Hematologic
--> General notes / thoughts on review
Two components of blood:
1. plasma
2. formed elements
a. erythrocyes (red blood cells, RBCs)
b. leukocytes (white blood cells, WBCs)
c. thrombocytes (platelets)
Critical system - tightly integrated with lympathatic, immune, circulatory, respiratory,
hormonal, metabolic systems / functions
While there are primary diseases of the hematologic system; the most common conditions (low RBCs: anemia; high or low WBCs; high or low platelets) are most often signs
of other conditions
I. Signs & Symptoms of Hematologic Disorders
ü Edema (sign)
Excessive fluid accumulation within the interstitial tissues or within body cavities
ü Infarction (sign)
localized region of necrosis caused by reduction of arterial perfusion
ü Thrombus (sign)
blood clot - solid mass within intact vessel or the heart
ü Embolus (sign)
Thrombus on the move that gets lodged distant from its place of origin
ü Lymphedema (sign)
Can be a sign of hematologic conditions - increased lymphatic load associated with
decreased plasma proteins
ü Bleeding / bruising (sign)
A sign when it happens with minor trauma or if bleeding continues longer than normal
ü Shock (sign)
Inadequate blood pressure to perfuse organs
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ü Lymphedenopathy (sign)
Abnormal enlargement of lymph nodes
ü Splenomegaly
enlarged spleen (spleen removes old RBC’s and antibody-laden bacteria or cells)
II. 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
S disturbed blood flow, propensity for anemia (low RBCs) - if nothing else slower RBC
recovery from a loss of blood
III. Blood Transfusions
ü A. 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%)
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
ü B. Bloodless medicine - goal to reduce blood loss with procedures
to avoid need of transfusions
IV. 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
Diagnosis by blood work
Treatment - therapeutic phlebotomy
Prognosis is good (from a mortality / morbidity perspective) but the condition is not
reversible - it is managed
by excessive iron absorption by small intestine
Uncoupling of absorption and needs - leads to iron deposition in cells, particularly the
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liver, pancreas and heart
Early signs include weakness, hepatomegaly, elevated liver enzymes; symptoms include
myalgias, joint pain, fatigue
Diagnosis by blood work
Treatment - therapeutic phlebotomy
Prognosis is good (from a mortality / morbidity perspective) but the condition is not
reversible - it is managed
V. Disorders of Erythrocytes
ü A. Anemias
ü 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
ü 2. Overview
Not technically a disease - really a sign of other underlying disorders - including but not
limited to:
1. dietary (folate, vitamin B12)
2. acute or chronic blood loss
3. iron deficiency (diet or absorption)
4. congenital defects (sickle cell anemia)
5. poison exposure
6. disease of bone marrow
7. chronic inflammatory, infectious or neoplastic disease
8. any disorder that upsets the balance between blood loss through bleeding or destruction and production of RBCs
ü 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
ü 4. Treatment
a. Underlying problem (cause) if possible
b. Blood transfusions
VI. Disorders of Leukocytes
ü A. Leukocytosis
ü 1. 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
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ü 2. Clinical manifestations
Signs and symptoms are usually those of infectious conditions (localized or systemic) fever, headache, shortness of breath
ü 3. Treatment
Underlying problem
ü B. Leukopenia
ü 1. Definition & Etiology
Decreased number of WBCs - < 5000 / ml caused by a variety of conditions:
1. HIV, hepatitis
2. alcohol
3. Nutritional deficiencies
4. connective tissue disorders (SLE)
5. bone marrow failure (i.e. following antineoplastic chemotherapy)
ü 2. Clinical manifestations
Asymptomatic (other than primary problem) Increased risk of infection
ü 3. Treatment
Underlying problem
VII. Neoplastic Diseases of the Blood and Lympth Systems
ü A. Bone marrow transplant
Treatment of choice for any hematologic neoplastic disease
ü B. 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
Three main clinical consequences:
1. Anemia
2. Infection
3. Bleeding tendencies
Blastic - large, immature (functionless) cells
cytic - immature, smaller cells
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Immunologically can also classify as T-cell / natural killer cell and B-cell leukemias
Three main clinical consequences:
1. Anemia
2. Infection
3. Bleeding tendencies
Acute myelogenous leukemia - AML - most common in adults
Acute lymphoblastic leukemia - ALL - most common in children
Chronic myeloid leukemia - CML Chronic lymphocytic leukemia - CLL - common in adults
ü C. Malignant Lymphomas
Cancers of lymphatic system
Two groups - Hodgkin’s lymphoma and Non-Hodgkin’s Lymphoma (HL and NHL) although the distinction has become less clear
More useful to categorize based on cell behavior - indolent vs. aggresive
HL is distinguished from others by presence of a cell known as the Reed-Sternberg cell
in the lymph nodes
HL - adults and children; B-cell malignancy; Clinical manifestations are variable, Box
14-6, Ann Arbor Staging Classification for HD - progresses by increased involvement of
lymph nodes and other lymph organs; Stage IV includes involvment 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
ü D. 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
ü E. 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
Polycythmia vera - increased production of RBCs
Essential thrombocythemia - most common - increased platelet count
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IIX. Disorders of Hemostasis
Primary hemostasis - formation of a platelet plug (collagen fibrils and von Willebrand’s
factor (vWF) in the subendothelial matrix of the blood vessel gets exposed to blood)
Secondary hemostasis - vascular damage exposes tissue damage
ü 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
ü 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
ü 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
ü 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
ü 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
ü F. Hemoglobinopathies
Abnormalities in the formation of HgB
Sickle cell disease (SCD) Genetic, result is HgB that changes from biconcave to crescent (sickle) shape
once oxygen is released - provides selective immunity
to maleria but leads to
difficulty in blood flow in microvascular resulting in acute and chronic tissue injury
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 occur in chest (heart or lung) or CNS
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Abnormalities in the formation of HgB
Sickle cell disease (SCD) Genetic, result is HgB that changes from biconcave to crescent (sickle) shape
once oxygen is released - provides selective immunity
to maleria but leads to
difficulty in blood flow in microvascular resulting in acute and chronic tissue injury
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 occur in chest (heart or lung) or CNS
Bone marrow transplant cures SCD
Sickle Cell trait - makes both types of HgB - rarely symptomatic
Thalassemias - inherited disorder with abnormalities in one of 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 HbG
2. structurally impaired RBCs
3. hemolysis or destruction of RBCs (anemia)
\ impaired oxygen carrying capacity Rx - transfusions