosis, hematoma

Hepatosplenomegaly
Musculoskeletal examination for bleeding and
extensibility
Joint exam for range of motion and effusions
If suspicious for non-accidental injury, assess for childs
motor developmental milestones
PLATELET
DISORDER
IMMUNE
THROMBOCYTOPENIC
PURPURA (ITP)
What is thrombocytopenia ??
Platelet count less that 150 X 10
9
/ L
Lifespan of a platelet is 7 10 days & normal count
for all ages is 150 450 X 10
9
/ L

Severity:
50 150 X 10
9
mild (low risk of bleeding)
20 50 X 10
9
moderate (bleed during op/ trauma)
< 20 X 10
9
severe (risk of spontaneous bleeding)

Definition of ITP
Isolated thrombocytopenia with otherwise normal blood
counts in a patient with no clinical apparent alternate
cause of thrombocytopenia e.g. HIV infection, SLE,
lymphoproliferative disorders, alloimmune
thrombocytopenia & congenital or hereditary
thrombocytopenia

Pathogenesis
Increased platelet destruction by antiplatelet IgG
autoantibodies
In 80% of children, ITP is an acute, self-limiting
disorder (resolves spontaneously within 6-8
wks)

*Reduced platelet count compensatory
increase of megakaryocytes in the bone marrow

Clinical Features
Most child present between 2 10 yo
Onset often acute
Majority gave history of viral infection in the
preceding 24 wk
Spectrum of bleeding
Cutaneous: petechiae, purpura
Mucosal bleeds: gum bleeds & epistaxis
Life threatening bleeds: intracranial
hemorrhage
Diagnosis
Diagnosis of exclusion
Based on history, physical examination, blood counts,
peripheral blood smear
Physical examination: no lymphadenopathy or
hepatospenomegaly
Blood counts: isolated thrombocytopenia, normal Hb &
white cell count
Peripheral blood picture: normal apart from reduced, larger
platelets, no abnormal cells
Bone marrow aspiration is indicated:
Atypical clinical features e.g. anaemia, neutopenia,
hepatosplenomegaly, marked lymphadenopathy
exclude acute leukaemia or aplastic anaemia

Before starting steroid therapy avoid partially inducing
an undiagnosed acute lymphoblastic leukaemia (ALL)

If theres failure to respond to immunoglobulin therapy

When persistent thrombocytopenia > 6 months

Thrombocytopenia recurs after initial response to
treatment
Other tests when theres atypical presentation
Antinuclear
factor and DNA
antibodies
Coombs
test
CMV
serology
(those < 1 yo)
Coagulation
profile
(non-accidental
injury, inherited
bleeding disorder)
HIV testing
(parents HIV
+ve / IVDU)
Immunoglobuli
n levels (those
with recurrent
infections)
Management
Most can be managed at home & not require
admission
Hospitalization if:
Platelet count < 20 X 10
9
/ L with evidence of bleeding
Platelet count < 20 X 10
9
/ L without evidence of
bleeding but inaccessible to health care
Parents request dt lack of confidence in homecare

Advices:
Precautions with physical activities
Avoid contact sports
Immediately seek medical attention if bleeding occurs
Treatment is indicated when:
Life threatening bleeding episode e.g. Intracranial
hemorrhage regardless platelet count
Platelet count < 20 X 10
9
/ L with mucosal bleeding
Platelet count < 10 X 10
9
/ L with any bleeding

Choice of treatment:
Oral prednisolone 2 mg/kg/day X 2/52 then taper off
Oral prednisolone 4 mg/kg/day X 4/7
IV immunoglobulin 0.8 mg/kg/dose for a single dose
* IV anti-Rh(D)
*Platelet transfusions are reserved for life-threatening
hemorrhage as they raise the platelet count only for a
few hours
Chronic ITP
Persistent thrombocytopenia after 6 months of
onset (occurs in 20%)

