Anemia and Polycythemia COPY COPY Flashcards
(301 cards)
1
Q
What percentage of the global population is affected by anemia?
How many emergency department visits in 2014 were primarily diagnosed with anemia?
A
A third of the global population
Approximately 188,000 visits
Anemia is a significant health concern worldwide.
2
Q
What is anemia defined as?
What are the two broad categories of anemia?
What factors may influence the categorization of anemia?
A
An absolute decrease in the number of circulating red blood cells (RBCs)
* Emergent
* Non-emergent
1. Rate of onset
2. Underlying hemodynamic reserve of the patient
Diagnosis is made when laboratory measurements fall below accepted normal values.
3
Q
What is the primary function of red blood cells (RBCs)?
What is hemoglobin composed of?
What hormone regulates the production of RBCs?
Where is erythropoietin primarily produced?
A
- Oxygen transport from the lung to the tissue and carbon dioxide transport in the reverse direction
- Four heme polypeptide subunits bound to an iron molecule
- Erythropoietin
- In the kidney (90%) and liver (10%)
This function is crucial for maintaining tissue oxygenation.
4
Q
What are reticulocytes?
What happens to reticulocytes as they mature?
What is the shape of erythrocytes?
A
Immature red blood cells that retain a ribosomal network for approximately 4 days
They lose their ribosomal network and become erythrocytes.
Biconcave discs(This shape aids in their function in oxygen transport)
They spend 3 days in the bone marrow and 1 day in peripheral circulation. Erythrocytes circulate for 110 to 120 days.
5
Q
What is the most common cause of emergent anemia?
What hemolytic condition can cause rapid intravascular destruction of RBCs?
A
- Acute blood loss
- Disseminated Intrvascular Coagulopathy(DIC)
Acute blood loss can occur due to various reasons, especially in trauma patients. DIC can lead to significant and acute blood loss.
6
Q
What are common sites of blood loss in trauma patients?
A
- Pleural
- Peritoneal
- Pelvic
- Long bone (e.g., thigh)
- Retroperitoneal spaces
These sites are critical to assess in trauma situations for potential blood loss.
7
Q
What sites should be considered for blood loss in non-traumatic circumstances?
A
- Gastrointestinal tract
- Retroperitoneal space
- Uterus
- Adnexa
These sites are particularly important in patients receiving anticoagulants.
8
Q
What is the most common non-hemolytic anemia?
A
Anemia of chronic disease
This type of anemia is related to inflammatory responses due to underlying diseases.
9
Q
What are the two types of hemolytic anemias?
A
- Intrinsic
- Extrinsic
Intrinsic hemolytic anemias are often due to genetic mutations, while extrinsic ones are caused by factors outside the RBC.
10
Q
What typically causes intrinsic hemolytic anemias?
A
- Genetic mutations
- Enzyme deficiencies (e.g., sickle cell disease)
These conditions lead to abnormal RBC production.
11
Q
What results in extrinsic hemolytic anemias?
A
Defects outside of the RBC (e.g., DIC)
Extrinsic factors can lead to destruction of otherwise healthy RBCs.
12
Q
What is the normal range of Hemoglobin (g/dL) for a 3-month-old?
A
10.4–12.2
Normal values for hemoglobin vary with age.
13
Q
What is the normal range of Hematocrit (%) for children aged 3–7 years?
A
34–40
Hematocrit levels indicate the percentage of blood volume occupied by red blood cells.
14
Q
What is the normal Red Blood Cell Count (×10^6) for an adult man?
A
4.4–5.9
Red blood cell count is an important measure in assessing overall health.
15
Q
What is the normal Hemoglobin (g/dL) range for adult women?
A
12.0–16.0
Hemoglobin levels in women are typically lower than in men.
16
Q
What is the normal Hematocrit (%) for a 3-month-old?
A
30–36
Hematocrit values can indicate hydration status and blood disorders.
17
Q
What is the normal Red Blood Cell Count (×10^6) for a child aged 3–7 years?
A
4.4–5.0
This range reflects the development and growth of children.
18
Q
What is the normal Hematocrit (%) for adult men?
A
40–52
Hematocrit levels can vary based on hydration and altitude.
19
Q
What is one cause of rapid intravascular red blood cell destruction?
A
Mechanical hemolysis associated with disseminated intravascular coagulation
This can occur in severe conditions where blood clotting is disrupted.
20
Q
Name a toxin that can lead to rapid intravascular red blood cell destruction.
A
Some poisonous venoms, such as those from the brown recluse spider or cobra
These toxins can cause significant damage to red blood cells.
21
Q
What infection is known to cause rapid red blood cell destruction?
A
Malaria
Malaria infects red blood cells, leading to their destruction.
22
Q
What deficiency can lead to severe red blood cell destruction when exposed to oxidant stress?
A
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
This condition makes red blood cells more susceptible to damage.
23
Q
What is an example of a transfusion reaction that causes rapid red blood cell destruction?
A
ABO incompatibility transfusion reaction
This occurs when the recipient’s immune system attacks the transfused blood.
24
Q
What type of hemolysis is associated with cold agglutinins?
A
Cold agglutinin hemolysis
This can occur due to infections like Mycoplasma organisms or infectious mononucleosis.
25
What is a symptom of clinically severe anemia?
Chest pain
## Footnote
This can be a result of decreased oxygen delivery to tissues.
26
What are some gastrointestinal signs of possible anemia?
Hematemesis, hematochezia, melena
## Footnote
These signs indicate potential sources of bleeding in the gastrointestinal tract.
27
What physical examination finding may indicate liver disease?
Hepatomegaly
## Footnote
Enlargement of the liver can be associated with various diseases, including those causing anemia.
28
True or False: Spontaneous bleeding, such as epistaxis, can be a sign of anemia.
True
## Footnote
Such bleeding may indicate a bleeding diathesis related to anemia.
29
What dietary history is relevant in the assessment of anemia?
Vegetarianism, poor nutrition
## Footnote
Certain diets may lead to deficiencies that can cause anemia.
30
What neurological signs may be assessed during a physical examination for anemia?
Altered positions or vibratory sense, ataxia, peripheral neuritis
## Footnote
These signs can indicate neurological involvement in severe anemia.
31
What might conjunctival jaundice indicate during an examination for anemia?
Liver dysfunction or hemolysis
## Footnote
Jaundice can result from increased bilirubin levels due to red blood cell breakdown.
