Part 2 - RBC Disorder (Hemolytic Anemia)

• Haptoglobin

• Hemopexin

In serum, what indices is decreased in both fragmentation and macrophage-mediated hemolysis

• Fragmentation (Intravascular)

A hemolysis associated with Coffee-Brown Plasma color

• Fragmentation (intravascular)

  • macrophage-mediated is negative on these

A hemolysis is positve free hemoglobin, methemoglobin, and prussian blue staining urine sediments

• Fragmentation = Schistocytes [fragment cells]

• Macrophage = Spherocytes [katong paakan diba]

What RBC morphology is associated with:

• Fragmentation (Intravascular) Hemolysis

• Macrophage-mediated (Extravascular) Hemolysis

• Vertical Structures:

  • Actin + protein 4.1 complex

  • Ankyrin + Protein 4.2 complex

PROTEIN STRUCTURE:

• Prevents loss of membrane and decrease in surface area-to-volume ration of RBC

• Horizontal Structure:

  • Spectrin-actin-protein4.1 junctional complex

PROTEIN STRUCTURE:

• Membrane eslasticity

• Prevents the membrane from fragmenting due to mechnical stress

• Microangiopathic Hemolytic Anemia (MAHAs)

  • RBC = shistocytes

• Group of disorder characterized by RBC fragmentation and thrombocytopenia

• Caused by mechanical shearing of RBC membrane as it rapidly passes through areas of small blood vessels that are blocked by microthrombi (clot)

• Abnormal narrowing of blood vessels

  • (+) what is the associated RBC morphology?

• Acquired (Pseudo) Stomatocytosis

INTRINSIC DEFECTS:

• May occur as a drying artifacts on Wright-stained peripheral blood films

• Other Causes:

  • Malignancies

  • Acute Alcoholism

  • Cardiovascular Disease

• Spur Cell (Acanthocytes) Anemia

INTRINSIC DEFECTS:

• Patients with severe liver disease

• Caused by excess free cholesterol resulting to remodeling of membrane into acanthocytes

• Paroxysmal Nocturnal Hemoglobinuria (PNH)

INTRINSIC DEFECTS:

• Absence of CD55 and CD59 of RBCs surface making then susceptible to spontaneous lysis by complement

• Mutation in PIGA gene

• MAJOR MANIFESTATIONS:

• anemia

• thrombosis

• bone marrow failure

• Paroxysmal Nocturnal Hemoglobinuria (PNH)

INTRINSIC DEFECTS:

• Associated with:

  • Smooth muscle dystonia

  • Budd-Chiary syndrom (hepatic vein thrombosis)

  • Chronic Renal Disease

• G6PD Deficiency

  • G6PD — protects hemoglobin from oxidative denaturation

INTRINSIC DEFECTS:

• RBCs are vulnerable to oxidative damage and subsequent hemolysis of oxidant stress

• Leads to FAVISM if ingesting fava beans

• Quantitative Spectrophotometric assay

INTRINSIC DEFECTS:

• Gold Standard to determine G6PD activity

• Pyruvate Kinase Deficiency

  • PIGA gene mutation = PNH

INTRINSIC DEFECTS:

• Most common form of hereditary nonspherocytic hemolytic anemia

• Mutations in PKLR gene

• MANIFESTATIONS:

  • ↓ ATP

  • ↑ 2,3-BPG

• EXTRAVASCULAR HEMOLYSIS

  • IgM Mediated

IGM or IGG MEDIATED HEMOLYSIS:

• Clearance of C3b-sensitized RBC by machropgae mainly in liver

• INTRAVASCULAR HEMOLYSIS

  • IgM Mediated

IGM or IGG MEDIATED HEMOLYSIS:

• Full IgM activation of classical complement pathway

• direct RBC lysis

• EXTRAVASCULAR HEMOLYSIS [macrophage]

  • IgG Mediated

IGM or IGG MEDIATED HEMOLYSIS:

• Formation of spherocytes by partial phagocytosis of IgG-sensitized RBCs

• Clearance of IgG and C3b-sensitized RBCs by macrophages in spleen and liver

• INTRAVASCULAR HEMOLYSIS

  • IgG Mediated

IGM or IGG MEDIATED HEMOLYSIS:

• full IgG activation of classical complement pathway

• direct RBC lysis

• Warum Autoimmune Hemolytic Anemia (wAIHA)

  • IgG

AUTOIMMUNE HEMOLYTIC ANEMIA:

• autoantibodies reast at 37*C

• Typical Findings = Polychromasia and Spherocytes

• Cold Agglutinin Disease (CAD)

AUTOIMMUNE HEMOLYTIC ANEMIA:

• IgM classes react optimally at 4*C

• Pathologic agglutinins can react at room temp

• Symptoms = acrocyanosis (bluish discoloration)

• Paroxysmal Cold Hemoglobinuria (PCH)

AUTOIMMUNE HEMOLYTIC ANEMIA:

• Due to biphasic IgG autoantibody with anti-P specificity

• At cold temp = antibody binds to P-antigen (donath landtevier), partially activating complement

• At 37*C = full complement activation and hemolysis occur

• Drug-Induced Immune Hemolytic Anemia

AUTOIMMUNE HEMOLYTIC ANEMIA:

• Decrease in Hemoglobin

• Positive DAT result