Comprehensive Hematology
Blood, the essence of life, can be a daunting subject to the typical nursing or medical student.
We are going to take a closer look at this subject to see if we can make it EZ for you.
Hematology: The study of blood and
blood diseases
• Blood
components
• Plasma
• Hematocrit
• Blood
functions
• Respiration
• Immunity
• Hemostasis
• Lab Values
• Blood
diseases
• Anemias
• Hemoglobinopathies
• Coagulopathies
• Decreased number
of
Cells
• Increased number of Cells
• Hematological Malignancies
Blood components (and
function)
• Plasma (55-60%)
• Water
(92%) and Electrolytes
(mostly Na, Cl): suspension
of blood components, electrolyte delivery, waste disposal, pH regulation
• Proteins (8%)
• Fibrinogen
and clotting factors: hemostasis
• Albumin: oncotic pressure, bind and
deliver
nutrients,
transport thyroid hormone/fatty acids/bilirubin, binds
Ca, buffers pH
• Globulins: immunity
• Hormones
(trace): tissue signals
• Solids
(Hematocrit) (40-45%)
• RBCs
(95%): respiration
• WBCs
(2%): immunity
• Platelets
(3%): hemostasis
Blood Genesis and
Disposal
• Plasma
proteins including clotting factors are produced
in the
liver
• Hormones are produced by endocrine glands
• Red
Blood Cells:
• Stem cells in the red bone marrow are stimulated by renal Erythropoietan to develop into Reticulocytes which enter the blood stream
• These baby RBCs then become mature RBCs in
7 days, as they expel
their nucleus and intracellular contents
• After 120 days the RBCs begin to lose
their flexibility, and when they are unable
to squeeze through the RBC obstacle course in
the spleen, they are consumed
by Macrophage, with their heme (Fe)
being recycled and their globin being
made into Bilirubin
• White Blood
Cells:
• Both Granulocytes (neutrophils, basophils, eosinophils) and Agranulocytes (Macrophage,
T Cells, B Cells) are derived
from Stem cells in the bone marrow; Live hours to days
• Platelets:
• Derived from the breakup of large Bone marrow cells
called
Megakaryocytes, these important players in coagulation live
about 10 days
Blood Functions
Respiration
• Respiration is the transport of oxygen from air to tissues, AND the
transport of carbon dioxide in the opposite direction (Ventilation- like opening a window to vent smell if the dog poops on the rug)
• RBCs
are the main player in the blood controlling respiration
• They contain hemoglobin which transports oxygen and carbon dioxide
• In the lungs, more oxygen is present in
alveoli than in
the blood, so it
diffuses across the
thin
membrane and attaches to the hemoglobin
• Conversely, in the lungs, more CO2 exists in
the blood than in the alveoli
so
it diffuses into the alveoli
and is cleared with exhalation
• In the tissue,
more oxygen is present in
the blood than in the interstitial space, so it
diffuses into tissue
• Conversely, in the tissue,
more CO2 exists in
the interstitial space, so it diffuses into the
blood and attaches to the hemoglobin
• Other factors influence the dissociation of O2 and hemoglobin, in
an attempt to deliver more O2 to the
tissues (think of what happens
when you exercise and need
more oxygen)
• Increased acidity (lactic
acid)
• Increased CO2 production in
tissues forces exchange with O2
• Increased temperature
• Excess oxygen is normally stored
in muscle by Myoglobin, which if it
needs to can forcibly pull oxygen from hemoglobin into tissue
Immunity
• Innate
Immunity
• Non-specific response to any perceived threat
• Humoral components
• Complement:
Lyse proteins that attack pathogens directly and activate other
components of immunity
• Cell mediated components (For their order of abundance, remember Never Let Monkeys Eat Bananas: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils)
• Granulocytes
• Neutrophils: The
suicide bomber of the immune
system, they explode themselves and destroy anything in
vicinity;
Pus is the result
of Neutrophil activity
• Basophils: The alarm cell of Innate immunity, they
release chemical warning signals like histamine and cytokines
• Eosinophils: Specialized to fight parasites and viral infections; These cells
are
implicated in most
allergic responses
• Agranulocytes
• Monocytes (Macrophage): Phagocytic cells
with a voracious appetite; These cells consume invaders and present pieces
of the invaders Antigens on their
membrane to Lymphocytes
• Mast Cells: The
