Anemias Flashcards
1
Q
anemia
A
decreased absolute number or decreased quality of circulating RBCs which reduces the oxygen carrying capacity of blood
2
Q
anemia is most commonly measured by
A
decreased Hgb (<13 g/dl in men; <12 g/dL in women)
decreased Hct (<41% in men; <36% in women)
decreased RBC
3
Q
anemia classification by severity
A
mild: Hgb ~10-13.5 g/dL
moderate: Hgb ~8-10 g/dL
severe: Hgb <7-8 g/dL
4
Q
anemia classification by pathophysiologic mechanisms
A
decreased erythropoiesis/hypoproliferative
ineffective erythropoiesis
increased RBC destruction
blood loss
5
Q
decreased erythropoiesis/hypoproliferative pathophysiologic mechanism
A
decreased stimulation (anemia of chronic inflammation, renal dz)
mild iron deficiency
marrow damage (myelofibrosis, aplastic anemia)
bone marrow suppression (drugs)
hypometabolic states (protein malnutrition, endocrine deficiencies)
6
Q
ineffective erythropoiesis pathophysiologic mechanism
A
sever iron deficiency
megaloblastic anemia
thalassemia
myelodysplastic syndrome
sideroblastic anemias
7
Q
increased RBC destruction pathophysiologic mechanism
A
congenital causes (sickle cell, thalassemias, GP6D deficiency)
acquired causes (autoimmune hemolytic anemia)
hypersplenism
8
Q
anemia classification by RBC morphology
A
size (macrocytic, microcytic, normocytic)
degree of hemoglobination (normochromic and hypochromic)
shape
9
Q
anemia classification by timing
A
acute (blood loss, hemolysis)
chronic
10
Q
anemia general clinical presentation
A
variable dependent on severity and onset dyspnea (exertional --> rest) fatigue, weakness, malaise pallor hypoxia signs and symptoms of hyperdynamic state
11
Q
signs and symptoms of hyperdynamic state
A
palpitations roaring pulsatile sound in ear increased HR bounding pulses systolic flow murmur
12
Q
anemia is never normal and etiology should be sought
A
evaluate for increased RBC destruction
evaluate for marrow suppression
evaluate for nutritional deficiencies (iron, folate, B12)
evaluate for bleeding
13
Q
anemia diagnostic evaluation
A
Hgb/Hct, RBC count, RBC indices platelets WBC/WBC differential reticulocyte count peripheral smear evaluate for iron deficiency evaluate for hemolysis
14
Q
evaluate for iron deficiency
A
iron
TIBC/transferrin
transferrin saturation
ferritin
15
Q
evaluate for hemolysis
A
LDH indirect bilirubin haptoglobin plasma/urinary Hgb urinary hemosiderin
16
Q
anemia treatment
A
treat underlying etiology
treat anemia
17
Q
anemia prognosis
A
risk factor for increased mortality in association with CKD, malignancy, heart failure, older adults, hospitalized adults
18
Q
normocytic anemias
A
acute blood loss anemia anemia of chronic disease aplastic anemia hemolytic anemias early iron deficiency anemia endocrine dysfunction: hypothyroidism, hypopituitarism chronic kidney disease leucoerythroblastic blood picture pure RBC aplasia protein starvation
19
Q
acute blood loss anemia etiologies
A
trauma
GI tract, lung, kidney, uterine disorders
20
Q
acute blood loss anemia clinical presentation
A
hypovolemia:
- vascular instability (increased HR, decreased BP, decreased organ perfusion)
- hypovolemic shock (confusion, dyspnea, diaphoresis, increased HR, decreased BP)
21
Q
acute blood loss anemia diagnostic evaluation
A
Hgb/Hct normal initially
after correction of hypovolemia, Hgb/Hct will decrease
normal RBC indices
inadequate reticulocyte response
22
Q
acute blood loss anemia treatment
A
supportive care (transfusion)
treat underlying condition
23
Q
anemia of chronic disease
A
seen in association with a variety of conditions (i.e. infection, inflammatory, neoplastic disease, tissue injury, etc.)
