Ch. 14
Goodman
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*The hematologic system involves the blood,
blood vessels and the associated organs.
*The study of hematology includes the diseases
of the hematological system.
* This critical system is tightly integrated with the
following systems: lymphatic, immune,
circulatory, respiratory. It is also integrated with
hormonal and metabolic functions.
***While there are primary diseases of the
hematological system, the most common
conditions are most often signs of other
conditions
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*2 components of blood:
◦ Plasma
◦ Formed elements
 Erythrocytes (RBCs)
 Leukocytes (WBCs)
 Thrombocytes (platelets)
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Edema (sign)
Excessive fluid accumulation within the
interstitial tissues or within body cavities
Infarction (sign)
localized region of necrosis caused by reduction
of arterial perfusion
Thrombus (sign)
blood clot - solid mass within intact vessel or the
heart
Embolus (sign)
Thrombus on the move that gets lodged distant
from its place of origin
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Lymphedema (sign)
Can be a sign of hematologic conditions - increased
lymphatic load associated with
decreased plasma proteins
Bleeding / bruising (sign)
A sign when it happens with minor trauma or if
bleeding continues longer than normal
Shock (sign)
Inadequate blood pressure to perfuse organs
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Lymphedenopathy (sign)
Abnormal enlargement of lymph nodes
Splenomegaly
enlarged spleen (spleen removes old RBC’s
and antibody-laden bacteria or cells)
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Aging and the Hematopoietic System
Decreased red marrow
Decreased intestinal iron absorption
Increased fragility of plasma membranes
Increased fibrinogen and platelet
adhesiveness
Earlier activation of coagulation system
(ergo…) disturbed blood flow, propensity for
anemia (low RBCs) - if nothing else slower
RBC recovery from a loss of blood
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Blood Transfusions
Reaction to blood and blood products
1. Febrile nonhemolytic reaction - most common (.5-1% of
transfusions), fever (at least 1 degree rise) but stable cells
2. Transfusion related acute lung injury - 1 in every 2000
transfusions; initially mild shortness of breath but can
progress to appear clinically as acute respiratory distress
syndrome (widespread inflammation, low ventilatory volumes,
poor oxygenation); with treatment can prevent / minimize
permanent lung damage
3. Acute hemolytic transfusion - 1 in every 25,000
transfusions - severe response due to
ABO incompatibility; RBCs are destroyed (lysis) - mortality
rate is high (17-60%)
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4. Allergic reactions - 1-3% of all transfusions,
most common with fresh frozen plasma
and platelet transfusions - allergic reaction
5. Anaphylaxis - 1 in 20,000 transfusions - acute
onset of hypotension, laryngeal edema
6. Sepsis - very rare; due to bacterial
contamination of blood products used in
transfusion
Bloodless medicine - goal to reduce blood loss
with procedures to avoid need of transfusions
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Disorders of Iron Absorption
Hereditary Hemochromatosis is an autosomal
recessive hereditary disorder characterized
by excessive iron absorption by small
intestine
Uncoupling of absorption and needs - leads
to iron deposition in cells, particularly the
liver, pancreas and heart
Early signs include weakness, hepatomegaly,
elevated liver enzymes; symptoms include
myalgias, joint pain, fatigue
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Diagnosis -by blood work
Treatment - therapeutic phlebotomy
Prognosis -is good (from a mortality /
morbidity perspective) but the condition is
not reversible - it is managed
Anemia
 1. Definition
 reduction in oxygen carrying capacity of
blood due to reduced quantity or quality of
RBCs
 HgB < 14 g/100 ml for men; 12 g/ 100 ml
for women
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2. Overview
Not technically a disease - really a sign of other
underlying disorders - including but not limited to:
** dietary (folate, vitamin B12)
**acute or chronic blood loss
** iron deficiency (diet or absorption)
** congenital defects (sickle cell anemia)
**poison exposure
** disease of bone marrow
**chronic inflammatory, infectious or neoplastic
disease
** any disorder that upsets the balance between
blood loss through bleeding or destruction
and production of RBCs
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3. Clinical manifestations
Mild - minimal and vague symptoms of
fatigue
Moderate to severe progression: weakness,
dyspnea on exertion, tachycardia, increased
angina in pre existing CAD, dementia
4. Treatment
a. Underlying problem (cause) if possible
b. Blood transfusions
Disorders of Leukocytes
A. Leukocytosis
** Definition & Etiology
 Increased number of leukocytes (WBCs) for a variety of causes
- including as a normal response stressors
 Common finding with infection - > 10,000 WBCs/mm^3
**Clinical manifestations
 Signs and symptoms are usually those of infectious
conditions (localized or systemic) fever, headache, shortness of breath
** Treatment
Underlying problem
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B. Leukopenia
**Definition & Etiology
Decreased number of WBCs - < 5000 / ml caused by a variety of
conditions:
* HIV, hepatitis
*alcohol
* Nutritional deficiencies
*connective tissue disorders (SLE)
* bone marrow failure (i.e. following antineoplastic chemotherapy)
**Clinical manifestations
Asymptomatic; increased risk of infection
**Treatment
Underlying problem
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**** Bone marrow transplant
Treatment of choice for any hematologic neoplastic disease
A. Leukemias
Malignant neoplasm of blood forming cells that replaces normal
bone marrow with a malignant clone
Acute vs. Chronic
Myeloid vs. Lymphocytic
Blastic vs. cytic
Acute progresses quickly; chronic slowly
Myeloid - bone marrow origin involving hematopoeitic stem cells