combat engineers of the immune system,
these cells release histamine that
vasodilates vascular tissue
allowing blood
cells
to migrate into tissues
• Natural Killer Cells: Less specific
versions of
the Killer T cells, these cells recognize foreign or
altered glycoproteins of cancerous or
virally infected cells and
kill the cell
• Adaptive Immunity
• Pathogen specific response with memory for future attacks
• Humoral components
• Antibodies
• IgG: Most abundant, transported across placenta, four separate classes
• IgA:
Found in blood and secretions (tears, sweat, saliva)
• IgM: Largest; 1st antibody produced during primary response; Present in
fetus
• IgD:
Located primarily on B lymphocyte
membranes
• IgE: Least concentrated in blood; Mediates many allergic responses;
Defends against parasites by attracting eosinophils
• Cell mediated components
• T Cells: The General of the immune army
• Killer
T Cells: Directly kill cancerous cells
and virally infected cells by using Perforins to pop the cell
membrane
• Helper T Cells: Control the interaction between Innate and
Adaptive immune systems and direct specific attacks
• B Cells
• Plasma Cells: Activated B Cells that produce Antibodies specific to the invading
Antigen
Hemostasis (covered in its own section in this blog)
Lab Note:
• Complete Blood Count (CBC) Respiration
• RBCs: 4-6 x1012/L
• Hematocrit: 35-50%
• Hemoglobin: 14-18 dg/L (male) or 12-16 dg/L (female)
• Reticulocytes: 10-100 x109/L
• Mean
Cell Volume (MCV): 80-100 fL
• Mean
Cell Hemoglobin: 26-34 pg
• Erythrocyte Sedimentation Rate (ESR): <20 mm/hr
• WBCs: 4-11 x109/L
• CBC
with differential Immunity
• Absolute Neutrophil Count
(aka polys, segs): 2-7.5
x109/L
• Lymphocytes: 1.3-4 x109/L
• Monocytes: 0.2-0.8 x109/L
• Eosinophils: 0.04-0.4 x109/L
• Basophils: 0.01-0.1 x109/L
• Coagulation Hemostasis
• Platelets: 150-400 x109/L
• PT:
10-13 sec
• INR:
0.9-1.2
• PTT:
30-40 sec
• Fibrinogen: 1.8-4 g/L
Blood
Diseases
Anemias
• Normocytic
• Anemia of
chronic disease
• Microcytic
• Iron deficiency
• Macrocytic
• B12 deficiency (Pernicious)
• Folate deficiency
Hemoglobinopathies
• Sickle Cell Anemia
• Thalassemia
Coagulopathies
• Hemophilia
• Thrombocytopenia
• Idiopathic Thrombocytopenic Purpura (ITP)
• Thrombotic Thrombocytopenic Purpura (TTP)
• Heparin Induced Thrombocytopenia (HIT)
• Disseminated Intravascular Coagulation (DIC)
Decreased number of Cells
• Neutropenia
• Agranulocytosis (granulocytopenia)
Increased
number of Cells
• Polycythemia
• Leukocytosis
• Thrombocytosis
Hematological malignancies
• Lymphoma
• Hodgkins
• Non-Hodgkins
• Leukemia
• Acute Lymphoblastic Leukemia (ALL)
• Acute Myeloblastic Leukemia (AML)
• Chronic Myeloid Leukemia (CML)
Anemia
• Defined as
a deficiency in RBCs or Hemoglobin, occurring one of three ways:
1. Decreased RBC
production:
Deficiencies
in Iron, Vitamin B12, or Folate, as well as
certain Chronic diseases can lead to less RBCs
being made
2. Increased RBC destruction:
Hemolysis
can lead to anemias
3. Blood loss: Menses and GI
bleeds are the most common causes
• S/S:
All anemias share some common signs
and
symptoms: Weakness,
Fatigue and
Dyspnea on exertion, Confusion
• Typically these vague symptoms occur around a Hct
of 25 and Hgb of
8, but
his depends upon overall health of an individual (a healthy teen may not show symptoms
until as low
as 10/3)
• Some anemias
have specific s/s that
will
be mentioned in the respective section
• Lab Data:
• Specific blood data is vital to determine type of anemia
• MCV (the RBC size) is
the
most important value to know, in fact anemias
are
classified according to this value
• Normocytic (MCV 80-100):
Anemia of
chronic
disease
• Microcytic (MCV below 80): Fe deficiency,
Thalassemia
• Macrocytic (MCV above 80): B12 deficiency (Pernicious), Folate deficiency
• Other data that help to differentiate anemias
are:
• Serum
Fe: Measures how much iron is bound to transferrin
• Transferrin: Iron transport
protein,
• TIBC: Indicates the iron receptors on Transferrin that are not filled
• Ferritin: Iron storage protein, indicates the potential to hold iron
• Normocytic (MCV 80-100)
• Anemia of
chronic disease
• Most common anemia in hospitalized patients
• Reduced stimulus to produce RBCS can be caused by infection, malignancies, kidney
failure, or widespread inflammation
