FBC Case AKellyJen

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)

Blood film – marked anisocytosis (oval macrocytes +++) and poikilocytes (tear drop & fragmented cells ++). Red cells normochromic. Neutropenia with marked neutrophil hypersegmentation. Thrombocytopenia.

Hb 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

Chronic alcoholic abuse/alcoholic liver disease

Almost all alcohol metabolised by the liverDirectly hepatotoxic3 stages of alcoholic liver disease Hepatic steatosis Alcoholic hepatitis Alcoholic cirrhosis

Hematologic changes in liver disease

AnaemiaLeukopenia 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

What does raised LD mean?

Associated with tissue damage diseases:AMI ( 36-55hrs after)CHFLiver disease (e.g. cirrhosis, alcoholism)Megaloblastic & pernicious anemia'sRBC destruction ( Hb)

What are Haptoglobins (Hp)?

2 - globulin that binds free Hb in bloodstream. Results in removal of the complex from circulationPrimary physiologic fn is the preservation of Fe

USE: Indicator Chronic HemolysisReflects: Hb

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 proteinReflection of body iron storesReliable indicator of Total body iron status

USE: Diagnosis of iron deficiencyor

Iron Excess

What does raised Ferritin reflect?

Acute & chronic liver diseaseAlcoholism ( during abstinence)MalignanciesInfectionInflammationAMIAnemia'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 jejunumThe 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 intakemalabsorption (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 habitMild jaundiceInsidious onsetPallorLoss of appetite

Bilateral peripheral neuropathy (vit B12 deficient only)Tiredness HeadachesIn 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 thrombocytopeniaClinical symptoms: scleral icterus, pallor, generalised weakness and increasing dyspnoea on exertionBiochemistry: low serum folate and red cell folate