Wide spectrum of manifestations:
Mild asymptomatic low platelet counts
Intermittent relapsing symptomatic
thrombocytopenia
Rare stubborn and persistent symptomatic &
hemorrhagic dz
Management
Treatment is mainly supportive
Counseling & educate patient & caretakers regarding
natural history of dz and how to detect problems and
possible complications early

Drug treatment (second line therapies) only for
chronic persistent bleeding that affects daily
activities or impairs quality of life
Pulses of steroids: oral Dexamethasone 1 mg/kg given
on 4 consecutive days every 4 weeks for 4 months
Intermittent anti Rh(D) immunoglobulin treatment for
those who are Rh D +ve : 45-50 g/kg.
may cause drop in Hb levels
HAEMOLYTIC
UREMIC
SYNDROME
What is HUS ??
characterized by progressive renal failure that is
associated with microangiopathic hemolytic
anemia and thrombocytopenia.

most common cause of acute renal failure in children

Pathogenesis: the primary event is damage to
endothelial cells

Cardinal lesion is composed of arteriolar and capillary
microthrombi (thrombotic microangiopathy) and red blood
cell fragmentation (schistocyte)
Clinical Features
From history
prodrome of fever,
bloody diarrhea (2-7 days before the onset of renal
failure)
Irritability, lethargy
Seizures
Acute renal failure
Oliguria / anuria

On examination,
Pallor, often severe
Hypertension
Edema, fluid overload

Schistocyte
-a fragmented part of a red blood cell
(irregularly shaped, jagged and
asymmetrical)
Treatment
Meticulous attention to salt and water balance
Aggressive nutritional support e.g. total
parenteral nutrition
Symptomatic
Tx of high blood pressure
Tx seizure
Kidney failure dialysis
Anaemia blood transfusions
Bleeding platelet transfusions

DISSEMINATED
INTRAVASCULAR
COAGULATION (DIC)
SYSTEMIC ACTIVATION
OF COAGULATION PATHWAY
Thrombosis of small
and midsize vessels
with organ failure
Bleeding
Intravascular
deposition of fibrin
in microvasculature

Consumption & depletion of
platelets and coagulation factors

Circulatory
collapse e.g.
in
meningococcal
septicaemia or
extensive
tissue damage
from trauma or
burns
Severe
sepsis
Shock
Common clinical conditions associated
with DIC



Obstetrical
complication
s
Amniotic fluid
embolism
Abruptio
placentae
Immunologic
disorders
Severe allergic
reaction
Transplant rejection
Sepsis
Escherichia coli
Nisseria
meningitidis
Malaria
Vascular
disorders

Trauma
Head injury
Fat embolism
Reaction to
toxin
Snake venom
Drugs
Malignancy
Lung, prostate,
pancreatic
Features
Predominant clinical features:
Bruising
Purpura
Hemorrhage

Pathophysiological process is characterised by
microvascular thrombosis & purpura fulminants
may occur


Diagnosis
Microangiopathic haemolytic anaemia
Thrombocytopenia
Prolonged prothrombin time
Prolonged activated partial thromboplastin
time
Low fibrinogen
Raised fibrinogen degradation products and
D-dimers
Reduction in naturally occurring
anticoagulants, protein C and S and
antithrombin
Schistocyte

Treatment approaches
Treat underlying cause (usually sepsis)
Tx complications (hypoxia, dehydration, acidosis, acute renal
failure)

If bleeding, replete coagulation factors
Fresh frozen plasma 2 U (to replace clotting factors)
Cryoprecipitate 10 U
Platelet transfusion

