APPROACH TO

BLEEDING CHILD
PRESENTERS
GETAMEHON GUADIE C-I
GETABALEW GIRMA C-I
MODERATOR;
Dr kussia (MD,PEDATRCIAN)
 Outline

• Hemostasis
• Approch to patient with bleeding disorder
• Lab investigatons
• Common bleeding disorder in pediatrics

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 Hemostasis
• Hemostasis is the active process that clots
blood in areas of blood vessel injury, yet
simultaneously limits the clot size only to the
areas of injury.
• The main components of the hemostatic
process are the vessel wall, platelets,
coagulation proteins, anticoagulant proteins,
and fibrinolytic system.

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 Hemostasis
Hemostasis has three stages
(1) vascular spasm, vasoconstriction, or intense
contraction of blood vessels,
(2) formation of a platelet plug and
(3) blood clotting or coagulation.

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 Vascular spasm or Vasoconstriction
Several things trigger this reaction.
An injury stimulates pain receptors, some of
which directly innervate nearby blood vessels and
cause them to constrict. This effect lasts only a
few minutes, but other mechanisms take over by
the time it subsides.
 Injury to the smooth muscle of the blood vessel
itself causes a longer-lasting vasoconstriction, and
platelets release serotonin, a chemical
vasoconstrictor,after plug formation
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 Formation of a Platelet Plug
• The formation of a platelet plug can be described as a series of
steps, but in actuality many of the steps take place
simultaneously

1. Platelet adhesion occurs when platelets bind to collagen

exposed by blood vessel damage.Most platelet adhesion is
mediated through von Willebrand factor (VWF).

2. After platelets adhere to collagen, they become

activated(shape,ADP,TXA2,SEROTONIN)
3. As platelets become activated, they express surface receptors
that can bind to fibrinogen, a plasma protein.

4. Activated platelets express phospholipids (platelet factor III) and

coagulation factor V, which are important in clot formation 6
 Coagulation
• If the vasospasm & the platelet plug are not
enough to stop the bleeding the third stage of
hemostasis begins: the formation of a blood
clot.
• A blood clot is a network of threadlike protein
fibers, called fibrin, that traps blood cells,
platelets, and fluid.

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8
Coagulation cascade

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 Fate of blood clot
• Once a blood clot has formed, it can follow one of two courses:
1. It can become invaded by fibroblasts
• This continues to complete organization of the clot into fibrous
tissue within about 1 to 2 weeks.
2. It can dissolve by a process called fibrinolysis .
.It involves the activity of plasmin (plazmin), an enzyme that
hydrolyzes fibrin. Plasmin is formed from inactive plasminogen, which
is a normal blood protein.

. It’s activated by thrombin, factor XII, tissue plasminogen activator (t-

PA), urokinase, and lysosomalenzymes released from damaged
tissues .

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 history
• Site /sites of bleeding
• Severity and duration of hemorrhage
• The age at symptom onset
• Was the bleeding spontaneous or after trauma?
• Was there a previous personal or family
history of similar problems?
• Sex and family hx.
• Only in male siblings and maternal uncles is
diagnostic of X-linked recessive inheritance
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 Cont’s
• Do symptoms correlate with the degree of
injury/ trauma?
• Does bruising occur spontaneously?
• Are there lumps with bruising for which there is
minimal trauma?
• Was there increased bleeding during surgery
or dental procedures?
• History of delayed/slow wound healing
• Menstrual history in post pubertal females
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• History of drug intake = drug-induced
thrombocytopenia .
• Unprovoked hemarthroses and muscle
hemorrhages suggest one of the hemophilias
• mucocutaneous bleeding (epistaxis, gingival
bleeding, menorrhagia) are more
characteristic of patients with qualitative
platelet disorders, thrombocytopenia, or von
Willebrand disease.
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• Joint swelling,joint pain, tingling sensetion, inability to
extend the hip, Vision problems, Change in alertness or
consciousness ,fainting,difficulty of breathing,palptation,
vomiting of blood,coughing up blood,bloody stools.
• Hx. of viral infection /EBV,HIV/.
• Rule out meningococcal infection,skin rash .
• Strong family history of autoimmune disorder (eg,
rheumatoid arthritis, systemic lupus erythematosus, or
Hashimoto's thyroiditis) may have chronic ITP.
• Hx of liver disease,renal ds,.
• Rat poison (superwarfarin).
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• A nutrition history should be obtained to assess the
likelihood of:-
(1) vitamin K deficiency, especially if the patient also is taking
broad-spectrum antibiotics,
(2) vitamin C deficiency, scurvy/gum bleebiing/, and
(3) general malnutrition and/or malabsorption.
.Bleeding isolated to a single organ or system (e.g., hematuria,
hematemesis, hemoptysis) less likely results from a hemostatic
abnormality than a local cause such as a neoplasm, an ulcer, or
angiodysplasia. Thus, careful anatomic evaluation of the
involved organ or system should be performed.
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 PE
• look for signs of bleeding or their sequelae and for signs of
a possible underlying disorder that can cause the
hemostatic derangement

