Thrombotic Thrombocytopenic purpura (TTP)

Related Subjects: |Microangiopathic Haemolytic anaemia |Haemolytic anaemia |Immune(Idiopathic) Thrombocytopenic Purpura (ITP) |Thrombotic Thrombocytopenic purpura (TTP) |Haemolytic Uraemic syndrome (HUS) |Thrombocytopenia |Disseminated Intravascular Coagulation (DIC)

Due to a deficiency in the metalloproteinase ADAMTS13, which is involved in the regulation of von Willebrand factor. Patients with TTP require specialist care, in a regional centre. It carries a 90% mortality rate if incorrectly treated

TTP has 5 distinct features - the Pentad

• 1. Thrombocytopenia
• 2. Haemolytic anaemia
• 3. AKI (less severe than HUS)
• 4. Neurologic symptoms
• 5. Fever

Aetiology

• Thrombotic Thrombocytopenic purpura is due to the deficiency of a specific metalloproteinase called ADAMTS13 due to an autoantibody that inhibits its activity which is to break down very high molecular weight multimers of von Willebrand factor.
• The absence of the enzyme leads to the accumulation of high molecular weight multimers of vWF in plasma which under some circumstances may promote platelet micro aggregate formation throughout the microcirculation, leading to the symptoms of TTP

Causes

• Idiopathic, Pregnancy, Stem cell transplantation
• Drugs - quinine, Clopidogrel, ticlopidine, Ciclosporin, tacrolimus

Clinical

• There may be some bleeding causing some petechiae and epistaxis
• Transient neurology e.g. fits, strokes, TIA
• Renal failure may be seen

Investigations

• Microangiopathic haemolytic anaemia + low platelets
• Smear shows Schistocytes and haemolysis
• Elevated urea and creatinine and LDH
• There are excess amounts of aggregates of von Willebrand factor
• This is due to a deficiency of a VWF protease called ADAMTS13
• APTT, TTT and Thrombin time and Fibrinogen levels are all NORMAL
• Haemolysis - raised LDH, raised retics, raised Unconjugated bilirubin, decreased haptoglobins

Differential TTP vs HUS vs Meningococcal septicaemia vs DIC

• Schistocytes and a frank microangiopathic haemolytic anaemia are much more marked in TTP than DIC
• While DIC and thrombotic microangiopathies share features such as microvascular occlusion and microangiopathic haemolytic anaemia, they are pathologically distinct.
• In TTP and HUS laboratory tests of coagulation, such as PT and PTT, are usually normal.
• Some would just label adult disease as TTP irrespective of neurological involvement

Differential

• Haemolytic uraemic syndrome - E. Coli 0157:H2 in children with renal failure and anaemia and low plt and normal clotting.
• Meningococcal sepsis - also fever and low plt but also coagulopathy
• Malignant hypertension, Preeclampsia, HELLP syndrome, SLE
• Neoplastic process e.g. disseminated malignancy

Management: urgent Haematology consult

• Untreated TTP is associated with high mortality due to multiorgan failure. Therapy with the early initiation of daily plasma exchange using fresh frozen plasma is crucial, and the majority of patients now survive the initial episode
• Patients with TTP require specialist care, potentially necessitating transfer to a regional centre. It carries a 90% mortality rate if incorrectly treated.
• Plasma exchange is the corner of all therapy for TTP - removes the autoantibodies that block ADAMTS13 activity. This may be combined with corticosteroids
• Caplacizumab may be prescribed as an adjunctive therapy in adults. Caplacizumab is a monoclonal antibody fragment (nanobody) that binds to von Willebrand factor, thereby inhibiting platelet adhesion. It is used for Acquired thrombotic thrombocytopenic purpura