If thrombosis, anticoagulation with IV heparin
COAGULATION
FACTOR DISORDER
Normal haemostasis
Haemostasis describes the normal process of
blood clotting. It takes place via a series of
tightly regulated interactions involving cellular
and plasma factors.
There are five main components:
i. Coagulation factors - are produced (mainly by
the liver) in an inactive form and are activated
when coagulation is initiated (usually by tissue
factor (TF), which is released by vessel
injury;
ii. Coagulation inhibitors - these either circulate
in plasma or are bound to endothelium and
are necessary to prevent widespread
coagulation throughout the body once
coagulation has been initiated
iii. Fibrinolysis - this process limits fibrin
deposition at the site of injury due to activity of
the key enzyme plasmin
iv. Platelets - are vital for haemostasis as they
aggregate at sites of vessel injury to form the
primary haemostatic plug which is then
stabilised by fibrin
v. Blood vessels - both initiate and limit
coagulation. Intact vascular endothelium
secretes prostaglandin I
2
and nitric oxide
(which promote vasodilatation and inhibit
platelet aggregation). Damaged endothelium
releases TF and procoagulants (e.g. collagen
and von Willebrand factor) and there are
inhibitors of coagulation on the endothelial
surface (thrombomodulin, antithrombin and
protein S) to modulate coagulation.
Haemophilia
Table 22-3. Investigations in haemophilia A and von Willebrand disease
PT, prothrombin time;
APTT, activated partial thromboplastin time;
RiCoF, ristocetin co-factor, measures vWD
activity.


Haemophilia A



von Willebrand
disease
PT Normal Normal
APTT or normal
Factor VIII:C or normal
vWF Antigen Normal
RiCoF (activity) Normal
Ristocetin-induced
platelet aggregation
Normal Abnormal
vWF multimers Normal Variable
Severity of haemophilia
Factor VIII:C Severity Bleeding tendency
<1% Severe Spontaneous
joint/muscle bleeds

1-5% Moderate Bleed after minor
trauma

>5-40% Mild Bleed after surgery

Definition
A group of blood disorders in which there is a
defect in the clotting mechanism.
Of X-linked recessive inheritance, but in 30%
there is no family history as it is a spontaneous
new mutation.
The most common haemophilias are:
Haemophilia A Deficiency of factor VIII (85%
cases)
Haemophilia B Deficiency of factor IX (15%
cases)
Clinical Manifestation

Bleeding in the neonatal period is unusual.
Usually presents with easy bruising when crawling
and walking (9-12 months age).
Haemarthrosis is characteristic of haemophilia.
Large joints are usually affected (knee, ankle,
elbow); swollen, painful joints are common.
Epistaxis, gum bleeding, haematuria also occur.
Intracranial haemorrhages can be life threatening.
Bleeding may also occur spontaneously or after
trauma, operation or dental procedures.
Severe arthropathy from recurrent
joint bleeds in haemophilia.
The aim of modern management is
to prevent this from occurring.
Diagnostic Investigations

Full blood count
Coagulation screen: PT, APTT
Specific factor assay: FVIII level (low in
Haemophilia A)
Specific factor assay: FIX level (low in
Haemophilia B)
Bleeding time if applicable.
Von Willebrand screen even if APTT normal.

Once a child is diagnosed to have haemophilia, check the viral
status at diagnosis and then yearly. This is because treatment
carries the risk of acquiring viruses. All haemophiliacs should
be immunized against Hepatitis B.
Treatment
1) Prophylactic
Ideally, treatment of severe
haemophilia should be to
prevent arthropathy and ensure
the best quality of life possible.
The dosage of prophylaxis is
usually 25-35 U/kg of Factor
VIII concentrate, given every
other day or 3 times a week.
For Factor IX, the dosage is 40-
60 U/kg, given every 2-3 days.
However, this form of
management is costly and
requires central venous access.
2) On demand treatment
clotting factors are
inadequate.
replacing the missing
factor
Factor VIII concentrates
are used in haemophilia
A,
Factor IX concentrates in
Haemophilia B


Fresh frozen plasma and
cryoprecipitate ideally SHOULD
NOT be used as there is a high
risk of viral transmission.

Dose of factor required can also be calculated using the
formulas below
Units of Factor VIII: (% rise required) x (weight in kg) x 0.5.
Units of Factor IX: (% rise required) x (weight in kg) x 1.4.

The percentage of factor aimed for depends on the type
of bleed.
For haemarthroses, 30-40 % is adequate.
For soft tissue or muscle bleed aim for 40- 50 % level.
(there is potential to track and cause compression/ compartment
syndrome)
For intracranial bleeds or patients going for surgery, aim for
100%.