• Should focus on whether symptoms are primarily

associated with the mucous membrane or skin
(mucocutaneous bleeding) or the muscle or joints
(deep bleeding).

• Look for petechiae, ecchymosis, hematomas,

hemarthroses and mucous membrane bleeding.
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Assess volume status (correct shock if
present)
-Examine oropharynx for evidence of
petechiae
-Pale skin and mucus membranes
-DYSMORPHIC FEATURES
-Change in mental status, such as confusion and
disorientation
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 INVESTGATIONS
• Patients who have a positive bleeding history
or who are actively hemorrhaging should have
a platelet count, bleeding time, PTT, and PT
• If the results are normal, a thrombin time and
VWF testing should be considered.
• In individuals with abnormal screening tests,
further specific factor work-up should be
undertaken.

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Test Mechanism Tested Normal Values Disorder
Prothrombin time Extrinsic and <12 sec beyond Defect in vitamin K-
common pathway neonate; 12-18 sec dependent factors;
in term neonate hemorrhagic disease
of newborn,
malabsorption, liver
disease, DIC, oral
anticoagulants,
ingestion of rat
poison
Activated partial Intrinsic and 25-40 sec beyond Hemophilia; von
thromboplastin time common pathway neonate; 70 sec in Willebrand disease,
term neonate heparin; DIC;
deficient factors XII
and XI; lupus
anticoagulant

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Thrombin time Fibrinogen to fibrin 10-15 sec beyond Fibrin split products,
conversion neonate; 12-17 sec in DIC,
term neonate hypofibrinogenemia,
heparin, uremia

Bleeding time Hemostasis, capillary 3-7 min beyond Platelet dysfunction,

and platelet function neonate thrombocytopenia, von
Willebrand disease,
aspirin

Platelet count Platelet number 150,000-450,000/mm3 Thrombocytopenia

Blood smear Platelet number and ---------- Large platelets suggest

size; RBC morphology peripheral destruction;
fragmented, bizarre
RBC morphology
suggests
microangiopathic
process (e.g.,
hemolytic uremic
syndrome,
hemangioma, DIC)

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 Cont…
• REPTILASE TIME. Unlike the thrombin time,
the reptilase time is not sensitive to heparin
and is prolonged only by reduced or
dysfunctional fibrinogen and fibrin split
products.
• MIXING STUDIES. Indicated if there is an
unexplained prolongation of the PT, PTT, or
thrombin time.

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• CLOTTING FACTOR ASSAYS. For most clotting
factors, their activity is measured against a pooled
normal plasma or standard where 100% activity is
expressed as 100 U/dL. For most clotting factors
the normal range is between 50-150 U/dL (50-
150%). 1 unit/mL equal to 100% of the factor
activity found in 1 mL of normal plasma.

• PLATELET AGGREGATION. When a qualitative

platelet function defect is suspected, platelet
aggregation testing is usually ordered.
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• CBC
• ultrasonography
• CT scan
• X-ray

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 common bleeding
disorders in pedatrics

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• Bleeding is the loss of blood or 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.

• an increased tendency to hemorrhage (usually with

insignificant injury) also occurs in a variety of clinical disorders
that are collectively called hemorrhagic diatheses.

