Haematological Disorders

B. Pimentel, M.D.
University Of Makati
College of Nursing

The Red Blood Cell

Transports oxygen, called oxyhemoglobin, when it gives up
its oxygen it is deoxyhemoglobin.
Also binds and transports carbon dioxide,
carbaminohemoglobin.
Makes up 97 % of RBC 250 million Hb molecules per
RBC
Men: 14-18 mg/dl blood
Women: 12-16 mg/dl blood

The Red Blood Cell

Types of Hemoglobin (Hb)
Hb A
96% of adult Hb (2 2)

Hb A2
3% of adult Hb (2 2)

Hb F
1 % of adult Hb (2 2)

The Red Blood Cell

The Red Blood Cell

The Red Blood Cell

Transfusion Therapy
Blood
group
A

Antigen

Antibody

Donor to

Anti-B

Recipient
from
A, O

Anti-A

B, O

AB

AB

Neither

AB

A, B, AB, O

Neither

AntiA/Anti-B

O, A, B, AB

Universal donor "O"

Universal recipient "AB"

Adverse Transfusion Reactions

Acute Hemolytic Reaction
Symptoms

Fever, chills and fever, the feeling of heat along the

vein in which the blood is being transfused
Pain in the lumbar region
Constricting pain in the chest, tachycardia, hypotension
Hemoglobinemia with subsequent hemoglo-binuria
and hyperbilirubin-emia.
"feeling of impending doom"

Adverse Transfusion Reactions

Acute Hemolytic Reaction
Causes
Human error!
Transfused red cells react with circulating antibody in the
recipient with resultant intravascular hemolysis

Adverse Transfusion Reactions

Acute Hemolytic Reaction
Frequency
Rare

Prevention
Proper identification of patients, pretransfusion blood
samples and blood components at the time of
transfusion

Adverse Transfusion Reactions

Delayed Hemolytic Reaction
Falling hematocrit

due to extravascular destruction of the transfused red blood

cells)

Positive direct antiglobulin (Coombs) test (DAT)

Occurs about 4-8 days after blood transfusion
Patients may manifest fever and leukocytosis
Appearing to have an occult infection.

Adverse Transfusion Reactions

Febrile Transfusion Reaction
Fever or chill fever
temperature rise of 1.5 F or 1.0 C from the baseline

Cytokines and antibodies to leukocyte antigens

reacting with leukocytes or leukocyte fragments
1 in 8 transfusions

Adverse Transfusion Reactions

Allergic urticaria
Laryngeal edema and bronchospasm
1% of recipients
If coupled with another sign, such as fever, evaluation
for a hemolytic reaction may be indicated.

Adverse Transfusion Reactions

Allergic Anaphylaxis
Anaphylactic or anaphylactoid
Respiratory involvement with dyspnea or stridor

Cardiovascular instability
hypotension, tachycardia, loss of consciousness,
cardiac arrhythmia, shock and cardiac arrest

Adverse Transfusion Reactions

Volume Overload
Transfusion-related volume overload
Infuse smaller volumes more slowly

Adverse Transfusion Reactions

Bacterial Contamination
Hypotension, shock, fever and chills, nausea and
vomiting, and respiratory distress
Gram stain and blood culture

IF A TRANSFUSION REACTION IS
SUSPECTED

Follow protocol for transfusion

reactions implemented by the
institution

IF A TRANSFUSION REACTION IS
SUSPECTED
Stop the transfusion immediately!
Disconnect the intravenous line from the
needle.
Seek medical attention immediately. If the
patient is suffering cardiopulmonary collapse,
and medical attention is not immediately
available, press for Code"

IF A TRANSFUSION REACTION IS
SUSPECTED
Check to ensure that the patient name and
registration number on the blood bag label
exactly with information on the patient's
identification
Do not discard the unit of blood that has been
discontinued because it may be necessary for the
investigation of the transfusion reaction.

Treatment for Transfusion Reactions

Reaction Type

Treatment - Adult

Pediatric

Follow-up

Acute
Hemolytic
Reactions

Diuretic therapy: Initially, give 40-80

mg Furosemide (Lasix)
intravenously. This dose can be
repeated once. Lack of response to
furosemide in 2-3 hours indicates
the presence of acute renal failure.

Pediatric dose: 1-2

mg/kg/dose.
May repeat once
at 2-4 mg/kg.

Treat shock and disseminated

intravascular coagulation with
appropriate measures if and when
they appear.

