Approach to a Bleeding Disorder

By: Hailemariam Bekele

Hayelom Michael
Outline
Introduction
History taking
Physical finding
Investigation
References

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 Introduction
Bleeding, technically known as hemorrhaging, is
the loss of blood escaping from the circulatory
system.
Bleeding can occur internally, where blood leaks
from blood vessels inside the body, or externally,
either through a natural opening such as
the mouth, nose, ear, urethra, vagina or anus, or
through a break in the skin.

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 Bleeding arises due to either traumatic injury,
underlying medical condition, or a combination.
'Medical bleeding' denotes hemorrhage as a
result of an underlying medical condition
Blood can escape from blood vessels as a result
of 3 basic patterns of injury:
Intravascular changes - changes of the blood
within vessels (e.g. clotting factors)

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 Intramural changes - changes arising within the
walls of blood vessels (e.g. aneurysms)
Extravascular changes - changes arising outside
blood vessels (e.g. infection)
Certain medical conditions can also make
patients susceptible to bleeding.
These are conditions that affect the normal
"hemostatic" functions of the body.
Hemostasis involves several components.
The main components of the hemostatic system
include platelets and the coagulation system.
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 Bleeding disorders
Inherited disorders

Acquired disorders

Inherited disorders: Coagulation Factor Deficiencies

Platelete disorders

Acquired disorders: Liver disease , Vitamin- k deficiency,

Anticoagulants,Platelet abnormalities

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History taking
For most hemorrhagic conditions, history plays
an important role in diagnosing the cause.

For a hemorrhagic condition the history should

determine the site or sites of bleeding, the
severity and duration of hemorrhage, and the age
at symptom onset.

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 Was the bleeding spontaneous or after trauma?
Does bruising occur spontaneously?
One should determine if symptoms correlate with
the degree of injury or trauma. Are there lumps
with bruises for which there is minimal trauma?
Was there a previous personal or family history
of similar problems?
recent transfusion?

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 Contd
If there has been joint pain, swelling or limitation of
movement
If there has been bleeding from umbilical stump
If there has been previous surgery or significant dental
procedures, was there any increased bleeding?
Delayed or slow healing of superficial injuries may
suggest a hereditary bleeding disorder.
In postpubertal females, it is important to take a careful
menstrual history.
Medications such as aspirin, other non- steroidal anti-
inflammatory drugs or herbal medications.
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Note:
Once the child is beyond the neonatal period, thrombotic
symptoms are relatively rare until adulthood.

In the neonate, physiologic deficiencies of procoagulants

and anticoagulants cause the hemostatic mechanism to be
dysregulated

Even in the absence of a family history, the presence of

thrombosis in the child or teenager should trigger an
evaluation of the individual for a hereditary or acquired
predisposition to thrombosis.
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 Non-steroidal anti-inflammatory drugs such as
ibuprofen, mefenamic acid, etc. and aspirin inhibit
platelet function whereas anticonvulsants,
antihistaminics, antituberculous drugs especially
rifampicin are known to cause
thrombocytopenia.

The overall health of the patient also is a clue to

the cause of bleeding. Congenital bleeding
disorders and ITP usually occur in children who
are otherwise well.
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 Physical Examination
Physical examination offers further clues to the
diagnosis

Is it bleeding? e.g. fixed drug eruption, erythema

nodosum, viral exanthem and mosquito bites The
examination should determine the presence of
petechiae, ecchymoses, hematomas, hemarthroses, or
mucous membrane bleeding.

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 Patients with defects in platelet/blood vessel wall
interaction usually have mucous membrane
bleeding; petechiae on the skin and mucous
membranes; and small, ecchymotic lesions of the
skin sometimes associated with hematomas.

