The Pentad of Thrombotic Thrombocytopenic Purpura (TTP)
The classic pentad of TTP consists of: (1) microangiopathic hemolytic anemia, (2) thrombocytopenia, (3) neurological abnormalities, (4) renal dysfunction, and (5) fever. 1
Critical Clinical Context
The complete pentad is present in only 40% of TTP cases, and diagnosis should never be delayed waiting for all five features to manifest. 2 The American Society of Clinical Oncology emphasizes that not all five features may be present in every case, yet TTP remains a life-threatening emergency requiring immediate recognition 1.
The Five Components Explained
1. Microangiopathic Hemolytic Anemia
- This represents intravascular red blood cell destruction caused by shear forces from platelet-rich microthrombi 1
- Manifests with schistocytes (fragmented red blood cells) on peripheral blood smear 3
- Associated findings include indirect hyperbilirubinemia from increased red cell destruction and reticulocytosis as a compensatory response 1
- A negative direct antiglobulin test (Coombs test) helps distinguish TTP from autoimmune hemolytic anemia 1
2. Thrombocytopenia
- Results from platelet consumption in forming microthrombi throughout the microcirculation 4
- TMA associated with TTP typically shows only moderate thrombocytopenia with few schistocytes, which is less severe compared to other thrombotic microangiopathies 4
- Platelet counts are characteristically low, often severely reduced 1, 5
3. Neurological Abnormalities
- Fluctuating neurologic symptoms are characteristic, ranging from confusion to focal deficits 6, 7
- Visual disturbances, including blurred vision or visual field defects, may occur 1
- Mental status changes can progress rapidly, as demonstrated in cases where patients deteriorate from normal mentation to requiring intubation within days 3
- Overlooking TTP in patients with neurological symptoms can delay diagnosis, as these manifestations may be attributed to other causes 1
4. Renal Dysfunction
- Presents as elevated creatinine, though typically less severe than in hemolytic uremic syndrome 1
- Renal involvement can occasionally be the predominant feature, with rapidly progressive renal dysfunction even in the absence of the complete pentad 2
5. Fever
- Part of the classic pentad but frequently absent 6, 7
- When present, fever results from the systemic inflammatory response to widespread microvascular thrombosis 8
Critical Diagnostic Pitfalls
Do not wait for the complete pentad before initiating treatment—this approach increases mortality. 7 The most dangerous error is dismissing TTP because all five features are not present 3.
- Missing atypical presentations: Cases may present with chest pain mimicking myocardial infarction, with initial peripheral smears showing no schistocytes, only to have schistocytes appear days later 3
- Misattributing symptoms: Thrombocytopenia may initially be attributed to drug-induced immune thrombocytopenic purpura, delaying recognition of TTP 3
- Overlooking cardiac involvement: Coronary artery microthrombi can cause sudden cardiac death, with presentations mimicking ischemic heart disease 8
Distinguishing TTP from Other Thrombotic Microangiopathies
The coexistence of severe blood pressure elevation with advanced retinopathy helps discriminate malignant hypertension-associated TMA from TTP 4. If needed, measurement of ADAMTS13 activity provides definitive differentiation: very low activity levels (<10%) confirm TTP, while normal or slightly reduced levels suggest hypertension-induced TMA 4.