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HIV-Associated Thrombotic Microangiopathy. Jack Kuritzky, PGY-2 UNC Internal Medicine April 16, 2010. Thrombotic Microangiopathy. Generic term for microvascular thrombosis from vascular diseases characterized pathologically by fibrinous clot TTP/HUS Malignant HTN Eclampsia/Preeclampsia

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hiv associated thrombotic microangiopathy

HIV-Associated Thrombotic Microangiopathy

Jack Kuritzky, PGY-2

UNC Internal Medicine

April 16, 2010

thrombotic microangiopathy
Thrombotic Microangiopathy
  • Generic term for microvascular thrombosis from vascular diseases characterized pathologically by fibrinous clot
    • TTP/HUS
    • Malignant HTN
    • Eclampsia/Preeclampsia
    • DIC
    • Connective Tissue Disease
idiopathic ttp
Idiopathic TTP
  • Pentad of symptoms
    • MAHA
    • Thrombocytopenia
    • Renal failure
    • Fever
    • Neurologic symptoms
maha and ttp
  • MAHA is not unique to TTP/HUS…
    • Malignant HTN
    • DIC
    • APLAS
    • Rheumatologic conditions (SLE or scleroderma)
    • Pre-eclampsia/eclampsia
    • HELLP syndrome
    • Mechanical trauma (artificial heart valves)
    • HIV
    • Hematopoietic progrenitor cell transplants
    • Myelodysplasia
    • Erythroleukemia
  • TTP is a diagnosis that requires exclusion of more plausible etiologies
idiopathic ttp1
Idiopathic TTP
  • Pentad of symptoms
    • MAHA, thrombocytopenia, renal failure, fever, neurologic symptoms
  • Pathophysiology
    • ADAMTS13 (von Willebrand metalloprotease) deficiency often due to an inhibitor
    • Normal ADAMTS13 cleaves Unusually Large VWf (ULVWf) into VWf
    • Presence of ULVWf leads to platelet aggregation, clumping, and ultimately microthrombi
  • Treatment with plasma exchange rests in its ability to remove ADAMTS13 inhibitor and replenish the ADAMTS13 protein
hiv associated thrombotic microangiopathy1
HIV-AssociatedThrombotic Microangiopathy
  • “TTP” was more commonly diagnosed in HIV patients during the pre-HAART era
    • Associated with advanced disease and low CD4 counts
    • Often found in conjunction with opportunistic infections
    • In a study of 350 consecutive admission to Hopkins inpatient HIV service 1996-1997…
      • 24% of patients had schistocytes
      • 7% had TTP-like syndrome w/anemia, thrombocytopenia, schistocytosis and renal dysfunction/neurologic disease
    • Associated with very high-mortality rates (70-100% at 3 months)
  • Once HAART became more commonplace, the incidence has decreased
    • Most studies document <1% incidence
hiv associated thrombotic microangiopathy2
HIV-AssociatedThrombotic Microangiopathy
  • ADAMTS13 Levels (almost) Normal
    • Limited to case series
    • Inhibitor typically not present
    • Correlate with severity of HIV/AIDS
      • Lower CD4 and High viral load = normal ADAMTS13 and no inhibitor
  • As a result, HIV-Associated Thrombotic Microangiopathy does not respond as well to Plasma Exchange
    • Do not need to remove inhibitor
    • Do not need to replenish ADAMTS13
  • Several case series and case reports document improvement with HAART
    • Improvement typically seen within one week
hiv associated tma pathogenesis
HIV-Associated TMA: Pathogenesis
  • Debated, studies ongoing, likely multifactorial
  • Infection of hematopoietic cells – explains thrombocytopenia
    • Affect maturation and differentiation of megakaryocytes
    • Leads to deposition of immune complexes on platelets and thus accelerated clearance
  • Endothelial cells infected
    • Leads to increased release of VWf, which has been observed clinically in several patients with HIV-Associated Thrombotic Microangiopathy
    • This may overwhelm available ADAMTS13  increased ULVWf  increased platelet clumping and aggregation
hiv associated thrombotic microangiopathy3
HIV-Associated Thrombotic Microangiopathy
  • Summary
    • Similar to TTP clinically, but has (more) normal ADAMTS13 levels
    • Associated with lower CD4 counts and higher viral loads
    • Responds to HAART better than plasma exchange
  • UNC Laboratory Medicine has contributed significantly to the research in this field
  • Becker, S, et al. HIV-Associated Thrombotic Microangiopathy in the Era of Highly Active Antiretroviral Therapy: An Observational Study. Clinical Infectious Diseases. 39: S267-275. 2004.
  • Brecher, ME et al. Is it HIV TTP or HIV-Associated Thombotic Microangiopathy. Journal of Clinical Apheresis. 23:186-190. 2008.
  • Egan, JA et al. Frequency and Significance of Schistocytes in TTP/HUS Patients at the Discontinuation of Plasma Exchange Therapy. Journal of Clinical Apheresis. 19: 165-167. 2004.
  • Gervasoni, C et al. Thrombotic Microangiopathy in Patients with Acquired Immunodeficiency Syndromes Before and During the Era of Introudction of Highly Active Antiretroviral Therapy. Clinical Infectious Diseases. 35:1534-1540. 2002.
  • George, JN. Causes of Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in adults. UpToDate. 2010.
  • Park, YA et al. ADAMTS13 Activity Levels in Patients with Human Immunodeficiency Virus-Associated Thrombotic Microangiopathy and Profound CD4 Deficiency. Journal of Clinical Apheresis. 24:32-36. 2009.
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