Infuse Factor VIII by slow IV push at a rate not exceeding
100 units per minute in young children.
Factor VIII is given every 8 - 12 hours.
Factor IX is given every 12 - 24 hours.

Duration of treatment depends on type of bleed:
Haemarthroses 2-3 days.
Soft tissue bleeds 4-5 days.
Intracranial bleeds or surgery 7-10 days.

Veins must be handled with care.
Never perform venous cut-down unless in an
emergency as it destroys the vein.
Complications
A. Joint destruction:
Recurrent haemarthroses into the same joint will
eventually destroy the joint causing osteoarthritis and
deformity.
This can be prevented by prompt and adequate factor
replacement.

B. Acquisition of viruses
Hepatitis B, C or HIV: immunisation and regular
screening recommended.

C. Inhibitors:
These are antibodies directed against the
exogenous factor VIII or IX neutralizing the clotting
activity.
Overall incidence is 15-25% in haemophilia A and 1-
3% in haemophilia B.
Can develop at any age but usually after 10 20
exposure days. It is suspected when there is lack of
response to replacement therapy despite high
doses.
Treatment requires bypassing the deficient clotting
factor. Currently 2 agents are available -
Recombinant activated Factor VII (rfVIIa or
Novoseven) and FEIBA.
Immune tolerance induction is also another option.
Management of inhibitors are difficult and requires
consultation with the haematologist in specialized
centres.

Supportive Treatment
Analgesia
There is rapid pain relief in haemarthroses once missing
factor concentrate is infused.
If analgesia is required, avoid intramuscular injections.
Do not use aspirin or the non-steroidal anti-inflammatory
drugs (NSAIDS) as they will affect platelet function.
Acetaminophen with or without opioids can provide
adequate pain control.

Dental care
Good dental hygiene is important as dental caries are a
regular source of bleeding.
Dental clearance with factor replacement will be required
in severe cases.



Immunisations
This is important and must be given: The
subcutaneous route is preferred.
Give under factor cover if haematomas are a
problem.

SPECIFIC GUIDELINES FOR MANAGEMENT
1) Intracranial haemorrhage (ICH)
Give factor replacement before suspected bleed is confirmed
by CT scan
Aim to increase Factor VIII level to 100%.
For haemophilia B if monoclonal factor IX is used a level of
80% is adequate and if prothrombin complex concentrate
(PCC) is used 50% level is recommended.
Urgent CT scan:
If CT scan confirms ICH : maintain factor level 80%100%
for 17 days and 50% for 821 days.
If CT scan show no evidence of ICH, admit 1 day for
observation.
Follow up for long term sequelae.
Lab investigations:
Pre-treatment factor assay level and inhibitor level
before starting treatment and to repeat after 3
days of treatment to ensure adequate levels have
been achieved and no inhibitor has developed.
Post treatment factor assay level ( hour after
infusion ) to ensure required factor level is
achieved ( if the level is not achieved , consider
development of inhibitors ) and should be
repeated after 3 5 days.
follow up CT scan after 2 weeks

2. Surgery
Pre-op investigations
Full coagulation profile PT, PTT
Pre-factor assay level and inhibitor level
Blood grouping, full antibody screening and full cross
matching if required.
Calculate dose
hour before operation, infuse patient with appropriate
factors.
Preferable level :
80-100% for factor VIII
70% for monoclonal factor IX
50% if prothrombin complex concentrate (PCC) used
Check post transfusion specific factor level hour later if
necessary or after surgery to ensure correct factor level is
achieved.
Clotting factor level should be maintained above
50% during the operation
and 24 hours after surgery.
Maintain adequate factor levels
Days 1-3 60-80%
4-7 40-60%
8-14 30-50%
Repeat factor assay and check inhibitor level on
day 3 to ensure adequate levels. Post
operatively a minimum of 10 to 14 days
replacement therapy is recommended.
3. Illiopsoas bleed
Symptoms: Pain/discomfort in the lower abdomen/upper
thighs
Signs: Hip flexed, internally-rotated, unable to extend
Danger: Hypovolaemia, large volumes of blood may be lost in
the retroperitoneum.

