Haematology Group B

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Haematology Group B

• Owen Naidoo
• Abdullah Osman
• Christine Tanzil
• Ayse Togac

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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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Ms FBC Full Blood Count
WCC 4X109 ? 4.8-10.9X109/L
RCC 3.01X1012 ? 4.2-5.4X1012 /L
Hb 92 ? 120-160g/L
Hct 27.6 ? 37-47
MCV 91.7 - 82-98fL
MCH 30.6 - 27-33pg/cell
MCHC 33.3 - 31-35g/dL
RDW 15.4 - 11-16
Platelets 199X109 - 140-440X109/L
Segs (poly morphonuclear neutrophils) 53 - 45-73
Bands (immature neutrophils) 9 ? 3-5
Monocytes 8 - 2-8
Atypical lymphocytes 2 - 0-6
Lymphoctyes 15 ? 20-40
Eosinophils 13 ? 0-4
CD4 lymphocytes 550 Lower end 440-1600 cells/mm3
Creatinine 0.24 ? 0.04-0.11mmol/L
Urea 3.0 ? 3-10mmol/L
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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

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What Haematological parameters are consistent
with the patients 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 FBCs 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.

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What Haematological parameters are consistent
with the patients 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 FBCs
  results.
• Thrombocytopenia is common in HIV. Symptoms
  include mucosal bleeding as well as easy
  bruising.
• Ms FBCs current platelet count is within the
  recommended range.

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• 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.

Lymphoctyes 15 ? 20-40
Bands (immature neutrophils) 9 ? 3-5
Monocytes 8 - 2-8
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What haematological parameters are consistent
with patients chronic renal failure? PART II
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• 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

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• 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.

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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.

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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.

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Creatinine clearance???

• Patients weight is not provided therefore cannot
  calculate Mrs FBCs creatinine clearance.

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The patient has mild eosinophilia what could
this parameter reflect? PART III
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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 gt350/?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)

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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.

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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.

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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.

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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.

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Explanation of what parameters HIV
pharmacotherapy is based on Part IV
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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

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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.

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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

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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 Pxs.
• Previous mainstay for assessing prognosis and
  response, and still is in many developing
  countries.

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Whats 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 HIVve Px.
  Used for timing of initiation of Tx monitoring
  the response.

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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 gt55 000 copies/mL (by RT PCR).

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WCC 4X109 ? 4.8-10.9X109/L
RCC 3.01X1012 ? 4.2-5.4X1012 /L
Hb 92 ? 120-160g/L
Hct 27.6 ? 37-47
MCV 91.7 - 82-98fL
MCH 30.6 - 27-33pg/cell
MCHC 33.3 - 31-35g/dL
RDW 15.4 - 11-16
Platelets 199X109 - 140-440X109/L
Segs (poly morphonuclear neutrophils) 53 - 45-73
Bands (immature neutrophils) 9 ? 3-5
Monocytes 8 - 2-8
Atypical lymphocytes 2 - 0-6
Lymphoctyes 15 ? 20-40
Eosinophils 13 ? 0-4
CD4 lymphocytes 550 Lower end 440-1600 cells/mm3
Creatinine 0.24 ? 0.04-0.11mmol/L
Urea 3.0 ? 3-10mmol/L
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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