hypoproliferative-primarily due to decreased erythropoiesis
typically normochromic, normocytic, mild severity
24
Q
anemia of chronic disease clinical presentation
A
history of chronic condition
usually minimal symptoms due to anemia
25
anemia of chronic disease laboratory evaluation
usually mild anemia (Hgb 10-11 g/dL)
usually MCV, MCH normal
decreased reticulocyte response
acute phase reactants (ESR, CRP) may be increased
iron studies
peripheral smear- normochromic, normocytic (not routinely needed)
bone marrow studies (not routinely needed)
26
anemia of chronic disease iron studies
serum Fe decreased
TIBC (transferrin) normal or decreased
TIBC saturation normal or decreased
serum ferritin normal or increased
27
if diagnosis of anemia of chronic disease is uncertain, consider additional tests
serum EPO --> would be low
reticulocyte response--> would be inappropriately low
soluble transferrin receptor
soluble transferrin receptor/ferritin ratio
28
anemia of chronic disease treatment
correction of underlying disorder
usually no specific treatment needed for anemia- transfusion or EPO-stimulating agent for severe/symptomatic anemia
29
anemia of critical illness
acute-event related anemia
develops following major event (surgery, trauma, MI, sepsis)
characterized by decreased RBC survival
30
anemia of critical illness labs
decreased Fe
increased ferritin
blunted EPO response
31
aplastic anemia
diminished or absent hematopoietic precursors in bone marrow
usually due to injury to pluripotent stem cell
causes pancytopenia
can be congenital or acquired
32
congenital palastic anemia
Fanconi anemia
33
acquired causes of aplastic anemia
idiopathic
drugs/chemicals
ionizing radiation
viral infection
others
34
aplastic anemia clinical presentation
```
can have abrupt or insidious onset
may have history of inciting event
symptoms due to thrombocytopenia
symptoms due to anemia
symptoms due to profound neutropenia
```
35
symptoms due to thrombocytopenia
mucosal hemorrhage
petechiae
increased menstrual flow
36
symptoms due to anemia
```
fatigue
pallor
lassitude
weakness
shortness of breath
pounding sensation in ear
```
37
symptoms due to profound neutropenia
recurrent infections
38
aplastic anemia diagnostic evaluation
```
CBC: pancytopenia
RBC indices: usually normocytic
decreased reticulocyte response
peripheral smear: decreased reticulocytes; abnormal cells NOT present
bone marrow biopsy (usually required)
tests to evaluate underlying etiology
```
39
aplastic anemia treatment
hematology referral
identify and treat underlying etiology if possible
supportive care for cytopenias (minimize bleeding risk, transfusions, aggressive infection prevention, antibiotics)
patients with moderate disease may be followed supportively without initiating curative treatment
40
aplastic anemia treatment for severe disease
immunosuppressive therapy: 1st line therapy for patients without available donor, older patients, patient preference
hematopoietic cell transplantation: 1st line therapy for majority of patients <50 yrs with available donor
41
aplastic anemia prognosis
untreated associated with >70% 1 year mortality
improved survival with availability of hematopoietic cell transplant
increased risk of developing clonal hematologic disorder
increased transfusions leads to risk of iron overload
42
macrocytic anemias
```
vitamin B12 deficiency
folate deficiency
hemolytic anemias
ethanol abuse
myelodysplastic syndromes
acute myeloid leukemias
drug induced anemia
liver disease
```
43
megaloblastic anemias
impaired DNA synthesis leading to large erythroid precursors and red cells
major causes: vitamin B12 deficiency (including pernicious anemia) and folate deficiency
44
vitamin B12 physiologic actions
required for growth/division of most cells
activates folic acid to allow it to participate in DNA synthesis/cell maturation
only source for humans is animal products
absorption can be passive or active (requires intrinsic factor)
body stores typically last 3-4 yrs
45
vitamin B12 deficiency
deficiency characterized by hematologic, neurologic, mucosal changes
can coexist with folate deficiency