Management:
Factor replacement: 50U/kg stat, followed by 25U/kg bd till
asymptomatic, then 20U /kg every other day for 10-14 days.
Ultrasound / CTscan to diagnose.
Physiotherapy - when pain subsides.
Repeat U/S to assess progress.

4. Haematuria

Bed rest.
Hydration (1.5 x maintenance).
Monitor for first 24 hours: UFEME & Urine C&S.
If bleeding persists for > 24 hours, start factor
concentrate infusion.
Perform KUB & Ultrasound of the kidneys.
DO NOT give anti-fibrinolytic drugs (tranexamic acid)
because this may cause formation of clots in the tubules
which may not recanalize.
5. Haemarthroses (Joint haemorrhages)

Most spontaneous haemarthroses respond to a single infusion
of factor concentrate. Aim for a level of 30 % to 40%.
If swelling or spasm is present, treatment to level of 50% is
required and infusion may have to be repeated at 12-24 hours
interval until pain subsides.
Minor haemarthroses may not require immobilization, elastic
bandage or slings and ice may help in pain relief.
Severe haemarthroses Splint in position of comfort.
Rest.
Early physiotherapy.


von Willebrand
disease (vWD)
Von Willebrand factor (vWF) has two major roles:
It facilitates platelet adhesion to damaged endothelium
It acts as the carrier protein for FVIII:C, protecting it from
inactivation and clearance.

quantitative or qualitative deficiency of von Willebrand
factor (vWF).

This causes defective platelet plug formation and,
since vWF is a carrier protein for FVIII:C, patients with
vWD also are deficient in FVIII:C

autosomal dominant


Clinical features
Bruising
Excessive, prolonged bleeding after surgery
Mucosal bleeding such as epistaxis and
menorrhagia.

In contrast to haemophilia, spontaneous soft
tissue bleeding such as large haematomas and
haemarthroses are uncommon.
Management
Treatment depends on the type and severity of the
disorder
Type 1 vWD -DDAVP,
secretion of both FVIII and vWF into plasma.
used with caution in children <1 year of age as it can cause
hyponatraemia due to water retention and may cause seizures,
particularly after repeated doses, and if fluid intake is not strictly
regulated.
More severe types of vWD - plasma-derived FVIII
concentrate
Intramuscular injections, aspirin and non-steroidal anti-
inflammatory drugs should be avoided in all patients with
vWD.
Vitamin K
deficiency
Acquired disorders of
coagulation
The main acquired disorders of coagulation affecting
children are those secondary to:
Haemorrhagic disease of the newborn due to vitamin K
deficiency

Liver disease

ITP (immune thrombocytopenia)

DIC (disseminated intravascular coagulation)

Vitamin K is essential for the production of active
forms of factors II, VII, IX, X and for the production
of naturally occurring anticoagulants such as
proteins C and S.

Vitamin K deficiency therefore causes reduced
levels of all of these factors.

The main clinical consequence of this is a
prolonged prothrombin time and an increased risk
of bleeding

This disorder can occur early, during the first week
of life, or late, from 1 to 8 weeks of age.

Children may become deficient in vitamin
K due to:
Inadequate intake (e.g. neonates, long-
term chronic illness with poor intake)

Malabsorption (e.g. coeliac disease, cystic
fibrosis, obstructive jaundice)

Vitamin K antagonists (e.g. warfarin).

Mild haemorrhage
Bruising
haematemesis
Melaena
prolonged bleeding of the umbilical stump or
after a circumcision.
However, some suffer from intracranial
haemorrhage, half of whom are permanently
disabled or die.
Prevention
Intramuscular vitamin K on the 1
st
day of life (0.5
to 1 mg)

Vitamin K should be given to all newborn
infants to prevent haemorrhagic disease of
the newborn.