From the Guidelines
Thrombotic thrombocytopenic purpura (TTP) is characterized by symptoms including fever, microangiopathic hemolytic anemia, renal dysfunction, and fluctuating neurological signs, such as confusion, coma, seizures, aphasia, hemiplegia, and papilledema. These symptoms are a result of the formation of diffuse hyaline microthrombi affecting the small vessels in the brain and various degrees of ischemic change, parenchymal hemorrhage, and subarachnoid hemorrhage (SAH) 1. Patients with TTP may also experience a range of other symptoms, including fatigue, weakness, and pallor due to anemia, as well as easy bruising, petechiae, and bleeding from mucous membranes due to the low platelet count.
Key Symptoms
- Fever
- Microangiopathic hemolytic anemia
- Renal dysfunction
- Neurological abnormalities, such as:
- Confusion
- Coma
- Seizures
- Aphasia
- Hemiplegia
- Papilledema
Pathophysiology
The symptoms of TTP are caused by the accumulation of unusually large von Willebrand factor multimers, which lead to platelet clumping in small blood vessels, creating widespread microvascular thrombi that damage organs and consume platelets 1. This process is often triggered by a severe reduction in ADAMTS13 enzyme activity.
Clinical Presentation
TTP is a medical emergency that requires immediate treatment, usually with plasma exchange therapy (plasmapheresis) and corticosteroids. The condition can affect multiple organ systems, leading to a diverse range of symptoms. Early recognition and treatment of TTP are critical to preventing long-term damage and improving outcomes 1.
From the Research
Symptoms of Thrombotic Thrombocytopenic Purpura (TTP)
The symptoms of TTP can be varied and may include:
- Microangiopathic hemolytic anemia (MHA) and thrombocytopenia with or without fever, renal failure, and neurologic manifestations 2
- Neurologic symptoms ranging from mild headaches to severe sequelae such as seizures, stroke, and coma 3
- Renal dysfunction, which can be transient and respond to therapeutic plasma exchange readily 2
- Anemia, thrombocytopenia, and LDH elevation 4
- Neurological symptoms, such as complex migraines, which can complicate diagnosis and delay treatment 3
- Petechiae, nosebleeds, and macroscopic urinary excretion of pigments 4
- Fever 4
- Disturbance of consciousness 5
- Purpura of the extremities 5
Clinical Presentation
TTP can present atypically, including with symptoms such as complex migraines, which can complicate diagnosis and delay treatment 3. The condition has heterogeneous modes of presentation, and if the diagnosis is strongly suspected, plasmapheresis can be started without laboratory confirmation 4.
Diagnostic Criteria
The occurrence of MHA and thrombocytopenia without an alternate cause is now sufficient to initiate therapy 2. ADAMTS13 activity may orient the diagnosis, but normal levels do not discard it 4. An ADAMTS13 activity below 6% is almost exclusive of TTP 4.
Importance of Early Recognition
Early recognition and prompt treatment are essential, as untreated TTP carries a high mortality rate 3. It is crucial to consider TTP in the differential diagnosis of patients presenting with a first-time complex migraine, as it can occasionally be the initial manifestation of this rare and serious condition 3.