Makindo Medical Notes.com

Related Subjects: |Microangiopathic Haemolytic anaemia |Haemolytic anaemia |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

Types

• Inherited TTP (Hereditary TTP or Upshaw-Schulman syndrome): genetic deficiency of the enzyme ADAMTS13, which is responsible for cleaving von Willebrand factor (vWF), a protein involved in blood clotting. Without ADAMTS13, unusually large vWF multimers accumulate, leading to excessive clot formation.
• Acquired TTP: production of autoantibodies that inhibit the activity of ADAMTS13. It can be triggered by various factors, including infections, certain medications, autoimmune diseases, pregnancy, and bone marrow transplantation.

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, headaches, confusion, seizures,
• Renal failure may be seen proteinuria, haematuria

Investigations

• FBC: anaemia and severe thrombocytopenia
• Blood 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
• ADAMTS13 activity is markedly reduced in most cases of TTP and inhibitors to this enzyme may be detected in acquired cases.

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 and Plasma Exchange (Plasmapheresis)

• 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/Plasmapheresis removes the autoantibodies that block ADAMTS13 activity.
  • Corticosteroids
  • Rituximab: targets B cells, which produce the autoantibodies against ADAMTS13. It
  • Caplacizumab is a monoclonal antibody fragment (nanobody) that binds to von Willebrand factor, thereby inhibiting platelet adhesion.
• With early diagnosis and treatment, the prognosis for TTP has significantly improved, with survival rates now exceeding 80-90%. However, without treatment, TTP can be rapidly fatal, so prompt recognition and intervention are critical. Long-term follow-up is often necessary to monitor for potential relapses or complications.