32
Name 9 causes of rapid intravascular RBC destruction
* Mechanical hemolysis associated with DIC
* Massive Burns
* Toxins- poisnous venoms, Brown recluse spider, cobra
* Severe G6PD deficiency with oxidative stress
* ABO Incompatibility
* Infections- Malaria, Clostridium sepsis
* Cold agglutinin hemolysis(Mycoplasma, Mononucleosis)
* PNH exacerbated by tranfusion
* Immune complex hemolysis(Quinidine)
33
History taking for clinical severe anemia
**General**
Out-of-hospital status, therapy, response to therapy
Bleeding diathesis
Previous blood transfusion
Underlying diseases, including allergies
Current medications, especially those causing platelet inhibition
**Trauma**:
Nature and Time of Injury, Blood Loss at Scene
**Nontrauma**
Skin: Petechiae, ecchymoses
Gastrointestinal: Hematemesis, hematochezia, melena, peptic ulcer
Genitourinary: Last menstruation, menorrhagia, metrorrhagia, hematuria
34
Physical examination for Clinically severe anemia
* Vital Signs Measured Serially* :
-Blood pressure, pulse, respiratory rate, oxygen saturation
-Level and content of consciousness
* Skin: pallor, diaphoresis, jaundice, cyanosis, purpura, ecchymoses, petechiae
* Cardiovascular: Murmurs, S3, S4, quality of femoral and carotid pulses
* Abdomen: Hepatosplenomegaly, pain, guarding, rebound on palpation, stool hemoglobin testing
35
History taking for non emergent anemia
**Symptoms of Anemia**
Chest pain, decreased exercise tolerance, dyspnea
Weakness, fatigue, dizziness, syncope
**Bleeding Diathesis**
Bleeding after trauma, injections, tooth extractions
Spontaneous bleeding, such as epistaxis, menorrhagia
Spontaneous purpura and petechiae
**Sites of Blood Loss**
Respiratory: Epistaxis, hemoptysis
Gastrointestinal: Hematemesis, hematochezia, melena
Genitourinary: Abnormal menses, pregnancies, hematuria
Skin: Petechiae, ecchymoses
Intermittent jaundice, dark urine
**Dietary history:** Vegetarianism, poor nutrition
Drug use and toxin exposure, including alcohol
Racial background, family history
Underlying disease
Uremia, liver disease, hypothyroidism
Chronic disease states, such as cancer, rheumatic or renal disease
Previous surgery
36
Physical examination for non emergent anemia
Skin: Pallor, Purpura, petechiae, angiomas, ulcerations
Eye: Conjunctival jaundice, pallor
Oral: tongue atrophy, papillary soreness
Cardiopulmonary: Heart size, murmurs, extra cardiac sounds, rales indicating pulmonary edema
Abdomen: Hepatomegaly, splenomegaly, ascites, masses, Lymph nodes
Neurologic: Altered positions or vibratory sense, ataxia, peripheral neuritis
Rectal and pelvic: masses
37
Evaluation of microcytic anemia MCV<81
**Step 1:**
Peripheral smear shows microcytic and hypochromic RBCs?
No- Lead Intoxication
Yes-then Step 2
**Step 2**
Iron decreased, Ferritin decreased, TIBC increased
Yes- Iron deficiency
No- Thalassemia, Sideroblastic anemia, Chronic(late)
38
What initial laboratory tests may be helpful in a patient suspected of acute blood loss?
* Complete blood count and peripheral smear
* Blood sample for type and crossmatch
* Prothrombin time and international normalized ratio
* Partial thromboplastin time
* Serum electrolyte levels
* Glucose level
* Creatinine level
* Urinalysis for free hemoglobin
## Footnote
These tests help assess the patient's condition and guide treatment decisions.
39
Why is obtaining a hemoglobin and hematocrit in the emergency department useful?
It helps determine a baseline even though it may not reflect the true degree of blood loss for many hours.
## Footnote
This is important for monitoring changes in the patient's status over time.
40
What does the initial laboratory evaluation for a patient with non-emergent anemia include?
* Complete blood count with leukocyte differential
* Reticulocyte count
* Peripheral smear
* RBC indices (MCV, MCH, MCHC)
## Footnote
These tests help classify the type of anemia and its underlying causes.
41
What does MCV measure in red blood cells?
What does MCH incorporate in its measurement?
What does a low MCHC value indicate?
RBC size and volume
RBC size and hemoglobin concentration
Hypochromia
## Footnote
Decreases reflect microcytosis, while increases reflect macrocytosis.
42
What is the RBC distribution width (RDW) a measure of?
What is a normal RDW value?
RBC homogeneity
13.5 ± 1.5%
## Footnote
RDW is calculated as the standard deviation of MCV divided by MCV multiplied by 100.
43
What additional measurements are useful in diagnosing underlying disease processes related to anemia?
* Coagulation status
* Serum electrolytes
* Glucose
* Blood urea nitrogen
* Creatinine
## Footnote
These measurements help identify causes of anemia beyond blood loss.
44
When the cause of anemia is unknown and the patient requires transfusion, what tests should be considered?
* Folate
* Vitamin B12
* Iron
* Total iron-binding capacity (TIBC)
* Reticulocytes
* Direct antiglobulin (Coombs test)
## Footnote
These tests help diagnose potential deficiencies before transfusion, as post-transfusion levels may be unreliable.
45
Evaluation of normocytic anemia MCV 81 -100
**Step 1**
Peripheral smear shows schistocytes, helmet cells, spherocytes, bite cells
No- Acute blood loss, Chronic disease,Chronic renal infsufficiency, Hypothyroidism, Bone marrow suppression, Aplastic anemia
Yes- Hemolysis, G6PD(bite cells), LDH increase, Haptoglogin decrease, go to Step 2
**Step 2**
Coombs test positive: Autoimmune hemolytic anemia
Coombs test negative: Non autoimmune hemolytic anemia
46
Evaluation of macrocytic anemia MCV >100
**Step 1**
Peripheral smear shows large oval shaped RBCs, hypersegmented neutrophils
No-Liver disease, Reticulocytosis, Myelodysplastic syndromes
ETOH abuse, Drugs
Yes- B12 deficiecny, Folate deficiency
47
What is the formula for calculating Mean Corpuscular Volume (MCV)?
What is the normal range for Mean Corpuscular Volume (MCV)?
Hematocrit (%) divided by RBC count (106/μL)
81–100 fL
## Footnote
Normal range for MCV is 81–100 fL
MCV measures the average volume of red blood cells
48
What is the formula for calculating Mean Corpuscular Hemoglobin (MCH)?
What is the normal range for Mean Corpuscular Hemoglobin (MCH)?
Hemoglobin (g/dL) divided by RBC count (106/μL)
26–34 pg
## Footnote
MCH indicates the average amount of hemoglobin per red blood cell
49
What is the formula for calculating Mean Corpuscular Hemoglobin Concentration (MCHC)?
What is the normal range for Mean Corpuscular Hemoglobin Concentration (MCHC)?
Hemoglobin (g/dL) divided by hematocrit (%)
31%–36%
## Footnote
MCHC measures the concentration of hemoglobin in a given volume of packed red blood cells
50
What are the general admission criteria for nonemergent anemia?
Cardiac symptoms, such as dyspnea or chest pain, or neurologic symptoms, such as syncope.
## Footnote
These symptoms indicate potential complications from anemia that require further evaluation.
51
What is the initial unexplained hemoglobin value that may warrant admission for nonemergent anemia?
<8–10 g/dL or hematocrit <25%–30% in selected patients.
## Footnote
These values indicate severe anemia that may require intervention.
52
What is a reason for difficulty in obtaining outpatient care for patients with low hemoglobin levels?
When comorbidity is present.
## Footnote
Comorbid conditions can complicate the management of anemia and necessitate hospital admission.
