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Haematology Group B

Haematology Group B. Owen Naidoo Abdullah Osman Christine Tanzil Ayse Togac. Patient details. 50 year old female Current Medical Conditions : Diabetes mellitus HIV Chronic renal failure (due to HIV) Current Treatment : Hemodialysis (3 times/week) Zidovudine (for number of years).

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Haematology Group B

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  1. Haematology Group B Owen Naidoo Abdullah Osman Christine Tanzil Ayse Togac

  2. Patient details • 50 year old female • Current Medical Conditions: • Diabetes mellitus • HIV • Chronic renal failure (due to HIV) • Current Treatment: • Hemodialysis (3 times/week) • Zidovudine (for number of years)

  3. Ms FBC Full Blood Count

  4. ZIDOVUDINE • Zidovudine (AZT) is an antiretroviral active against HIV. • Crosses BBB and inhibits HIV • Toxic effects include: anaemia, leucopenia, neutropenia. • i.e. should monitor FBD on a regular basis

  5. What Haematological parameters are consistent with the patient’s HIV? • CD4 cells, the major cells targeted by HIV, are killed and replaced in large numbers, until immunodeficiency results, leading to depleted CD4 lymphocyte numbers. • Ms FBC’s CD4 level is on the lower end of the range, thus indicating some form of immunodeficiency. • Treatment for HIV is based on this CD4 lymphocyte number.

  6. What Haematological parameters are consistent with the patient’s HIV(cont.)? • Anaemia occurs in 25% of asymptomatic HIV cases. • Can be due to drugs (eg Zidovudine) or can be due to chronic inflammatory disease. • Indicators of anaemia include low RCC, Hb, and Hct, all of which are evident in Ms FBC’s results. • Thrombocytopenia is common in HIV. Symptoms include mucosal bleeding as well as easy bruising. • Ms FBC’s current platelet count is within the recommended range.

  7. HIV is associated with leukopenia. • Leukopenia refers to low neutrophil, lymphocytes and monocytes. • Ms FBC has monocytes within the range, however lymphocytes are below the ideal range. Also the number of immature neutrophils is well above the range. This is indicative of low neutrophil numbers, and thus consistent with HIV.

  8. What haematological parameters are consistent with patient’s chronic renal failure? PART II

  9. Anaemia is associated with chronic renal failure and is mainly due to a deficiency of a hormone called erythropoietin (epo). Epo is produced by the kidney and in renal failure there is insufficient production. Epo stimulates red blood cell production from the bone marrow and a deficiency of epo leads to anaemia

  10. In Mrs FBC, she has a low red cell count, haemoglobin and hematocrit, indicated by her blood tests: • RCC 3.01x1012 /L • Hb 92g/L • Hct 27.6% • Target Hb/Hct in CRF is 11-12g/dL/33-36% • This is consistent with anaemia, where majority of patients with chronic renal failure are anaemic.

  11. If Anaemia is left untreated in CRF…. • Increase in cardiac output • Left ventricular hypertrophy • Decreased Pulmonary diffusion • Decreased oxygen utilization • Decreased cognitive function • Impaired functional ability • Impaired immune responsiveness • Congestive heart failure • Treatment for anaemia in patients with CRF is erythropoietin, where Hct has increased by 4-6% after 4 weeks of treatment.

  12. Other parameters associated with CRF… • Urea levels in Mrs FBC is 3mmol/L, indicating it is in the low end of the range. Low Urea levels are associated with decreased protein intake, severe liver disease, water retention and reduced synthesis. • Serum creatinine level is increased, where it is associated with a decrease in GFR and indicating chronic renal failure. Because Zidovudine is predominantly renally excreted, dosage adjustment is required.

  13. Creatinine clearance??? • Patient’s weight is not provided therefore cannot calculate Mrs FBC’s creatinine clearance.