Water loading: The patient should be

hydrated to maintain urinary
output of at least 100 mL/hr until
urine is free of hemoglobin.
Infuse a loading dose of 0.9% sodium
chloride or 5% dextrose in 0.45%
sodium chloride. Chart hourly
urine output. Maintain the urine
output by administering
intravenous fluid at 100 mL/hour
until the urine is free of
hemoglobin. If the patient's
urinary output does not increase,
with this hydration any additional
fluids should be infused with
caution.

Pediatric patients
should receive a
smaller loading
volume of fluid
in proportion to
their body
surface area.

Treatment for Transfusion Reactions

Reaction Type

Treatment - Adult

Delayed
Hemolytic
Transfusion
Reactions

Specific treatment generally is not

necessary

Pediatric

Follow-up

Supplemental transfusion of blood lacking

the antigen corresponding to the
offending antibody may be necessary
to compensate for the transfused cells
that have been removed from the
circulation.

Treatment for Transfusion Reactions

Reaction Type

Treatment - Adult

Pediatric

Follow-up

Allergic
Transfusion
Reactions

Antihistamines(e.g., Benadryl). Give

50-100 mg orally or intravenously. If
urticaria develops slowly,
antihistamines may be given orally.

Pediatric dose: 1-2

mg/kg intramuscularly
or intravenously for
25-50 mg per average
dose.

Routine use of Benadryl as premedication

for all transfusions, regardless of a history
of allergic reactions, is discouraged.

Aminophylline for wheezing, at a dose

of 125-250 mg intravenously slowly
over a period of about five minutes

Pediatric dose: 3
mg/kg/dose in
intravenous drip over
of 20 minutes.

Epinephrine for severe, acute reactions

including laryngeal edema or
bronchospasm Give 0.1-0.5 mg (0.1-0.5
mL of a 1:1000 solution)
subcutaneously. Subcutaneous dose
may be repeated at 10-15 minute
intervals. The total subcutaneous dose
in a 24-hour period, with rare
exception, should not exceed 5 mg.

Pediatric dose: 0.03

mL/M2 (0.03 mg/M2
of a 1:1000 solution)
given subcutaneously.
A single pediatric
dose should not
exceed 0.3 mg.

Treatment for Transfusion Reactions

Reaction Type

Treatment - Adult

Pediatric

Follow-up

Febrile
Transfusion
Reactions

Premedicate the patient with

acetaminophen or other
antipyretic agents when previous
reactions have been extremely
bothersome. Pediatric dose: 10
mg/kg to a maximum of 600 mg.

Aspirin will adversely affect the patient's

platelet function, so non-aspirin
antipyretic agents are preferable.

Severe shaking
Chills

(rigors) can be controlled by the

sedative effect of Benadryl or
Demerol (25-50 mg given
intramuscularly or intravenously

Note: Demerol may cause acute

respiratory arrest. An opiate
antagonist (Narcan) should be
immediately available.

Sepsis Due to
Bacterial
Contamination
of Donor Blood

Treatment of septic shock includes:

terminating the suspected
transfusion immediately, cardiovascular and respiratory support,
blood culture of the patient, and
administration of broad spectrum
antibiotics including antipseudomonas coverage if the
blood component involved is Red
Blood Cells.

Anemia
Abnormally low number of RBC or Hb levels
Reduced oxygen carrying capacity
Causes
Blood loss
Increased rate of red cell destruction
Hemolytic anemia

Deficient or impaired red cell production

Anemia
Risk factors
Poor diet
Intestinal disorders
Menstruation
Pregnancy
Chronic conditions
Family history

Anemia
NOT A DISEASE but a symptom
Dependent on severity, speed of development, age,
health status and compensatory mechanisms
Associated with impaired O2 transport, alteration in
RBC structure or with chronic illness
Not expressed until 50% of RBC mass is lost

Anemia
Signs and symptoms
The main symptom of most types of anemia is
fatigue

Weakness
Pale skin
Tachycardia
Shortness of breath
Chest pain
Dizziness
Cognitive problems
Numbness or coldness in your extremities
Headache

Anemia
Iron Deficiency Anemia
Most common form of anemia

Affects about one in five women

Half of pregnant women and 3 percent of men in the
United States.

The cause is a shortage of the element iron

Nutritional imbalance
Slow, chronic bleeding disorders
Inability to recycle plasma iron

Anemia
Vitamin Deficiency Anemias
Folate and vitamin B-12 deficiency
Intestinal disorder that affects the absorption of
nutrients
Fall into a group of anemias called megaloblastic
anemias, in which the bone marrow produces
large, abnormal red blood cells.

