Haemostasis and ITP

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Transcript Haemostasis and ITP

Haemostasis
Tiffany Shaw
MBChB II
2002
Haemostasis Pathway
Injury
Collagen exposure
Platelet adhesion
Release reaction
Platelet aggregation
Primary haemostatic plug
Tissue Factor
Coagulation Cascade
Secondary haemostatic plug
Fibrin
Coagulation Cascade
Integrity of Haemostasis
Depends on:
1. Vessel wall
2. Platelets (no. and function)
3. Coagulation factors
Vessel Wall
• Release tissue factor that initiates
coagulation cascade.
• Exposed collagen results in platelet
adhesion (using vWF as a bridge).
• Hereditary haemorrhagic telangiectasia
• Scurvy
• Senile purpura
Hereditary Haemorrhagic
Telangiectasia
Low Platelet Number
• N = 150 – 450
• Excessive bleed / Spontaneous bleed
• Mucosal surfaces / Skin
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Immune Mediated Thrombocytopenia
Drug induced
Haemolytic Uraemic Syndrome
DIC
Platelet Dysfunction
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Abnormal platelet aggregation
Normal platelet count
Excessive / spontaneous bleed
Mucosa / Skin
• Inherited disorders
• Drug induced
Eccymoses
Coagulation Factors Deficiency
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Spontaneous bleeding into deep tissues
Increased post-traumatic haemorrhage
Factor 8 – Haemophilia A
Factor 9 – Haemophilia B
vWF – Von Willebrand’s disease
Von Willebrand’s Factor:
• Protein produced by endothelial cells which mediates
platelet adhesion to endothelium and carries factor 8 in
plasma.
Haemaphilia A
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Factor 8 deficiency
50 / million people
Sex-linked
Most detected in childhood
Mild symptoms ~ spontaneous bleed
Chronic joint disease after repeated bleed
Haemophilia B
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Factor 9 deficiency
= Christmas disease
Also sex-linked
Similar presentation as haemophilia A
Much rare
Haemoarthroses
Von Willebrand’s Disease
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vWF deficiency
Autosomal dominant (F = M)
Most common inherited bleeding disorder
Bleeding from mucosa
Excessive blood loss in trauma
Bleeding into deep tissue (rarer)
Liver Disease
• Mixed – both coag deficiency and platelet
problem
• Reduced coag factor synthesis
(1, 2, 5, 7, 9, 10)
• Cirrhosis  Hypersplenism 
Thrombocytopenia
DIC
Generalised activation of coag cascade
Wide-spread fibrin formation
Thrombosis
Low coag factor
Bleeding
DIC
Consequence of Thrombosis:
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4.
Tissue infarction  Renal impairment
CVA
PE
DVT
Consequence of Bleeding:
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2.
Purpura
GI Bleed
DIC
Causes of coag cascade activation:
1. Sepsis
2. Disseminated cancer
3. Obstetric complications (e.g. retained product of
conception)
4. Fulminant liver disease
5. Anaphylaxis
6. AML
Drug Induced Coag Factor Def
Heparin:
• Inactivates certain coag factors (e.g. 9a,
10a, 11a, 2)
• Also impairs platelet function
Warfarin:
• Block synthesis of Vit K dependent factors
(2, 7, 9, 10)
Other Disorders
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Vitamin K deficiency
Autoantibodies to coag factors
Haemorrhagic disease of the newborn
Massive transfusion
Investigations for Bleeding
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Platelet Count
Bleeding time
Activated Partial Thromboplastin Time
Prothrombin Time (INR)
Plasma level assay
Investigations for Bleeding
Condition
Test
Wall Defect
All tests are normal.
Low Platelet
Low platelet count +
Platelet Dysf
Normal platelet count +
bleeding time
bleeding time
Haemophilia
APPT +
Plasma level
vWD
APPT +
bleeding time +
Liver Disease
INR + APPT + platelet count
Drug Induced
INR + APPT + plasma level
DIC
All tests are abnormal.
plasma level
Management
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Replace deficiency
Treat underlying cause
Reversal of drug effects
Supportive therapy
Extra Notes on ITP
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Platelets become coated by autoantibodies
Removed by RES  reduced lifespan
Low platelet count
Acute / Chronic
Purpura / Spontaneous bleed /
Asymptomatic
• May resolve spontaneously or require
medical treatment
Extra Notes on ITP
• Isolated low platelet count
< 20
• Increased megakaryocytes in bone marrow
• Normal INR + APPT
• Increased bleeding time
Extra Notes on ITP
Mx:
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Do nothing
Prednisolone
Splenectomy
Other immunosuppresives
Extra Notes on IPT
May be associated with:
• Haematological malignancies
• Viral infections (e.g. HIV)
• C.T. disorders (e.g. SLE)
 Test for c.t. disorders.
70-Year-Old with ITP
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Incidental finding in 1993
Platelet count = 60
Asymptomatic
Referred to haematologist
Test for c.t. disorders
U/S for spleen size
Bone marrow biopsy
70-Year-Old with ITP
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Negative for c.t. disorders
Spleen size normal
Bone marrow: increased megakaryoccytes
Continue monitoring (weekly FBC)
70-Year-Old with ITP
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December 1993
Bruising with minimal trauma
Platelet count = 43
Start Prednisolone
After 6/52  platelet count 190
Slowly dropped again after withdrawal
Asymptomatic
70-Year-Old with ITP
• Continue monitoring
• Platelet transfusion if serious bleeding
occurs
• Consider splenectomy if worsens
• Discharged to GP last week