Disease Correlation

Accurate heme derivative testing is crucial for diagnosis, monitoring, and management of these conditions

Liver Diseases

Laboratory Findings
- Elevated Total Bilirubin: Typically > 1.0 mg/dL
- Elevated Direct (Conjugated) Bilirubin: Increased proportion of direct bilirubin
- Elevated Liver Enzymes: ALT and AST (indicators of liver inflammation/damage)
Disease State Correlation
- Liver inflammation impairs bilirubin conjugation and excretion, leading to hyperbilirubinemia and elevated liver enzymes
- Specific patterns of bilirubin and liver enzyme elevation can help differentiate between different types of hepatitis

Laboratory Findings
- Elevated Total Bilirubin: Variable, may be normal in early stages
- Elevated Direct (Conjugated) Bilirubin: Increased proportion of direct bilirubin
- Elevated Liver Enzymes: Variable, may be normal or decreased in advanced stages
- Decreased Albumin: Indicator of impaired liver synthetic function
- Prolonged Prothrombin Time (PT): Indicator of impaired liver synthetic function
- Thrombocytopenia: Low platelet count due to portal hypertension and splenomegaly
Disease State Correlation
- Cirrhosis is characterized by chronic liver damage and scarring, leading to impaired bilirubin metabolism, decreased protein synthesis, and other complications
- Elevated bilirubin, decreased albumin, and prolonged PT reflect the severity of liver dysfunction

Laboratory Findings
- Elevated Total Bilirubin: Typically > 2.0 mg/dL
- Elevated Direct (Conjugated) Bilirubin: Predominantly direct bilirubin
- Elevated Alkaline Phosphatase (ALP) and Gamma-Glutamyl Transferase (GGT): Indicators of biliary obstruction
Disease State Correlation
- Obstruction of the bile ducts prevents bilirubin excretion, leading to conjugated hyperbilirubinemia and elevated ALP and GGT

Definition: Anemias caused by increased destruction of red blood cells
Examples: Hereditary spherocytosis, sickle cell anemia, autoimmune hemolytic anemia
Laboratory Findings * Elevated Total Bilirubin: Typically < 5.0 mg/dL * Elevated Indirect (Unconjugated) Bilirubin: Predominantly indirect bilirubin * Increased Reticulocyte Count: Indicates increased red blood cell production by the bone marrow * Decreased Hemoglobin and Hematocrit: Indicators of anemia * Increased Lactate Dehydrogenase (LDH): Released from damaged red blood cells * Decreased Haptoglobin: Binds free hemoglobin and is depleted in hemolytic anemia
Disease State Correlation
- Increased red blood cell breakdown leads to elevated indirect bilirubin, increased reticulocyte count, and decreased hemoglobin

Definition: A group of genetic disorders caused by deficiencies in enzymes of the heme synthesis pathway
Laboratory Findings
- Elevated levels of specific porphyrins and porphyrin precursors in urine, blood, or feces
- Specific patterns of porphyrin elevation depend on the type of porphyria
Acute Intermittent Porphyria (AIP): Elevated urine porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) during acute attacks
Porphyria Cutanea Tarda (PCT): Elevated urine uroporphyrins
Disease State Correlation * Enzyme deficiencies in the heme synthesis pathway lead to the accumulation of specific porphyrins and porphyrin precursors, causing various symptoms

Definition: Anemia caused by insufficient iron levels, leading to impaired heme and hemoglobin synthesis
Laboratory Findings * Decreased Hemoglobin and Hematocrit: Indicators of anemia * Decreased Mean Corpuscular Volume (MCV): Microcytic anemia * Decreased Serum Iron: < 60 μg/dL (10.7 μmol/L) * Decreased Ferritin: < 20 ng/mL (women), < 20 ng/mL (men) * Increased Total Iron-Binding Capacity (TIBC): > 450 μg/dL (80.6 μmol/L) * Decreased Transferrin Saturation: < 20%
Disease State Correlation
- Inadequate iron stores impair heme and hemoglobin synthesis, leading to microcytic anemia and decreased iron levels

Definition: A genetic disorder characterized by excessive iron absorption and accumulation in tissues
Laboratory Findings * Elevated Serum Iron: > 170 μg/dL (30.4 μmol/L) * Elevated Transferrin Saturation: > 50% * Elevated Ferritin: > 200 ng/mL (women), > 500 ng/mL (men) * Decreased Total Iron-Binding Capacity (TIBC): < 240 μg/dL (42.9 μmol/L)
Disease State Correlation
- Excessive iron absorption leads to iron overload, causing tissue damage and organ dysfunction

Definition: Exposure to lead, which inhibits enzymes in the heme synthesis pathway
Laboratory Findings * Elevated Blood Lead Levels: > 5 μg/dL * Elevated Zinc Protoporphyrin (ZPP) in Red Blood Cells: Indicates impaired heme synthesis * Decreased Hemoglobin: Anemia
Disease State Correlation
- Lead inhibits ALA dehydratase and ferrochelatase, disrupting heme synthesis and causing neurological and developmental problems

Definition: Anemia associated with chronic inflammatory conditions
Laboratory Findings * Decreased Hemoglobin and Hematocrit: Indicators of anemia * Decreased Serum Iron: < 60 μg/dL (10.7 μmol/L) * Decreased Total Iron-Binding Capacity (TIBC): < 240 μg/dL (42.9 μmol/L) * Decreased Transferrin Saturation: < 20% * Normal or Increased Ferritin: > 20 ng/mL (women), > 20 ng/mL (men)
Disease State Correlation
- Inflammation leads to increased hepcidin production, which reduces iron absorption and release, causing anemia

Condition	Total Bilirubin	Direct Bilirubin	Indirect Bilirubin	ALT/AST	ALP/GGT	Serum Iron	Ferritin	TIBC	Transferrin Saturation
Hepatitis	↑	↑	↑	↑	↑	N	N	N	N
Cirrhosis	↑	↑	↑	↑/↓	N/↑	N	N/↑	↓	N/↑
Biliary Obstruction	↑	↑↑	N	N	↑↑	N	N	N	N
Hemolytic Anemia	↑	N	↑↑	N	N	↑	↑	↓	↑
Iron Deficiency Anemia	N	N	N	N	N	↓	↓	↑	↓
Hemochromatosis	N	N	N	↑	N	↑↑	↑↑	↓	↑↑
Anemia of Chronic Disease	N	N	N	N	N	↓	N/↑	↓	↓

↑ = Increased, ↓ = Decreased, N = Normal, ↑↑ = Significantly increased, N/↑ = Normal or Increased, N/↓ = Normal or Decreased

Bilirubin: A yellow pigment produced from the breakdown of heme
Liver Enzymes: ALT (alanine aminotransferase) and AST (aspartate aminotransferase)
Hemolytic Anemia: Anemia caused by increased destruction of red blood cells
Porphyria: A genetic disorder caused by deficiencies in enzymes of the heme synthesis pathway
Iron Deficiency Anemia (IDA): Anemia caused by insufficient iron levels
Hemochromatosis: A genetic disorder characterized by excessive iron absorption and accumulation in tissues
Lead Poisoning: Exposure to lead, which inhibits enzymes in the heme synthesis pathway
Anemia of Chronic Disease (ACD): Anemia associated with chronic inflammatory conditions
MCV: Mean Corpuscular Volume, a measure of red blood cell size
Ferritin: A protein that stores iron
Total Iron-Binding Capacity (TIBC): A measure of the blood’s capacity to bind iron
Transferrin Saturation: The percentage of transferrin that is bound to iron
Porphyrins: Intermediates in heme synthesis