Individuals with a clotting factor deficiency such

as factor VIII or factor IX deficiency have
symptoms of deep bleeding into muscles and
joints with much more extensive ecchymoses and
hematoma formation.
10/6/2017 approach to pediatrics bleeding disorders 14
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 Petechiae are pathognomonic of platelet-related
bleeding
Bruises in any area that appear excessively large
for the degree of trauma or those with underlying
palpable hematomas may be seen in patients with
significant bleeding disorders
Swelling of any joint without a history of
significant trauma is definitely abnormal.
Similarly, deep tissue and intramuscular bleeds
should prompt the diagnosis of a coagulation
factor deficiency
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 If it is bleeding, then is it localized or generalized?
A single site involved, it is more likely to be a
localized bleeding rather than a generalized
bleeding disorder
If generalized, is it platelet type or coagulation
type of bleeding? Is it congenital/hereditary or
acquired disorder? Symptoms of a longer
duration are indicative of a congenital disorder
such as von Willebrand Disease (vWD) or
coagulation-factor deficiencies

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 Look for hepatosplenomegaly
Do a rectal exam for evidence of GI bleeding
Look for physical signs and symptoms of diseases related to
capillary fragility: Petechiae secondary to coughing,
sneezing, Valsalva maneuver, blood pressure measurement.

Note: The possibility of physical abuse must be considered

in the evaluation of any child with unusual patterns of
bruising or bleeding.

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Laboratory Evaluation
 Laboratory Investigation

Tests for Platelet

I. Platelet count
II. Bleeding Time(BT)
Tests for coagulation
factors
I.ProthrombinTime(PT)
II. Activated Partial
Thromboplastin
Time(aPTT)
III.Thrombin Time(TT)
IV.Fibrinogen assay
 Platelet count & Bleeding Time
Platelet count must be done in a suspected bleeding
disorder.
Bleeding Time (BT)
Significance
Assess Primary Hemostatic defect(vessel wall or
platelet).
Dependent on adequate functioning of plt. & Bl.Vs.
Range
4-8 min
Interpretation
Causes of prolonged BT
I. Thrombocytopenia.
II. VWD.
III. Platelet function disorder
IV. Disorder of blood vesseles.
 Prothrombin Time(PT)
Significance
Reflects overall activity of the Extrinsic Pathway.
Most sensitive to changes in Factor V,VII,X.
Lesser to Factor I & II.
Principle
Platelet poor plasma+Tissue Thromboplastin+Calcium

In Presence of F VII Extrinsic pathway is activated & clot

formed
Normal Range
11 to 16 seconds(with rabbit thromboplastin)
10-12 seconds(with human thromboplastin)
Interpretation
Causes of prolonged PT
1. Deficiency of Factor VII,X,V,II,I
2. Vit K deficiency
3. Liver disease
4. Oral anticoagulants
Activated Partial Thromboplastin Time
Significance (aPTT)
Reflects efficiency of Intrinsic Pathway.
Sensitive to changes in Factor VIII,IX,XI,XII.
Also sensitive to heparin & circulating anticoagulants.
The test measures the clotting time of plasma after the
activation of contact
So it indicates the overall efficiency of the Intrinsic
pathway
Normal range
26 to 40 seconds.
Interpretation
Causes of prolonged aPTT
1. Deficiency of Factor VIII(Hemophilia A).
2. Deficiency of Factor IX(Hemophilia B).
3. Heparin therapy.
4. Circulating anticoagulants.
5. Liver disease.
 Thrombin Time(TT)
Significance
Asses the final step of coagulation i.e. conversion of
fibrinogen to fibrin in presence of thrombin.
Bypasses Extrinsic & Intrinsic pathway.
Principle
Thrombin is added to plasma and the clotting time is
measured.
TT is affected by the concentration and reaction
of fibrinogen and by the presence of inhibitory substances.

Normal range
A patients TT should be within 2 s of the control
(i.e. 1519 sec). Times of 20 s and longer are definitely
abnormal.
Interpretation
Causes of prolonged TT
1. Disorders of fibrinogen-
Afibrinogenaemia.
Hypofibrinogenaemia.
Dysfibrinogenaemia.
2. Liver disease.
3. heparin therapy.

