FBC

1. FBC Case B

2. Ms FBC • 50 year old • Diabetes mellitus • HIV – treated with Zidovudine many years • Chronic renal failure (due to HIV) • Haemodialysis 3 times a week

3. Full blood count

4. Explain the haematological parameters which are consistent with the patient’s HIV. • Progressive cytopenias (anemia, thrombocytopenia, leukopenia) commonly occur in HIV-infected patients • The pathophysiologic mechanisms are multifactorial and include direct effects of HIV on haemapoetic precursor cells, alterations in the microenvironment of the bone marrow, and immulogic destruction of peripheral blood cells.

5. Explain the haematological parameters which are consistent with the patient’s HIV. • Anaemia is common in HIV • Intrinsic factor production is inadequate leading to absorbance of vitamin B12 & folic acid • Chronic infection with human parvovirus B19 reduces RBC precursors in the presence of already impaired erythropoiesis secondary to HIV infection • Results in Hb and low red blood cell

6. Explain the haematological parameters which are consistent with the patient’s HIV. • Patients with HIV infection may have severe neutropenia and pancytopenia. • Direct damage on haemopoietic precursor cells, which is consistent with the patients low neutrophil count. • Also anti-HIV drugs have additive effect on neutropenia as they cause bone marrow suppression (known as “additive toxicity”).

7. Explain the haematological parameters which are consistent with the patient’s HIV. • Other parameters includes # Reduced platelet count. # Prolonged prothrombin time. *Due to stimulated macrophages releasing large amounts of plasminogen activator. • In this patient platelets count were within range. this may be due to the use of Ziduvodine • Zidovudine known as AZT _ prevent HIV fragments and antibodies from binding to platelets and marking them for destruction.

8. Explain the haematological parameters which are consistent with the patient’s HIV. • Drugs used for HIV (e.g. acyclovir, AZT, ganciclovir) also cause myelosupression to a greater extent. • Opportunistic infections and malignancies in HIV potentiates myelosupression • Lymphocytopenia and Reactive lymphocytosis seen in this patient is caused by HIV specifically.

9. Explain the haematological parameters which are consistent with the patient’s HIV. • HIV infects CD4 T-cells, causes  CD4 T-cellsnumbers • not seen in this patient as the count are within the normal range), dramatic decreases only occur in untreated HIV cases. When the count fall below 200cells/mm3 they are said to have AIDS. • Patients infected with HIV have increased eosinophil and basophil levels (will be explained later by Tuan).

10. Haematological Parameters Which Are Consistent With Chronic Renal Failure in Ms FBC

11. Chronic Renal Failure • Firstly, there is a defining parameter of renal failure which is an elevation of serum creatinine levels. This reflects the decrease in kidney function and thus GFR. • Secondly, the patient is displaying anaemia with a reduction in red cell counts, haemoglobin and haematocrit. • Finally, the red blood cell indices which indicate what type of anaemia are within range (MCV, MCH, MCHC and RDW). This indicates that this patient is experiencing normocytic, normochromic anaemia.

12. Allow me to explain… Normocytic, normochromic anaemia has a few possible causes: • acute blood loss • excessive haemolysis • anaemia of a chronic disease

13. What’s happening in this patient? • In this patient the anaemia could have been caused by acute blood loss or excessive haemolysis. However, it is more likely that the anaemia is due to the chronic renal failure due to a history of diabetes mellitus. The hormone required to produce red blood cells erythropoietin (EPO) is mainly produced by the kidney. With a reduction in functional kidney mass, the amount of EPO produced each day is reduced leading to normocytic, normochromic anaemia. Another possibility is that the patient is deficient of iron, folate and vitamin B12 to the extent where the RBC indices balance up to appear normocytic and normochromic.

14. The patient has mild eosinohilia – what could this parameter reflect? Eosinophil • Granular leukocyte (type of white blood cell) • Phagocytic but less effective than neutrophils • The primary stimuli for eosinophil production are interleukin IL-5, IL-3, and the granulocyte-macrophage colony-stimulating factor (GM-CSF) • Manufactured in the bone marrow • transferred into the bloodstream and the gut lining • Produced by immune system to combat parasitic organisms • once the parasite has been removed, the level of eosinophils in the bloodstream is allowed to return to normal

15. Eosinophilia • Condition that cause abnormally high levels of eosinophils to develop in either the blood or body tissues • Body keep producing eosinophils at a high rate • Accumulate in the blood and tissues • Build-up of eosinophils ultimately leads to body damage.

