Integrative S2 Flashcards

1
Q

Important laboratory evidences of hemolysis

A

Low Hb (result from hemolysis of RBC).

  • Increase retic count (BM compensation to hemolysis).
  • Indirect hyperbilirubinemia (increase TSB mainly of indirect type).
  • Increase plasma lactic dehydrogenase (LDH).
  • Increase urine and fecal urobilinogen.
  • In IVH occur Hburia, Hbnemia and Hemosideriuria.
  • Blood film: to assess red cell morphology like: sickle cells, spherocytes, etc.
  • Further investigation according to suspected causes of hemolysis like Hb electrophoresis, osmotic fragility test, coomb’s test and many other tests.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

EVH

IVH

A

Pallor (from anemia).

  • Jaundice (from hemolysis).
  • Splenomegaly (main site of hemolysis).
  • Pallor (from anemia).
  • Jaundice (from hemolysis).
  • Dark color urine.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Classification of hemolytic anemia

A

Inherited Hemolytic anemias

  1. Enzymo-pathies
    e. g. G6PD deficiency and pyruvate kinase deficiency
  2. Membrano-pathies
    e. g. Hereditary elliptocytosis

spherocytosis

&

hereditary

3.Haemoglobino-pathies

Quantitative Hb-pathies: Thalassaemias Qualitative Hb-pathies: Hb S, C, D, E etc

II. Acquired Hemolytic anemias

  1. Immune
    - Autoimmune: warm and cold types.
    - Alloimmune: hemolytic transfusion reaction and hemolytic disease of newborn.
    - Induced by drugs.
  2. Non immune
  • Infection as malaria, clostridia.
  • Chemical / physical as burns, drowning.
  • Mechanical hemolysis as MAHA (TTP, HUS, DIC).
  • Acquired membrane defect as PNH, liver disease.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Main causes of IV hemolysis

A
  • Incompatible blood transfusion, usually to ABO incompatibility.
  • G6PD deficiency.
  • RC fragmentation syndromes.
  • Few types of warm and cold AIHA.
  • Paroxysmal nocturnal hemoglobinurea (PNH).
  • Some drug induce HA.
  • Hemolytic anemia due to Unstable Hb.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is G6PD deficiency

A

Definition: Sex-linked inherited disorder characterized usually by acute IVH following exposure to oxidant stress (like infections, drugs or fava beans) due to deficiency of RBC enzyme G6PD.

Variants of G6PD enzyme:

• About 52 variants with normal activity and about 400 variant with deficient activity mostly of Mediterranean type.

G6PD deficiency worldwide disease and quite frequent in Iraq especially in south area and in Iraq most variant is Mediterranean type.

Pathophysiology of hemolysis: Absence of G6PD enzyme with subsequent absent of reduce glutathione which essential for protection of RBC (membrane and Hb) from damage by oxidant effect which include free radicals formation from fava beans, drugs or infections.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Important triggering factors are: Acute hemolytic anemia G6PD D

A

Viral, bacterial infections.

– Acute illness as DKA.

– Drugs like antimalarial, sulphonamides, chlora, aspirin, and vitamin K analogous.

– Toxins as naphthalene.

– Fava bean (Favism).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

3 main syndromes of presentation are: G6PD D

A

Acute hemolytic anemia triggered by drugs, infections or fava beans. Acute hemolytic attack characterize by sudden pallor, jaundice, red or dark color urine due to hemoglobinuria, fever and abdominal pain. Attack last usually 2-6 days followed by spontaneous recovery. Spontaneous anemia is rare but hemolytic crises are frequent precipitate by triggering factors. Important triggering factors ar

  • Neonatal jaundice: G6PD deficiency is one of important hematological causes of NNJ.
  • Chronic non spherocytic hemolytic anemia (CNSHA):

chronic lifelong EVH (anemia, splenomegaly and jaundice).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Favism

A

Syndrome of IVH after ingestion of fava bean (fresh, dried, frozen, and even pollens) or some time to other components like topical henna. Offending agents are DIVICINE and ISOURAMIL. Hemolysis is related to dose, body mass, and more in children.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Laboratory findings: of G6PD D

Management

A
  • Blood picture normal between the hemolytic crises.
  • Variable degree of anemia during the hemolytic episode with typical findings of IVH.
  • Blood film during acute hemolysis showing normochromia, polychromasia, with nonspecific red cell morphology, sometimes showing bitten cell and blister cells.
  • Reticulocytosis and Heinz body detection.
  • Positive screening tests for enzyme activity.
  • Specific assay for red cell G6PD (best to done 2 wks after the attack) to avoid high enzyme level in young red cells and reticulocytes.
  • DNA analysis for G6PD gene in certain condition.

Management: Avoid precipitating factors.

