FBC Case A Kelly Jen MyLinh

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)

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.

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

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

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

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.

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.

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.

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

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

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

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

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.

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).

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).

Do the results support the diagnosis of megaloblastic anaemia?

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.

Megaloblastic Anaemia

…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

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

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