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Sem3: PATH30030 Hematology/Immunosupression > L3 Anemia II > Flashcards

L3 Anemia II Flashcards

1
Q

Morphological Class of Hemolytic Anemias?

A

Mostly NORMOCYTIC

Can be associated with MACROCYTOSIS (in cases of elevated reticulocyte count)

MICROCYTIC –Thalassemia

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2
Q

____________: Premature destruction of erythrocytes

A

Haemolysis: Premature destruction of erythrocytes

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3
Q

Intrinsic vs. Extrinsic Causes of Hemolytic Anemia

A

Intrinsic RBC Defect : Due to a defect within RBCs

➢ Red cell membrane disorders

o Hereditary spherocytosis

o Hereditary elliptocytosis

➢ Disorders of haemoglobin synthesis

o Thalassemia

o Sickle cell anaemia (HbSS)

o Haemoglobin C disease

➢ RBC enzyme deficiencies

Extrinsic RBC Defect: Healthy RBCs are produced but later destroyed

➢ Immune-mediated

o Incompatible blood transfusions

o Haemolytic disease of the newborn

o Drug-induced

➢ Non-immune

o Mechanical trauma

o Infections (e.g., malaria)

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4
Q

Increase in the rate of destruction of RBD => more ________produced => _________

A

Increase in the rate of destruction of RBD => more bilirubin produced => jaundice

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5
Q

Differenced between Extravascular and Intravascular Hemolysis

A

Extravascular

Causes: Autoimmune Hemolytic Anemia (AIHI), hereditary disorders

Spherocytes (round w/ palor at center)

Normal or low serum haptoglobin

Direct antiglobulin test (DAT) ++++ (AIHA)

No haemoglobinaemia/-uria

No methemoglobin formation

+/-Splenomegaly, +/-Hepatomegaly

Extramedullary hematopoiesis

Intravascular

CAUSES: Shear stress/mechanical damage, Autoimmune diseases, Toxins, Tumour lysis syndrome

Schistocytes (helmet shaped)

Very low/absent serum haptoglobin (RBCS damaged in vessels => haptoglobin binds free hemoglobin)

DAT usually negative

Hemoglobinemia(excess of hemoglobin in the blood plasma)

Hemoglobinuria (hemoglobin found in abnormally high concentrations in the urine)

Haemosiderinuria,methaemoglobinaemia/-uria

NO splenomegaly

+/-Acute renal tubular necrosis

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6
Q

Examples of Hyperproliferative and Hypoproliferative aAnemia?

A

HYPERproliferative Anemia:

Anemia due to Hemolysis

Anemia due to hypersplenism

Thalesmina (Microcytic)

HYPOproliferative Anemia:

Aplastic anemia (normocytic)

Iron deficiency anemia (microcytic)

Megaloblastic anemia (Folate and vitamin B12 deficiency) (macrocytic)

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7
Q

Pathogenesis/Manifestation/Treatment of Heredity Spherocytosis

A

Pathogenesis:

  • Defect in ankyrin, spectrin→ spherocytes
  • Extravascular haemolysis (macrophages in spleen destroy RBCs)

Manifestation

  • Haemolysis→ increased bilirubin →Jaundice
  • Splenomegaly
  • Pigment gallstones
  • Increased risk for aplastic crisis (due to parvovirus B19 infection)
  • Increased red cell osmotic fragility

Treatment:

  • Splenectomy
  • Folic acid
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8
Q

Fetal vs. Adult Hemoglobin?

A

Foetal: Hb F (2α:2γ) → ~80% at birth is Hb F

Adult: Hb A (2α:2β) → >95% of adult Hb is Hb A

Hb A2 (2α:2δ)

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9
Q

Disorders of Hemoglobin synthesis involving gene defect(s) resulting in reduced production of globin chains?

A

α-thalassaemia (reduced α chain synthesis)

ß-thalassaemia(reduced ß chain synthesis)

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10
Q

α-thalassaemia is ____________ disease and can be expressed both ____________ and ____________

A

α-thalassaemia is ‘Dose-dependent’ disease and can be expressed both prenatally and postnatally

depending how many globin chains effected by mutaion: varies from mild to very severe disease

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11
Q

Globulin chains precipitated in those with Thalasseimia?

A

Heinz Bodies

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12
Q

Varies forms of α-thalassaemia?

