T6 RBC disorders

anemia - physiological consequences

decrease RBC mass → decrease O2 carrying capacity → tissue hypoxia

anemia - disease?

sign of underlying disease

anemia - causes

blood loss, increased RBC destruction (hemolysis), decreased RBC production

anemia - body compensation

increase O2 delivery & increase O2 utilization by tissues

anemia - body compensation - increase O2 delivery

increase: respiration rate depth, heart rate, cardiac output, blood circulation rate

restricts blood flow to vital organs

anemia - body compensation - increase O2 utilization by tissues

increase 2,3-DPG → right shift O2 dissociation curve → enhance O2 release to tissues

bohr effect

low pH & high CO2 promote O2 unloading

anemia - symptoms

fatigue, weakness, headache, dizziness, fainting, dyspnea, palpitations, dark urine (hemolysis)

anemia - physical examination

skin pallor, koilonychia, pale conjunctiva, jaundice, splenomegaly

reticulocyte count

(no. of reticulocytes / 1000 RBCs) x 100

corrected reticulocyte count

(patient hematocrit / normal hematocrit (45%)) x % reticulocyte

classification of anemia

morphologic, etiologic, mechanistic

morphologic classification of anemia

based on RBC size & Hb content

morphologic classification of anemia - subtypes

macrocytic, microcytic, normocytic normochromic

MCV

measures size / volume of RBC

MCH

measures amount of Hb per RBC

MCHC

measures concentration of Hb in given volume of RBC

microcytic hypochromic anemia - RBC

small, pale

microcytic hypochromic anemia - common causes

iron deficiency anemia, anemia of chronic disease, thalassemia, sideroblastic anemia

normocytic normochromic anemia - RBC

normal sized, normal colour

normocytic normochromic anemia - common causes

acute blood loss, anemia of chronic disease, aplastic anemia, hemolytic anemia

macrocytic anemia - RBC

enlarged

macrocytic anemia - common causes

vitamin B12 or folate deficiency, alcoholism, liver disease, myelodysplastic syndromes

etiologic classification of anemia - subtypes

blood loss, increased RBC destruction (hemolysis), decreased RBC production

blood loss - acute

trauma, surgery, GI bleeding

blood loss - chronic

menorrhagia, parasitic infection, occult GI bleeding

increased RBC destruction (hemolysis) - subtypes

intracorpuscular (intrinsic) & extracorpuscular (extrinsic)

intrinsic hemolysis - types

membrane defects, enzyme defects, Hb defects

intrinsic hemolysis - membrane defects

hereditary spherocytosis & hereditary elliptocytosis

intrinsic hemolysis - enzyme defects

G6PD deficiency & pyruvate kinase deficiency

intrinsic hemolysis - Hb defects

thalassemia & hemoglobinopathies

intrinsic hemolysis - others

paroxysmal nocturnal hemoglobinuria (PNH)

extrinsic hemolysis - types

immune hemolysis & non-immune hemolysis

extrinsic hemolysis - immune

autoimmune hemolytic anemia (AIHA), allo-immune hemolytic anemia, drug-induced immune hemolytic anemia

extrinsic hemolysis - non-immune

microangiopathic hemolytic anemia (MAHA)

decreased RBC production - types

bone marrow suppression, nutritional deficiencies, chronic diseases

bone marrow suppression - types

aplastic anemia & leukemia

nutritional deficiencies - types

iron deficiency & B12 / folate deficiency

chronic diseases - types

renal failure, chronic inflammation

hereditary spherocytosis - inheritance pattern

inherited & spontaneous mutation

hereditary spherocytosis - autosomal dominant

mutation in ankyrin & beta spectrin

hereditary spherocytosis - autosomal recessive

mutation in alpha spectrin & band 4.2

hereditary spherocytosis - heterozygous

mild symptoms

hereditary spherocytosis - homozygous

severe

hereditary spherocytosis - pathophysio

defective proteins → membrane destabilize → membrane loss → spherocytes

hereditary spherocytosis - signs symptoms

anemia, jaundice, splenomegaly, gallstones

hereditary spherocytosis - lab findings

spherocytes, polychromasia, high MCHC, high reticulocyte, high bilirubin, high Hb

hereditary spherocytosis - special tets

osmotic fragility

hereditary spherocytosis - osmotic fragility

increase → hemolysis starts and complete at higher NaCl concentration

hereditary elliptocytosis - inheritance pattern

autosomal dominant

hereditary elliptocytosis - mutation in

alpha & beta spectrin, protein 4.1, can be related to ankyrin-band 3 interaction

hereditary elliptocytosis - pathophysio

cytoskeleton defect → impair ability of spectrin dimers to associate → weaken horizontal stability