increased frequency in older age
46
vitamin B12 deficiency etiologies
inadequate absorption
inadequate dietary intake
medications (PPI, H2 receptor antagonists, metformin)
HIV infection
47
vitamin B12 deficiency caused by inadequate absorption
pernicious anemia
gastrointestinal disease
gastric surgery
48
pernicious anemia
vitamin B12 deficiency due to lack of intrinsic factor
auto-antibodies destroy gastric parietal cells which produce intrinsic factor leading to atrophic gastritis +/- neutralize intrinsic factor
49
risk factors for pernicious anemia
Caucasians of northern European ancestry
increased age
autoimmune disease
50
vitamin B12 deficiency clinical presentation
slow in onset (years)
anemia: may have sings/symptoms related to pancytopenia if severe
glossitis, vaginal atrophy, malabsorption may be present
neurologic changes: neuropathy, balance disturbance, neuropsychiatric symptoms
increased risk of osteoporosis
51
vitamin B12 deficiency diagnostic evaluation
decreased Hgb/Hct - not all patients develop anemia, if anemia severe may develop pancytopenia
RBC indices: increased MCV, normal MCH
reticulocyte count normal to decreased
decreased serum vitamin B12
metabolite testing
peripheral smear
bone marrow biopsy usually not required
52
vitamin B12 deficiency metabolite testing
increased serum/urinary methylmalonic acid
increased serum homocysteine levels (also increased in folic acid deficiency)
53
vitamin B12 deficiency peripheral smear
macroovalocytes
hypersegmented neutrophils
anisocytosis
poikilocytosis
54
vitamin B12 deficiency diagnostic evaluation other tests (not commonly needed)
increased iron
increased indirect bilirubin
increased LDH
decreased haptoglobin
55
vitamin B12 deficiency diagnostic evaluation for pernicious anemia
antibodies to intrinsic factor
increased serum gastrin levels
decreased serum pepsinogen I levels
decreased ratio pepsinogen I :: pepsinogen II
56
vitamin B12 deficiency treatment
referral to hematologist not usually required
transfusion rarely required
rule out concurrent folate deficiency
vitamin B12
57
vitamin B12 dosing for deficiency
pernicious anemia: typically treated with parenteral (IM/subcu) vitamin B12
oral supplementation: generally recommended to use after vitamin B12 status has been normalized with parenteral treatment
58
vitamin B12 deficiency prognosis
Hgb increases within 10 days and returns to normal within 8 weeks
neurologic changes improve over 3 months (max improvement ~6-12 months)
patients with pernicious anemia appear to have increased risk of GI tract malignancies
59
vitamin B12 deficiency prevention
at risk populations may benefit from B12 supplementation- vegetarians, status post gastric surgery
60
folate physiologic actions
required for many tissue reactions
activated folic acid involved in DNA synthesis
61
folate deficiency
deficiency characterized by hematologic changes and pregnancy complications/neural tube defects
can coexist with vitamin B12 deficiency
62
folate deficiency risk factors
increased age
chronic alcohol use
certain medications
pregnancy/lactation
63
folate deficiency etiologies
most common cause is nutritional and/or increased requirements
nutritional due to inadequate intake (developing countries) and/or alcoholism
conditions associated with increased requirements: pregnancy, lactation, chronic hemolytic anemia
64
folate deficiency clinical presentation
quicker onset (4-5 months)
anemia: may have signs/symptoms related to pancytopenia if severe deficiency
pregnancy complications/neural tube defects
neurologic manifestations are rare
65
folate deficiency diagnostic evaluation
decreased Hgb/Hct
RBC indices: increased MCV, normal MCH
pancytopenia may develop if deficiency is severe
reticulocyte count normal to decreased
decreased serum folate levels/RBC folate
metabolite testing: increased homocysteine levels
peripheral smear
bone marrow aspiration/biopsy not usually required
66
folate deficiency peripheral smear
macroovalocytes
hypersegmented neutrophils
anisocytosis
poikilocytosis
67
folate deficiency treatment
referral to hematologist not usually necessary
folic acid (1-5 mg/day orally) x 1-4 months