53
Differential Diagnosis
of Anemias Caused by Decreased Red Blood
Cell Production Subclassification by Red
Blood Cell Indices
**Hypochromic Microcytic Anemias (Decreased MCV and Hemoglobin Concentration)**
Iron deficiency
Thalassemia
Sideroblastic anemia or lead poisoning
Chronic disease (e.g., cancer, renal disease); can also be normochromic and normocytic
**Macrocytic (Elevated MCV)**
Vitamin B12 deficiency
Folate deficiency
Liver disease
Hypothyroidism
**Normocytic (Normal MCV and Hemoglobin Concentration)**
Primary bone marrow involvement: Aplastic anemia, myeloid metaplasia with
myelofibrosis, myelophthisic anemia
Resulting from underlying disease: Hypoendocrine state (thyroid, adrenal,
pituitary), uremia, chronic inflammation, liver disease
54
What is the most common cause of anemia globally?
Iron deficiency anemia
## Footnote
Iron deficiency anemia is frequently seen in the emergency department (ED).
55
Define absolute iron deficiency.
Low or exhausted total body iron stores
## Footnote
Absolute iron deficiency reflects a lack of sufficient iron in the body.
56
Define functional iron deficiency.
Inadequate iron supply to the bone marrow
## Footnote
Functional iron deficiency occurs when there is enough iron in the body but it is not accessible for erythropoiesis.
57
What critical functions does iron serve in the body?
Erythropoiesis, mitochondrial function, DNA synthesis, cellular enzymatic reactions
## Footnote
Iron is essential for many biological processes.
58
Where is dietary iron absorbed?
Duodenum
## Footnote
Nutritional deficiency or malabsorption syndromes can lead to iron deficiency anemia.
59
What should always be excluded in the setting of iron deficiency anemia?
Occult blood loss
## Footnote
This is especially important in older patients and menstruating women.
60
What changes occur in RBCs after iron stores are depleted?
Changes in size, number, and hemoglobin content
## Footnote
Symptoms like fatigue can occur before anemia is evident.
61
What are some non-hematologic symptoms of iron deficiency?
Fatigue, impaired muscle-tissue oxidative capacity, decreased activity of iron-containing enzymes
## Footnote
These symptoms arise before anemia is present.
62
What is the nature of most anemias secondary to iron deficiency?
Non-emergent
## Footnote
Symptoms relate to the body's adaptation to low hemoglobin levels over time.
63
What laboratory evaluations are used for diagnosing iron deficiency anemia?
Fasting level of serum iron, serum ferritin, TIBC
## Footnote
Laboratory interpretation and pitfalls must be considered.
64
What is the cost-effective oral iron replacement therapy?
Ferrous sulfate
## Footnote
The dosage is 325 mg PO for adults three times daily.
65
What side effects may occur with oral iron supplementation?
Nausea, vomiting, constipation
## Footnote
Ascorbic acid can improve iron bioavailability but may increase side effects.
66
What should patients be warned about regarding iron supplementation?
Iron frequently leads to black stools
## Footnote
Black stools can also indicate gastrointestinal bleeding.
67
When is parenteral iron therapy necessary?
Poor oral tolerance or absorption
## Footnote
Parenteral iron is more effective in certain conditions like CKD and inflammatory bowel disease.
68
How quickly may a patient experience improvement after initiating iron replacement therapy?
As few as 24 hours
## Footnote
Reticulocytosis may appear within 3-4 days in children, longer in adults.
69
How long does it take for complete repletion of iron stores?
Approximately 3 to 6 months
## Footnote
The hemoglobin concentration rises on a similar schedule.
70
What can cause failures of iron replacement therapy?
Patient noncompliance, insufficient replacement, incorrect diagnosis, additional complicating processes
## Footnote
Anemia of chronic disease can complicate iron deficiency.
71
What is the composition of normal adult hemoglobin (HbA)?
It is made up of two alpha chains and two beta chains (α2β2)
## Footnote
HbA is the most common type of hemoglobin in adults.
72
What are the components of fetal hemoglobin (HbF)?
It contains two alpha and two gamma chains (α2γ2)
## Footnote
HbF is predominant during fetal development.
73
What type of genetic disorder is thalassemia?
It is a genetic autosomal recessive disorder
## Footnote
This means that two copies of the mutated gene are needed for a person to be affected.
74
What is the primary pathophysiological mechanism of thalassemia?
Decreased synthesis of and abnormal structure of globin chains
## Footnote
This leads to ineffective erythropoiesis and hemolytic anemia.
75
What types of globins are affected in beta thalassemia?
Beta-globin synthesis is reduced or absent, leading to an excess of alpha-globins
## Footnote
This results in the formation of alpha-globin tetramers.
76
How are beta thalassemias classified?
They are classified into silent (carrier), minor, intermedia, and major variants
## Footnote
This classification is based on the severity of the disease.
77
What is the difference between transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT)?
TDT requires regular, lifelong transfusions, while NTDT may not require transfusions
## Footnote
Patients can shift clinically between these categories based on transfusion needs.
78
What is a common symptom of homozygous β-chain thalassemia (thalassemia major)?
Severe anemia, hepatosplenomegaly, jaundice, abnormal development, and premature death
## Footnote
Symptoms typically become evident by age 2.
79
What is the typical presentation of heterozygous β-chain thalassemia (thalassemia minor)?
Mild to moderate anemia, typically asymptomatic, rarely requires transfusion
## Footnote
Most prevalent in Asia, the Middle East, and Mediterranean countries.
80
What are the gene loci responsible for alpha-thalassemia?
Four gene loci
## Footnote
The severity of the disease increases with the number of gene deletions.
81
What is the diagnostic test for thalassemia?
Hemoglobin electrophoresis and genetic testing
## Footnote
Peripheral smear shows microcytic, hypochromic anemia.
82
What is the treatment goal for transfusion therapy in TDT?
Correction of anemia, suppression of ineffective erythropoiesis, and inhibition of increased gastrointestinal iron absorption
## Footnote
Transfusion is typically required every 2 to 5 weeks.
83
What are the risks associated with recurrent blood transfusions in TDT?
Increased risk of blood-borne infection, alloimmunization, and iron overload
## Footnote
Iron overload can lead to multi-organ dysfunction and is a common cause of death.
84
What is the role of iron chelation therapy in thalassemia management?
Reduces systemic and hepatic iron burden
## Footnote
It is particularly important in patients who receive frequent transfusions.
85
What is hydroxyurea used for in thalassemia treatment?
It induces fetal hemoglobin production to improve chronic anemia and reduce transfusion needs
## Footnote
It is well tolerated with minimal long-term adverse effects.
86
What is the potential curative treatment for patients with TDT?
Hematopoietic stem cell transplantation (HSCT)
## Footnote
It has disease-free survival rates greater than 80% at 2 years.
87
What are the emerging therapies for thalassemia?
Gene therapy and gene editing
## Footnote
Clinical trials are currently in progress for these therapies.
88
What is the normal range for fasting serum iron?
60–180μg/dL
## Footnote
Fasting serum iron levels can vary diurnally and should be drawn in the morning
89
What fasting serum iron level indicates iron deficiency?
<60μg/dL
## Footnote
Levels can be increased by conditions such as hepatitis, hemochromatosis, hemolytic anemia, or aplastic anemia
90
What is the normal range for total iron-binding capacity?
250–400μg/dL
## Footnote
Total iron-binding capacity can be increased in late pregnancy or hepatitis
91
What total iron-binding capacity level indicates iron deficiency?