Anemia
Anemia of Chronic Disease
Interfere with the production of red blood cells,
resulting in chronic anemia
Kidney failure also can be a cause of anemia
The kidneys produce a hormone called
erythropoietin, which stimulates your bone marrow
to produce red blood cells.

A shortage of erythropoietin, which can result from kidney

failure or be a side effect of chemotherapy, can result in a
shortage of red blood cells.

Anemia
Aplastic Anemia
Life-threatening anemia caused by a decrease in
the bone marrow's ability to produce all three
types of blood cells red blood cells, white
blood cells and platelets
Cause of aplastic anemia is unknown

autoimmune disease
Chemotherapy
Radiation therapy
Environmental toxins

Anemia
Anemias associated with bone marrow disease
Leukemia and myelodysplasia, can cause
anemia by affecting blood production in the
bone marrow
Effects vary from a mild alteration in blood
production to a complete, life-threatening
shutdown of the blood-making process
Myelodysplasia is a pre-leukemic condition
that can cause anemia.

Other cancers of the blood or bone marrow, such

as multiple myeloma, myeloproliferative disorders
or lymphoma, can cause anemia.

Anemia
Hemolytic Anemias
Red blood cells are destroyed faster than bone
marrow can replace them.
Autoimmune disorders can produce antibodies
to red blood cells, destroying them prematurely
Hemolytic anemias may cause yellowing of the skin
(jaundice) and an enlarged spleen.

Anemia
Hereditary Spherocytosis
Mutations in the ankyrin molecule with a
secondary deficiency of spectrin along the cell
membrane
Reduced red cell stability
Does not affect oxygen carrying capacity
Splenic sequestration

Anemia
Sickle cell anemia
Defective form of hemoglobin that forces red
blood cells to assume an abnormal crescent
(sickle) shape.

Mutation for the gene coding for the -globulin chain

Valine is substituted for glutamic acid

HbS

Red cells die prematurely, resulting in a chronic

shortage of red blood cells.
Block blood flow through small blood vessels in the
body, producing other, often painful, symptoms.

Anemia
- Thalassemia
Common in Asians
Deletion of glubulin chain loci
4 possible degrees of thalassemia:

Silent carrier, loss of a single globulin gene

thalassemia trait, loss of a pair of globulin gene
HbH disease, only a single gene is present
Hydrops fetalis, deletion of all globulin

Polycythemia Vera
An acquired disorder of the bone marrow that
causes the overproduction of all three blood cell
lines
white blood cells, red blood cells, and platelets

It is a rare disease that occurs more frequently in

men than women, and rarely in patients under
40 years old.
causes is unknown

Polycythemia Vera
Usually develops slowly, and most patients are
asymtomatic
abnormal bone marrow cells proliferate
uncontrollably leading to acute myelogenous
leukemia

Patients have an increased tendency to form

blood clots that can result in strokes or heart
attacks
Some patients may experience abnormal bleeding
because their platelets are abnormal

Polycythemia Vera
Symptoms

Headache
Dizziness
Pruritus
Fullness in the left upper abdomen
Erythema (face)
Shortness of breath
Orthopnea
Symptoms of phlebitis

White Blood Cells

Collectively known as White Blood Cells (WBC)
Formed elements of the blood with organelles
and a nucleus but lack hemoglobin
Protect the body against microorganisms and
remove dead cells and debris from the body

White Blood Cells

White Blood Cells

Per l blood

Per l of blood
5,000 10,000

Total WBC count

Neutrophils

50 - 70%

2,000 7,000

Lymphocytes

20 - 40%

1,000 4,000

Monocytes

1 6%

50 600

Eosinophils

1 5%

50 500

Basophils

0 2%

0 - 100

WBC Disorders
Leukopenia
Decreased peripheral white cell count due to decrease
numbers of any specific types of leukocytes

Leukocytosis
Nonneoplastic elevation of WBC count

WBC Disorders
Neutropenia
Reduction in the number of granulocytes
(<1500/l)
Increased risk of infection
Reduced phagocytosis response

WBC Disorders
Neutropenia
Decreased or defective granulopoiesis
Aplastic anemia
Anti-neoplastic agents
Other drugs: chloramphenicol, sulfonamides,
chlorpromazine

Accelerated removal or destruction

Aggressive and chronic infections

WBC Disorders
Manifestation of Neutropenia
Infections
Signs and Symptoms
Malaise, chills, fever
Ulcerative necrotizing lesions of the mouth, skin
vagina and GI tract

WBC Disorders
Reactive Leukocytosis
Increase number of WBC
Common reaction due to a variety of
inflammatory states caused by microbial or nonmicrobial stimuli
Usually non-specific

WBC Disorders
Causes of Leukocytosis
Polymorphonuclear leukocytosis

Acute bacterial infections

Eosinophilic leukocytosis

Allergic disorders

Monocytosis

Chronic infections

Lymphocytosis

Chronic immunologic disease

Neoplastic Proliferation of White Cells

1.
2.
3.
4.