weak horizontal stability of membrane leads to…

loss of biconcave shape, increase cell fragility

hereditary elliptocytosis - subtype

southeast asian ovalocytosis

southeast asian ovalocytosis - inheritance

autosomal dominant

southeast asian ovalocytosis - mutation

SLC4A1 gene (band 3 protein)

southeast asian ovalocytosis - lab findings

theta cells

acanthocytosis - lab findings

spur cells

acanthocytosis - cause

abnormal membrane lipids

acanthocytosis - seen in

abetalipoproteinemia → autosomal recessive → mutation in MTP gene

G6PD deficiency - inheritance

x-linked recessive

G6PD deficiency - mutation

single point mutation in G6PD gene

G6PD deficiency - common where

mediteranian → malaria areas

G6PD deficiency - clinical features

asymptomatic, hemolytic crisis, intravascular or extravascular hemolysis, hemoglobinuria

G6PD deficiency - lab findings

bite cells, blister cells, spherocytes, polychromasia, heinz bodies

G6PD deficiency - screening / diagnostic test

fluorescent spot test

G6PD deficiency - fluorescent result

no light → no NADPH → enzyme deficient

G6PD deficiency - subtypes

acute hemolytic anemia, neonatal jaundice, congenital non-spherocytic hemolytic anemia

G6PD deficiency - acute hemolytic anemia

triggered by oxidative stress → damage RBC due to insufficient NADPH production

G6PD deficiency - acute hemolytic anemia - common triggers

drugs, infections, fava beans

G6PD deficiency - neonatal jaundice - results in

severe hyperbilirubinemia, risk of kernicterus (bilirubin induce brain damage)

G6PD deficiency - congenital non-spherocytic hemolytic anemia

hyperbilirubinemia, low serum haptoglobin, increase LDH

pyruvate kinase deficiency - inheritance

autosomal recessive

pyruvate kinase deficiency - mutation

PKLR gene

pyruvate kinase deficiency - pathophysio

insufficient ATP production → membrane instability, loss of water from cells, shrink, Na+/K+ imbalance, premature destruction

pyruvate kinase deficiency - lab findings

burr cells, spiculated RBCs

pyruvate kinase deficiency - confirmatory test

quantitative PK activity & DNA analysis

pyruvate kinase

rate-limiting enzyme in final step of glycolysis → convert PEP to pyruvate to produce ATP

importance of ATP in RBCs

maintains membrane integrity, Na+/K+ ATPase activity, prevent hemolysis

PK deficiency → glycolytic block leads to

increase 2,3-DPG → promote oxygen release

allo-immune hemolytic anemia - types

ABO incompatibility & Rh incompatibility

allo-immune hemolytic anemia - ABO incompatibility

person receives blood transfusion with incompatible ABO antigens

allo-immune hemolytic anemia - ABO incompatibility - lab test

agglutination and hemolysis

allo-immune hemolytic anemia - Rh incompatibility

Rh negative receives Rh positive blood → develop anti-Rh antibodies

allo-immune hemolytic anemia - Rh incompatibility - lab test

agglutination and hemolysis

allo-immune hemolytic anemia - Rh incompatibility - example

hemolytic disease of newborn

autoimmune hemolytic anemia - types

warm & cold

warm autoimmune hemolytic anemia - antibody

IgG

warm autoimmune hemolytic anemia - mechanism

antibody binds to RBC → membrane altered → spherocytes → spleen removes

warm autoimmune hemolytic anemia - lab findings

spherocytosis, polychromasia, nucleated RBC

warm autoimmune hemolytic anemia - DAT & IAT result

positive, positive

cold autoimmune hemolytic anemia - antibody

IgM

cold autoimmune hemolytic anemia - mechansim

antibody binds to RBC → forms immune complexes → activates complement → hemolysis

cold autoimmune hemolytic anemia - lab result

RBC agglutination

cold autoimmune hemolytic anemia - symptoms

raynaud’s phenomenon (pale fingers in cold)

cold autoimmune hemolytic anemia - DAT & IAT results

positive, negative

drug-induced immune hemolytic anemia - types

drug adsorption, immune complex, autoimmune antibody

drug-induced immune hemolytic anemia - drug adsorption

drug binds to RBC surface → immune system forms antibodies against these drugs → extravascular hemolysis

drug-induced immune hemolytic anemia - immune complex

drug forms immune complex with antibodies → activate complement → intravascular & extravascular hemolysis

drug-induced immune hemolytic anemia - autoimmune antibody

alter immune regulation → body makes autoantibodies against RBC antigens → hemolysis