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Ovid: Oxford Handbook of Genitourinary Medicine, HIV, and Aids

Editors: Pattman, Richard; Snow, Michael; Handy, Pauline; Sankar, K. Nathan; Elawad, Babiker Title: Oxford Handbook of Genitourinary Medicine, HIV, and Aids, 1st Edition Copyright ©2005 Oxford University Press > Table of Contents > HIV/AIDS > Chapter 51 – HIV: reticulo-endothelial disorders Chapter 51 HIV: reticulo-endothelial disorders P.492
Haematological disorders Common haematological abnormalities may lead to consideration of HIV as the cause. Direct effect of HIV itself or 2° to concurrent infection, malignancy, and therapeutic agents. ↓ haemopoiesis, altered coagulation, and immunemediated cytopenias with ↓ bone marrow cellularity and dysplasia common findings. Anaemia Most common form of cytopenia and an independent prognostic factor. Usually due to ↓ erythropoiesis but other mechanisms e.g. infection, drug toxicity, malignancy, dietary deficiencies, and blood loss may contribute. Chronic anaemia causes fatigue, exertional dyspnoea and a hyperdynamic state which, if severe, may lead to angina, congestive cardiac failure, and confusion. Diagnosis and evaluation Examine and test for iron, vitamin B12 and folate deficiencies, haemolysis and blood loss according to red cell indices. Eliminate possible causes by excluding infection and malignancy and reviewing drug therapy. Bone marrow examination may be required.

  • HIV-related. Normocytic, normochromic anaemia ↑ frequency and severity as HIV progresses. May be a direct effect of HIV on bone marrow progenitor cells, ↓ erythropoietin production and ↑ cytokines (inhibit haemopoiesis). Improves or normalizes with HAART providing drug effects do not supervene.
  • Drug toxicity
    • Macrocytosis and normal haemoglobin—typical with zidovudine (AZT).
    • Macrocytic anaemia—caused by AZT and stavudine. AZT exerts broader myelosuppressive effects, more frequent in patients receiving higher doses (in ~1% receiving 500mgs a day) and those with advanced disease. Anaemia may require blood transfusion following discontinuation of AZT. In patients with a low level of endogenous erythropoietin (<500IU/L), recombinant human erythropoietin may resolve anaemia thereby ↓ need for transfusion.
    • Normocytic, normochromic anaemia—associated with normal or ↓ reticulocyte count, 2° to bone marrow suppression. Causes include anaemia of chronic infection and drugs (e.g. ganciclovir, cotrimoxazole, amphotericin, and interferons).
    • Haemolytic anaemia—features are macrocytosis, ↓ haptoglobin, and ↑ lactic dehydrogenase, indirect bilirubin, and reticulocyte count. Common causes include drugs e.g. dapsone (with methaemoglobinaemia), ribavirin, and primaquin. Glucose-6-phosphate dehydrogenase (G6PD) deficiency predisposes to dapsone and primaquin haemolysis. Autoimmune haemolytic anaemia (AIHA) with positive Coomb’s test also occurs.
  • P.493

  • Bone marrow infiltration (usually causes pancytopenia)
    • Opportunistic infection (OI)—most commonly Mycobaterium avium complex, (also tuberculosis and cytomegalovirus).
    • Tumours—lymphoma and rarely Kaposi’s sarcoma.
  • B19 parvovirus infects erythroid precursors. In immune deficiency persistent infection may result in severe chronic normocytic normochromic anaemia. Diagnosed by detecting B19 parvovirus antibodies and DNA (by polymerase chain reaction) in serum and/or bone marrow. Responds well to high dose intravenous immunoglobulins (0.4g/kg/day) which contain parvovirus antibodies but may require repeated blood transfusions.

P.494
Thrombocytopenia Occurs in up to 30%. May be result of drug toxicity, immune and non-immune destruction, or defective platelet production. Commonly an isolated haematological abnormality with ↑ levels of anti-platelet immunoglobulin. HIV-related immune thrombocytopenia frequent early finding tending to deteriorate as HIV progresses. Results from clearance of immunoglobulin coated platelets by reticulo-endothelial system. Diagnosis and evaluation Exclude underlying causes e.g. drug toxicity, liver disease, and lymphoma. In their absence the presence of normal or ↑ megakaryocytes on bone marrow examination is sufficient to diagnose HIV-induced thrombo-cytopenia. Treatment

  • Mild and asymptomatic—HAART, switch/discontinue implicated drugs.
  • Symptomatic or before surgical procedures—intravenous immunoglobulins, steroids, and HAART.
  • Substantial bleeding—packed red cells and platelet transfusion.

Thrombotic thrombocytopenic purpura Rare, of unknown aetiology, usually seen in early stages of HIV infection. Characterized by hyaline microvascular deposits. Clinical features include fever, renal impairment, neurological deficit, and microangiopathic haemolytic anaemia. Good response to plasmapheresis, steroids, and anti-platelets. Neutropenia HIV directly implicated, especially in advanced stages. More commonly due to drug toxicity, associated infection, and bone marrow infiltration. Risk of bacterial infection ↑ significantly when absolute neutrophil count <500cells/µL. Drugs causing neutropenia include AZT, ganciclovir, co-trimoxazole, pentamidine, α-interferon, and chemotherapeutic agents. Diagnosis and evaluation Careful review of medication. Withdraw offending drug/s if absolute neutrophil count is <500cells/µL. If cause uncertain consider bone marrow examination. Treatment

  • HAART—variable response
  • Granulocyte colony stimulating factor:
    • HIV-induced
    • drug-induced (if implicated drug cannot be reduced or stopped).

P.495
Coagulation disorders ↑ risk of thrombotic disease associated with low CD4 counts, OIs, neoplasms, and HIV-associated autoimmune disorders such as AIHA.

  • Lupus anticoagulant may be detected with thrombo-embolic disease.
  • ↓ levels of active protein S frequently found, although not associated with immune suppression.
  • Contributing prothrombotic factors include; ↓ plasminogen activator inhibitor level, abnormal platelet aggregation and ↑ von Willebrand factor.

P.496
Persistent generalized lymphadenopathy Generalized lymphadenopathy involving ≥2 extra inguinal sites persisting for more than 3 months. Of no prognostic significance but other causes of generalized lymphadenopathy should be excluded. Occurs in up to 70% of patients within 1 year of seroconversion but may co-exist with other manifestations of HIV infection. Lymph nodes usually symmetrical, >1cm in size, rubbery, and non-tender. May be accompanied by hepatosplenomegaly. Mediastinal lymphadenopathy usually has other causes. Important diagnoses to consider in HIV associated lymphadenopathy

  • Persistent generalized lymphadenopathy
  • Bacterial infections (including mycobacteria)
  • 2° syphilis
  • Lymphoma
  • Histoplasmosis
  • Multicentric Castleman’s disease

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