• Typically no iron is in the transportation phase (low serum Fe, low transferrin)
because no iron is being called to bone marrow for erythropoiesis
• The transferrin that is present
is filled up with iron (low TIBC) because nothing is using
the iron that
is present
• Most iron is sitting around in storage (high ferritin)
• There is no deficiency in iron so do not treat with iron;
Focus
on treating the underlying cause
• Microcytic (MCV <80)
• Fe deficiency anemia
• Most common anemia worldwide
• In women, menses and pregnancy are main causes
• In men, GI bleeds are the usual suspect
• Unique S/S:
• May be asymptomatic till severe
• May see spoon shaped fingernails, brittle hair,
smooth tongue, stomatitis, or pica
• Since there is
an overall low level of
iron in the body (low Serum Fe),
few
Fe proteins
are made by liver (low transferrin,
low ferritin), and the transferrin that
is present
has little iron (high TIBC)
• Treat with Fe supplementation for months, but warn of probable constipation
• Thalassemia: Genetic
absence of 1 to 4 of the 4 globins in each hemoglobin; No Fe
deficiency so iron studies
are
normal
• Macrocytic (MCV above 100)
• Vitamin B12 deficiency
• The body has
3 years
of B12 storage so this anemia develops over years
• B12 requires Intrinsic
factor from the stomach parietal cells to be absorbed in the
Ileum, so any disruption = deficiency
• The most common cause is Pernicious anemia,
an
autoimmune attack
on the parietal cells
• Others causes include gastrectomy, ilectomy,
celiac
sprue, Crohns
• Unique s/s:
• Neurological defects
due
to Neuropathy is specific for B12 anemia and
include numbness in extremeties,
loss of vibratory sense, ataxia, increased DTRs, + Babinski,
Dementia
• Other s/s are similar to Folate deficiency anemia including beefy red tongue
• Treat with B12 injections that may be weekly or monthly for life
• Folate deficiency
• The body has 3 months of
Folate storage,
but if the diet is poor in green vegetable a deficiency may develop
• Malabsorption may also be a cause but
not near as common as
diet related
• Typical anemia signs/symptoms with the beefy red tongue and stomatitis
• Treat with several weeks of
Folate supplementation
Hemoglobinopathies
• Sickle Cell Anemia (SCA)
• Autosomal recessive disease characterized by a defect
in
the hemoglobin structure,
caused by one abnormal amino acid
• The defect
causes cells to sickle when oxygen levels or
pH is low
• Almost
exclusively in people of African descent
(1 in 400 have disease)
• The defect leads to near immunity against
Malaria as
the
invader can not
penetrate the altered cell membrane
• Can carry only one copy of the defect and be a carrier with few symptoms
or
may carry two copies and have full blown Sickle Cell Disease
• Sickle Cell Disease: Periodic flare ups often caused by low oxygen or dehydration
• Hemolysis: Sickle cells can not pass inspection in the spleen and are destroyed
by Macrophage leading to increased levels of bilirubin and Gallstones; This
increased bilirubin overloads the Liver from doing its job so Jaundice and Scleral Icterus
may
be seen; Iron overload may also occur
• Splenomegaly: Due to overuse the spleen becomes enlarged and is
at risk for infections or rupture
• Vaso-occlusive crisis: Sickle cells obstruct
small vasculature leading to ischemic pain
in bones, hands,
legs, chest,
etc;
Strokes are common;
Priapism can occur
and is an emergency; Leg ulcers
are
common
• Treat infections promptly (fever or leukocytosis = antibiotics); Vaccinate against
S.Pneumoniae and H.Influenzae
• Acute treatment
of
acute crisis include hydration, analgesics, and oxygen
• Transfusion reserved for refractory crisis,
or
chest ischemia,
strokes
and
priapism
Pharm Note: Hydroxyurea is a chemotherapy drug that destroys
sickle cells, and may help to make crisis
less
common; Caution is used as
the drug can be toxic to bone marrow and cause pancytopenia
Coagulopathies
• Hemophilia
• Genetic
deficiency in certain Intrinsic
clotting factors leading to abnormally slow clotting
• Lack of
Factor 8 is
the
most common (Hemophilia A), but lack of
9 and 11 exist
• Hemophilia A only effects males
• Many hemophiliacs contracted HIV due to multiple transfusions
prior to screening
• Due to normal platelet
plug
formation and extrinsic coagulation,
all cuts do not abnormally bleed, especially those on the surface.