>400μg/dL
## Footnote
This level can decrease in infection
92
What is the normal percentage of saturation of serum iron of total iron-binding capacity?
15%–45%
## Footnote
A level below 15% indicates iron deficiency
93
What is the normal range for serum ferritin?
10–10,000mg/mL
## Footnote
Serum ferritin reflects iron stores and may increase as an acute-phase reactant in infection
94
What serum ferritin level indicates iron deficiency?
<10mg/mL
## Footnote
Low serum ferritin is a strong indicator of depleted iron stores
95
What is the standard for assessment of iron stores?
Bone marrow stainable iron
## Footnote
Presence of hemosiderin granules in reticuloendothelial cells indicates adequate iron stores
96
What is absent in iron deficiency regarding bone marrow stainable iron?
Hemosiderin granules
## Footnote
The absence of these granules is indicative of iron deficiency
97
What is usually necessary for silent carriers, beta thalassemia minor, and alpha thalassemia trait?
No treatment is necessary
## Footnote
These groups typically do not require intervention.
98
What are the goals of transfusion therapy for thalassemia?
* Correction of anemia
* Suppression of ineffective erythropoiesis
* Inhibition of increased gastrointestinal iron absorption
## Footnote
These goals help manage the complications of thalassemia.
99
How often does transfusion therapy for TDT typically occur?
Every 2 to 5 weeks
## Footnote
This frequency maintains a pre-transfusion hemoglobin between 9 and 10.5 g/dL.
100
Why is transfusion usually started in young patients with TDT?
To ensure normal growth and physical activity capacity
## Footnote
Early intervention is crucial for development.
101
What risks are associated with recurrent transfusions?
* Blood-borne infection
* Alloimmunization
* Iron overload
## Footnote
Iron overload can lead to multi-organ dysfunction and is a common cause of death.
102
When should transfusion be considered for patients with NTDT?
* During significant stress (e.g., pregnancy, surgery, infection)
* When hemoglobin levels are low
## Footnote
Guidelines for NTDT transfusion are not well established.
103
What is the effect of transfusion therapy combined with iron chelation therapy in TDT patients?
Improves long-term survival
## Footnote
Iron chelation therapy helps reduce systemic iron burden.
104
What is deferoxamine and its administration method?
The first commercially available chelator, administered parenterally or subcutaneously
## Footnote
It requires a demanding treatment regimen often leading to poor adherence.
105
What are the two oral chelators available for iron chelation therapy?
* Deferiprone
* Deferasirox
## Footnote
These chelators offer more convenient administration compared to deferoxamine.
106
How is hydroxyurea used in NTDT cases?
Induces fetal hemoglobin
## Footnote
It is hypothesized to improve chronic anemia and reduce transfusion needs.
107
What are common side effects of hydroxyurea?
* Mild transaminitis
* Nausea or vomiting
* Transient bone marrow suppression
## Footnote
Generally well tolerated with no major long-term adverse effects.
108
What is the impact of hydroxyurea on transfusion requirements in patients with severe NTDT?
Can lead to a complete cessation of transfusion requirement
## Footnote
Particularly in those requiring more than 3 transfusions per year.
109
What is splenectomy and its effect on thalassemia patients?
A surgical procedure that can improve hemoglobin concentration
## Footnote
It decreases the need for recurrent transfusions.
110
What is hematopoietic stem cell transplantation (HSCT) and its potential outcome?
A potentially curative therapy for TDT with disease-free survival rates greater than 80% at 2 years
## Footnote
Suitable only for a subset of patients due to age and donor compatibility.
111
What are the risks associated with HSCT?
* 5% to 10% risk of mortality
* Potential permanent fertility impairment
## Footnote
These risks must be weighed against the potential benefits.
112
What emerging therapies are being explored for thalassemia?
Gene therapy and gene editing
## Footnote
Clinical trial data is currently in progress.
113
What is sideroblastic anemia?
A defect in porphyrin synthesis leading to impaired hemoglobin production and excess iron deposition in RBC precursors
## Footnote
It can be congenital, idiopathic, or acquired.
114
What are the serum levels associated with sideroblastic anemia?
Increased serum iron, ferritin, and transferrin saturation levels
## Footnote
These changes occur due to impaired hemoglobin production.
115
What is a ringed sideroblast?
An erythroid precursor with a minimum of five siderotic granules covering the nucleus after Prussian blue staining
## Footnote
It is a characteristic finding in sideroblastic anemia.
116
What is the most common congenital cause of sideroblastic anemia?
X-linked sideroblastic anemia (XLSA)
## Footnote
It results from mutations in the ALAS2 gene.
117
What are the clinical features of idiopathic sideroblastic anemia?
Pallor and splenomegaly, with iron-containing inclusion bodies in RBCs
## Footnote
It is common in elderly patients and considered a pre-leukemic state.
118
What percentage of patients with idiopathic sideroblastic anemia may develop acute myelogenous leukemia?
Approximately 5%
## Footnote
This highlights the potential severity of the condition.
119
List some acquired causes of sideroblastic anemia.
* Drugs
* Alcoholism
* Copper deficiency
* Lead poisoning
* Zinc toxicity
* Myelodysplastic syndrome
* Myeloproliferative disorders
## Footnote
Specific drugs include chloramphenicol, isoniazid, linezolid, and penicillamine.
120
What diagnostic feature may suggest lead poisoning in sideroblastic anemia?
Basophilic stippling on the peripheral smear and metaphyseal lead lines on imaging
## Footnote
Elevated blood lead levels confirm the diagnosis.
121
How can alcohol abuse affect heme synthesis in sideroblastic anemia?
It can lead to disordered heme synthesis
## Footnote
This can often be corrected by alcohol cessation or parenteral pyridoxal phosphate.
122
What is the recommended management for most cases of congenital or acquired sideroblastic anemia?
Pyridoxine (vitamin B6) treatment, typically 100 mg PO three times a day
## Footnote
Most patients may still require transfusion.
123
What should be managed if long-term transfusion therapy is necessary?
Iron overload
## Footnote
This usually responds well to chelation therapy.
124
What treatment can be curative for some patients with congenital or myelodysplastic sideroblastic anemias?
Stem cell transplantation
## Footnote
This option may provide a definitive solution for select patients.
125
Clinicopathologic Correlation
of Manifestations of Megaloblastic Anemia
**Clinical Features/ Pathologic Condition**
Lemon yellow skin /Combination of pallor with low-grade icterus
from ineffective erythropoiesis
Petechiae, mucosal bleeding/ Thrombocytopenia
Infection// Leukopenia
Fatigue, dyspnea, orthostasis Anemia
Sore mouth or tongue /Megaloblastosis of mucosal surfaces
Diarrhea and weight loss /Malabsorption from mucosal surface change
Paresthesias and ataxia/ Related to myelin abnormality in vitamin B12
deficiency only
126
What is anemia of chronic disease (ACD) secondary to?
Reduced erythropoiesis and reduced RBC survival time in chronic inflammatory states
## Footnote
ACD results in decreased iron release from macrophages secondary to increased cytokines and hepcidin
127
What type of disorder is anemia of chronic disease?
