Prolonged reduced fibrinogen levels

Dysfunctional fibrinogen (hypo/afibrinogenemia)

Hemostatic Mechamism
Substances that interfere with fibrin polymerization (heparin or
Vascular response
fibrin split products) reptilase time
Platelet adhesion
Mixing Studies
o
If there is unexplained prolongation of PT, PTT, or TT
Platelet aggregation
o
Normal plasma + patients plasma repeat lab exam
Clot formation

Correction of PT/PTT by mixing clotting factor defeciencies

Clot stabilization

Not corrected + bleeding inhibitor

Limitation of Clotting (AT III, Protein C, Protein S, TFPI)

Not corrected, no bleeding lupus- like anticoagulant

Re-establishment of vascular patency fibrinolysis and vascular
Clotting factor assays
healing (plasmin)
Coagulation Cascade
Hemophilia
Introduction
Hemophilia A factor VIII deficiency (85%)
Hemophilia B Factor IX deficiency (10-15%)
Most common & serious congenital coagulation factor deficiencies
Prevalence 1:5000 males
No racial predilection
Clinical finding same
Classification
Severe deficiency <1% factor activity
Spontaneous bleeding
Moderate deficiency 1-5% factor activity
Mild trauma to induce bleeding
Mild deficiency >5% factor activity
May be asymptomatic, took years to diagnose
Manifestations
Clot formation is delayed & fragile
When bleeding occurs in the closed space tamponade
Open wound profuse bleeding
Bleeding symptoms may be present in utero
Neonates intracranial bleeding
Easy bruising, intramuscular hematomas, hemathroses
Bleeding from minor trauma of the mouth persist for days
Hemophilia
Hisotry
Illiopsoas bleeding life threatening
Site, severity, duration of bleeding
Inability to extend the hip
Age of the symptom onset
Confirmed by UTZ or CT scan
Spontaneous after trauma
Aggressive therapy
Previous history or family history of bleeding
Life threatening bleeding:
Does bruising occur spontaneously?
CNS, upper airway bleeding
Is there has been previous surgery or dental procedure?
External, GI bleeding
Menstrual history
Genetic
Physical Examination
Symptoms primarily associated with mucous or skin (mucocutaneous
bleeding) defects in platelet or blood vessel wall interaction (vW
disease)
Or muscle and joints bleeding (deep bleeding) clotting factor
deficiency
Presence of petechiae, ecchymoses, hematomas, hemathroses, or
mucous bleeding
Laboratory
Hemostatic Disorder in Children

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Treatment
Prevention of trauma
Pyschosocial
Avoid aspirin & NSAID
Replacement therapy
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Recombinant factor VIII/IX
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Cryoprecipitate/eryosupernate
Joint bleeding
o
R: Rest
o
I: Ice Pack
o
C: compression
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E: Elevation
Supportive therapy

Bleeding time (BT)

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Assesses platelet function and their interaction with vascular wall

o
Platelet <100,000/microliter prolonged BT
o
Disproportionate BT qualitative platelet defects or VW disease
aPTT
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Measures the initiation of clotting (intrinsic pathway)

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Doesnt measure factor VII, XIII, or anticoagulant
PT
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TT
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Measures extrinsic pathway

Normal in deficiencies of factor VIII, IX, XI, or XII
Measures final step of the clotting cascade

 Multidiciplinary
Chronic Complication
Chronic joint destruction
Risk of transfusions associated disease
Development of inhibitor
Disseminated Intravascular Coagulation
Introduction
Consumptive coagulopathy
Consumption of clotting factor, platelets &anticoagulant proteint
Widespread intravascular deposition of fibrin tissue ischemia &
necrosis, generalized hemorrhagic state, hemolytic anemia
Disseminated Intravascular Coagulation
Trigger factors
o Hypoxia
o Acidosis
o Tissue necrosis
o Shock
o Endothelial damage
o Septic shock
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Thrombocytopenia
Introduction
The characteristic of platelets
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Size
1-4 micrometer (younger platelets are larger)
o
Mean platelet volume (MPV)
8.9 1.5 micrometer3
o
Distribution
1/3 in the spleen, 2/3 in blood stream
o
Life span
7-10 days
Bleeding may occur because:
o
Reduce in number (thrombocytopenia)
o
Defective in function
Classification
Thrombocytopenia based on platelet size
Macrothrombocytes (MPV)
ITP or condition with increased platelet turnover (eg. DIC)
Bernard soulier syndrome
May Heggin anomaly and other MYH-9-related diseases
Swiss cheese platelet syndrome
Montreal platelet syndrome
Gray platelet syndrome
Various mucopolysaccharidoses
Microthrombocytes (MPV)
Wiskott-Aldrich syndrome
TAR syndrome
Some storage pool diseases
Iron deficiency anemia
Normal size (MPV normal)
Disease with hypocelllular marrow or infiltrated with malignant
Immune Thrombocytopenia
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The most frequent cause of thrombocytopenia is immune mediated