However, certain areas such as
muscles, joints, the digestive
tract, and brain are very prone to bleed for prolonged time
• PTT
is abnormal in the presence of
a normal PT
• TX:
factor replacement
(one specific factor or FFP)
• Disseminated Intravascular Coagulation (DIC)
• DIC
is caused by an abnormal and massive activation of the coagulation cascade to the point that all
factors
are
used up
• Remember that
tissue factor activated the cascade? Well bacterial endotoxins look enough like tissue factor to do the same. Therefore, Sepsis is
a common cause of DIC
• Other causes
include Obstetric
complications,
Trauma, and Malignancy
• Bleeding:
• Tends to occur in DIC that
develops rapidly as factors are used up and not
replenished
• Bleed
tends to occur both superficially (ecchymoses) and in GI/GU (melena,
hematuria)
• PT/PTT and D-dimer are all increased; Fibrinogen and Platelets are decreased
• TX:
replace factors (FFP), platelets, and fibrinogen (cryoprecipitate)
• Thrombosis
• Tends to occur in DIC that
develops
more
slowly
• Mottling and tachycardia may be indications that organ infarctions
are
occuring,
most often in CNS and Kidney
• PT/PTT may not be significantly elevated as factors have had time to be replenished
• TX:
possibly with Heparin to avoid infarcts
but
is controversial
• What do I do? I/Os,
Vitals, Pulses
qhr; Check for volume overload; Abdominal girth q4hr
• Thrombocytopenia
• Defined as
a decreased number of platelets below 150
• Severity
• 100-150: Abnormal bleeding is
unusual
• 20-70: Increased bleeding during surgery or trauma
• <
50:
Minor spontaneous
bleeding: easy bruising, petechiae,
epistaxis, menorrhagia,
bleeding gums
• < 20: Major spontaneous
bleeding such as intracranial and GI
• Causes
• Decreased production: Bone marrow invasion (mets) or injury (drugs like alcohol, chemo, radiation); often in the presence of
pancytopenia
• Increased destruction: Immune mediated (ITP) or nonimmune causes
(TTP, HIT)
• Immune Thrombocytopenic Purpura (ITP) – often referred to as
Idiopathic
TP
• Autoimmune antibody production against platelets, typically after viral infection,
leads
to consumption by macrophage in the spleen; Usually in children and women 20-40yo
• S/S:
Petichiae, ecchymoses, and mucosal bleeding are most common
• DX: Plt <
20, remainder of CBC usually normal unless significant bleeding (low H/H)
• TX:
• Steroids reduce Macrophage activity
• IV immune globulins saturate Macrophage receptors so less
ability to recognize
the marked platelets
• Splenectomy reduces
recurrences of ITP in 80%
• Platelet transfusions
for
serious hemorrhagic
episodes, but
new plts are targeted
• Thrombotic Thrombocytopenic Purpura (TTP)
• Idiopathic d/o causing platelets to collect in small vessels and are then destroyed, similar to DIC,
except instead of factors,
platelets
are
involved
• S/S:
Hemolytic anemia, Neuro problems (AMS, hemiplegia), Fever, Renal insufficiency
PT/PTT normal
• TX: Do not give platelets! Plasmapheresis (removal,
cleansing,
and
reinfusion) of
platelets
usually effective; Monitor platelet
count which should increase
• Heparin Induced Thrombocytopenia (HIT)
• Heparin abnormally bonds to too many platelets causing massive complexes
that
form
thrombus mainly in the lower limbs; These complexes
are
then attacked and destroyed
• Platelet counts can range from 10-200,
but classic
definition is a reduction of 50% from baseline,
with recent
Heparin use and other causes (hypervolemia) ruled out
• Despite low platelet
counts, HIT is mainly a thrombotic,
not a bleeding disorder
• HIT develops in 3% of
patients
on
Unfractionated Heparin, but
only 0.1% on low molecular weight heparins
(Lovenox)
• 40% of
those who develop HIT will develop significant thrombosis
3-12 days
after starting Heparin infusion
• S/S:
Skin necrosis, septic
appearance from massive immune response
• End result can be MI, Stroke, DVT/PE and limb amputations
• TX: Prompt withdrawal of Heparin and replacement
with an alternative such as
Argatroban (fda approved), Fondaparinux (Similar to Lovenox w/0% chance of
HIT)
Decreased
number of cells
• Neutropenia
• Abnormally low number of