A multifactorial, acquired disorder of iron homeostasis
## Footnote
ACD is commonly associated with chronic inflammatory states
128
List common causes of anemia of chronic disease
* Malignancy
* Arthritis
* Renal insufficiency
* Chronic heart failure
* Chronic obstructive lung disease
* Chronic infections (e.g., tuberculosis, osteomyelitis)
## Footnote
These conditions lead to chronic inflammation and affect iron metabolism
129
In which demographic is anemia of chronic disease commonly found?
Older adults
## Footnote
ACD is linked to increased morbidity and mortality in this population
130
What are the typical symptoms of anemia of chronic disease?
Symptoms related to the underlying disease, not from the anemia itself
## Footnote
ACD symptoms are often overshadowed by the primary condition
131
Describe the typical laboratory findings in anemia of chronic disease.
Low serum iron levels, low TIBC, normal or elevated ferritin levels
## Footnote
TIBC stands for Total Iron Binding Capacity
132
What is the typical morphology of red blood cells in anemia of chronic disease?
Normochromic, normocytic, though can be microcytic
## Footnote
Morphology may vary depending on the underlying conditions
133
What finding is typically observed in the bone marrow of patients with anemia of chronic disease?
Normal bone marrow but abnormality in the mobilization of iron from reticuloendothelial cells
## Footnote
This reflects impaired iron availability despite normal erythropoiesis
134
How can anemia of chronic disease be differentiated from iron deficiency anemia?
By TIBC, ferritin, bone marrow examination, and non-responsiveness to a trial of iron therapy
## Footnote
A complete search for occult blood loss is also important
135
True or False: Acute or emergent therapy is usually required for anemia of chronic disease.
False
## Footnote
Management often focuses on the underlying cause rather than immediate intervention
136
Fill in the blank: ACD is characterized by low serum iron levels, low TIBC, and _______.
normal or elevated ferritin levels
137
What is macrocytic anemia primarily caused by?
Vitamin B12 or folic acid deficiency
138
Macrocytic anemia is characterized by which two conditions?
Ineffective erythropoiesis and pancytopenia
139
What are the two categories of macrocytic anemias?
* Megaloblastic * Nonmegaloblastic
140
What is the most common cause of macrocytic anemia?
Megaloblastic macrocytic anemia
141
List some disease states that can cause nonmegaloblastic macrocytic anemia.
* Alcoholism * Liver dysfunction * Hypothyroidism * Myelodysplastic syndromes * Certain drugs (e.g., hydroxyurea, methotrexate, zidovudine, valproic acid)
142
What is the most common symptom reported in patients with macrocytic anemia?
Easy fatigability
143
What unique neurological symptoms can arise from vitamin B12 deficiency?
* Paresthesias of hands or feet * Decreased proprioception * Decreased vibratory sense * Weakness and spasticity of lower extremities * Altered reflexes * Variable mental changes
144
True or False: The neurologic manifestations of folic acid deficiency are distinct from those of vitamin B12 deficiency.
False
145
What devastating condition can result from vitamin B12 deficiency?
Subacute combined degeneration of the spinal cord
146
What is the recommended daily intake of folic acid for adults?
Approximately 240 μg/day
147
Where is folic acid absorbed in the body?
Upper jejunum
148
What is the adult requirement of vitamin B12?
1 or 3 μg/day
149
What is the most common cause of vitamin B12 deficiency?
Chronic malabsorption resulting from pernicious anemia
150
What type of anemia may occur if megaloblastic anemia is not responsive to folate or vitamin B12?
Related to antimetabolites used in chemotherapy or rare inherited disorders of DNA synthesis
151
What condition is often associated with non-megaloblastic macrocytic anemia and normocytic anemia?
Hypothyroidism
152
Fill in the blank: Folic acid is commonly found in _______.
[green vegetables, cereals, and fruit]
153
What can cause elevated homocysteine levels in vitamin B12 deficiency?
Thrombosis
154
Which drugs are commonly implicated in causing macrocytosis and anemia?
* Antiretrovirals * Phenytoin * Chemotherapeutic agents * Valproic acid * Azathioprine
155
Causes of Folate Deficiency
**Inadequate dietary intake**
Poor diet or overcooked or processed food diet
Alcoholism
**Inadequate uptake**
Malabsorption with sprue and other chronic upper intestinal tract disorders, drugs such as phenytoin and barbiturates, or blind loop syndrome
**Inadequate use**
Metabolic block caused by drugs, such as methotrexate or trimethoprim
Enzymatic deficiency, congenital or acquired
**Increased requirement**
Pregnancy
Increased red blood cell (RBC) turnover: Ineffective erythropoiesis, hemolytic anemia, chronic blood loss
Malignant disease: Lymphoproliferative disorders
**Increased excretion or destruction or dialysis**
156
Causes of Vitamin B12
Deficiency
**Inadequate dietary intake**
Total vegetarianism: No eggs, milk, or cheese
Chronic alcoholism (rare)
**Inadequate absorption**
Absent, inadequate, or abnormal intrinsic factor, as seen in patients with
pernicious anemia and gastrectomy; in pernicious, autoimmune antibodies act against gastric parietal cells and intrinsic factor
Abnormal ileum, as can occur in sprue and inflammatory bowel disease
**Inadequate use**
Enzyme deficiency
Abnormal vitamin B12–binding protein
**Increased requirement by increased body metabolism**
**Increased excretion or destruction**
157
What is the normal range for Vitamin B12 levels in μg/L?
300–900 μg/L
## Footnote
Values below 200 μg/L indicate deficiency.
158
What Vitamin B12 level indicates deficiency?
<200 μg/L
## Footnote
Vitamin B12 levels are usually normal in folate deficiency.
159
What is the deficient level for Folate in μg/L?
<3 μg/L
## Footnote
Vitamin B12 deficiency may elevate folate levels by blocking transfer of serum folate to RBCs.
160
What is the normal range for Lactate dehydrogenase in IU?
95–200 IU
## Footnote
Megaloblastic anemia can elevate levels 4–50 times normal.
161
How much can Lactate dehydrogenase be elevated in megaloblastic anemia?
4–50 times normal
## Footnote
It is normal in other macrocytic anemias and elevated two to four times normal in hemolytic anemias.
162
True or False: Vitamin B12 deficiency can elevate folate levels.
True
## Footnote
This occurs by blocking the transfer of serum folate to RBCs.
163
What technique is used to measure Vitamin B12 levels?
Microbiologic or radioisotope
## Footnote
This technique is standard for assessing Vitamin B12.
164
What technique is used to measure Folate levels?
Microbiologic or radioisotope
## Footnote
This technique helps diagnose folate deficiency.
165
What does an elevated Lactate dehydrogenase level indicate?
Possible megaloblastic anemia or hemolytic anemia
## Footnote
Normal levels can be seen in other macrocytic anemias.
166
What is the usual dosage for patients with megaloblastic anemia secondary to folate deficiency?
1 mg of oral folic acid per day
## Footnote
It is important to follow RBC folate levels to determine effectiveness and improvement in clinical symptoms.
167
What is the most common cause of vitamin B12 deficiency?
Malabsorption
168
What is the initial parenteral therapy for vitamin B12 deficiency?
1000 mcg IM daily for 7 to 10 days
## Footnote
Followed by monthly 1000 mcg IM injections.
169
What alternative dosing schedule may be considered for vitamin B12 deficiency?
Weekly 1000 mcg IM doses for 4 weeks
## Footnote
This is between daily and monthly injections.
