Thrombotic thrombocytopenia purpura Flashcards
Define thrombotic thrombocyopenic purpura.
TTP is a clinical syndrome characterised by MAHA and thrombocytopenic purpura. Without treatment it is fatal.
Overlaps with HUS used to be said to overlap with TTP which has the additional features.
PENTAD rarely seen:
- MAHA
- Thrombocytopenic purpura
- AKI
- Neurological features
- Fever
What are the causes of TTP?
- post-infection e.g. urinary, gastrointestinal
- pregnancy
- drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
- tumours
- SLE
- HIV
What are the risk factors for TTP?
- Black ethnicity
- Female
- Obesity
- Pregnancy *near term or post-partum period
- Cancer therapy
- HIV infection
- Bone marrow transplantation
- Antiplatelet agents
- Quinine
What are the functions of von Willebrand factor?
- Carrier protein for factor VIII, protecting it from rapid degeneration
- Bridge connecting platelets to damaged endothelium
What is the pathophysiology of TTP?
- Production of unusually large vWF multimers causes platelets to clump within vessels
- Lack of ADAMTS-13 (the enzyme which cleaves vWF) causes these large multimers to remail in circulation
- Considered a spectrum with HUS and TTP often difficult to distinguish
How common is TTP?
- Rare
- HUS and TTP is higher in women and black ethnic groups
- Avg age 39yrs
What are the clinical features of TTP?
- Thrombocytopenia (epistaxis, bruising, petechiae, gingival bleeding, haematuria, menorrhagia, gastrointestinal bleeding, retinal haemorrhage, haemoptysis).
- Neurological - confusion, headache, paresis, aphasia, dysarthria, visual problems, encephalopathy, coma.
- Fever,
- Anaemia - pallor, jaundice (haemolytic anaemia), fatigue, arthralgia, myalgia.
- AKI - Proteinuria, micro-haematuria, raised urea and creatinine.
Other:
- Prodrome resembling a flu-like illness,
- Fatigue, generalised malaise, arthralgias
- Chest pain, heart failure, arrhythmias, hypotension.
- Abdominal pain.
What are the signs of TTP on examination?
Examination may be normal or:
- Fever.
- Purpura - non-palpable small purpuric spots or petechiae occur with thrombocytopenia, ie platelet count <50 x 109/L.
- Jaundice - secondary to haemolysis.
- Severe hypertension.
- Neurological problems as above.
- Splenomegaly.
What investigations would you do for TTP?
Bloods-
- Peripheral blood smear - schistocytes consistent with haemolysis, hallmark of disease but doesn’t distinguish from other thrombotic microangiopathies
- FBC - Hb <8g/L, low platelets (<20x10^9/L)
- Urea and creatinine - mildly elevated in 50%
- Coagulation studies - normal
- LDH - high due to ischaemia/necrosis
- Haptoglobin - significantly decreased in heamolysis
- Bilirubin - elevated
- Reticulocyte count - elevated
Urinalysis - proteinuria and microscopic haematuria
ADAMTS13 activity level and anti-ADAMTS13 antibodies - measured before treatment. Controversial whether it helps management
Direct Coombs’ test - negative (excludes immune cause of haemolytic anaemia)
Serology: HIV, Hep B and C, autoantibody screen, pregnancy test
What is the management of TTP?
- Corticosteroids to immunosuppress
- Aspirin for platelet aggregation
- Plasma exchange to replace ADAMTS-13
Long term: Patients are kept on aspirin long term to decrease platelet aggregation.
Other:
- Caplacizumab - mAb blocks the interaction between von Willebrand factor and platelets
- Folic acid +/- transfusion
- Splenectomy - no longer done now that there is plasma exchange
What are the complications of TTP?
- Stroke
- Renal dysfunction
- Acute MI
- Central catheter complications e.g. pneumothorax, bleeding
- Complications from plasma exchange e.g. thrombosis, hypotension
- Long-term corticosteroid treatment effects
- Transfusion related complications
What is the prognosis with TTP?
With the use of plasma exchange, mortality has fallen from >90% to between 10% and 30%.
Approximately 90% of patients will respond to plasma exchange within 3 weeks, with most responding within 10 days.