A

Silent carrier: 1 gene lost (-α/αα). No symptoms, normal lab

α-thalassaemia trait: 2 genes lost (–/ααor -α/-α). Similar to β-thalassaemia minor

Hb H disease: 3 genes lost. Severe as β-thalassemia intermedia

  • Increased Hb H (β4) →Heinz bodies
  • Hb H has high O2affinity →tissue hypoxia

Hydrops fetalis:

  • Hemoglobin composed entirely of Gamma chains, No α-chains
  • HbBarts(γ4) high O2 affinity →tissue hypoxia
  • Lethal in utero without intrauterine transfusions
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13
Q

Various Forms of β-thalassaemia

A

Minor

  • Heterozygosity
  • Asymptomatic
  • Mild anaemia, microcytosis
  • Increased HbA2 (2α2δ) and HbF(2α2γ)

Intermedia: varying degrees of anemia, but no transfusions are needed

Major (Cooley’s anaemia): Most severe form

  • Homozygosity
  • No symptoms at birth
  • Symptoms develop at 6-9 months
  • Severe anaemia, requires lifelong transfusion
  • Increased HbF(2α2γ): >90%
  • Normal or increased HbA2 and Increased HbA
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14
Q

β-thalassaemia major (aka_________) Pathologenesis?

A

β-thalassaemia major (aka Cooley’s Anemia) Pathologenesis?

Reduced β- Globin synthesis => lack of beta-globin chains

=> insoluble alpha aggregates => abnormal Erythroblasts

=> most RBCs destroyed in bone marrow

=> surviving destroyed by macrophages in spleen

=> Because of ineffective erythropoiesis:

INCREASED RBC production in Liver, Spleen, Heart

INCREASED Iron absorption

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15
Q

β-thalassaemia major (aka. ________) Clinical features?

A

β-thalassaemia major (aka. Cooley’s Anemia)

Hepatosplenomegaly

Haemolysis → jaundice and bilirubin gallstones

Secondary hemochromatosis (frequent transfusions) and increased dietary iron absorption

Facial bone abnormalities, “chipmunk face” (increased size of maxilla)

“Crewcut” skull on X-ray (due to maxillary overgrowth caused by erythroid hyperplasia in Bone Marrow)

Transfusion-associated infections; infections due to asplenia

Heart failure (due to iron overload) –most common cause of death

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16
Q

The most common cause of death from Cooley’s Anemia?

A

➢Heart failure (due to iron overload)

17
Q

How to diagnose Hereditary Spherocytosis?

A

Test for RBC fragility to diagnose => place in solution to see point at which breakup occurs (RBC osmatic fragility increased)

18
Q

_______________________ is done to identify normal and abnormal haemoglobins and assess their quantity

A

Haemoglobin electrophoresis is done to identify normal and abnormal haemoglobins and assess their quantity

19
Q

Mutation leading to Sickle Cell DIsease

A

β-globin gene point mutation: Glu for Val at 6thcodon

20
Q

Homozygous vs. Heterozygous for sickle cell mutation

A

Homozygous (SS) -Sickle cell anemia: Severe haemolytic anaemia

Chronic haemolysis

intermittent microvascular occlusions

tissue damage

Heterozygous (AS) -Sickle cell trait: Asymptomatic (or mild symptoms) -Resistance against malaria

21
Q

In sickle cell Anemia under __________ conditions Hb S forms polymers →sickling →_________

A

Under low oxygen conditions, Hb S forms polymers →sickling→occlusion of small vessels

22
Q

Factors that influence sickling?

A

Increased HbF makes symptoms better (infants are asymptomatic until 5-6 months of age)

Increased HbF makes symptoms better (infants are asymptomatic until 5-6 months of age)

Increased concentration of HbS (dehydration of RBC) makes symptoms worse

Increased HbF makes symptoms better (infants are asymptomatic until 5-6 months of age)

Decreased pH decreases oxygen affinity to Hb → fraction of deoxygenated HbS increased => symptoms worse

Inflamed microvascular beds →slower transit time of RBCs →prone to sickling and occlusion worse

23
Q

Clinical Features of Sickle Cell Anemia

A
  • Dactylitis: Swollen hands and legs
  • Acute chest syndrome -Pleuritic chest pain, hypoxaemia, fever, tachypnoea, and infiltrate(s) on CXR
    • Vasoocclusion in the lung tissue
    • Pulmonary inflammation (e.g., due to infection) may trigger it
    • Asthma is a contributing factor
  • Cerebral infarct
    • Stroke by age of 40 (peak incidence in late childhood and early teenage years) in 25% of patients
    • Another third of patients: silent cerebral infarcts (→cognitive deficits)
  • Priapism -45% of males after puberty
    • Autosplenectomy: Chronic stasis and trapping of sickled RBC’s leads to infarctions, fibrosis and eventually shrinkageof the spleen by adolescence.
24
Q

Sickle Cell Disease Treatments?