170
What dosing regimen is recommended if neurologic symptoms are present in vitamin B12 deficiency?
1 mg IM every other day for up to three weeks, followed by 1 mg IM weekly for up to twelve weeks
## Footnote
Afterward, monthly 1 mg IM doses are necessary as needed.
171
How quickly can levels of RBC, WBC, and platelets return to normal after vitamin B12 therapy?
Within 4 weeks
172
What may develop during hematopoietic recovery after vitamin B12 therapy?
Iron deficiency
## Footnote
This should be treated in the usual manner.
173
Is it recommended to use vitamin B12 or folate supplements in patients with undiagnosed anemia?
No
174
Drugs or Chemicals that causes Aplastic Anemia
* Chloramphenicol
* Phenylbutazone
* Anticonvulsants
* Insecticides
* Solvents
* Sulfonamides
* Gold
* Benzene
175
What hematologic parameter aids in the diagnosis of normocytic anemia associated with hypoproduction?
Reticulocyte count
## Footnote
Reflects new RBC bone marrow production
176
How often are reticulocytes released from bone marrow?
Every 1 to 3 days
177
What does the reticulocyte count reflect?
New RBC bone marrow production
178
What is the normal range for the reticulocyte count?
1% to 3%
179
How is the corrected reticulocyte count calculated?
Measured percentage of reticulocytes × patient’s hematocrit ÷ normal hematocrit for age and gender
180
What are the two classifications of normocytic anemias?
Hemolytic and nonhemolytic
181
What typically causes nonhemolytic anemias?
Chronic disease states or bone marrow failure
182
What defines hemolytic anemia?
Premature destruction of RBCs
183
Name a common cause of non-hemolytic normocytic anemia.
Anemia of chronic disease
184
What conditions may lead to anemia of chronic disease?
* Chronic inflammation
* Rheumatoid arthritis
* Chronic infections
* Malignancy
185
What causes anemia of chronic renal failure?
Decreased erythropoietin production, hemolysis, and increased blood loss
186
What is the treatment for anemia of chronic renal failure?
Erythropoietin replacement therapy
187
What results from hypoendocrinism?
Hypometabolic state with poor bone marrow response to erythropoietin
188
What is aplastic anemia caused by?
Destruction of myeloid stem cells
189
What are the symptoms of aplastic anemia?
* Anemia
* Infections due to neutropenia
* Mucosal bleeding from thrombocytopenia
190
What is the overall 5-year survival rate for severe aplastic anemia?
30% to 40%
191
What are myelodysplastic syndromes characterized by?
Cytopenia, myelodysplasia, and ineffective hematopoiesis
192
What is a common laboratory finding in myelodysplastic syndromes?
Normocytic anemia, thrombocytopenia, and neutropenia
193
What is the definitive diagnosis for myelodysplastic syndromes?
Bone marrow examination with evidence of dysplastic cell lines
194
What is primary myelofibrosis associated with?
Primary bone marrow fibrosis and splenomegaly
195
What may primary myelofibrosis ultimately transform into?
Acute leukemia
196
What type of treatment is generally used for myeloproliferative neoplasms?
Supportive treatment
197
How can hemolytic anemias be classified?
Based on:
* Coombs test reactivity
* Intrinsic versus extrinsic defects
* Intravascular versus extravascular hemolysis
* Congenital or acquired forms
## Footnote
Multiple classification systems exist for hemolytic anemias.
198
What characterizes acute hemolytic anemias?
Shortened life span of the erythrocyte requiring rapid diagnosis and intervention
## Footnote
They are relatively rare compared to chronic hemolytic conditions.
199
What may chronic hemolytic disorders be related to?
Primary blood disorders or other disease states
## Footnote
Examples include sickle cell anemia and chronic renal failure.
200
What symptoms should emergency physicians consider for hemolysis?
Typical symptoms of anemia plus:
* New-onset jaundice
* Hematuria
* Fever
* Hepatosplenomegaly
* Abdominal or back pain
* Altered mental status
## Footnote
A thorough past medical and family history is critical.
201
What occurs during intravascular hemolysis?
Free hemoglobin is released into circulation, binding to haptoglobin and hemopexin
## Footnote
This complex is transported to the liver, conjugated to bilirubin, then excreted.
202
What can cause acute renal failure in intravascular hemolysis?
Hemoglobin complexes plugging the microtubules
## Footnote
This occurs when the hemolytic process overwhelms the binding and transport system.
203
What are some causes of mild anemia in intravascular hemolysis?
Mechanical hemolysis from prosthetic valves or chronic diseases
## Footnote
Examples include paroxysmal nocturnal hemoglobinuria.
204
What can cause severe acute anemia in intravascular hemolysis?
ABO incompatibility, autoimmune hemolytic anemias, infections, DIC, or toxins
## Footnote
These conditions require emergent intervention.
205
What are the clinical features of extravascular hemolysis?
Mild to moderate anemia, intermittent jaundice, and enlargement of the spleen
## Footnote
Occurs when RBCs are removed by macrophages due to abnormalities.
206
What are common causes of extravascular hemolysis?
* Hereditary spherocytosis
* G6PD deficiency
* Sickle cell disease
* Autoimmune hemolytic anemias
## Footnote
These conditions lead to premature removal of RBCs.
207
What happens to hemoglobin during extravascular hemolysis?
It is recycled and converted to bilirubin, then conjugated by the liver
## Footnote
This occurs in the reticuloendothelial system.
208
What can increase splenic function to a pathologic degree?
Primary splenic overactivity, antibody-mediated changes, or RBC membrane abnormalities
## Footnote
These factors affect the normal function of the spleen in hemolysis.
