Makindo Medical Notes

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

Thrombotic Thrombocytopenic Purpura (TTP) is 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 center. It carries a 90% mortality rate if untreated, but the mortality can be drastically reduced with prompt plasma exchange.

Types

• Familial Relapsing TTP: Caused by autosomal recessive inheritance of ADAMTS13 deficiency. Without ADAMTS13, unusually large von Willebrand Factor (vWF) multimers accumulate, leading to excessive clot formation. Low ADAMTS13
• Sporadic TTP: Results from an IgG autoantibody against ADAMTS13. Can be triggered by infections, medications, autoimmune diseases, pregnancy, and bone marrow transplantation. Normal ADAMTS13

Causes

• Idiopathic, Pregnancy, Stem cell transplantation
• Medications: quinine, Clopidogrel, ticlopidine, Ciclosporin, tacrolimus

Clinical

• Bleeding signs like petechiae and epistaxis
• Transient neurological symptoms: fits, strokes, TIA, headaches, confusion, seizures
• Renal issues: proteinuria, hematuria

Investigations

• FBC: anemia and severe thrombocytopenia
• Blood Smear: shows schistocytes and hemolysis
• Elevated urea, creatinine, and LDH levels
• Presence of excess von Willebrand factor aggregates
• This is due to deficiency of ADAMTS13 protease
• APTT, PT, Thrombin time, and Fibrinogen levels are all NORMAL
• Hemolysis indicators: raised LDH, reticulocytes, unconjugated bilirubin, decreased haptoglobins
• ADAMTS13 activity is markedly reduced in most TTP cases; inhibitors may be detected in acquired cases.

Differential Diagnosis (TTP vs HUS vs Meningococcal Septicemia vs DIC)

• Schistocytes and marked microangiopathic hemolytic anemia are more prominent in TTP than DIC
• TTP and HUS usually show normal coagulation tests, unlike DIC
• In adult presentations, some cases are labeled as TTP regardless of neurological involvement

Other Differentials

• Hemolytic Uremic Syndrome (HUS): Often in children with E. coli 0157:H7 infection; presents with renal failure, anemia, low platelets, and normal clotting
• Meningococcal Sepsis: Similar signs but also coagulopathy
• Other Conditions: Malignant hypertension, Preeclampsia, HELLP syndrome, SLE, Disseminated malignancy

Management: Urgent Haematology Consult and Plasma Exchange (Plasmapheresis)

• Untreated TTP has high mortality due to multiorgan failure. Early initiation of daily plasma exchange using fresh frozen plasma is critical for survival.
• TTP patients should be managed in a specialist center, with possible transfer to a regional center. Incorrect or delayed treatment has a high mortality rate.
• Plasma Exchange/Plasmapheresis: Removes autoantibodies against ADAMTS13
• Corticosteroids: Used to reduce inflammation and immune response
• Rituximab: Targets B cells producing ADAMTS13 autoantibodies
• Caplacizumab: A monoclonal antibody fragment that binds to von Willebrand factor to inhibit platelet adhesion
• With early diagnosis and treatment, TTP survival rates exceed 80-90%. However, without prompt treatment, TTP can be rapidly fatal. Long-term follow-up may be required to monitor for relapses or complications.