ANEMIA, NEUTROPENIA Y TROMBOCITOPENIA EN INFECCION POR HIV

LUIS MIGUEL ALVAREZ SILVA RESIDENTE MEDICINA INTERNA HOSPITAL SANTA CLARA UNIVERSIDAD EL BOSQUE ABRIL 2005

EPIDEMIOLOGIA
ANEMIA

70-95% LEUCOPENIA (LINFOPENIA) 6580% TROMBOCITOPENIA 25-40%

CAUSAS ANEMIA
PERDIDAS

SANGUINEAS DISMINUCION EN LA PRODUCCION DE GR AUMENTO EN LA DESTRUCCION DE GR PRODUCCION INEFICIENTE DE GR

FACTORES DE RIESGO

HISTORIA CLINICA DE SIDA CONTEO DE CD4 <200 CEL/Ul CARGA VIRAL EN PLASMA SEXO FEMENINO RAZA NEGRA USO DE ZIDOVUDINA EDAD AVANZADA IMC BAJO HISTORIA DE NEUMONIA BACTERIANA CANDIDIASIS ORAL FIEBRE

Table 1. Causes and Mechanisms of Anemia in HIV Infection

Cause of Anemia
Decreased RBC production (reticulocyte count low, indirect bilirubin normal or low)

Mechanism
A. Neoplasm infiltrating bone marrow Lymphoma Kaposi's sarcoma Hodgkin's disease

Others B. Infection
Mycobacterium avium complex (MAC) Mycobacterium tuberculosis Cytomegalovirus (CMV)

B19 parvovirus
Fungal infection Others C. Drugs See Table 2 D. HIV

Abnormal growth of BFU-E

Anemia of chronic disease Blunted erythropoietin production/response E. Iron deficiency anemia secondary to chronic blood loss

A. Folic acid deficiency Dietary Ineffective production (reticulocyte count low, indirect bilirubin high) Jejunal pathology: malabsorption B. B12 deficiency Malabsorption in ileum Gastric pathology with decreased production of intrinsic factor Production of antibody to intrinsic factor, as in pernicious anemia Increased RBC destruction, aka hemolysis (reticulocyte count high, indirect bilirubin high) A. Coombs' positive hemolytic anemia B. Hemophagocytic syndrome C. Thrombotic thrombocytopenic purpura (TTP) D. Disseminated intravascular coagulation (DIC) E. Drugs Sulfonamides, dapsone Oxidant drugs in patients with glucose 6-dehydrogenase (G6PD) deficiency

Table 2. Drugs That Commonly Cause Myelosuppression in the Patient With HIV Antiretrovirals Zidovudine Lamivudine Didanosine Zalcitabine Stavudine Ganciclovir Foscarnet Cidofovir Flucytosine Amphotericin Sulfonamides Trimethoprim Pyrimethamine Pentamidine Cyclophosphamide Doxorubicin Methotrexate Paclitaxel Vinblastine Liposomal doxorubicin Liposomal daunorubicin Interferon-alfa

Antiviral agents

Antifungal agents Anti-Pneumocystis carinii agents

Antineoplastic agents

Immune response modifiers

IMPORTANCIA CLINICA ANEMIA

DISMINUCION EN LA SUPERVIVENCIA 96,9% Vs 84.1% Y 59.2% EN ANEMIA SEVERA AUMENTO EN LA PROGRESION DE LA ENFERMEDAD: EN PACIENTES CON CD4>200/Ul QUE DESARROLLABAN ANEMIA EL RIESGO RELATIVO DE MUERTE AUMENTO EN UN 148%, Y CON CD4 <200/Ul un 56%

IMPACTO ANEMIA

MAL FUNCIONAMIENTO FISICO: DISTRESS FISIOLOGICO, DISMINUCION EN LA CALIDAD DE VIDA, REGULAR DESEMPEO LABORAL, TRANSTORNOS DEL SUEO

CAUSAS TRATABLES DE ANEMIA

DEFICIENCIAS NUTRICIONALES (MALNUTRICION Y MALABSORCION) ANEMIA EN ENFERMEDAD CRONICA DROGAS MIELOSUPRESIVAS HIPOGONADISMO DEFICIENCIA DE VIT B12 Y/O A. FOLICO HISTIOCITOCIS HEMOFAGOCITICA MIELOFIBROSIS O MIELODISPLASIA NEOPLASIA (LINFOMA NO HODGKIN) INFECCIONES OPORTUNISTAS DE LA MEDULA OSEA