Lympho - involving lymphoid or lymphatic system
Blastic - large, immature (functionless) cells
cytic - immature, smaller cells
Immunologically can also classify as T-cell / natural killer cell
and B-cell leukemias
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Three main clinical consequences:
1. Anemia
2. Infection
3. Bleeding tendencies
Acute myelogenous leukemia - AML - most
common leukemia in adults
Acute lymphoblastic leukemia - ALL – diagnosed
most commonly in children
Chronic myeloid leukemia - CML – occurs most
often in adults
Chronic lymphocytic leukemia - CLL – a common
type of adult leukemia
Malignant Lymphomas
 Cancers of lymphatic system
 Two groups - Hodgkin’s lymphoma and NonHodgkin’s Lymphoma (HL and NHL) although the distinction has become less
clear
 More useful to categorize based on cell
behavior - indolent vs. aggressive
 HL is distinguished from others by presence
of a cell known as the Reed-Sternberg cell
in the lymph nodes
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HL - adults and children; B-cell malignancy;
Clinical manifestations are variable, Box
14-6, Ann Arbor Staging Classification for HD
(Hodgkin’s Disease) - progresses by
increased involvement of lymph nodes and
other lymph organs; Stage IV includes
involvement of extralymphatic
organs (liver, lung, skin)
NHL - large group (~30 types) of lymphoid
malignancies that present as solid tumors
arising from lymphatic cells - 5th most
common type of cancer in the US with an
incidence of ~67,000 / year; clinical
manifestations are variable
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Multiple Myeloma
MM - primary malignant neoplasm of plasma
cells arising in bone marrow
Progression causes damage to kidney,
recurrent infections, often affects the nervous
system
Increased incidence (doubled in past 2
decades) (~16,000 new cases / year) thought in part to increase in population >
85 years old
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Myeloproliferative Disorders
Originate from a hematopoietic stem cell that
has transformed to allow the cell to mature
and function with uncontrolled function common characteristics include:
1. hypercellular bone marrow
2. tendency to thrombosis and hemorrhage
3. increased risk of evolving into acute
leukemia
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Polycythemia vera - increased production of
RBCs
Essential thrombocythemia - most common increased platelet count
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***The following 2 processes occur normally in
response to tissue insult and bleeding
Primary hemostasis - formation of a platelet plug
initiated when collagen fibrils and von
Willebrand’s factor (vWF) in the subendothelial
matrix of the blood vessel get exposed to blood
Secondary hemostasis –formation of fibrin
through the coagulation cascade
vascular damage exposes ‘tissue factor’ which
initiates the cascade
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A. von Willebrandʼs Disease
Most common inherited bleeding disorder Disorder of primary hemostasis - mucosal
and skin bleeding and prolonged oozing after
trauma or surgery
Rx - replacement of vWF
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B. Hemophilia
Deficiency of clotting factors
Disorder of secondary hemostasis - easy
bruising, prolonged bleeding
If severe can spontaneously bleed - into
joints, muscles, organs
Rx - replacement of clotting factors
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C. Thrombocytopenia
Decreased platelets (< 150,000/mm^3) caused by either reduced production or
increased destruction; usually a sign of other
problems
Mucosal bleeding is a common sign
May be presenting sign of aplastic anemia
(bone marrow failure)
Rx - underlying cause; platelet transfusions
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D. Aspirin / NSAIDs
Single dose of ASA can impair platelet
function for 48 hours
NSAIDs are less potent
ASA and NSAIDs are contraindicated before
surgery
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E. Disseminated Intravascular Coagulation
DIC - thrombotic disease caused by overactivation of
the coagulation cascade Paradoxical in that clotting and hemorrhage occur
simultaneously within the vascular
system
Widespread clotting and fibrin deposition in
circulation, causes backflow and increased pressure
which leads to hemorrhage
Common after shock, sepsis, obsteteric /
gynecological complications, cancer, massive trauma
Alteration in normal balance of pro and anticoagulant
factors
Rx - underlying cause
F. Hemoglobinopathies
 Abnormalities in the formation of HgB
 1. Sickle cell disease (SCD)  Genetic, result is HgB that changes from
biconcave to crescent (sickle) shape once oxygen
is released but leads to difficulty in blood flow in
microvascular areas resulting in acute and
chronic tissue injury
** provides selective immunity to malaria (thought
to have originated in countries where people
were getting sick from malaria) so that through
the sickle cell mutation, those that carry the SCT
have selective resistance or immunity to malaria
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Acute crises or episodes - pain caused by
blockages of sickled RBCs in any
organ, bone or joint; location and severity vary
widely
Life threatening crises occur when these occur in
chest (heart or lung) or CNS
Bone marrow transplant cures SCD
Sickle Cell trait – an individual with this trait does
NOT have the disease
An individual with SCT makes both types of HgB
(hemoglobin A which is normal and hemoglobin S
which is abnormal)- this individual is rarely
symptomatic
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2. Thalassemias - inherited disorder with
abnormalities in one or more of the 4 globin
genes; leads to varying degrees of abnormally
functioning HgB
Clinical manifestations based on extent to which
the globin genes are impacted and are related to:
1. defective synthesis of HgB
2. structurally impaired RBCs
3. hemolysis or destruction of RBCs (anemia)
\ impaired oxygen carrying capacity Rx - transfusions
Created by:
Andrea C. Mendes PT, DPT
and
Sean M. Collins PT, ScD