Bleeding Disorders Flashcards
The three roles of Von Willebrand’s Factor
- Bring platelets into contact with exposed sub-endothelium
- Make platelets bind to each other
- Binds to factor VIII, protecting it from destruction in circulation
Symptoms of Von Willebrand’s Disease (VWD)
Behaves like a platelet disorder:
○ Epistaxis
○ Menorrhagia
○ Bruising
○ Increased bleeding post tooth extraction
Describe VWD Type 1
○ Autosomal Dominant
○ Most common type ~80%
○ Decreased levels of vWF
Describe VWD Type 2
○ Abnormal vWF, lacks high molecular weight multimers
Describe VWD Type 2A
○ Defective platelet adhesion due to decreased high molecular weight vWF multimers (vWF protein too small)
Describe VWD Type 2B
○ Pathological increase of vWF-platelet interaction
Describe VWD Type 2M
○ Decreased vWF-platelet interaction
Describe VWD Type 2N
○ Type ‘‘Normandy’”
○ Abnormal binding of vWF to Factor VIII
Describe VWD Type 3
○ Autosomal Recessive
○ Most severe
○ Complete absence of vWF
Investigations of VWD
○ Bleeding time (prolonged)
○ APTT (may be prolonged)
○ Factor VIII Level (may be reduced)
○ Defective platelet aggregation with ‘risocetin’
Management of VWD
○ Tranexamic Acid: for mild bleeding
○ Desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade Bodies in endothelial cells
○ Factor VIII concentrate: surgery and major bleeds
○ Avoid aspirin and NSAIDs
Four causes of Thrombocytopaenia
- Reduced Platelet Production
- Increased Platelet Consumption
- Abnormal Distribution of Platelets
- Dilutional
Differential Diagnosis of Reduced Platelet Production
○ Abnormal Megakaryocyte Development ▫ Congenital mutation of c-MPL thrombopoietin receptor ▫ May-Hegglin syndrome ▫ Wiskott-Aldrich syndrome ▫ Drugs, Chemicals ▫ Viral Infections
○ Generalised Bone Marrow Failure
▫ Haematological Malignancy (Leukaemia, Myeloma, Aplastic Anaemia, Myelodysplasia, Myelofibrosis)
▫ Secondary to cytotoxic drugs and radiotherapy
▫ Infection: HIV, CMV, Hepatitis B and C
▫ Alcohol Excess
▫ Megaloblastic Anaemia
Differential Diagnosis of Platelet Consumption/Destruction
○ Immune Mediated
▫ Idiopathic / Primary Autoimmune (Immune Thrombocytopaenia)
○ Other
▫ Secondary: SLE, CLL, Lymphoma
▫ Infections: HIV, Hepatitis B and C, Malaria
▫ Drug Induced: Rifampicin, Penicillins, Sulphonamides, Heparin, Quinine
▫ Post-Transfusion Purpura
▫ Thrombotic Thrombocytopenic Purpura
▫ Disseminated Intravascular Haemolysis
Differential Diagnosis of Abnormal Distribution of Platelets
○ Splenomegaly
Differential Diagnosis of Dilution Thrombocytopaenia
○ Massive Transfusion
○ IVT
Symptoms of Thrombocytopaenia
○ Petechiae (small pinprick red dots) on skin ○ Increased bruises ○ Mucosal bleeding in mouth ○ Nose Bleeds ○ Blood in Urine or Stools ○ Rarely ICH (fatal in 25% of cases)
Potential Blood Film Findings in Thrombocytopania
○ Uniformly large platelets, due to inherited causes: Bernard - Soulier syndrome
○ Very small platelets in male infants (esp. w/eczema): Wiskott - Aldrich syndrome, or X-linked thrombocytopaenia
○ ITP: can have large and small platelets
○ Abnormality of morphology of red cells may suggest alternative diagnosis
▫ Red Cell Fragments: Thrombotic Thrombocytopenic Purpura (TTP), DIC
○ Platelet clumping: pseudo-thrombocytopaenia; an ethylenediaminetetraacetic acid (EDTA) artifact
Describe Immune Thrombocytopaenia (ITP)
○ Acquired immune disorder
○ Isolated thrombocytopaenia (all other blood parameters normal)
○ Platelet count < 100 x 104
○ Incidence 1:10 000
○ Incidence equal across sexes, except 3rd and 4th decade of life, F > M
○ Cause: unknown, can be proceeded by infection or vaccination
Describe the THREE stages of ITP
○ Newly Diagnosed: 0 -3 months
○ Persistent: 3-12 months
○ Chronic: > 12 months
Describe the pathophysiology of ITP
○ Anti-platelet antibodies directed against both platelets and megakaryocytes
▫ Antibody coated platelets are targeted for destruction by macrophages in spleen, sometimes in liver, and by direct platelet-lysis
▫ Antibodies that target megakaryocytes reduce platelet production
○ Regulatory T cells are reduced in patients with ITP
○ Skewing towards T helper 1 and 17 autoimmune phenotypes
○ Cytotoxic T cells also directly lyse platelets
Describe the management of “newly diagnosed” ITP
○ Newly Diagnosed ITP (0 - 3 months)
▫ Steroids (prednisolone, dexamethasone, methylprednisolone)
▫ Intravenous Immunoglobulin (IVIG)
Describe the management of “persistent” ITP
○ Persistent ITP (3 - 12 months) = immunosuppression
▫ Mycophenolate mofetil (MMF)
▫ Thrombopoietin receptor agonists (TRAs - eltrombopag, romiplostim). New agents that stimulate bone marrow to produce platelets. Good for sparing corticosteroids and immunosuppressants. May increase risk of thrombosis; use with caution in patients with other thrombosis or cardiac risk factors
▫ Rituximab
▫ Azathioprine
Describe the management of “chronic” ITP
○ Chronic ITP (> 12 months)
▫ Continuous TRAs
▫ Repeated Rituximab (+/- dexamethasone)
▫ Continuous MMF
▫ Others: (danazol, dapsone, hydroxychloroquine)
▫ Splenectomy; before splenectomy, platelet disruption scan is performed to see whether platelets are predominately removed by spleen.
Describe the principles of treatment of ITP
○ Platelet count > 30 x 104 rarely need treatment, unless bleeding risk (taking anticoagulant) or about to undergo surgery
○ Adults with platelet count > 10 x 104 are routinely treated
○ Adults with platelet count between 10 - 30 x 104 are treated depending on; age, risk factors, bleeding and others symptoms (i.e. fatigue), lifestyle ‘risk’ factors
○ Patient with infections: H Pylori, HIV, Hepatitis, should be treated accordingly