Leukemia neoiplasms of the hematopoietic

stem cells
Malignant lymphomas cohesive tumor
lesions; neoplastic lymphocytes
Plasma cell dyscrasias arising from the
bones; localized disseminated proliferation of
antibody forming cells
Histocytoses proliferative lesions of
histiocytes

Neoplastic Proliferation of White Cells

Leukemia
Malignant neoplasm of the hematopietic stem
cells
BM replaced by unregulated, proliferating,
immature neoplastic cells blood leukemia
enter spleen, lymph nodes
Most common cancer in the paediatric age
Leading cause of death in children between 3
and 14 years old

Neoplastic Proliferation of White Cells

Classification of Leukemia
A. According to cell type and state of cell
maturity

B.

Lymphocytic immature lymphocytes and their

progenators
Myelocytic pluripotent myeloid stem cells and
interferes with maturation of all granulocytes, RBC
and platelets

Acute or Chronic

Acute immature cells (blast)

Chronic well differentiated leukocytes

Neoplastic Proliferation of White Cells

Acute Leukemia (Cell Kinetic Studies)

Block in the differentiation of leukemic cells with
prolonged genration time clonal expansion of
the transformed stem cells + failure of
maturation accumulation of leukemic blast
suppress normal hematopoietic stem cells

Acute Leukemia
Features
Sudden onset (3 months)
Depressed marrow function
Bone pain and tenderness
Generalized lymphadenophaty
Splenomegaly, hepatomegaly
CNS: headache, vomiting

Acute Lymphocytic Leukemia (ALL)

Most common leukemia in children (80%)
Treatable and potentially curable
Classified according to lymphocytes and state
of maturation

1.
2.
3.
4.
5.

Early B cell
Pre-B cell
Mature B cell
Early T cell
Mature T cell

Acute Myleocytic Leukemia (AML)

Acute Non-lymphocytic Leukemia (ANLL)
Most common in adults; >50% 60years old
70% of adults will enter remission with
induction chemo
25-35% of those in remission will have a 5 year
survival rate

BM transplant

Acute Myleocytic Leukemia (AML)

Treatment
Selective radiation
Chemotherapy
1.
2.
3.

Induction
Intensification
Maintenance and consolidation

Bone marrow transplant

Chronic Leukemia
Insidious onset
Incidental findings during routine exam

Chronic Lymphocytic Leukemia

Proliferation and accumulation of mature
lymphocytes which are immunologically
incompetent
B cell line (US)
T cell line (Asia)

Hairy cell leukemia

Chronic Myelocytic Leukemia

15% of all leukemias
Chromosomal abnormality (Ph1)
Mostly B cell disease

Leukocytosis
Splenomegaly
Hepatomegaly
Lympadenopathy

Bone marrow transplant 5 year survival for

50-75% of patients

Chronic Myelocytic Leukemia

Two distinct phases
Chronic
Last about 3-4 years
Near end accelerated phase: fever, night sweats,
malaise

Acute
2-4 months
Poor prognosis, palliative management

Malignant Lymphomas
Primary solid tumors of the lymphoid system
Cancers involving lymphocytes during
maturation or storage in the bone marrow
Third most common malignacy in children

Malignant Lymphomas
Hodgkins Lymphoma
Disorders primarily involving the lymphoid
tissues
Anatomical spread
Morphological presence of Reed-Sternberg cells
60-90% cure rate

Malignant Lymphomas
Manifestations of Hodgkins
A symptoms
Painless progressive enlargement of a single or group
of nodes (neck)
May spread continuously through out the lymphatic
system

B symptoms
Fever, night sweat, weight loss
Fatigue, anemia

Malignant Lymphomas
Treatment for Hodgkins
Radiation
Chemotherapy

Malignant Lymphomas
Non-Hodgkins Lymphoma
Involves lymphoid tissue and may spread to
various tissues
Mostly B cell (80%)
Cause may be viral or genetic
EBV
Immunosuppresed patients
AIDS
After organ transplant

Malignant Lymphomas
Treatment
Early stage radiation
Late stage chemo and radiation
BM transplant