rule out concurrent B12 deficiency
transfusion rarely required
68
folate deficiency prevention
supplemental folic acid recommended in pregnancy, low-weight premature neonates
69
microcytic anemias
iron deficiency anemia
sideroblastic anemia
thalassemia
70
degree of microcytosis
mild: MCV >70 fL
severe: MCV <70 fL
71
mild microcytosis conditions
```
iron deficiency
thalassemias
sideroblastic anemia
lead toxicity
anemia of chronic disease (usually normocytic)
```
72
severe microcytosis conditions
```
thalassemias
iron deficiency (severe)
```
73
iron
major physiologic role to carry O2 in Hgb
present in meats, eggs, iron-fortified cereal, beans
absorbed in stomach, duodenum, upper jejunum
circulates in plasma bound to transferrin
stored as ferritin (and hemosiderin)
effective recycling mechanisms to conserve iron
no mechanism for iron excretion
nutritional requirements vary with development and physiologic processes
74
iron deficiency characterized by
hematologic changes
alterations within fast-growing tissues
75
iron deficiency anemia etiologies
```
blood loss (overt or occult)-menstrual losses, GI losses
dietary deficiency
reduced GI absorption
increased requirements (growth, pregnancy, lactation)
```
76
iron deficiency anemia clinical presentation
may have underlying condition that increases likelihood of deficiency
variable onset
signs/symptoms of anemia (weakness, headache, irritability, fatigue/exercise intolerance, pallor, increased HR)
severe deficiency can lead to smooth tongue, brittle nails, spooning of nails, cheilosis, hair loss, pagophagia, restless leg syndrome
neurodevelopment delay in children
77
iron deficiency anemia diagnostic evaluation
decreased Hgb/Hct
RBC indices: decreased/normal MCH and MCV
+/- increased platelets
decreased reticulocyte response
peripheral blood smear
serum/plasma ferritin, iron, TIBC (transferrin), TIBC saturation
bone marrow biopsy rarely required
search for source of blood/iron loss (medical history, GI evaluation)
78
iron deficiency anemia peripheral smear
```
anisocytosis
microcytosis
poikilocytosis
hypochromia
target cells with severe deficiency
```
79
iron deficiency anemia iron studies
serum iron decreased
TIBC (transferrin) normal to high
Transferrin saturation decreased
plasma ferritin decreased
80
iron deficiency anemia treatment
identify and treat etiology
iron (oral/IV) continue for 3-6 months after normalization of Hgb and correction of underlying etiology
severe anemia may require RBC transfusion
81
iron deficiency anemia prognosis
pagophagia often disappears as soon as iron therapy begun
improved sense of wellbeing within 1st days of treatment
modest reticulocytosis (peaks at 7-10 days)
Hgb rises slowly and will return to normal ~6-8 weeks
82
iron deficiency anemia prevention
iron supplementation for exclusively breast-fed infants, iron fortified formula for formula fed infants
universal lab screening for infants 9-12 months of age
boys should be screened at least once during peak growth period
girls aged 12-18 yrs and non-pregnant women of childbearing age should have screening every 5-10 yrs
pregnant women should receive low dose iron and routine screening for presence of iron deficiency anemia
83
sideroblastic anemia
congenital or acquired defects leading to impaired incorporation of iron into heme molecule
primarily laboratory diagnosis based on identification of siderocytes in peripheral blood with Wright-Giemsa stain or sideroblasts on bone marrow examination with Prussian blue stain
84
siderocyte
abnormal RBC in peripheral circulation with Pappenheimer bodies
85
sideroblast
erythroblast with stainable deposits of iron in cytoplasm
86
ring sideroblast
abundant iron deposits in erythroblast that form ring around nucleus
87
sideroblastic anemia diagnostic evaluation
moderate anemia (Hct 20-30%
decreased MCV most common
associated decreased in WBC, increased/decreased platelets may be present if associated with myelodysplastic syndrome
peripheral smear shows siderocytes with pappenheimer bodies
diagnosis confirmed with demonstration of sideroblasts on bone marrow examination with prussian blue stain