209
Classification of Hemolytic
Anemia
**Intrinsic**
Enzyme defect: Pyruvate kinase deficiency, G6PD deficiency
Membrane abnormality: Spherocytosis, Paroxysmal nocturnal hemoglobinuria
Hemoglobin abnormality: Hemoglobinopathies, Thalassemias (anemias)
**Extrinsic**
Immunologic: Alloantibodies, autoantibodies
Mechanical: Microangiopathic hemolytic anemia, prosthetic heart valve disease
Environmental: Drugs, toxins, infections, thermal
Abnormal sequestrations
210
Drugs Associated With
Hemolysis in G6PD
Analgesics and antipyretics: acetanilid, aspirin, phenacetin
Antimalarials: Primaquine, quinacrine, quinine
Nitrofurantoin
Sulfa drugs: Sulfamethoxazole, sulfacetamide, sulfones
Miscellaneous: Naphthalene, fava beans, methylene blue, phenylhydrazine,
nalidixic acid
211
Diseases Associated With
Autoimmune Hemolytic Anemia
**Neoplasms**
Malignant: Chronic lymphocytic leukemia, lymphoma, myeloma, thymoma,
chronic myeloid leukemia
Benign: Ovarian teratoma, dermoid cyst
**Collagen Vascular Disease**
Systemic lupus erythematosus
Periarteritis nodosa
Rheumatoid arthritis
**Infections**
Mycoplasma
Syphilis
Malaria
Bartonella
Virus: Mononucleosis, hepatitis, influenza, coxsackievirus, cytomegalovirus
**Miscellaneous**
Thyroid disorders, ulcerative colitis
Drug immune reactions
212
Drugs Associated With
Immune Hemolytic Anemia
**Hapten and drug absorption mechanisms**:
Penicillin, Cephalosporin, Tetracycline, Hydrocortisone, Oxaliplatin, Tolbutamide
**Immune complex mechanism:**
Metformin, quinine, quinidine, amphotericin b, thiopental, diclofenac, doxepin, probenecid
**Autoantibody mechanism:**
Cephalosporins, methyldopa, mefenamic acid, fludarabine, procainamide, diclofenac
**Non-immunologic protein adsorption:**
Cephalosporins, carboplatin, cisplatin, oxaliplatin
**Miscellaneous drug: **
insecticides, chlorpromazine, acetaminophen, ibuprofen, thiazides, omeprazole, erythromycin, streptomycin
213
History and Physical
Examination for Hemolytic Anemia
**History**
Alteration of color in urine or feces
Association with drugs, cold, sleep
Early or recent-onset anemia history with symptoms
Ethnic background
Family history of anemia or jaundice
Drug or toxic exposure
Disease states associated with hemolysis, such as systemic lupus erythematosus, renal failure, lymphoma, infectious mononucleosis, prosthetic heart valve
**Physical Examination**
Jaundice
Hepatosplenomegaly
Ulcerations, particularly in the lower extremities
Enlarged lymph nodes
214
Diagnostic Tests
for Hemolysis
Peripheral blood smear
Corrected reticulocyte index
Haptoglobin levels
Plasma free and urinary hemoglobin
Lactate dehydrogenase level
Fractionated bilirubin level
Direct and indirect Coombs test
Red blood cell (RBC) membrane stability (osmotic fragility)
215
What does an increased lactate dehydrogenase indicate in congenital red blood cell defects?
↑
## Footnote
Indicates tissue damage or hemolysis.
216
What is the haptoglobin level in hemoglobinopathies such as sickle cell disease?
↓
## Footnote
Haptoglobin is consumed in the process of binding free hemoglobin.
217
What laboratory finding is associated with hereditary spherocytosis?
Negative Coombs Test
## Footnote
Indicates that the hemolysis is not due to autoimmune causes.
218
What type of red blood cell defect is characterized by 'bite' cells?
Enzyme defects (e.g., G6PD)
## Footnote
These cells result from oxidative damage.
219
In autoimmune hemolytic anemia, what is the reticulocyte count?
↑
## Footnote
Indicates an increased production of red blood cells in response to hemolysis.
220
What laboratory finding is characteristic of infections like malaria?
Negative Coombs Test
## Footnote
Indicates that hemolysis is due to infectious causes rather than autoimmune.
221
What are the peripheral smear findings in microangiopathic hemolytic anemia?
Schistocytes, helmet cells
## Footnote
These findings indicate fragmentation of red blood cells.
222
What happens to the reticulocyte count in liver disease?
↑
## Footnote
Reflects a compensatory response to anemia.
223
What is the haptoglobin level in transfusion reactions?
↓
## Footnote
Due to hemolysis from the transfusion.
224
Fill in the blank: In paroxysmal nocturnal hemoglobinuria, the reticulocyte count is _______.
↑
225
True or False: Spur cells are associated with autoimmune hemolytic anemia.
False
## Footnote
Spur cells are typically seen in liver disease.
226
What is a common finding in the peripheral smear for toxins like nitrates?
Spherocytes
## Footnote
These cells are formed due to membrane damage.
227
What is the haptoglobin level in hypersplenism?
↓
## Footnote
Indicates increased destruction of red blood cells.
228
What is sickle cell disease?
An inherited autosomal recessive mutation that produces an abnormal hemoglobin known as HbS
229
How many people in the United States are affected by sickle cell disease?
Approximately 100,000 people
230
What percentage of sickle cell trait carriers are not of African American descent?
Up to 10%
231
What are the six different types of hemoglobin expressed in humans?
* HbA (α2β2) * HbA2 (α2δ2) * HbF (α2γ2) * Three embryonic hemoglobins
232
What mutation occurs in sickle cell disease?
Replacement of glutamic acid by valine at the sixth position of the beta chain
233
What is the difference between sickle cell trait and sickle cell disease?
Sickle cell trait (HbAS) is heterozygous with about 40% HbS; sickle cell disease (HbSS) is homozygous with over 85% HbS
234
What is the hallmark manifestation of sickle cell disease?
Painful vaso-occlusive crises
235
What are potential precipitating factors for a painful crisis in sickle cell disease?
* Antecedent infection * Cold exposure * Stress such as trauma
236
What are common locations for pain during a sickle cell crisis?
* Abdomen * Chest * Back * Extremities
237
What should be suspected in a patient with sudden acute neurologic abnormalities and sickle cell disease?
Stroke
238
What is the use of Transcranial Doppler (TCD) in sickle cell disease?
To identify children at high risk of stroke
239
What is acute chest syndrome?
The most common pulmonary condition associated with sickle cell disease
240
What are common symptoms of acute chest syndrome?
* Fever * Cough * Hypoxia * Chest pain * Dyspnea
241
What is the initial management for acute chest syndrome?
* Hydration * Analgesia * Maintenance of oxygenation and ventilation * Empiric antibiotics
242
What can cause an aplastic crisis in sickle cell disease?
Suppression of erythropoiesis by an acute post-infectious condition or folate deficiency
243
What is acute splenic sequestration syndrome?
Acute splenic enlargement from increased intrasplenic sickling and obstruction
244
What vaccinations are crucial for sickle cell patients to prevent infections?
* Pneumococcal * H. influenza type b * Meningococcal
245
What is the increased risk associated with functional asplenia in sickle cell disease?
Increased risk of infection with encapsulated organisms
246
What is the typical reticulocyte count in sickle cell disease?
Elevated reticulocyte counts
247
What are the leading causes of death in sickle cell disease?
* Acute chest syndrome * Sepsis * Multi-organ failure
248
Fill in the blank: Patients with sickle cell trait (HbAS) are usually _______.
asymptomatic
249
True or False: Pregnancy in women with sickle cell trait is associated with an increased risk of adverse events.
False
250
What are the common complications of sickle cell disease?
* Neurologic complications * Acute chest syndrome * Splenic sequestration
251
Organ Damage Seen in Sickle
Cell Disease
**Organ or System /Injury**
Skin/ Stasis ulcer
Central nervous system/ Cerebrovascular accident
Eye/ Retinal hemorrhage, retinopathy
Cardiac/ Congestive heart failure
Pulmonary /Intrapulmonary shunting, pulmonary hypertension,
embolism, infarct, infection
Vascular/ Occlusive phenomenon at any site
Liver /Hepatic infarct, hepatitis resulting from transfusion, hepatic sequestration, intrahepatic cholestasis
Gallbladder / Increased incidence of bilirubin gallstones caused by hemolysis
Spleen/ Acute sequestration
Urinary / Hyposthenuria, hematuria, glomerulosclerosis, end-stage renal disease
Genital / Decreased fertility, impotence, priapism
Skeletal / Bone infarcts, osteomyelitis, aseptic necrosis
Placenta /Insufficiency with fetal wastage
Leukocytes /Relative immunodeficiency
Erythrocytes/ Chronic hemolysis
252
What is sickle cell–β-thalassemia disease most commonly associated with?