16. Causes of eosinophilia • There are many causes of increased eosinophil production by the body • Connective tissue diseases • Helminthic infections • Parasitic worm • Idiopathic hypereosinophilic syndrome • Neoplasia • Tumor – new and abnormal growth • Lymphocytic leukemia • Allergies • Asthma • Allergic rhinitis • Food • Medications (drug reaction) • Dialysis and recent blood transfusion

17. Eosinophilia and Ms FBC’s condition High eosinophils level • HIV • Cutaneous manifestations • Frequently occur in patients who are infected with HIV • Due to the alterations in the immune system • Initial signs of virus-related immunosuppression

18. Eosinophilia and Ms FBC’s condition High eosinophils level • Zidovudine • Develop opportunistic infections and other complications of HIV infection • Anaemia • In severe cases require blood transfusion • Myalgia • Eosinophilia-Myalgia Syndrome

19. Eosinophilia and Ms FBC’s condition High eosinophils level • Dialysis • Allergic symptoms occur immediately after initiation of dialysis • Possibly due to inadequate rinsing of the dialyser

20. Eosinophilia and Ms FBC’s condition High eosinophils level • Diabetes mellitus • Uncontrolled blood glucose level • Increase risk of skin ulceration and infection

21. Treatment of eosinophilia • There are no direct treatment for eosinophilia • Treat the underlying caused of eosinophylia • Once the caused have been removed, the level of eosinophils in the bloodstream is allowed to return to normal

22. HIV pharmacotherapy is likely to be based on which parameter? • HIV pharmacotherapy is mainly based on CD4 count. • However Viral Load also plays an important role in HIV pharmacotherapy. It helps to decide whether to start anti-HIV treatment. • These two tests are crucial in helping to decide when to start treatment, and to monitor the effects of the treatment.

23. What is CD4 counts? • CD4 cells, or T-helper cells, are white blood cells which organise the immune system’s response to some imcroorganisms, including bacteria, fungal infections and viruses. • The CD4 count is the measurement of the number of CD4 cells, in a cubic millimeter of blood. Ie CD4 cells/mm3. • The CD4 count of a person who is not infected with HIV may lie anywhere between 500 and 1200. • However The Human Immunodeficiency Virus (HIV) can infect and replicate within cells of CD4 and use them to produce more HIV copies, resulting in destruction of CD4 cells.

24. What CD4 counts predict • A CD4 count between 500 and 200 indicates that some damage to the immune system has occurred. • If CD4 count drops below 350, or start falling rapidly, anti-HIV treatment should be discussed whether or not to start. • If CD4 count falls below 250-200 anti-HIV drugs treatment are recommended to start. This is because it is the level at which the risk of AIDS-related illness is greatly increased. • It is recommended that people start treatment before their CD4 count falls below 200, as people who start treatment with a CD4 count below 200 face a greater risk of death, in the short-term than those who start before their CD4 count drops below this level.

25. Factors that can alter in the CD4 count • CD4 count can go up and down in response to infections, stress, smoking, exercise, the menstrual cycle, the contraceptive pill, the time of day and even the seasons of the year. • Different types of CD4 counting-machine also give different readings.

26. What is the viral load test? • Viral load is the term used to describe the amount of HIV in blood. The more HIV in blood, the faster CD4 cells are likely to disappear, and the greater risk of developing symptoms or further illness within the next few years. • Viral load tests estimate the number of HIV particles in the liquid, or plasma part of the blood. The result of a viral load test is described as the number of copies of HIV RNA/mm. • Viral load should ideally only be measured when the person is well. If there is an infection or have recently had a vaccination, the viral load could temporarily increase.

27. What information can Viral Load provide in relation to HIV pharmacotherapy? • In combination with CD4 count, Viral Load can provide information on the likely course of HIV infection and may help to predict risk of developing symptoms in the future. • Among people with the same CD4 count, those with higher Viral Load tend to develop symptoms more quickly than those with lower viral load. • Among people with the same Viral Load, those with lower CD4 counts tend to develop symptoms more quickly.

28. Relationship between CD4 and Viral Load • % of people who develop AIDS within 3 years (assuming no treatment) A high viral load, regardless of CD4 cell count, increases risk of AIDS-related illness. ** indicates lack of data