Neutrophils
• Since these cells are the main defense against
bacteria, infections
are
common
• Similar to Agranulocytosis (Granulocytopenia) except these terms
refer to low
Basophils and Eosinophils
• Often caused (75%) by drugs that suppress the bone marrow
• S/S:
Fever/Chills, Mouth ulcers,
Diarrhea, Dysuria, Dysphagia, Dyspnea
• TX:
Mainly preventative;
Maintain
strict precautions with these patients
Increased number of cells
• Polycythemia
• Increase in the number of RBCs
• Can be a congenital problem,
termed Polycythemia Vera
• Increased Hct, Hypertension, HSM, Pruritis,
H/A, Vertigo, Tinnitus
• Can be due to high altitudes, or illegal blood doping with EPO
• Leukocytosis
• Increase in the number of WBCs
• Often an indication of
an
acute bacterial infection, but
may
also be caused by Steroids
as these drugs
force WBCs
to
leave tissues
(lower immunity) and reside in blood
• Thrombocytosis
• Increase in the number of Platelets
• Can occur with Polycythemia Vera, or during acute inflammation states (Surgery)
Hematological malignancies
• Lymphoma:
• Cancers
of the lymphatic system,
usually involving abnormal growth of
B or T cells
• Because it is
a cancer of WBCs, leukocytosis is
present
• Hodgkins
• This form of lymphoma is characterized clinically as the orderly spread of
the disease from one lymph node to another
• The current cure rate is
93% making it one of the most treatable cancers, and leading to its TV name, the good Hodgkins (Larry David)
• Most common symptom is
painless, rubbery, lymphadenopathy (LAN)
• Systemic symptoms
may
or may not be seen, including fever, night
sweats, weight loss, pruritus, and cough
• Bimodal age distribution occurring most
frequently between 15-30 and above 50
• Lymph Node biopsy needed for diagnosis, revealing Reed-Sternberg cells
• Radiation and Chemotherapy effective agents in treatment, though S/E of
treatment
include sterility,
pulmonary fibrosis,
and
peripheral neuropathy
• Non-Hodgkins
• Twice as
common as Hodgkins
• The distinguishing characteristic
of Non-Hodgkins
is the lack of
Reed Sternberg
cells
on biopsy;
If
these cells are absent, the predictability of spreading is very
low as this type of
Lymphoma often spreads outside of the lymph system
• Due to the likelihood of spreading outside of lymph, there is
a much higher rate of mortality and failure of
treatment; High grade lives a few months while low grade
lives around 5 years
• Most common early
symptom is also painless LAN, Weight loss,
reddened skin
• May invade Liver (LFTs,
bilis elevated)or Bone marrow (Thrombocytopenia,
Anemia); Hilar LAN
may
cause Vena Cava compression syndrome
• TX: Chemo and Radiation may slow progres
• Leukemia:
• Cancers of
blood or bone marrow, resulting in a proliferation of
immature WBCs, and an underproduction of RBCs (Anemia) and Platelets (Thrombocytopenia)
• Symptoms
for
all types may include anemic s/s,
abnormal bleeding,
bone pain and frequent infections
• 4 main types
divided into Acute (very immature cells) and Chronic (relatively immature,
yet
abnormal) & Myeloid (Granulocytes-Neutrophils) and Lymphocytic (T and B cells)
• Acute Myeloblastic Leukemia (AML):
• Occurs
mainly in adults, with WBC widely
varied from 1-100
• Very unresponsive to treatment
if over 60,
and
often rapidly fatal
• Acute Lymphoblastic Leukemia (ALL):
• Most common cancer under the age of 15
• Most responsive leukemia to treatment, but if untreated can kill in months
• 75% remission and 50% completely cured
• Chronic Myeloid Leukemia (CML):
• Often asymptomatic until discovered on routine CBC
that
reveals a WBC
count of 50-200
• Typically occurs over 40 years
of age and may remain indolent until progressing to aggressive Acute Leukemia with total life span after diagnosis averaging 3 years
• Treatment
ineffective once the Acute blast stage has
been reached
• Chronic Lymphocytic Leukemia (CLL):
• Often asymptomatic until discovered on routine CBC
that
reveals a WBC
count
of 50-200, almost completely Lymphocytes
• Most common leukemia after the age of
60
• Treatment
has little effect on survival times, but typically CLL progresses slow