Spontaneous recovery will happen and blood transfusion if required.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the most common HA in north Europe

A

Hereditary Spherocytosis

  • Definition: Inherited disorder usually autosomal dominant disease resulting from an intrinsic defect involving red cell membrane proteins, making the RBC osmotically fragile and spherocytic in shape with variable degree of hemolysis in the spleen.
  • Not common in Iraq, while consider is the common hereditary HA in North Europe.
  • Pathophysiology: Defect in membrane proteins (Spectrin, Ankyrin and Band-3 proteins) making the lipid bilayer not supported by the skeleton proteins result in spherocytic shape of red cells which destructed in RES (mainly in the spleen).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Laboratory findings: of hereditary spherocytosis

A
  • Variable anemia, increase MCHC.
  • Peripheral blood showing spherocytosis or microspherocytes.
  • Reticulocytosis.
  • Right shift on Osmotic Fragility Test (OFT) which confirm the presence of spherocytic cells.
  • Normal direct coomb’s test (exclude autoimmune hemolytic anemia).
  • Membrane proteins or gene defect analysis (Diagnostic test).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Clinical features: of Hereditary Spherocytosis

A
  • Majority present in first 10 years of life, with pallor, jaundice and splenomegaly.
  • Anemia may present at any age and usually start at infancy or childhood.
  • It one of hematological cause of NNJ.
  • HA may aggravate by infections or during the pregnancy.
  • Complications as gall stones, leg ulceration, growth retardation and iron overload.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Beta thalassemia

Types of beta thalassemia:

A

Important disorder because it is common and severe disorder.

  • One of the most common inherited hematological disorders in Iraq, that gene frequency around 4-5% of population.
  • Beta thalassemia more common in broad belt of Mediterranean region, part of North-West Africa, Middle East to South East Asia.
  • βo mean absent of β globin chain, while β+ mean reduce in β globin chain.

Types of beta thalassemia:

  • β Thalassemia major (βo βo) or (β+ β+) or (βo β+).
  • β Thalassemia minor (βo β) or (β+ β).
  • β Thalassemia intermedia of more complicated genetic background.
  • β Thalassemia with other Hb variants (like Sickle, HbC, HbE, etc).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

β- Thalassaemia major

Clinical features:

A

Homozygous or compound heterozygous inheritance of beta chain defect: (βo βo) or (β+ β+) or (βo β+).

Clinical features:

  • First diagnosis between age of 6 m- 2 yrs and evidences start after the age of 3 months (time of Hb-switching).
  • Presentation usually with pallor, jaundice, poor feeding, failure to thrive, abdominal swelling (due to HSM).
  • Later the clinical picture depends on management approach, and run into two categories:
  1. Well transfused patients: showing early normal development and at puberty develop features of iron overload (liver, cardiac and endocrine).
  2. Inadequately transfused patients: early sever symptoms of disease with severe anemia, jaundice, HSM, bone changes particularly thalassemia face.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

β- Thalassaemia major

Laboratory findings:

A

CBC: usually severe anemia, variable WBC and platelets counts.

MCV and MCH are both markedly reduced.

  • Blood film: sever hypochromic microcytic anemia, NRBC, sever anisopoikilocytosis, target, tear drop cells and basophilic stippling.
  • Reticulocytes: slight to moderately increase but not to degree of anemia (usually range 2-8%).
  • Hb electrophoresis (key for diagnosis) HbF 10-90 %. HbA absent. HbA2 variable.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Management

بيتا ثلاسيميا ميجور

A

• Prevention:

  • Population screening for carrier detection and choice of marriage.
  • Antenatal screening and choice of termination of pregnancy.
  • BM transplant.
  • Symptomatic treatment with blood transfusion in associated with iron chelation agents to reduce risk of iron overload.
  • Life long folic acid supplementation.
  • Splenectomy in indicated cases.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

β- Thalassaemia minor

A

Heterozygous inheritance of genetic defect ……… (β β+) or (β βo).

  • Clinically usually asymptomatic and may discovered by chance.
  • Mild anemia and splenomegaly are rare. During stressful condition especially in pregnancy the patients may become symptomatic because of aggravation of mild anemia.
  • It is important challenge to differentiate β- Thalassaemia minor from iron deficiency anemia.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

β- Thalassaemia minor

Laboratory findings:

A

Mild anemia.

  • MCH and MCV are reduced (more reduction to the degree of anemia in compare with iron deficiency anemia).
  • RBC count usually high (normal or low RBC count in IDA).
  • Reticulocyte count is slightly increased (usually low in IDA).
  • Blood film showing hypochromia, microcytic red cells with mild anisopoikilocytosis including few target cells.
  • Increase in Hb A2 4-6%, consider key for diagnosis: (normal range of Hb A2 is 1.8-3.5%).

