Thrombotic Thrombocytopenic Purpura (TTP) and HIV-Associated Immune Thrombocytopenia (ITP)
What is TTP?
TTP is a rare, life-threatening blood disorder caused by severe deficiency (<10%) of ADAMTS-13 enzyme activity, leading to accumulation of ultra-large von Willebrand factor multimers that trigger widespread microvascular thrombosis and ischemic organ damage 1.
Pathophysiology
TTP occurs through two mechanisms:
- Immune TTP (iTTP): Autoantibodies against ADAMTS-13 enzyme (most common in adults)
- Congenital TTP (cTTP): Genetic mutations in ADAMTS13 gene (rare, ~250 mutations identified)
ADAMTS-13 normally cleaves ultra-large von Willebrand factor (UL-VWF) in the bloodstream. When ADAMTS-13 activity drops below 10%, UL-VWF accumulates on endothelial surfaces and in circulation, causing excessive platelet adhesion and aggregation. This creates microthrombi throughout the body, resulting in the pathognomonic features of TTP 1, 2.
Clinical Presentation
Patients present with severe thrombocytopenia (usually <30 × 10⁹/L) and microangiopathic hemolytic anemia (low hemoglobin, elevated lactate dehydrogenase, schistocytes on blood smear), plus variable end-organ damage 1, 2.
Common symptoms include:
- Neurologic manifestations (39-80%): headache, confusion, seizures
- Abdominal pain (35-39%)
- Fever
- Renal dysfunction
Diagnosis
Use clinical prediction scores (French score or PLASMIC score) to assess likelihood of severe ADAMTS-13 deficiency before laboratory confirmation. Diagnosis requires ADAMTS-13 activity <10% in the proper clinical context 1, 2.
How Does HIV Cause ITP?
HIV causes ITP through immune dysregulation leading to antiplatelet antibody production and increased platelet destruction by the reticuloendothelial system, not through the ADAMTS-13 deficiency mechanism seen in TTP 3, 4.
Key Distinction: HIV-ITP vs HIV-TTP
These are two separate conditions that must be distinguished:
HIV-Associated ITP
- Mechanism: Immune-mediated platelet destruction via antiplatelet antibodies
- ADAMTS-13 activity: Normal (>10%)
- Incidence: 6-15% of HIV-infected patients develop thrombocytopenia 4
- Severity: Typically less severe than primary ITP
- Treatment: Highly active antiretroviral therapy (HAART) is first-line; addresses underlying immune dysregulation 4
HIV-Associated TTP (Rare)
- Mechanism: Severe ADAMTS-13 deficiency (<10%)
- Occurs: Usually when CD4+ count <250 × 10⁶/L 5
- Presentation: Often triggered by concurrent infection or malignancy (>50% of cases) 5
- Treatment: Plasma exchange plus antiretroviral therapy 6, 7
- Mortality: 22% despite plasma exchange 5
Pathophysiology of HIV-ITP
HIV causes ITP through multiple mechanisms:
- Direct immune dysregulation: HIV infection disrupts normal immune function, promoting autoantibody formation against platelet surface antigens
- Molecular mimicry: HIV antigens may cross-react with platelet antigens
- Impaired platelet production: HIV can directly infect megakaryocytes in bone marrow
- Enhanced platelet clearance: Opsonized platelets are cleared by splenic macrophages 3, 4
Clinical Approach
Screen all ITP patients with risk factors for HIV infection 8, 4. Risk factors include:
- Sexual risk behaviors
- Injection drug use
- Geographic regions with high HIV prevalence
- Unexplained lymphopenia
For confirmed HIV-associated ITP, initiate HAART as primary therapy—this addresses the underlying immune dysfunction and often improves platelet counts without additional immunosuppression 4.
Critical Pitfall
Do not confuse HIV-associated ITP with HIV-associated TTP—they require fundamentally different treatments. Always check ADAMTS-13 activity in HIV patients presenting with thrombocytopenia and hemolytic anemia to distinguish between these conditions 6, 9. HIV-TTP requires urgent plasma exchange, while HIV-ITP responds to antiretroviral therapy.