1 / 14

HIV-Associated Thrombotic Microangiopathy

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

galena-fletcher
Download Presentation

HIV-Associated Thrombotic Microangiopathy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. HIV-Associated Thrombotic Microangiopathy Jack Kuritzky, PGY-2 UNC Internal Medicine April 16, 2010

  2. 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

  3. Idiopathic TTP • Pentad of symptoms • MAHA • Thrombocytopenia • Renal failure • Fever • Neurologic symptoms

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. REFERENCES • 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.

  11. THE END Madrid on Good Friday

  12. THE END Sevilla

  13. THE END Barcelona

  14. THE END Valencia

More Related