Management: No need for specific management, except in periods of stress like pregnancy.

19
Q

Four types of alpha thalassemia according to genetic defects are

A

One gene deletion

(α α/ α-)

α + thalassemia trait (silent carrier)

Two gene deletion

(α -/ α-) or (α α/ –)

α o thalassemia trait (carrier α thalassemia)

Three gene deletion

(α -/ –)

Hemoglobin-H disease

Four gene deletion

(- -/ –)

hydrops fetalis syndrome (Hb Bart’s)

20
Q

Types of sickle cell disorders:

A
  • Sickle cell anemia (HbSS): Homozygous inheritance to sickle cell gene defect.
  • Sickle cell trait (HbSA): Heterozygous inheritance to sickle cell gene defect.
  • Sickle cell with other globin chain disorders like β-thalassemia, α thalassaemia, Hb C.
21
Q

Sickle cell disease (HbSS)

Pathophysiology

A
  • Hemoglobin S (beta chain variant) result from substitution of the Glutamic acid position 6 of the beta chain by Valine.
  • This changes result in conformational changes of RBC with deoxygenation and polymerization of HbS make the RBC sickle in shape and unable to pass through ECs.
  • Red cells with deoxygenation become sickle in shape initially of reversible event until the membrane damage occur become irreversible leading to EVH in the macrophage of RES.
  • Factors triggering the sickling process may include; increase HbS, decrease HbA, decrease HbF, deoxygenation, dehydration, acidosis, infection, fever, pregnancy and anesthesia.
22
Q

Geographic distribution of sickle cell & Clinical features:

A

More in black, West Africa, area of high malaria prevalence. In Iraq in more in south, especially in Basra.

extremely variable including:

Chronic HA

Splenomegaly

Sickle cell crisis

Other features: Infections especially by pneumococci, meningococci and H- influenza, retinopathy, gall stones, liver abscess, leg ulceration, and decrease in growth and development.

23
Q

Chronic HA: of sickle cell

A

features will not be apparent until the age of 3-6 months (time of Hb switching), and is characterized by variable degree of anemia, jaundice and splenomegaly, extenuated by episodes of sickle cell crisis.

24
Q

Sickle cell crisis is any new syndrome developing rapidly in a patient with sickle cell disease, include:

A

(1) Vaso occlusive crises at any site like painful bone crisis, acute abdomen, acute brain syndrome, acute chest syndrome and priapism.
(2) Acute sequestration crisis; sudden trapping of the blood in the spleen, characterize by severe sudden anemia and huge tender spleen.
(3) Aplastic crisis; sudden anemia, low reticulocyte count and reduce level of jaundice. Usually follows parvo viral B19 infection.
(4) Hemolytic crisis; sudden drop in Hb level, increase in reticulocyte count and bilirubin level.

25
Q

Laboratory findings: of sickle cell anemia

A
  • Variable degree of anemia (usually 6-8 gm/dl).
  • Blood film showing many sickle cells and target cells.
  • Increase in reticulocyte count.
  • Sickling test positive (not need in SCD but essential in SC trait).
  • Hb electrophoresis showing HbS 80-90%, HBF 2-20%, no HbA and normal HbA2
26
Q

Course and prognosis & treatment of sickle cell

A

Course and prognosis: High mortality in first few years especially in under-developed countries, due to pneumonia and meningitis and splenic sequestration. Most patients however survive well into adult life.

Treatment:

  • Avoid precipitating factors.
  • Blood transfusion in indications.
  • Folic acid supplementation.
  • Good general nutrition and hygiene.
  • Vaccination to pneumococcal, hemophilus, meningococcal, hepatitis B with regular oral penicillin.
  • Crisis management.
  • Hydroxyurea usually use to increase HbF level.
  • Stem cells transplantation can cure the disease.
27
Q

Sickle cell trait (HbSA)

Laboratory findings:

A

Laboratory findings:

  • Mild anemia and even normal Hb, PCV and red cell indices.
  • Blood film usually normal with absence of sickle cells.
  • Sickling test is positive (essential for diagnosis).
  • Hb electrophoresis shows 50% HbS and 50% HbS.

No need for any specific management.

28
Q

So important investigations required for diagnosis of immune hemolytic anemia are:

A
  • CBC and blood film: anemia with some morphological abnormality of RBC.
  • Retic count increase.
  • Direct coomb’s test: Positive
  • In-direct coomb’s test: Positive or negative.
29
Q

What are the difference bet direct & indirect coomb’s test

A

Direct coomb’s.