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 BLEEDING DISORDERS IN PEDIATRICS

A. Hereditary coagulation disorders

– Hemophilia A
– Hemophilia B
– Von Will brand's disease
B.Acquired coagulation disorders
– Vitamin K deficiency
– Liver disease
– DIC
– Coagulation disorders caused by antibodies
– Massive transfusion syndrome
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• C.Platelet disorders
. Platelate function disorder
- Congenital
-Acquired
• -Thrombocytopinic (dereased number of platelates)
-Idiopathic thrombocytopenic purpura (ITP).
-Thrombotic thrombocytopenic purpura (TTP).
-Drug induced thrombocytopenic purpura .
-congenital

D. Vascular disordes
-Congenital 28
 A. Hereditary coagulation
disorders
• – Uncommon
• – Usually involve deficiency of one factor only
– Deficiencies of all factors can occur, but most
common are:
• Hemophilia A – factor VIII deficiency
• Hemophilia B – factor XI deficiency
• Von Will brand’s syndrome
• Others are rare
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 Hemophilia A (classic hemophilia)
• • The most common of hereditary clotting factor deficiencies
• • Due to by factor VIII deficiency
• The prevalence about 1 in 5000 of the male population
• Inherited as X-linked disorder
• – But up to 30 % have no family history and results from
spontaneous mutation
• Woman can have hemophilia
• Turner syndrome ( XO)

• Father with hemophilia/ mom as a carrier

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Hemophilia A: X-linked

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 Hemophilia A
• Clinical featuers
– Atypical profuse bleeding at circumcision
– Bruising at neonatal vaccines
– Joints and soft tissue bleeds and excessive bleeding when they
start to be active
– Prolonged bleeding after teeth extraction
– Recurrent painful hemarthrosis
– Muscle haemoatomas
– Spontaneous haematouria
– GIT hemorrhage
– Spontaneous intracranial hemorrhage (rare)
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 Hemophilia A
• Clinical features
– Severe disease – factor level < 1%
• Frequent spontaneous bleeding from early life
• Haemarthroses are common and may lead to joint deformity
• Bleeding into muscles is also common
– Moderate disease – factor level 1 – 5 %
• Post traumatic Bleeding
• Occasional apparently spontaneous episodes
-Mild disease – factor level > 5 %
• Usually with bleeding only after injury or surgery
• Diagnosis in this group is often delayed until quite late in life33
 Hemophilia A

• Clinical features

Massive right haemorrhage

in the area of buttock
Gross swelling from acute 34
haemarthroses of the knee joints
 Hemophilia B
• Also known as Christmas disease
• Caused by a deficiency of factor IX
• The inheritance and clinical features are
identical to hemophilia A
• Only can be distinguished by specific
coagulation factor assays
• The incidence is only about 1 in 30 000 males
• Hemophilia B is treated with factor IX
concentrates
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 Von Willbrand’s disease
• Hereditary coagulation abnormality caused by
either:
– Reduced level of vWF
– Abnormality in vWF
Due to Point mutation
or

Major deletion
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 Von Willbrand’s disease
• vWF is a protein that has two roles
– It promote adhesion of platelets to the
endothelium
– It is a carrier molecule for factor VIII,
protecting it from premature destruction
• So in vWD there is:
– Defective platelet function
– Factor VIII:C deficiency
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 Von Willbrand’s disease
• • vWD has been classified into three types:
• – Type 1 vWD
• • Characterized by a mild reduction in vWF and is
usually inherited as an autosomal dominant
• – Type 2 vWD
• • Loss of high-molecular-weight multimers, and it too
is usually inherited as an autosomal dominant – Type
3 vWD
• • Characterized by severe reduction in vWF and
usually inhereted as autosomal recessive
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 Von Willbrand’s disease
• • Clinical features
• – Typically there is mucus membrane bleeding
(Epistaxis, easy bruising, and menorrhagia in
women are common complaint )
• – The severity of symptoms are variable with
types
• • Type 1, 2 usually mild symptoms
• • Type 3 severe symptoms

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 Haemostasis tests in hereditary
coagulation disorders
Haemophilia A Haemophilia B VW disease

Bleeding time Normal Normal Prolonged

Prothrombin Normal Normal Normal
time

APTT Prolonged Prolonged Prolonged

Factor VIII Low Normal Low or normal
Factor IX Normal Low Normal
VWF Normal Normal Low

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B. Acquired coagulation disorders
• Acquired coagulation disorders
– More common than inherited disorders
– Usually multiple clotting factors
– Includes
• Vitamin K deficiency
• Liver disease
• DIC
• Coagulation disorders caused by antibodies
• Massive transfusion syndrome
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 Vitamin K deficiency

