ANEMIA

College of Medicine & KKUH

19/02/2015

Khalid Al-Anazi

Cytopenias **Low WBC counts:

- Neutropenia - Lymphocytopenia - Monocytopenia

**Low Hb level: - Normocytic Anemia - Microcytic Anemia - Macrocytic Anemia

**Low PLT counts: - Primary - Secondary - Immune & non-immune

**Pancytopenia

Common causes of anemia

1 -Acute trauma and blood loss

2 -Chronic infections e.g. hookworm and parasitic infections.

3 -Chronic diseases e.g. chronic renal failure.

4 -Nutritional anemia

5 -Bone marrow failure syndromes:

aplastic anemia & myelodysplastic syndrome

6 -Neoplastic disorders:

leukemia, lymphoma & solid tumors

7 -Endocrine diseases & hormona imbalance

8 -Immune mediated hemolytic anemia

9 -DIC & toxin exposure

The most common causes of anemia

1 -Iron deficiency anemia

2 -Thalassemia

3 -Sickle cell disease

4 -Aplastic anemia

5 -Hemolytic anemia

6 -Pernicious anemia

7 -Fanconi anemia

Classification of anemias

1 -Microcytic hypochromic

2 -Normocytic normochromic

3 -Macrocytic

Investigations of anemia

Treatment of anemia

* Rx of cause; symptomatic Rx; DIET

* Supplements: iron; folate; vit B 12

* IV iron; blood transfusion

Classification of hemolytic anemias

*Hereditary or acquired

*Immune or non-immune

*Intravascular or extravascular;

intracorpuscular or extracorpuscular

*Warm antibody or cold antibody type

*Membrane, enzyme or globin chain defect ;

drug-induced, infection or disease-related

Hereditary hemolytic anemias

-Sickle cell anemia

-Thalassemias

-Hereditary spherocytosis

-Hereditary elliptosis

-G-6-PD deficiency

-Pyruvate kinase deficiency

Acquired hemolytic anemias

1 -Immune hemolytic anemias:

( a )Autoimmune hemolytic anemia

( b )Alloimmune hemolytic anemia

( c )Drug-induced hemolytic anemia

2 -Mechanical hemolytic anemia

3 -Paroxysmal nocturnal hemoglobinuria

4 -Infection-related hemolysis

5 -Drug-induced hemolysis

  Intracorpuscular defects Extracorpuscular defects

Hereditary - Hemoglobinopathies- Enzymopathies- Membrane defects

 -  Familial HUS

 Acquired

 - PNH

-Mechanical destruction [microagiopathy]

  * Drugs          * Toxins  * Infections   * Autoimmune 

Causes of microangiopathic

hemolytic anemia

1 -HUS

2 -TTP

3 -Valve or arterial graft hemolysis

4 -Mechanical: trauma and burns

Drugs that commonly cause hemolysis

1 -Antimalarials: chloroquine, promaquine

2 -Antimicrobials :

sulfonamides, chloramphenicol,

bactrim, nitrofurantoin.

3 -Miscellaneous: aspirin, dapsone

Intravascular defects Extravascular defects

 1- MAHA2- PNH3- Infections4- Snake bites5- Blood transfusion reactions

 1- Hemoglobinopathies2- Enzymopathies3- Membrane defects4- Autoimmune hemolytic anemia

Warm antibody hemolytic anemia

IgG antibodies bind at 37 o C

Cold antibody hemolytic anemia

IgM antibodies bind at 4 o C

1- Idiopathic: 50%

2- CLL

3- Lymphoma

4- Multiple myeloma

5- Ulcerative colitis

6- HIV

7- SLE, RA

8- Solid tumors

1- Infections:

(a) Mycoplasma (b) EBV

2- Neoplasms:

(a) CLL

(b) Multiple myeloma

(c) Walenstrom macroglobulinema

(b) Kaposi sarcoma

** Elderly individuals

** Exacerbation by cold; in winter

** Acrocyanosis: blue fingers and toes

 

Hemolytic anemia

Clinical aspects Laboratory findings

1- Anemic manifestations:

* Dizziness * Headache

* Fatigue * Palpitations

* Pallor * SOB

2- Jaundice

3- Dark urine

4- Splenomegaly

5- Gallstones

6- Leg ulcers

- ↓ Hb

- ↑ MCV

- ↑ Reticulocyte count

- ↑ LDH

- ↑ Total & indirect bilirubin

- ↓ or absent haptoglobin

- Sickling test

- HB electrophoresis: Hb S; HbF

- Coombs test: direct & indirect

- Osmotic fragility test

- Blood film:

* Sickle cells * Spherocyts

* Reticulocytes * Elliptocytes

* Target cells * Microcytosis

* Pencil cells * Macrocytosis

* Hypochromasia

Causes of Normocytic Anemia

A- Anemia of chronic illness: ** Anemia of chronic renal insufficiency

** Anemia of chronic liver disease; multifactorial ** Anemia of endocrine disease:

- Addison's disease - Hypothyroidism

B- Hemolytic anemias: ** Sickle cell diseaseC- Bleeding; acute blood lossD- NutritionalE- Early iron deficiency anemiaF- Mixed Anemia [Iron/Folate/Vit B12 deficiency]

Blood film of SCA

Causes of Microcytic anemia

1 -Iron deficiency anemia 2 -Thalassemia; α , β

3 -Sideroblastic anemia 4 -Anemia of chronic illness

5 -Anemia of inflammation 6 -Lead poisoning

Blood Film of Thalassemia

Blood Film of IDA

Differentiation IDA & Anemia of chronic illness

Lab. Index Iron deficiency

 

Chronic Illness

 

Hb ↓ ↓

MCV ↓ ↓ or Normal

MCH ↓ Normal

MCHC ↓ Normal

Iron ↓ ↓

Ferritin ↓ ↑

TIBC ↑ ↓

Sol. Transferrin

Receptor Level ↑ Normal

Transferrin

Saturation↓ ↓

RDW ↑ Normal or ↑

Blood Film

Microcytic; Hypochromic

Pencil & Target cells

Normocytic; Normochromic

Microcytic in severe cases

BM Bx ↓ or Absent Present

Causes of Macrocytosis

1 -Folate deficiency 2 -Vitamin-B12 deficiency

3 -Pernicious anemia 4 -Alcohol intake

5 -Pregnancy 6 -Hypothyroidism

7 -Liver disease 8 -Hemorrhage & hemolysis

9 -Myelodysplastic syndrome & aplastic anemia 10 -Multiple myeloma and acute leukemia

11 -Malabsorption syndrome 12 -COPD

13 -Copper deficiency 14 -Splenectomy

15 -Drugs & Toxins: ** Arsenic poisoning ** Bactrim

** Nitrous oxide poisoning ** Metformin ** Anti-retroviral Rx ** Hydroxyurea ** Anti-TB Rx ** Methotrexate

Macrocytic anemia

Common causes:

1 -Diet: malmnutrition, malabsorption

2 -Drugs: antifolate drugs, antimicrobials

& anticonvulsdants

3 -Alcohol intake

4 -Liver disease

5 -Thyroid disease

6 -Malignancy: leukemia & myeloma

7 -BM failure: MDS & aplastic anemia

Clinical & laboratory manifestations of macrocytic anemia

Clinical aspects Laboratory findings

1- Signs of malnutrition:

emaciation

2- Manifestations of anemia:

* Dizziness

* Headache

* Fatigue

* Palpitations

* Pallor

* SOB

3- Signs of liver disease

3- Signs of thyroid disease

4- Signs of BM failure:

Pallor

Ecchymoses

Petechiae

 

- ↓ Hb

- ↑ MCV

- PLT: normal or ↓

- ↑ LDH

- Hct, MCH, MCHC

- ↓ blood counts; pancytopenia:

chronic liver disease, hypersplenism, MDS,

aplastic anemia & vitamin B12 deficiency

- Renal & hepatic profiles

- Coagulation profile

- Thyroid function tests

- Vitamin B12 & folate levels

- Blood film:

* Macrocytosis

* Hypersegmentation of neutrophils

* Rouleaux formation, plasma cells

* Dysplastic changes & blast cells

- Bone marrow Bx:

* Megaloblastic changes

* Dysplastic changes

* Blasts & plasma cells

Blood film of ITP

Blood Film of MAHA

Beta-Thalassemia Major

- Autosomal recessive

- Mutations in Hb Beta gene: 250 different mutations described

* Clinical manifestations:

- Anemia

- Splenomegaly

- Promiment bones: frontal bossing, prominent cheeks

- Hepatomegaly

- Iron overload

* Management:

- Supportive care

- Folic acid

- Blood transfusions

- Iron chelation

- Gene therapy

- HSCT

Complications of SCD

Complication or

organ involvedExamples and details

Infections

1- Pneumonia

2- Urinary tract infection

3- Pyelonephritis

4- Meningitis

5- Acute cholecystitis

6- Bacteremia and septicemia

Microorganisms involved:

Streptococcal pneumonia ; Salmonella species ;

Neisseria meaningitidis ;

Hemophilus influenzae ;

Chlamydia pneumonia; Staphylococus aureus ; Myloplasma pneumoniae ; Parvovirus B-19

Sickle cell crises Venoocclusive ; hemolytic ; aplastic ; splenic sequestration crises

Bone involvement Dactylitis ; avascular necrosis of bone e.g. femoral head (osteonecrosis) ; osteomyelitis

