Thrombocytopenia Flashcards
What is ITP?
Autoimmune disorder characterised by antiplatelet antibodies leading to platelet destruction.
What platelet count is characteristic of ITP?
Below 100 x10^9/mL
What are the types of ITP?
Acute and chronic
What is the aetiology of ITP? (x6)
- Most commonly idiopathic
- ACUTE: 2-weeks post-viral infection
- CHRONIC: infections (malaria, EBV, HIV), autoimmune diseases (SLE, thyroid), malignancies, drugs (quinine).
What is the pathophysiology of ITP? (x3 points)
Autoantibodies that bind to glycoprotein IIb/IIIa and glycoprotein Ib/IX on the plasma membrane results in thrombocytopenia. There is also impairment of platelet production due to suppression of megakaryocyte development by autoantibodies and T-cell mediated destruction of platelets and megakaryocytes in the bone marrow.
What is the epidemiology of ITP: Age? Gender?
Acute more common in children (2-7y/o); chronic more common in adults. In adults, it is 4 times more common in women.
What are the signs and symptoms of ITP? Note about absence of a symptoms? (x2) !
Easy bruising, mucosal bleeding, menorrhagia, epistaxis. Petechiae, purpura, ecchymoses. NO SPLENOMEGALY (which you would get in myelodysplastic disorders which presents very similarly). Absence of systemic symptoms.
What are the investigations for ITP? (x4)
- FBC: low platelets, but NORMAL PT/APTT/fibrinogen (normal because APTT/PT measures clotting factors; not platelets).
- Autoantibodies: antiplatelet antibody but not routinely tested. Anticardiolipin antibodies and ANA may also be present
- BLOOD FILM: to rule out pseudothrombocytopenia caused by platelet clumping giving false low counts (as seen in blood collected in EDTA bottles)
- BONE MARROW: exclude other pathology. Should see normal or raised megakaryocytes.
What is the role of fibrinogen?
It is catalysed by thrombin into fibrin which forms clots.
What is the purpose of investigations for ITP?
Exclude myelodysplasia, acute leukaemia, and marrow infiltration which can all present with thrombocytopenia.
What is HUS?
Characterised by triad of microangiopathic haemolytic anaemia (MAHA), thrombocytopenia and AKI.
What are the two types of HUS? Alternative name?
D+ (diarrhoea-associated) and D- (inciting factor is not known i.e. no prodromal illness, no diarrhoea, associated with dysregulation/uncontrolled activation of complement). D- is also known as ATYPICAL HUS.
What is the aetiology of HUS? (x7 (x4 and x4))
- INFECTION: Verotoxin-producing E. coli from contaminated water, meat and dairy (aka Shiga toxin producing E. coli), Shigella, neuraminidase-producing infections such as pneumococcal pneumonia, HIV.
- DRUGS: OCP, ciclosporin, mitomycin, 5-fluorouracil
- Malignant hypertension
- Malignancy
- Pregnancy
- SLE
- Scleroderma (hardening and tightening of skin and connective tissues)
What is the pathophysiology of HUS D+? (x3 points)
- Infection, drug etc. causes endothelial injury resulting in platelet aggregation, release of unusually large vWF multimers and activation of platelets and clotting cascade.
- This results in small vessel thrombosis, particularly in the glomerular-afferent arteriole and capillaries, which undergo fibrinoid necrosis (antigen-antibody complexes are deposited into blood vessel walls with fibrin)
- The thrombi also promote intravascular haemolysis
What are the risk factors for HUS? (x2)
Family history – these patients have abnormalities in their alternative complement pathways which predispose them to the condition. Also bone marrow transplant.