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2nd Line Investigation

Relevant 2nd line investigations are carried out with

each of the patterns of abnormalities in first line tests.
 Scenario #1
PT-Normal
PTT-Normal
TT-Normal
Fibrinogen -Normal
?
Platelet count-Normal
Interpretation
1. Primary hemostasis disorder.
2. Disorders of platelet function(cong or acquired).
3. Vascular disorders of hemostasis.
4. Factor XIII deficiency( fibrin stablizing factor)
5. vWD.
 Scenario # 2
PT-Eleveted
PTT-Normal
TT-Normal
Fibrinogen -Normal
?
Platelet count-Normal
Interpretation
1. Factor VII deficiency.
2. Liver disease.
3. Vit K deficiency.
4. At the start of oral anticoagulant therapy.
5. Mild deficiency of Factor II, V, X.
2nd line investigations
1. Mixing test.
2. Factor VII assay.
3. Liver function test.
 Mixing study
Correction test using PT or aPTT
PRINCIPLE
Unexplained prolongation of PT
or aPTT can be investigated
with simple correction test by
mixing the pt`s plasma with
normal plasma.
Correction (should be within
few seconds) indicates a possible
factor deficiency, whereas failure
to correct suggests the presence
of an inhibitor.

METHOD
Perform a PT and/or aPTT on
control, patient`s,and a 50:50
mixture of the control and pt`s
plasma.
 Scenario # 3
PT-Normal

?
PTT-Eleveted
TT-Normal
Fibrinogen -Normal
Platelet count-Normal
Interpretation
1. Congenital deficiency of F VIII, FIX,.
2. vWD
3. Heparin
4. Circulating anticoagulants-
Specific (Anti factor VIII).
Second line investigations
1. Mixing test.
2. Factor VIII & factor ix assay
 Scenario # 4
PT-Eleveted
PTT-Eleveted
TT-Normal
Fibrinogen -Normal
Platelet count-Normal
?
Interpretation
1. Vit k def.
2. On oral anticoagulants.
3. Liver dis.
4. Rare congenital or acq. Deficiency of factor v,x,ii
5. Combined factor V+VIII deficiency.
2nd line investigations
1. Mixing test.
2. Specific factor assay. 3.Liver function test.
 Scenario # 5
PT-Eleveted

?
PTT-Eleveted
TT-Eleveted
Fibrinogen Normal/Abnormal
Platelet count-Normal
Interpretation
1. Unfractionated heparin
2. Hypofibinogenaemia
3. Afibrinogenemia
4. Dysfibrinogenemia
5. Systemic hyperfibrinolysis
6. Some cases of liver disease.
2nd line investigations
Reptilase or ancord time
 Reptilase or Ancord Time
Reptilase & Ancord are purified enzymes from
snake.
May be used to replace Thrombin in TT test.
Snake venom is not inhibited by heparin
Normal time for clotting in presence of Heparin.
Clotting time will be prolonged in presence of
decreased Fibrinogen.
 Scenario # 6
PT-Eleveted
PTT-Eleveted
TT-Normal ?
Fibrinogen Normal/low
Platelet count-Low
Interpretation
Chronic liver disease esp.cirrohsis.

2nd line investigations

1. Specific factor assay.
2. Peripheral blood smear.
3. Bone marrow aspirate.
 Scenario # 7

?
PT-Normal
PTT-Normal
TT-Normal
Fibrinogen -Normal
Platelet count- low

Interpretation
1. Thrombocytopenia.
2. Heparin use.
2nd line investigations
1. Peripheral blood smear.
2. Bone marrow aspirate.
 References
1. American Academy of pediatrics
(http://pedsinreview.aappublications.org/cgi/content/fu
ll/29/4/121)
2. Nelson Textbook of Pediatrics, 18th ed.
3. Current Pediatric Diagnosis & Treatment , 18th edition
4. Pediatrics on call journal, may 2005 vol.2 issue 5
5. Up to date

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