-Vitamin K is a fat soluble vitamin

– Obtained from green vegetables and bacterial synthesis in the
gut
– Important on coagulation factors II, VII, IX and X and on
proteins C and S.
– Without it, these factors cannot bind calcium.
Its deficiency is caused by
– haemorrhagic disease of the newborn
– Biliary obstruction
– Malabsorption of vitamin K
– Vitamin K antagonist drugs
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 Liver disease
– Biliary obstruction results in malabsorption of
vitamin K and therefore decresed synthesis of factors
II, VII, IX and X
– Also there are decreased in factor V and fibrinogen
– Dysfibrinogenemia
– Thrombocytopenia.
– Functional abnormalities of platelets
– Hypersplenism associated with portal hypertension
– DIC
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 Disseminated coagulation disorders (DIC)

• – There is widespread deposition of fibrin within blood

vessels with consumption of coagulation factors and
platelets occurs as a consequence of:
1.entry of procoagulant material into circulation
. Malignancy , Incompatible blood transfusion
2.diffuse endothelial damage or
. Septicemia ,Severe burns–
3.generalized platelet aggregation.
. Some bacteria, viruses and immune complexes may have
direct effect on platelets.
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 DIC
• Infections • Obstetric complications
– Gram neg septicaemia – Amniotic fluid embolism
– Septic abortion – Eclampsia, retained placenta
• malignancy • Miscellaneous
– Widespread mucin secreting adenocarcinoma – Liver failure
– Acute promyelocytic leukaemia – Hypothermia
• Hypersensitivity reactions – Severe burns
– Anaphylaxis – Snake venoms
– Incompatible blood transfusion – Acute hypoxia
• Widespread tissue damage
– Following surgery/trauma
– After severe burns

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 DIC
• Clinical features
– Bleeding, particularly from venipuncture
– Purpura
– Generalized bleeding in GIT, oropharynx,
lungs, urogenital tract, vaginal bleeding
– Less frequently, microthrombi may cause skin
lesions, renal failure, gangrene of fingures

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C. PLATELETS DISORDERS

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 c. platelate disorders
• platlate disorders are ;
1 .Thrombocytopinia (dereased number of platelates) due to
– Reduced platelet production in the bone marrow
• The most common cause of thrombocytopenia
– Excessive peripheral destruction of platelets
-Idiopathic thrombocytopenic purpura (ITP).
-Thrombotic thrombocytopenic purpura (TTP).
-Drug induced thrombocytopenic purpura

– Abnormal distribution of platelets

. splenomegally

– Dilutional loss
• Massive transfusion of stored blood

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 Platelet disoders

2.Platelat function disorder

- Congenital
-Acquired

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 1. Thrombocytopenia
Impaired production Increase consumption
Bone marrow failure Immune
Autoimmune (idiopathic)
Megaloblastic anaemia
Associated with SLE, CLL
Aplastic anemia Infections
Myelofibrosis Drug-induced
Multiple myeloma Post-transfusion purpura
Feto-maternal alloimmune
MDS
HIV infection DIC
Marrow infiltration TTP
Leukaemia 59

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 cont’s
• Increased destruction of
platelets
-Idiopathic thrombocytopenic purpura (ITP).
-Thrombotic thrombocytopenic purpura (TTP).
-Drug induced thrombocytopenic purpura .

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Idiopathic thrombocytopenic purpura (ITP)

• It is most common cause of acute onset of

thrombocytopenia in an otherwise well child is
(autoimmune) idiopathic thrombocytopenic purpura (ITP).
• In a small number of children, estimated at 1 in 20,000, 1-4
wk after exposure to a common viral infection, an
autoantibody directed against the platelet surface develops
with resultant sudden onset of thrombocytopenia
• Thrombocytopenia due to immune destruction of platelets.
• The antibody-coated platelets are removed following
binding to Fc receptors on macrophages.

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 ITP

• Thrombocytopenia due to immune destruction

of platelets.
• The antibody-coated platelets are removed
following binding to Fc receptors on
macrophages.
• Both acute and chronic forms of ITP exists
– Acute ITP more commonly seen in pediatric
population
– Chronic form is more common in adults
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 ITP
• Acute ITP
-acute onset
– Common in children
– Usually following vaccination or infection(viral)
-70–80% have spontaneous resolution with in 6mon
-autoantibody directed against theplatelet surface develops
– 10% the disease become chronic (lasting > 6 months) C/features:
1. No symptoms
2. Mild symptoms: bruising and petechiae, occasional minor
epistaxis, very little interference with daily living
3. Moderate: more severe skin and mucosal lesions, more
troublesome epistaxis and menorrhagia
4. Severe: bleeding episodes—menorrhagia, pistaxeis
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• Chronic ITP
. Relatively common disorder
. Occur mainly in women between 15 – 50 years old
. This is the most common cause of thrombocytopenia
without anemia and neutropenia
. Usually idiopathic but can be seen in associated with
other disorders as SLE, HIV, CLL.
. The platelets are sensitized with autoantibodies (IgG), this
results in their premature removal from the circulation by
the macrophages of RES, especially in the spleen.
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ITP: pathogenesis

