HIV and haematology Rewriting the textbooks

HIV has changed everything… 1.Common findings 2.Rare and life-threatening HIV-related conditions 3.Treatment-related changes

NEVER FORGET People with HIV have other diseases as well

Anaemia Virtually 100% of HIV positive individuals by the time AIDS develops. Negative prognostic indicator – independent of CD4 count and viral load

Cytopenias Decreased production Increased destruction/ sequestration/ loss

Decreased red cell production 1.Anaemia of chronic disorders: decreased responsiveness to erythropoietin (cytokine related) RE iron blockade shortened red cell survival 2.Ineffective erythropoiesis 3.Marrow infiltration

Increased red cell loss 1.Splenomegaly 2.Immune destruction

Thrombocytopenia Early: Increased loss >>> decreased production Later: Decreased production becomes increasingly important

ITP in HIV Frequently occurs before any other manifestation of HIV May be severe and life-threatening Responds to HAART and standard therapy – splenectomy contraindicated

Thrombocytopenia Increased loss: splenomegaly Decreased production: ineffective thrombopoiesis marrow infiltration

Neutropenia Decreased production >>> increased loss Ineffective – marked dysplastic changes especially in the presence of additional marrow infection. Suppression Splenomegaly Autoimmune destruction

Neutrophil dysplasia

Typical bone marrow findings Cellularity: Normal to reduced Few adipocytes Increased macrophages Tatty and disorganised Fine fibrosis Open sinusoids Serous degeneration

HIV bone marrow

Serous degeneration

Marrow appearances continued… Evidence of inflammation plasma cells lymphoid aggregates macrophages

Macrophages

Marrow appearances continued… Erythropoiesis: reduced and right-shifted disordered increased iron stores Granulopoiesis: normal to reduced dysplasia Thrombopoiesis: ITP: normal to increased dysplasia

ITP

Rare and life-threatening conditions

Microangiopathic haemolysis TTP HUS DIC

Pure red cell aplasia Not on ART – Parvovirus B19 On ART – AZT (Zidovudine) Consider autoimmune

Haemophagocytic syndrome

Don’t forget… Lymphomas Myeloma Other rarer malignancies Infections –TB, cryptococcus… Coagulation – antibodies to factors, lupus anticoagulant Thrombosis – inflammation, reduced Protein S, endothelium

Mycobacteria

Cryptococcus

Drug effects Zidovudine – AZT pure red cell aplasia reduced erythropoiesis macrocytosis myeloid suppression Cotrimoxazole neutropenia, thrombocytopenia 3TC Lamivudine – pure red cell aplasia