  14. The patient has mild eosinophilia – what could this parameter reflect? PART III

  15. What is eosinophilia? • The term eosinophilia refers to conditions in which there is an abnormal absolute increase in amounts of eosinophils are found in either the circulating blood or in body tissues • In this patient the percentage of eosinophils in the bloodstream is triple (13%) the normal percentage (0-4%) • When the absolute peripheral blood eosinophil count is >350/L • The absolute number is obtained by multiplying the percentage of eosinophils times the white blood cell count • Absolute number of eosinophils in this patient = 4 x 109/L x 13% = 5.2 x 108/L = 520/L • Emphasis is placed on the number of eosinophils circulating in the peripheral blood, although an increase in eosinophils can be observed in other body fluids (eg, cerebrospinal fluid [CSF], urine) and many body tissues (eg, skin, lung, heart, liver, intestine, bladder, bone marrow, muscle, nerve)

  16. When does eosinophilia occur? • Eosinophilia occurs in a wide range of conditions. • Its commonest causes in the UK are allergic diseases such as asthma and hay fever, whereas worldwide the main cause is parasitic infection. • It can also occur in relation to common skin diseases, medicine reactions, and parasitic infections. • Other rarer causes include: • lung diseases, eg Loeffler's syndrome • vasculitis (inflammation of blood vessels), eg Churg-Strauss syndrome • some tumours, eg lymphoma • liver cirrhosis • some antibody deficiencies; not typically AIDS • However our patient has HIV • other rarer skin diseases, eg dermatitis herpetiformis • unknown causes, labelled hypereosinophilic syndrome.

  17. How does eosinophilia occur? • Increased numbers of eosinophils are produced to fight off allergic disease or parasitic infections. • This is helpful in combating parasitic infections but not in cases of allergic diseases as they accumulate in tissues and cause damage. • For example, in asthma, eosinophilia causes damage to the airways of the lung.

  18. What are the symptoms of eosinophilia? • The symptoms of eosinophilia are generally those of their underlying condition. • For example, eosinophilia due to asthma is marked by symptoms such as wheezing and breathlessness, • Whereas eosinophilia due to parasitic infections may lead to abdominal pain, diarrhoea, fever, or cough and rashes. • Medicine reactions often give rise to skin rashes, and they often occur after taking a new drug. • Rarer symptoms of eosinophilia can include weight loss, night sweats, lymph node enlargement, other skin rashes, and numbness and tingling due to nerve damage.

  19. How is eosinophilia diagnosed? • Eosinophilia in the bloodstream is diagnosed from a simple blood test. • To determine the number/percentage of eosinophils in the blood • Tissue eosinophilia is diagnosed by the examination of the relevant tissue. • For example, a piece of skin tissue can be removed (a skin biopsy) and examined under a microscope. • Further tests may include blood tests to measure levels of antibodies, chest X-ray, CT scans of the chest and abdomen, skin or lung biopsies, examination of the bone marrow, urinalysis, liver and kidney function tests and bronchoscopy.

  20. Explanation of what parameters HIV pharmacotherapy is based onPart IV

  21. HIV • HIV • Multiplies in-vivo • Damages the cell immune system • Therefore the best measures of disease are; • Amount of virus in-vivo • Amount of remaining cellular immune function

  22. HOW CAN WE DO THIS? • Estimate remaining cellular immune function • Measure CD4 T-cell count with flow cytometry etc. • Estimate amount of virus • Measure “viral load” estimated by viral RNA present in-vivo using RT PCR.

  23. Why CD4 T-Cells? • HIV targets all cells with the CD4 glycoprotein. • Cd4 also serves as receptors, for the HIV envelope protein gp120 to bind to. • CD4 T-cells are the major targets • Therefore CD4 T-cells become depleted with progressing infection

  24. More on CD4…… • Relatively insensitive predictor of HIV progression • CD4 response to treatment not always a reliable predictor of treatment effect. • Most accurate predictor of risk of opportunistic infection although unreliably in infants and asplenic Px’s. • Previous mainstay for assessing prognosis and response, and still is in many developing countries.

  25. What’s Viral Load Good For? • Currently most accurate and reliable predictor of the rate and likelihood of HIV disease progression. • Combination with CD4 count  provide very accurate assessment of prognosis of HIV+ve Px. Used for timing of initiation of Tx & monitoring the response.

  26. Does She Need Therapy? • Therapeutic Guidelines recommend therapy for all Px with established HIV infection if: • symptomatic including those with HIV-associated opportunistic infections, malignancies, central nervous system disease, thrombocytopenia OR • asymptomatic adults with CD4 350/microlitre or HIV viral load >55 000 copies/mL (by RT PCR).

  27. Does She Need Therapy?…. • Guidelines in Australia are based on CD4 and VL tests. • Therefore based on available tests (CD4 count) this patient does not qualify for HIV pharmacotherapy

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