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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]
THANK YOU
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