What are the diagnostic criteria for Thrombotic Thrombocytopenic Purpura (TTP)?

From the Guidelines

Thrombotic thrombocytopenia purpura (TTP) is recognized by a high index of suspicion for the diagnosis and timely recognition of clinical findings such as evidence of RBC destruction (schistocytosis), anemia, thrombocytopenia, and renal insufficiency. The diagnosis of TTP is primarily based on clinical presentation and laboratory findings, including severe thrombocytopenia, microangiopathic hemolytic anemia, and elevated lactate dehydrogenase (LDH) levels 1. Key diagnostic features include:

• Severe thrombocytopenia (platelet count typically below 30,000/μL)
• Microangiopathic hemolytic anemia with schistocytes (fragmented red blood cells) on peripheral blood smear
• Elevated LDH, reduced haptoglobin, and elevated indirect bilirubin
• Negative direct Coombs test
• Demonstrating severely reduced ADAMTS13 activity (typically <10%) with or without the presence of ADAMTS13 inhibitors

According to the American Society of Clinical Oncology clinical practice guideline 1, the management of TTP involves:

• Holding immune checkpoint inhibitor therapy (ICPi) and discussing resumption with the patient after taking into account the risks and benefits
• Administering corticosteroids, such as prednisone 0.5-1 mg/kg/d for grade 2 TTP and methylprednisolone 1 g IV daily for 3 days for grade 4 TTP
• Initiating plasma exchange therapy (PEX) according to existing guidelines for grade 4 TTP
• Considering rituximab for refractory or relapsing cases

Prompt recognition and treatment of TTP are crucial to prevent increased mortality and morbidity, as delay in identification is associated with poor outcomes 1.

From the Research

Recognition of Thrombotic Thrombocytopenia Purpura

Thrombotic thrombocytopenia purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia linked to disseminated microvascular platelet rich-thrombi 2. The recognition of TTP is crucial to initiate appropriate treatment.

Clinical Presentation

TTP has a varied presentation and a tendency to mimic several disorders 3. However, it may be at least provisionally diagnosed in the patient with thrombocytopenia and microangiopathic hemolytic anemia without alternate cause. The clinical presentation of TTP includes:

• Microangiopathic hemolytic anemia
• Severe thrombocytopenia
• Organ ischemia linked to disseminated microvascular platelet rich-thrombi
• Ischemic end organ injury due to microvascular platelet-rich thrombi 4

Laboratory Diagnosis

The laboratory diagnosis of TTP is based on the measurement of ADAMTS13 activity, which is the pathophysiological hallmark of TTP 5. An ADAMTS13 activity level of less than 10% supports the diagnosis of TTP in appropriate clinical contexts. Other laboratory tests that can assist in the diagnosis of TTP include:

• ADAMTS13 assays, including the measurement of the antigen and activity
• Detection of autoantibodies to ADAMTS13
• Inhibitor tests to distinguish immune-mediated from congenital TTP 6, 5

Diagnostic Criteria

The diagnostic criteria for TTP include:

• Thrombocytopenia
• Microangiopathic hemolytic anemia
• ADAMTS13 activity level of less than 10%
• No alternate cause for the thrombocytopenia and microangiopathic hemolytic anemia 3, 6
• Clinical prediction scores can be used to estimate the pretest probability of severe ADAMTS13 deficiency and guide initial management decisions 6