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Vascular and platelet disorders are associated with bleeding from the mucous membranes
and into the skin
Coagulation disorders are associated with bleeding from joints or soft tissue
What are some clinical differences between platelet/vessel wall diseases and coagulation
diseases?
Mucosal bleeding and petechiae are common in plt/vessel wall disesease but rare in
coagulation.
Deep hematomas are rare in plt/vessel wall disease but seen as a characteristic feature in
coagulation disorders.
Bleeding from skin cuts tend to be persistent in plt/veseel wall disease but at minial in
coagulation
Lastly the prevalence due to sex is equal in plt/vessel but predominat (80%) male in
coagulation disease
VBDs are characterized by easy bruising and spontaneous bleeding from small vessels.
Bleeding is mainly in the skin causing petechial or ecchymoses.
Hereditary VBDs
1. Herediatary Hemorrhagic Telangiectasia
4. Steroid purpura associated with long term steroid use or Cushings Syndrome; caused by
defective vascular supportive tissue
Thrombocytopenia
High incidence in women 15-50 yrs and most common cause of thrombocytopenia
without anaemia or neutropenia
Usually idiopathic but can be seen in assoc. with SLE (systemic lupus erythematous),
Helicobacter pylori, CLL or Hodgkins.
Pathogenesis: IgG (plt autoimmune antibody) is directed against antigen sites on the GP IIb/IIa
or Ib complex.
Clinical Features: insidious onset with petechial bleeding, easy bruising and menorrhagia. In
severe cases, mucosal bleeding (epistaxis or gums) occur.
Diagnosis: low plt count (10-100x 10^9/L); normal or increased megakaryocytes; sensitive tests
demonstrate anti-GP GP IIb/IIIa or GPIb antibodies on plts surface or in serum
Treatment with corticosteroids, IV immunoglobulins, Immunosuppressive drugs (Rituximab),
splenectomy, thrombopoietin-receptor agonists, plt transfusions or SCT.
Acute ITP
Most common in children, following after vaccination (75% prevalence) or infection such as
Mono or Chickenpox.
Diagnosis is one of exclusion.
3. Infections such as viral/protozoal may cause thrombocytopenia
4. Post transfusion purpura. Antibodies develop against human plt antigen-1a (HPA-1a)
5. Drug-induced immune thrombocytopenia. Quninine, quinidine and heparin
6. Thombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome
(HUS)
In TTP there is a
defeiciency in ADAMTS13
metalloprotease which breaks down
VWF. In adults neurological
changes and liver dysfunction
occur. Congenital TTP is due to
mutated ADAMTS13 (lack of
synthesis) and acquired is due to
autoantibody IgG which leads to
multimetric VWF complexes
(strings) in plasma (forms occlusive
plt thrombi).
In HUS ADAMTS13
Acquired
1. Antiplatelet drugs
Aspirin therapy is the most common cause of defective plt function. Aspirin inhibits
cyclooxygenase which impairs thromboxane A2 synthesis.
Effects? No release rxn and aggregation with arachidonic acid, collagen, adrenaline or ADP
It produces abnormal PFA-100. Assoc. with GI bleeding
2. Hyperglobineamia
Assoc. with myeloma or Waldenstrom disease; impairs plt adhesion, release and aggregation
3. Uremia
Heparin, dextrans, alchol and radiographic agents cause defective plt function
4. Myeloproliferative and myelodysplastic disorders
Intrinsic abnormalities of plt function
Thrombomimetics
Drugs that increase plt production by activating the thrombopoietin receptor on megakaryocytes.
Eg. Thromboplastin, eltrombopag
Effect? Disturbed liver function and increased BM reticulin; long term use causes marrow
fibrosis (reverts when drug is stopped)