Detect Ig (Ab) on RBC membrane

In-Direct coomb’s test

Detect Ig (Ab) in the serum of patient

30
Q

Classification of immune hemolytic anemia

A
  1. Immune
  • Autoimmune: warm and cold types.
  • Alloimmune: hemolytic transfusion reaction and hemolytic disease of newborn.
  • Induced by drugs.
  1. Non immune • Infection as malaria, clostridia.
  • Chemical / physical as burns, drowning.
  • Mechanical hemolysis as MAHA (TTP, HUS, DIC).
  • Acquired membrane defect as PNH, liver disease.
31
Q

Warm autoimmune hemolytic anemia

Etiology

Pathogenesis

A

This AIHA in which the auto-antibody best reacts with red cells at 370C, is usually an IgG class and is usually associated with extravascular hemolysis.

Etiology:

1- Idiopathic in about 1/3 of cases.

EVAN SYNDROME: idiopathic AIHA associated with immune thrombocytopenia of different antibodies.

2- Secondary in association with other disorders like; autoimmune disorders, lymphoproliferative disorders, ovarian carcinoma, some drugs like alpha methyldopa and infections mainly viral infection.

Pathogenesis: RBC coated with IgG and/or complements which destruct in RES mainly the spleen causing EVH.

32
Q

EVAN SYNDROME

A

idiopathic AIHA associated with immune thrombocytopenia of different antibodies.

33
Q

Clinical features: of warm AIHA

A
  • Insidious onset of pallor, jaundice and splenomegaly.

* Features of secondary causes may found.

34
Q

Laboratory findings:
ttt
Of warm AIHA

A

Laboratory findings:

– Anemia, with many spherocytes on blood film.

– Reticulocytosis.

– Sometimes associated with immune TCP (Evan syndrome).

– Most important is positive direct Coombs test.

– Right shifting osmotic fragility test.

Treatment:

  • Treat underlying causes.
  • Corticosteroid, splenctomy, immunosuppresion, and other lines.
35
Q

Cold autoimmune hemolytic anemia

A

This AIHA in which the auto-antibody best reacts with red cells at 4 C, is usually an IgM class and is usually associated with extravascular hemolysis and less commonly IVH.

36
Q

Cold autoimmune hemolytic anemia

Etiology

Clinical features:

A

Etiology:

  • 1- Idiopathic (CHAD); cold hemagglutinin disease.
  • 2- Secondary in association with lymphoproliferative disorders and certain infections like mycoplasma pneumoniae and infectious mononucleosis.

Clinical features:

  • Patient may have chronic hemolysis aggravated by cold.
  • Mild jaundice and splenomegaly may be present. Patient may develop acrocyanosis.
37
Q

Laboratory findings: of cold AIHA

A
    • Anemia, red cells agglutination on peripheral blood and features of associated disorders.
    • Direct Coomb’s test is classically positive.
    • Positive cold agglutinin test.
38
Q

PNH (paroxysmal nocturnal hemoglobinuria)

A

Rare acquired chronic clonal disorder of marrow stem cells. Classically young adult, gradual onset triad of IVH, thrombosis and pancytopenia.

LO8

Dark color urine and nocturnal Hburia is prominent evidence. Thrombosis commonly occur in hepatic veins (Budd-Chiari syndrome).

39
Q

Pathophysiology of PNH

A

Many somatic mutations that make the RBC sensitize to lyses by complement resulting in chronic IVH.

40
Q

Lab findings: of PNH

A
  • Pancytopenia with increase retic count.
  • Findings of IVH.
  • Positive Ham’s test.
  • Flow-cytometry showing low CD55 and CD59.
41
Q

They are many disorders result from red cell fragmentation by different mechanism like:

A
  1. Cardiac hemolysis: artificial heart valve, graft and patches.
  2. Arteriovenous malformations.
  3. MAP (microangiopathic HA): hemolysis occur when the RBC pass through fibrin strand deposited in small vessels; it may occur secondary to:

o o o o o

TTP-thrombotic thrombocytopenic purpura. HUS-hemolytic uremic syndrome.

DIC-disseminated intravascular coagulopathy.

Malignant disease (adenocarcinomatosis).

Malignant hypertension, pre-eclampsia, HELLP syndrome.

  1. March Hburia: IVH due to mechanical RBC destruction on foot surfaces between small bones.
42
Q
  1. MAP (microangiopathic HA): hemolysis occur when the RBC pass through fibrin strand deposited in small vessels; it may occur secondary to:
A

TTP-thrombotic thrombocytopenic purpura. HUS-hemolytic uremic syndrome.

DIC-disseminated intravascular coagulopathy.

Malignant disease (adenocarcinomatosis).

Malignant hypertension, pre-eclampsia, HELLP syndrome.

43
Q

March Hburia

A

IVH due to mechanical RBC destruction on foot surfaces between small bones.