>20.000/mm3 in 2% of cases
plateelt destruction due to:
o
Interval between diagnosis of ITP and ICH
Autoantibodies
o
<4 weeks in 51% of cases
Drug-dependent antibodies
o
4 weeks 9 years in 49% of cases
alloantibodies
Treatment
Clinical Features
Supportive
o
No treatment is required when platelet count >20.000/mm3,
asymptomatic or has mild bruising but no evidence of mucous
membrane bleeding
o
Competitive sport should be avoided
o
Depoprovera or any long-acting progesterone in suspending
menstruation for several months
o
Aspirin, nonsteroidal antiinflammatory agents and any other drug
the interfere with platelet function should not be given
Farmacological treatment
Treatment choice: steroid, IVIG, and anti D
Indication
1. Platelet count <20.000/mm3 and significant mucous membrane
bleeding
2. Platelet <10.000/mm3 and minor purpura
o
Steroid Therapy
Mechanism
Inhibits phagocytosis of antibody coated platelet in the
Predisposising Factors
spleen prolongs platelet survival
50-80% infection (usually viral) prior to thrombocytopenia
Improves capillary and thereby improve platelet economy
Dose and Duration
About 20% a specific infection can be identified , eg. Rubella,
measles, varicella, pertusis, mumps, infectious mononucleosis,
Dose 2mg/kg/day (max. 60 mg/day) in divided dose. Tap of
CMV, parvovirus or bacterial
in 5-7day interval and stopped at the end of 21-28 days .
Measles or smallpox vaccination
Regardless of the response
In severe cases methylprednisolone 30mg/kg/day (max
Manifestations
1g/day) for 3 days
Skin
Prolonged use of steroids is undesirable
eccyhmoses/purpura usually on the anterior surface of lower
Worsen the thrombocytopenia and depress platelet
extrimities and body prominences (ribs, scapula, shoulders, legs,
pubic)
production
Side efect
Mucous membranes
weight gain, cushingoid facies, fluid retention, acne,
subconjungctival , buccal mucosa, soft palate
hyperglicemia, hypertension, mood swings, pseudotumor
Menorrhagia
cerebri, growth retardation, and avascular necrosa
Hematemesis &melena infrequent
o
IVIG
Others
Mechanism of action
nose, gum, GI, kidneys (usually at the onset of the disease )
Reticuloendothelial Fc-receptor blockade
With the exception of hemorragic manifestations, the physical
Activation of inhibitor pathways
examination is not significant
Decrease autoantibody synthesis
The spleen is palpable in <10% , the presence of splenomegaly

Indication
suggests the probability of leukemia, SLE, infectious manonucleosis
Neonatal Symptomatic immune Thrombocytopenia infant
or hypersplenism
less than 2 years old are generally more retractory to steroid
Cervical lymphadenopathy is not present, unless the precipitating
treatment
factor is viral infection
Alternative therapy to corticosteroid therapy
Laboratory Findings
Much more expensive and has significant side efects
Low platelet count:
Not significantly clinically better than steroid to justify expense
o
Always <150.000/mm3
& side efect
o
Often <20.000/mm3 in patients with severe generalized
In acute ITP 80% respond initially and more rapid compared to
hemorrhagic manifestations
steroid treatment
o
MPV
Total dose 2g/kg body weight , given as follow:
Blood smear:
0.4 g/kg /day for 5 days
o
Thrombocytopenia must be confirmed by peripheral blood
1g/kg/day for 2 days
examination to exclude the diagnosis pseudothrombocytopenia.
Anti-D therapy
The presence of megathrombocytes and other hematologic o
Plasma derived gamma immune globulin of anti Rh antigen
manifestation
Mechanism
o
Blood smear normal apart from thrombocytopenia
Blockade of Fc receptor of reticuloendothelial cell
Anemia present in proportion to amount of blood loss
Platelet is increased after 48 hours. Therefore the therapy is
Bone marrow aspiration
not appropriate for emergency treatment
o
Indication
Splenectomy
Atypical presentation
o
Indication:
Poor response to therapy
Severe acute ITP with acute life-threatening bleeding and not
To exclude other hematologic disorders such as leukemia
responsive to medical treatment
o
Characteristic:
Chronic ITP with bleeding symptoms or pit count persistently
megakaryocyte, immature and absence of budding
below 30.000/mm3 and not responsive to medical treatment
Normal erythroid and myeloid cells
for several years
Occasionally eusinophilia
In very active patient subject to frequent trauma, early
Erythroid hyperplasia if significant blood loss
splenectomy may be indicated
Intracranial Hemorrhage
o
Because the hazards of overwhelming postsplenectomy infection
o
Incidence : 0.1-0.5 %
(OPSI) the procdure should be performed after clear indication
o
Age : 13 months 16 years
Life threatening hemorrhage
o
Platelet count:
o
Platelet transfusion
<10.000/mm3 in 73% of cases
o
Methylprednisolone 500mg/m2 IV per day or 3 days
10-20.000/mm3 in 25% of cases

o
IVIG 2/kg for 12 hours infusion
Age older than 10 years, insidious onset, female are associated with
o
Emergency splenectomy
chronic ITP
Prognosis
50-60% chronic ITP eventually stabilize with any other therapy and
Excellent, 50% recover within 1 month % 70-80% within 6 months
without splenectomy
Spontaneous remission after 1 year in uncommon but may occur even
after several years
When demonstration underlying cause, the prognosis is related to the
cause