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CHRONIC ITP
• CLINICAL FEATUERS
– Petechial haemorrhage
– Purpura
– Easy brusing
– Menorrhagea in women
– Epistaxis
– Gum bleeding
– Major haemorrhage is rare
– Intracranial bleeding – very rare
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Petechia

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Purpura

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Thrombotic Thrombocytopenic Purpura
• TTP is rare bleeding disorder which is characerazed by;
• fever
• microangiopathic hemolytic anemia
• thrombocytopenia
• abnormal renal function,
• and central nervous system changes
• it can be congenital and it usually presents in adults
and occasionally in adolescents
• The majority of cases of TTP are caused by an
autoantibody– mediated deficiency of a
metalloproteinase (ADAMTS-13) . 61
 Drug-InducedThrombocytopenia
• some drugs are associated with immune
thrombocytopenia as the result of either an
immune process or megakaryocyte injury.
• valproic acid, phenytoin, carbamazepine,
sulfonamides, vancomycin, and trimethoprim-
sulfamethoxazole and Heparin are commonly
used drugs in pedatrics which causes
thrombocytopenia.

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 Abnormal distribution of platelets
• . splenomegally

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Congenital Thrombocytopenic Syndromes

.Congenital amegakaryocytic thrombocytopenia

– first few days to wk of life
– petechiae and purpura
– bone marrow shows an absence of megakaryocytes
– mutation in the stem cell TPO receptor
• Thrombocytopenia-absent radius (TAR) syndrome
. Absence or hypoplasia of megakaryocytes
. with bilateral radial anomalies of variable severity
. remits over the first few yr of life.

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65
 Neonatal Thrombocytopenia
• Thrombocytopenia in the newborn is rarely indicative of a
primary disorder of megakaryopoiesis but,
• it is more often the result of either systemic illness or
transfer of maternal antibodies
• it often occurs in association with congenital viral
infection, especially rubella; cytomegalovirus; protozoal
infection, such as toxoplasmosis; syphilis; and perinatal
bacterial infection, especially those caused by Gram-
negative bacilli
• But it also occurs because of transplacental transfer of
maternal antibodies directed against fetal platelets
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 2.Platelat function disorder

Congenital Abnormalities of Platelet Function

• Bernard-Soulier syndrome
– Defect in VWF receptor (GPIb complex)
– thrombocytopenia, with giant platelets and markedly
prolonged bleeding time (>20 min).
– VWF are normal
.Glanzmann thrombasthenia
.defect in the GPIIb-IIIa complex(fibrinogen receptor)
. bleeding time Is markedly prolonged
Gray platelet syndrome :absence of platelet α granules
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 Acquired Disorders of
Platelet Function
.Platelet function is impaired in a number syestemic of
illeness:liver disease, kidney disease (uremia)
-These disorders frequently cause prolonged bleeding
time and are often associated with other abnormalities
of the coagulation mechanism
.Drugs: aspirin is The most commonly used drug in
adults that alters platelet function,
In children NIAIDS ,valproic acid, and high-dose
penicillin are commonly used drugs which affect
platelet fuction

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 4. Disorders of the Blood Vessels

• HENOCH-SCHöNLEIN PURPURA:
– sudden development of a purpuric rash, arthritis,
abdominal pain, and renal involvement
– coagulation studies are normal
– inflammatory damage to the endothelium of the capillary
and postcapillary venules
• EHLERS DANLOS SYNDROME.
• OTHER ACQUIRED DISORDERS like;
Scurvy, SLE, chronic corticosteroid therapy, and severe
malnutrition are associated with “weakening” of the
collagen matrix that supports the blood vessels.
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 Referances
• Nelson text book of pediatrics,20th edition
• Robins and cotran pathologic bases of
diseases,8th edtion
• guyton physiology 2006

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Thank
you!
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