1. HIV and haematology Rewriting the textbooks

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

3. NEVER FORGET People with HIV have other diseases as well

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

5. Cytopenias Decreased production Increased destruction/ sequestration/ loss

6. 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

7. Increased red cell loss 1.Splenomegaly 2.Immune destruction

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

9. 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

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

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

12. Neutrophil dysplasia

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

15. HIV bone marrow

16. Serous degeneration

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

18. Macrophages

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

20. ITP

21. Rare and life-threatening conditions

22. Microangiopathic haemolysis TTP HUS DIC

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

24. Haemophagocytic syndrome

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

26. Mycobacteria

27. Cryptococcus

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