Kalsoom SaleemCMS # 8107

Glucose-6-Phosphate Dehydrogenase Enzyme Deficiency• Pathophysiology

Glucose-6-Phosphate Dehydrogenase Enzyme Deficiency

Causative Agents• Food-Fava beans • Medications-Sulfasalazine

Reduced Glutathione• Consumed during oxidative

stress

Attack RBCs• Globin chain-denaturing

hemoglobin

Heinz Bodies• Precipitation of hemoglobin-

intracellular inclusions

Intravascular Hemolysis Extravascular Hemolysis• Phagocytosis of less

damaged RBCs

Bite Cells• Plucked out by phagocytes

Morphology

Microscopic

-Red Cells with precipitates of denatured globin (Heinz bodies)-Bite shape of cells (Bite Cells)

Morphology

Gross

Yellow coloration of cornea due to hemolysis of RBCs causing jaundice

Etiology

Drugs (Sulfonamides, Ciprofloxacin, Aspirin, Sulfonylureas)

GeneticKidney Failure

DiabetesFood (Fava Beans)

Symptoms

Rapid heart rateFast breathing

SplenomegalyPale Skin

Elevated Body TemperatureDark to yellow-orange urine

Complete Blood Count and Reticulocyte Count

Heptaglobin Test

Renal Function Test

Diagnosis

Avoiding specific medications, foods and environmental exposures

Dialysis-in kidney failure

SupplementsBlood transfusion

Treatment

Prognosis

• Patients with G6PD enzyme deficiency get fewer illnesses as compared to other people and the possible outcome is general recovery from disease.

Proxymal Nocturnal HemoglobinuriaPathogenesis

MorphologyMicroscopic

•Hypercellular marrow with erythroid hyperplasia.

Morphology Gross

Flushing of skin due to pancytonpenia

Etiology

•Somatic mutation in PIGA gene in stem cells (bone marrow)

Symptoms

Abdominal pain

Headaches

Back pain

Weakness/Fatigue

Splenomegaly

Recurrent infections

Dia

gnos

isFlow Cytometry (detection of mutant gene, percentage and degree of deficient RBCs)

Bone Marrow Analysis

Acid Hemolysis Test

•Corticosteroids•Iron Replacement Therapy

Treatment•Splenectomy•Folate Supplements

Treatment Stem Cell TransplantationTreatment

•Complement Inhibitors (Ecluzimab)

•Blood Transfusion

Treatment

Prognosis

Death results after 10-11 years of diagnosis with decreased cell number

Autoimmune Hemolytic Anemia• Some people develop antibodies -interact with determinants on RBCs - causing

hemolytic anemia.• Classified according to

• nature of the antibody • presence of predisposing conditions.

• Warm Antibody Immunohemolytic Anemia: • It is caused by the IgG or IgA (rarely) immunoglobulins which are active at room

temperature (370C) that attach to RBCs membranes making their Fc portion exposed which get attached to Fc receptors on monocytes and macrophages. This will allow them to phagocytize the RBC membranes changing them to spherocytes. Spherocytes are not flexible as normal RBCs and are, therefore, erythrophagocytosed in Spleen leading to hemolysis.

Autoimmune Hemolytic Anemia

• Cold Antibody Immunohemolytic Anemia:• Circulating antibodies esp. IgM causes the destruction of RBCs• Their concentration in normal being is too low to trigger disease • Patients with CAIA have higher concentrations of IgM• At low temperatures i.e. below 300C, IgM antibodies bind to glycoproteins on the

surface of RBCs activating the complement system which then damages the RBCs by forming Membrane Attack Complex injecting proteins into the RBCs forming pores leading to membrane instability causing intravascular hemolysis. If the complement response is insufficient, then extravascular hemolysis occurs due to deposition of MAC proteins viz. C3b and C4b on RBCs activating opsonization process and their destruction by phagocytosis in spleen.

Idiopathic

 HIV infection

autoimmune diseases (e.g.systemic lupus erythematosus (SLE)

lymphoproliferative disorders (e.g. non-Hodgkin's lymphoma)

lymphoproliferative disorders

Mycoplasma pneumonia

Infections such as Epstein-Barr virus

Idiopathic

EtiologyWarm AIHA Cold AIHA

Fatigue

Fever

Splenomegaly

Symptoms

Symptoms

Breathing difficulty

Symptoms

JundiceDark UrineChest Pain

Com

plet

e Bl

ood

Coun

t

Bilir

ubin

Lact

ate

Dehy

drog

enas

e

Test Ur

ine

Hem

oglo

bin

Diagnosis

Treatment

Blood Transfusion

Corticosteroids

Immunosuppressants

Plasmapheresis

Bone Marrow Transplant

Life style changes

MalariaPathogenesis

Morphology Microscopic• Blood smear showing red blood cells that contain developing P.

vivax parasites

EtiologyFemale

Anopheles Mosquito

Infected blood

through Blood

Transfusion

Organ Transplant

SymptomsAbdominal

pain

Poor appetite

Muscle aches Orthostatic hypotension

High fevers

Headache Chills and sweats

Diarrhea, nausea, and

vomiting

Blood Test

Serological TestingDiagnosis

Treatment

Quinine followed by

doxycycline or clindamycin

Chloroquine tablets (eg

avloclor, malarivon or nivaquine)

Atovaquone with proguanil

(malarone)

Artemether with

lumefantrine (riamet)