 LA

MEJOR TRANSFUSION ES LA QUE NO SE REALIZA

COMCENTRADOS DE GR SIN BLANCOS USO SISTEMATICO DE FILTROS IRRADIAR HEMODERIVADOS

TRATAMIENTO
DESPUES DE DESCARTAR OTRAS CAUSAS DE ANEMIA ERITROPOYETINA ALFA 400000 U SC C/SEM+HIERRO SUPLEMENTARIO

MONITORIA DE LA RESPUESTA A LAS 4 SEM

AUMENTO DE HB >1 GR/DL CONTINUA LA MISMA DOSIS

AUMENTO DE HB <1GR/DL AUMENTO DOSIS 60000 c/SEM

AUMENTA HB<1MG/DL AUMENTA HB 1 GR/DL CHEQUEAR FE++, FOLATO, VIT B12 CONTINUA MISMA DOSIS SI SON NORMALES SUSPENDER ERITROPOYETINA

13 GR/DLDISMINUIR ERITROPOYETINA 10000 U C/SEM PARA MANTENER HB DESEADA

Table 3. Use of Hematopoietic Growth Factors

Erythropoietin G-CSF GM-CSF

Indication

Anemia due to HIV, chronic inflammatory or infectious disease, or use of antiretrovirals, anti-infectives and/or cancer chemotherapy

Neutropenia < 1000 cells/dL due to HIV, anticancer chemotherapy; anti-infective agents

Evaluation required at baseline

Initial dosing

Serum erythropoietin level </= 500 IU/L Absence of other causes of anemia

100 mcg/kg administered subcutaneously 3 times/week

1 mcg/kg administered subcutaneously daily

5 mcg/kg administered subcutaneously daily

Subsequent dosing Side effects

Titrate as necessary to maintain response (approximately 10,000 U/wk) Pain at injection site Fever

Titrate as necessary to maintain response

Elevated lactic dehydrogenase Elevated alkaline phosphatase Bone pain

Flu-like syndrome Myalgias Bone pain Fatigue Fever

Targeted effect

Hemoglobin >/= 11 g/dL in women; >/= 12 g/dL in men

ANC >/= 1000 cells/dL

EFECTOS ADVERSOS

DESARROLLO DE ACS ANTI-GM-CSF AUMENTO DE LA REPLICACION VIRAL EN AUSENCIA DE ANTIRETROVIRALES FALTAN ESTUDIOS: RELACION COSTO BENEFICIO, IMPACTO DE LA TERAPIA, TASA DE INFECCION, SOBREVIDA Y CALIDAD DE VIDA

NEUTROPENIA

ALTERACION EN LA MIELOPOYESIS (INHIBICION DE PROGENITORES O MEDIADA POR FACTORES SOLUBLES, ALTERACIONES DEL ESTROMA QUE DISMINUYEN EL ESTIMULO DE MIELOPOYESIS TOXICIDAD POR MEDICAMENTOS ANTICUERPOS ANTI NEUTROFILOS

TROMBOCITOPENIA

RESULTADO DE LA VIREMIA POST INFECCION DESTRUCCION PERIFERICA AUMENTADA POR HIPERPLASIA DEL SISTEMA RETICULO ENDOTELIAL DESTRUCCION DE PLAQUETAS POR AUTOANTICUERPOS O INMUNOCOMPLEJOS CIRCULANTES INHIBICION DE PRECURSORES PLAQUETARIOS

Table 4. Treatment Options in HIV-ITP 1. Zidovudine (1000 mg/day) Response rate, 70% Best responses with platelets > 20,000/mm3 at baseline 2. Other effective antiretroviral agents and combinations 3. Interferon-alfa 4. Splenectomy 5. IVIG or anti-Rh (D), especially useful when rapid response is required for acute bleeding or procedures 6. Danazol 7. Corticosteroids 8. Can potentially leave untreated if platelets > 20,000/mm3

GRACIAS