Renal involvement Hyposthenuria; glomerulopathy; end-stage renal disease; microalbuminuria; renal insufficiency; contrast and

analgesic nephropathies

Pulmonary involvement Pulmonary emboli ; restrictive lung disease; acute chest syndrome ; pulmonary hypertension; lung infections

Cardiac complications Cardiomyopathy; myocardial infarction; heart failure

Neurological sequelae Ischemic stroke; silent cerebral infarctions; convulsions

Chronic hemolysisAnemia (may be severe); cholelithiasis; priapism; risk of aplasia; hyperbilirubinemia; leg ulcers; pulmonary hypertension

Miscellaneous

Complications

Delayed growth; delayed sexual maturation; proliferative retinopathy; iron overload and hemochromatosis;

organ dysfunction and failure; drug toxicity; narcotic dependence and abuse; priapism; hyposplenism, splenic

dysfunction and auto-splenectomy.

 

General Measures

1- Analgesia for pain

2- Oral and intravenous hydration

3- Folic acid supplements

4- Penicillin prophylaxis

5- Antimicrobials for infectious complications

6- Blood transfusion

7- Exchange blood transfusion

8- Oxygen supplementation

9- Mechanical ventilation in respiratory distress

10- Joint replacement therapy for a vascular

necrosis e.g. hip joint

11- Chelation therapy for iron overload 

Specific and targeted therapies

1- Drugs that increase HbF production

hydroxyurea; vorinostat; valproic acid; panobinostat;

sodium dimethylbutyrate; decitabine and azacytidine; pomalidomide

2- Anti-oxidant therapies:

glutamine; N-acetylycystine; alpha-lipoic acid; omega - 3 fatty acids

3- Gardos channel inhibitors

4- Vascular tone targetting: IV magnesium

5- Anti - sicking agents e.g. Aes-103

6- Blockade of adhesive pathways:

intravenous immunoglobulin;

anti-selectins; propranolol; tinzaparin

7- Anticoagulants for vascular thrombosis

8- Anti-platelet agents: prasugrel

9- Anti- inflammatory agents:

regadenoson

10- Statins; for vascular protection

11- Phytomedicines; including

plant mixtures

12- Investigational therapies

e.g. nitrous oxide

 

Potentially curative therapies

 

 

1- Gene replacement therapy

 

2- Various forms of stem cell therapies

 

Preventive measures

1- Avoidance of dehydration, extremes of temperature,

physical exhaustion, high altitude without

oxygen supplementation, certain medications

such as meperidine and G-CSF

 

2- Health education

 

3- Screening programs

 

4- Family and genetic counselling

Complications of blood transfusion

Early complications Late complications

1- Hemolytic reactions:

Immune & delayed

2- Non-hemolytic febrile reactions

3- Allergic reactions to proteins:

anaphylactic reactions in IgA defy

4- TRALI; transfusion-related

acute lung injury

5- Secondary reactions to

bacterial contamination

6- Circulatory overload:

pulmonary edema

7- Air embolism

8- Thrombophlebitis

9- Hyperkalemia

10- Hypothermia

11- Clotting abnormalities:

with massive transfusions

12- Citrate toxicity

1- Transmission of infections:

* Viral infections:

- Hep A negligible

- Hep B 1:100,000

- Hep C ˂ 1: 1,000,000

- HIV 1&2 ˂ 1: 4,000,000

- CMV

- JC virus

* Bacterial infections:

- Salmonella

- Treponema pallidum

- Staph. aureus & epidermidis

- Brucella

- Yersinia enteroclitica

- Bacillus

2- GVHD: donor T- cells

3- Iron overload with repeated transfusions

4- Immune sensitization: rhesus D antigen

 

Massive blood transfusions

Replacement of patient's total blood volume within 24 hours

Complications:

1- Coagulation abnormalities & bleeding diathesis;

due to consumption of PLTs & clotting factors

2- Elecrtrolytic & acid base balance disturbances:

Hyperkalemia & hypocalcemia

3- Hypothermia

Management:

1- Replacement of PLTs, cryoprecipitates & packed RBCs

2- Anticoagulants may be needed

3- Warm all IV fluids

4- Corrections of electrolytic disturbances

How to minimize transfusion complication

* Transusion of blood products:

once needed / required quantity only

* Transfusion of packed RBCs [ not whole blood]

* Screening of donors

* Screening of donated blood products

* Leukofiltration

* Leukodepletion

* Transfusion of compatible blood

* Donation & transfusion: under aseptic techniques

* Elderly; cardiac or respiratory disease:

Slow rate: 4-6 hours ; Diuretics

* IV adrenaline, hydrocortisone & diphenhydramine

* Hold or stop blood product transfusion in case of reaction:

Send samples to: blood bank & microbiology laboratory.

Blood Film of AML

Blood Film of MDS

BM Bx of Aplastic Anemia

BM Bx of Myelofibrosis

Malarial Blood Film [Plasmodium falciparum]

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