A

PROPHYLAXIS:

  • Penicillin daily
  • Vaccination against Pneumococcus
  • Folic acid supplementation

TREATMENT:

  • Transfusions (complications: iron overload, alloimmunization, infection)
  • Red cell exchange (for example, if acute stroke or acute chest syndrome)
  • Hydroxyurea (to increase HbF→makes symptoms better because of decreasing cc of HbS)
25
Q

Example of a Red Cell Metabolic Defect?

Pathogenesis?

What Triggers Hemolysis?

A

Glucose-6-phosphate dehydrogenase (G6PD) deficiency:

Protective Against Malaria

Decreased levels of reduced glutathione (antioxidant) → Oxidative stress (e.g., infections etc.) → oxidation of Hb → Heinz bodies

Haemolysis triggered by

o Drugs and infections that cause oxidative hemoglobin damage

o Ingestion of fava beans

26
Q

Which Hemolytic Anemia is triggered by Fava Bean Consumption?

A

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

27
Q

Investigations for Intrinsic Anemia?

A

Blood count and blood film

  • Raised reticulocyte count
  • Nucleated red cells in peripheral circulation
  • Poikilocytosis/spherocytes/sickle cells

Hemoglobin electrophoresis

Specific RBC enzyme assay

Clinical features (ß-Thalassaemia)

  • Skeletal abnormalities (maxillary overgrowth, “crewcut” skull)
  • Extramedullary haematopoiesis (hepatosplenomegaly)
28
Q

Which Anemia is associated with “crewcut” skull?

A

ß-Thalassaemia Major (aka Cooley’s Anemia)

29
Q

Warm vs. Cold Antibody Hemolysis

A

Warm antibody haemolysis

IgG antibodies active at 37ᵒC

Extravascular RBC lysis

Red cell opsonisation

Cold antibody haemolysis

IgM antibodies active < 37ᵒC

Intravascular RBC lysis

Complement fixationAnaemia II

30
Q

Investigations/ Therapy for Immune Hemolytic Anemia

A

Investigations

Direct Coombs antiglobulin test positive

Test for:

Increased unconjugated bilirubin

Increased LDH

Decreased plasma haptoglobin

Treatment

Steroids

IV Ig

Splenectomy

Treatment of underlying etiology

Immune

31
Q

Non-Immune Hemolytic Anemia Causes?

A

Damaged microvasculature (Microangiopathic disorders)

Cardiac abnormalities

Burns ( >10% of the body surface area)

INFECTIONS(e.g., malaria)

32
Q
A
33
Q

Low Hemoglobin levels, MCV < 80 fL.

What tests are done next?

What Conditions are associated with this?

A

MCV < 80 fL: Microcytic hypochromic

Proceed with Serum iron studies and Hb Ekectrophoresis

▪ Low iron, low ferritin, high TIBC (Total iron-binding capacity) → Iron deficiency anaemia

▪ Low iron, normal/high ferritin, low TIBC → Anaemia of chronic disease (~20%)

▪ Normal/high iron & ferritin, normal TIBC, abnormal Hb pattern on electrophoresis → Thalassaemia

34
Q

Low Hemoglobin levels, MCV 80-100 fL.

What tests are done next?

What Conditions are associated with this?

A

MCV: 80 - 100 fL: Normocytic normochromic (MOST COMMON ANEMIA)

Proceed with Reticultyte Count (number of immature red blood cells (reticulocytes) in bone marrow)

>2% Reticulocytes → Hyper-proliferative anaemia

▪ Acute blood loss

▪ Haemolytic anemia

<2% → Hypoproliferative anaemia

▪ Anaemia of chronic disease (~80%)

▪ Renal disease, Leukaemia, metastases, Aplastic anaemia, Myelofibrosis

35
Q

Low Hemoglobin levels, MCV >100 fL.

What tests are done next?

What Conditions are associated with this?

A

MCV > 100 fL: Macrocytic

Test for:

Peripheral smear: Hypersegmented neutrophils, megalocytes

Bone marrow: Megaloblasts

PRESENT → Megaloblastic anaemia

▪ B12 deficiency +/-

▪ Folate deficiency

▪ Drug-induced (e.g.,methotrexate)

ABSENT → Non-megaloblastic

▪ Myelodysplastic syndromes

▪ Liver disease

▪ Chronic alcoholism

▪ Increased reticulocytes (Hyper-Proliferative Anemia)

Sem3: PATH30030 Hematology/Immunosupression (11 decks)

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