Hematology: Red Cell Enzyme Defects

What pathway is the G6PD enzyme a part of? What does it do?

hexose monophosphate pathway

it is an important part of producing GSH, which is needed to protect hemoglobin from oxidative denaturation

Name the abnormal G6PD and its prevalence:

reduced *activity* of G6PD

Gd Mediterranean, caucasians

Name the abnormal G6PD and its prevalence:

reduced *stability* of G6PD

Gd A (-), black

Name the abnormal G6PD and its prevalence:

defect unknown

Gd Canton, asian

How is G6PD inherited?

sex-linked

What reaction is G6PD a part of?

Hexose monophosphate pathway

glucose-6-phosphate --G6PD--> NADPH

glutathione --NADPH--> GSH

What is the common cell morphology/inclusion of G6PD deficiency? What is the component of this incusion?

Heinz bodies: precipitated denatured hemoglobin

Patients with G6PD deficiency can live a normal life until their red cells are challenged. What are some of these challenges that trigger it?

hemolysis from drugs (antimalarial drugs (Primaquine and Quinine), sulfa drugs, analgesics), infection, Favism, Mothball poisoning (Naphtalene)

What are the clinical features of G6PD deficiency?

they vary depending on the hemolytic episode-- hemoglobinuria, hemoglobinemia, jaundice, anemia

What are the lab features of G6PD deficiency?

increased retics (from hemolysis), polychromasia, poik, Heinz bodies, bite/helmet cells, spherocytes, deficiency in G6PD

What does the dye reduction test for G6PD screening detect? What is a normal and abnormal result?

detects failure of red cells to generate NADPH

normal: blue color --> rust color

abnormal: stays blue color

What does the fluorescent spot test for G6PD screening detect? What is a normal and abnormal result?

detects failure to convert NADP to NADPH

successful conversion will fluoresce

normal: fluorescence

abnormal: no fluorescence

What does the ascorbate cyanide test for G6PD screening detect? What is a normal and abnormal result?

detects the failure to produce hydrogen peroxide when added to sodium ascorbate, sodium cyanide, and glucose-- this causes the hemoglobin in the deficient cells to become oxidized and form methemoglobin/deoxyhemoglobin which makes the solution dark brown.

normal: solution stays red

abnormal: solution turns dark brown

What is the treatment for G6PD deficiency?

avoid causative agent

What is the purpose of pyruvate kinase?

converts PEP to pyruvate in the Embden-Meyerhoff pathway of glycolysis

What happens when a patient is PK deficient?

RBCs fail to generate enough ATP to maintain normal red cell membrane function

What is the inheritance pattern of pyruvate kinase deficiency?

autosomal recessive

What are the clinical S/S of pyruvate kinase deficiency?

splenomegaly, jaundice, anemia

(may develop in infancy or early childhood; some mild cases may not be detected until adulthood)

What are the lab findings of pyruvate kinase deficiency?

polychromasia, poik, H-Js, NRBCs, echinocytes (Burr cells)

PK deficiency will have a increased or decreased osmotic fragility?

normal OF at first, increased when sample is incubated

What does the fluorescent spot test for PK deficiency detect? What are the normal and abnormal results?

detects NADH: NADH (fluor) -----> NAD (no fluor)

normal: no fluor after 60 min incubation

abnormal: fluor after 60 min incubation

What is the therapy for PK deficiency?

splenectomy

What is the inheritance pattern of methemoglobin deficiency?

autosomal recessive

What happens to methemoglobin in methemoglobin deficiency?

cannot carry oxygen

methgb reductase is deficient so methgb cannot convert to oxyhgb, creates a build up of methgb

What color is the patient's blood in methemoglobin deficiency?

chocolate brown (build up in methgb)

What are the clinical S/S of methemoglobin deficiency?

*cyanosis*: tissues can't carry oxygen so tissues turn blue

Are people with methemoglobin deficiency anemic?

No, not ACTUALLY anemic

the methemoglobin cannot carry oxygen so many patients exhibit symptoms *similar* to anemia-- the body wants to make more RBCs to get more oxygen

What are the lab findings of methemoglobin deficiency?

increased methemoglobin (can't convert to oxyhgb, so builds up)

decreased methemoglobin reductase activity

normal hemoglobin electrophoresis patterns

What are the treatment options for methemoglobin deficiency?

the disorder is usually benign and only treated for cosmetic reasons

old treatment not used anymore is IV methylene blue used to activate the NADPH-methemoglobin reductase system