1. FBC Case A
Kelly
Jen
MyLinh

2. The case…
A 61 year old man presented with a 3 week history of generalised weakness & increasing dyspnoea on exertion. He has a history of alcoholism, has been divorced for 2 years and lives alone. He has not worked since being retrenched at the age of 55.
On examination pallor and scleral icterus were noted. There was clinical evidence of chronic alcoholic liver disease with portal hypertension. The spleen was palpable (2 cm)

3. Hb MCV WCC Neutrophils Monocytes Lymphocytes Platelets
33 g/L
130 – 180
MCV
125 fL
80 – 100
WCC
2.4 x 109/L
4.0 – 11.0 x 109/L
Neutrophils
30% 0.72 x 109/L
2.0 – 7.5 x 109/L
Monocytes 5%
0.2 – 0.8 x 109/L
Lymphocytes
65%
1.5 – 4.0 x 109/L
Platelets
49 x 109/L
150 – 400 x 109/L
Blood film – marked anisocytosis (oval macrocytes +++) and poikilocytes (tear drop & fragmented cells ++). Red cells normochromic. Neutropenia with marked neutrophil hypersegmentation. Thrombocytopenia.

4. Chronic alcoholic abuse/alcoholic liver disease
Almost all alcohol metabolised by the liver
Directly hepatotoxic
3 stages of alcoholic liver disease
Hepatic steatosis
Alcoholic hepatitis
Alcoholic cirrhosis

5. Hematologic changes in liver disease
Anaemia
Leukopenia
Thrombocytopenia
Often with splenomegaly in portal hypertension

6. Other changes in liver disease
Late stage liver disease…
Liver starts out yellow, fatty and enlarged
As disease progresses, atrophies
Brown
Shrunken
No longer fatty
Biochem…
Elevated serum transaminase
Hyperbilirubinaemia
Hypoproteinaemia
anaemia

7. What is LD?
Intracellular enzyme widely distributed in all tissues of the body.
Catalyzes the conversion of
lactate  pyruvate
LD released from cells when damaged
Intracellular enzyme that is widely distributed in the tissues of the body. Particularly in the kidney, heart, skM, brain, liver & lungs.
Elevated LD levels are nonspecific on their own- as found in nearly every tissue of the body.
LD released from cells when they are damaged. Rises over 3-4 days after damage & declines to normal over 5-7 days.

8. What does raised LD mean?
Associated with tissue damage diseases:
AMI ( 36-55hrs after)
CHF
Liver disease (e.g. cirrhosis, alcoholism)
Megaloblastic & pernicious anemia's
RBC destruction ( Hb)
Increases in reported values usually indicate cellular death & leakage of the enzyme from the cell.

9. What are Haptoglobins (Hp)?
2 - globulin that binds free Hb in bloodstream. Results in removal of the complex from circulation
Primary physiologic fn is the preservation of Fe
USE: Indicator Chronic Hemolysis
Reflects:  Hb
Transport glycoprotein synthesized solely in the liver.
Hemolysis = breakdown of RBC’s & release Hb
Megablastic anemia = RC turnover marrow.
Decrease in Hp (w. normal liver fn) is most likely to occur w. increased consumption Hp due to intravascular Hemolysis.

10. What happens when Haptoglobins are reduced?
Hp Decreased or absent in:
Hemogloinemia
Intramedullary Hemolysis (e.g. Megaloblastic anemia)
Acute or Chronic liver disease
[ ] Hp is inversely related to degree of Hemolysis and duration of hemolytic episode

11. Ferritin Complex of ferric hydroxide and protein
Reflection of body iron stores
Reliable indicator of Total body iron status
USE: Diagnosis of iron deficiency or
Iron Excess
Ferritin: ’s with age
er in men than in women
er in women using COCs
er in red meat eaters compared with vegetarians

12. What does raised Ferritin reflect?
Acute & chronic liver disease
Alcoholism ( during abstinence)
Malignancies
Infection
Inflammation
AMI
Anemia's other than Iron deficiency
E.g.. Megaloblastic anemia

13. Serum Folate 0.7 (7-45) nmol/L Explain why folate deficiency is likely in this case?

14. FOLATE Absorption of folate occurs in the jejunum
The principal storage site is in the liver
distribution depends mostly on an enterohepatic recirculation, in which folate in a methylated form is reabsorbed from bile into the serum.
After folate enters most tissues, including erythrocytes, it remains throughout the life span of the cell.

15. FOLATE DEFICIENCY CAUSES:
inadequate dietary intake
malabsorption (e.g. jejunal disease)
increased demands (e.g. pregnancy, infancy, leukemia)
Drug induced (e.g. anticonvulsants, oral contraceptives, MTX and alcohol).

16. Folate Deficiency and Alcohol
Alcohol ingestion interferes with intermediate metabolism of folate, its intestinal absorption and enterohepatic salvage
interfering with the release of folate from the liver into the bile -> a rapid DECREASE in the SERUM FOLATE LEVEL).

17. Do the results support the diagnosis of megaloblastic anaemia?

18. Megaloblastic Anaemia
Folic acid deficiency and Vitamin B12 deficiency anaemia are the two most common examples.
These deficiencies cause defective DNA synthesis, whereas RNA synthesis and synthesis of cytoplasmic components unaffected -> (cytoplasmic maturity>nuclear maturity) -> megaloblast in marrow.

19. Megaloblastic Anaemia

20. …continued
Blood films show oval macrocytes and hypersegmented neutrophil nuclei (with 6 lobes)
In severe cases, WCC and platelet count also fall (pancytopenia). The bone marrow show characteristic megaloblastic erythroblasts.
Dyspoiesis increases intermedullary cell death (ineffective erythropoeisis) with resultant indirect hyperbilirubinemia and hyperuricaemia

21. Clinical features Glossitis (sore pale smooth tongue)
Altered bowel habit
Mild jaundice
Insidious onset
Pallor
Loss of appetite
Bilateral peripheral neuropathy (vit B12 deficient only)
Tiredness
Headaches
In severe anaemic pxs may present with CHF

22. Yes, the results do support the diagnosis!!
Blood film: marked anisocytosis (oval macrocytes+++), poikilocytes (tear drop and fragmented cells++), neutropenia with marked neutrophil hypersegmentation and thrombocytopenia
Clinical symptoms: scleral icterus, pallor, generalised weakness and increasing dyspnoea on exertion
Biochemistry: low serum folate and red cell folate