Mediterranean descent
## Footnote
The severity of the disease is related to the concentration of HbS in RBCs and the decrease in MCHC.
253
What peripheral smear findings are associated with sickle cell–β-thalassemia disease?
Combination of sickled cells and normocytic target cells.
254
How does the severity of sickle cell–β-thalassemia disease compare to homozygous HbSS?
Generally milder but can also be severe.
255
What percentage of sickle cell disease cases in the United States and United Kingdom is accounted for by HbSC?
30%.
256
What genetic mutations result in HbSC?
Co-inheritance of HbS and HbC beta globin gene mutations.
257
What mutation causes the HbC defect?
Glutamic acid to lysine mutation at position six on the beta chain.
258
What are the characteristics of patients with HbSC disease?
* Higher mean Hb
* Lower absolute reticulocyte counts
* RBC lifespan is twice that of HbSS.
259
What initial diagnostic test is used for sickle cell disease?
Hemoglobin electrophoresis.
260
What is the typical reticulocyte count in sickle cell disease?
Three or four times the upper limit of normal.
261
A reticulocyte count 3% or lower than the patient’s usual value may suggest what condition?
Aplastic crisis.
262
What is the primary goal of current therapies for sickle cell disease?
Symptomatic relief and interruption of the cycle of deoxygenated sickling.
263
What is the recommended analgesic protocol for adults with severe pain in sickle cell disease?
Intravenous morphine sulfate, 5 to 10 mg every 2 to 4 hours, or intravenous hydromorphone, 1.5 mg every 3 to 4 hours.
264
What is the major disadvantage of treatment protocols for sickle cell pain?
Tendency to treat patients reflexively rather than considering potential acute complications.
265
What antisickling agent reduces pain crises and the need for blood transfusions?
Hydroxyurea.
266
What are the beneficial effects of hydroxyurea?
* Induction of fetal hemoglobin
* Mild myelosuppression.
267
What is the typical dosing range for hydroxyurea?
20 to 25 mg/kg/day PO.
268
What is the goal of transfusion therapy for symptomatic anemia in sickle cell disease?
Hemoglobin level no higher than 10 g/dL, and a target HbS < 30%.
269
What are some complications of long-term transfusion therapy?
* Alloimmunization
* Delayed hemolytic reactions
* Infection transmission
* Iron overload.
270
What is the first-line therapy for priapism in sickle cell disease?
Aspiration of blood from the corpus cavernosum and irrigation with an α-adrenergic agent.
271
What is the only current cure for sickle cell disease?
Stem cell transplantation.
272
What survival rates are associated with stem cell transplantation from an HLA-matched, disease-free sibling?
Greater than 90%.
273
What are some experimental therapies showing promise for sickle cell disease?
* Steroids
* Statins
* Heme oxygenase
* Hb affinity modulators
* Antioxidants
* Gene therapy.
274
When is hospitalization recommended for patients with sickle cell disease?
If pain cannot be adequately controlled or in cases of acute chest syndrome, acute infections, acute osteomyelitis, acute stroke, or other complications.
275
What is the common term for erythrocytosis?
Polycythemia
276
What defines the disorder of polycythemia?
An elevated RBC count, usually greater than the hematocrit
277
What is the relationship between MCV and serum iron in polycythemia?
Low MCV is usually related to low serum iron and iron stores
278
What major complications are associated with polycythemia?
Increased blood viscosity leading to reduced tissue flow, thrombosis, and hemorrhage
279
What hematocrit level indicates significant viscosity increase in polycythemia?
Hematocrit rises past 60%
280
What symptoms may be present in polycythemia?
* Mild headaches
* Vertigo
* Dizziness
* Blurred vision
* Hyperviscosity
* Thrombosis
* Epistaxis
* Spontaneous bruising
* Gastrointestinal bleeding
281
What examination findings may indicate polycythemia?
* Plethora
* Engorgement
* Venous congestion
* Venous congestion of the optic fundus
* Splenomegaly
* Signs of congestive heart failure
282
What types of polycythemia are there?
* Primary
* Secondary
* Apparent
283
What is apparent polycythemia?
A decrease in plasma volume, with RBC volume not exceeding the upper limit of normal
284
What is primary polycythemia vera (PV) caused by?
JAK2 mutations
285
What are common initial symptoms of primary polycythemia vera?
* Headache
* Weakness
* Dizziness
* Excessive sweating
* Plethora
* Pruritus after hot water exposure
286
What are the most serious complications of primary polycythemia vera?
* Thrombotic episodes
* Bleeding
* Risk of leukemic or fibrotic transformation
287
What is the mainstay therapy for primary polycythemia vera?
Phlebotomy to a hematocrit of less than 45%
288
What is recommended to prevent thrombosis in polycythemia vera patients?
Once-daily low-dose aspirin (40 to 100 mg PO)
289
What additional treatment is suggested for high-risk patients with polycythemia vera?
Hydroxyurea at a dose of 500 mg PO twice daily
290
What complications may necessitate additional therapy in polycythemia vera?
* Hyperuricemia
* Refractory increased RBC mass
* Severe pruritus
* Excessive splenomegaly
* Symptomatic thrombocytosis
291
What is the emergency treatment for symptomatic polycythemia?
Phlebotomy
292
What is the initial goal for hematocrit reduction in an emergency treatment of polycythemia?
Lower the hematocrit toward 60%
293
What should be considered in patients with suspected inappropriate erythropoietin response?
Computed tomography to evaluate renal pathologic conditions and malignancies
294
How is secondary polycythemia classified?
According to appropriate erythropoietin response to abnormal tissue oxygen levels
295
True or False: Patients with secondary polycythemia frequently have central nervous system symptoms.
False
296
What is the typical treatment approach for patients with symptomatic polycythemia?
Remove approximately 500 mL of blood and replace it with saline
297
What is the ultimate goal for hematocrit level in polycythemia treatment?
Less than 45%
298
What is indicated for patients with known polycythemia?
Serial outpatient phlebotomies
299
What should be considered for newly diagnosed or symptomatic patients?
Admission for further diagnostic evaluation
300
Causes of Absolute
and Relative Polycythemia
**Absolute Erythrocytosis**
Right-to-left shunt
Pulmonary disease
Carboxyhemoglobinemia
High-altitude acclimatization
High affinity hemoglobins
Sleep apnea syndrome
Renal disease: focal sclerosing glomerulonephritis, renal transplantation
Tumors: hepatoma, adrenal tumors, meningioma, pheochromocytoma, hemangioblastoma
Drugs: Androgenic steroids, Recombinant erythropoietin
Polycythemia vera
**Relative Erythrocytosis**
Loss of fluid from vascular space: emesis, diarrhea, diuretics, burns, hypoalbuminemia
Chronic plasma volume contraction: hypoxia, hypertension, tobacco use, ethanol abuse
301
Diagnostic Criteria
for Polycythemia Vera
**Major Criteria**
1. Hemoglobin >16.5 g/dL in men or >16 g/dL in women or hematocrit >49%
in men or >48% in women or increased red blood cell mass
2. Bone marrow tri-lineage proliferation with pleomorphic mature megakaryocytes
3. Presence of JAK2 mutation
**Minor Criterion**
Subnormal serum erythropoietin level
