Signs and Symptoms of Thrombotic Thrombocytopenic Purpura (TTP)
Thrombotic Thrombocytopenic Purpura (TTP) is characterized by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurological abnormalities, renal dysfunction, and fever, though not all five features may be present in every case. 1
Core Clinical Manifestations
Microangiopathic hemolytic anemia: Evidenced by schistocytes (fragmented red blood cells) on peripheral blood smear, elevated lactate dehydrogenase (LDH), decreased hemoglobin, and decreased haptoglobin 1, 2
Thrombocytopenia: Often severe, with platelet counts typically below 30 × 10^9/L 2
Neurological symptoms: Present in 39-80% of patients, including headache, confusion, seizures, focal neurological deficits, and altered mental status 2
Renal dysfunction: May present as elevated creatinine, though typically less severe than in hemolytic uremic syndrome 1
Fever: May be present but not required for diagnosis 3
Additional Clinical Manifestations
Abdominal pain: Occurs in 35-39% of patients due to microvascular ischemia 2
Cardiac involvement: May include chest pain, arrhythmias, and myocardial infarction due to microvascular thrombosis 4
Bleeding manifestations: Patients may experience purpura, petechiae, epistaxis, gingival bleeding, or more severe hemorrhage 5, 6
Visual disturbances: May include blurred vision or visual field defects 1
Laboratory Findings
Severe ADAMTS13 deficiency: Activity levels <10% of normal, often with detectable inhibitory autoantibodies against ADAMTS13 4
Elevated LDH: Typically markedly increased due to hemolysis 7
Indirect hyperbilirubinemia: Due to increased red blood cell destruction 1
Negative direct antiglobulin test (Coombs test): Distinguishes from autoimmune hemolytic anemia 1
Reticulocytosis: Compensatory response to hemolysis 1
Risk Factors and Special Populations
Demographics: Higher incidence in adults than children, females than males (3.19 times higher), and Black individuals compared to non-Black individuals (7.09 times higher) 2
Precipitating factors: May include pregnancy, infections, autoimmune disorders, certain medications, or malignancy 4
Diagnostic Considerations
Early recognition is critical: TTP is a hematological emergency with high mortality if untreated 7
Clinical prediction tools: Platelet count <30 × 10^9/L and creatinine <2.0 mg/dL are helpful predictors for TTP diagnosis before ADAMTS13 results are available 2
Differential diagnosis: Must distinguish from other thrombotic microangiopathies including atypical hemolytic uremic syndrome (aHUS), disseminated intravascular coagulation (DIC), and HELLP syndrome 4
Disease Course and Prognosis
Rapid progression: Without treatment, TTP can rapidly progress to life-threatening complications 7
Response to treatment: Patients can be classified as early responders (normalization of platelet count by day 5) or late responders (requiring more prolonged therapy) 8
Relapse risk: Approximately 16% of patients experience at least one relapse after achieving clinical remission 2
Mortality: Untreated TTP has a mortality rate approaching 90%, but with prompt treatment, survival rates exceed 90% 2
Common Pitfalls in Diagnosis
Incomplete pentad: The classic pentad of symptoms is present in only a minority of patients; absence of all five features does not exclude TTP 3
Delayed recognition: Waiting for all classic symptoms to appear before initiating treatment increases mortality 7
Misdiagnosis: TTP may be confused with other causes of thrombocytopenia and hemolytic anemia 9
Overlooking TTP in patients with neurological symptoms: Neurological manifestations may be attributed to other causes, delaying diagnosis 1
Remember that TTP is a medical emergency requiring immediate intervention with plasma exchange and immunosuppression to prevent life-threatening complications 1, 2.