88
siderocytes with pappenheimer bodies
hypochromic RBCs with basophilic iron deposits
89
sideroblastic anemia treatment
```
remove underlying etiology if able
supportive care (including transfusion if needed)
```
90
sideroblastic anemia prognosis
variable based on underlying etiology
major causes of death are secondary hemochromatosis due to transfusions and leukemia
91
anemia of old age
Hgb values in healthy older adults generally lower than younger adults
differences in Hgb between males and females decreasing with age
currently not uniformly accepted definition of anemia in older adult
92
pediatric anemias
```
anemia of prematurity
pathologic anemia (birth-3 months)
physiologic anemia (6-9 weeks)
pathologic anemia (3-6 months)
pathologic anemia (toddlers-adolescence)
```
93
pathologic anemia: birth - 3 months
blood loss
immune hemolytic disease
congenital infection
congenital hemolytic anemia
94
physiologic anemia: 6-9 weeks
most common cause of anemia in young infants
95
pathologic anemia: 3-6 months
hemoglobinopathy
96
pathologic anemia: toddlers - adolescence
acquired causes more likely (i.e iron deficiency)
anemia due to lead poisoning
97
anemia dur to lead poisoning
can occur due to decreased Hgb synthesis and hemolysis
usually mild and normocytic
98
hemolytic anemia
anemia due to shortened RBC survival
characterized by increased EPO levels, increased reticulocyte response, accumulation of Hgb degradation products
99
various classifications of hemolytic anemia
acquired vs, congenital
acute or chronic
mild or severe
compensated or uncompensated
pathophysiologic
site of hemolysis (intravascular vs extravascular)
intrinsic vs. extrinsic process (intracorpuscular vs. extracorpuscular defects)
100
intravascular hemolysis
usually caused by mechanical injury, complement fixation, intracellular parasites, exogenous factors, toxic factors
101
examples of intravascular hemolysis
microangiopathic hemolytic anemia (thrombotic microangiopathy, leaky prosthetic heart valves)
paroxysmal nocturnal hemoglobinuria
transfusion reaction (ABO incompatibility
infection (clostridial sepsis)
102
extravascular hemolysis (more common)
RBC destruction within phagocytes in spleen, liver, bone marrow
103
examples of extravascular hemolysis
hemoglobinopathy
enzyme deficiencies
membrane defect
autoimmune hemolytic anemia
104
intracorpuscular (intrinsic RBC defect) process
hemoglobinopathy (sickle cell disease, thalssemia, unstable Hgb)
enzyme deficiencies (G6PD deficiency)
membrane defect (hereditary spherocytosis, elliptocytosis)
paroxysmal nocturnal hemoglobinuria
105
extracorpuscular (process extrinsic to RBC) process
```
autoimmune hemolytic anemias (warm or cold-reacting, drugs)
microangiopathic hemolytic anemia
liver disease
hypersplenism
infections
oxidant agents
IV immune globulin infusion
```
106
hemolytic anemia clinical presentation
symptoms of anemia
symptoms of hemolysis (extravascular or intravascular) - gallstones
severe forms may be associated with skeletal changes due to overactive bone marrow
107
clinical presentation of extravascular hemolysis
associated with jaundice and hepatosplenomegaly
108
clinical presentation of intravascular hemolysis
associated with jaundice and dark urine
109
hemolytic anemia diagnostic evaluation
decreased Hgb/Hct
peripheral smear: macrocytes, polychromasia, nucleated RBCs may be seen
increased reticulocyte response: may be reduced (especially in intravascular hemolysis); leads to increased MCV
increased LDH
decreased haptoglobin (more significant decreased w/ intravascular hemolysis)
increased unconjugated bilirubin, increased urobilinogen
hemoglobinemia, hemoglobinuria, hemosiderinuria (intravascular hemolysis)
variable iron studies
further eval based on most likely etiology
110
hemolytic anemia treatment
based on underlying etiology
splenectomy often helpful for patients with extravascular hemolysis
111
congenital hemolytic anemias
```
G6PD deficiency
hereditary spherocytosis/elliptocytosis
sickle cell disease
thalassemias
thrombotic microangiopathy (TTP, complement-mediated thrombotic microangiopathy)
```
112
G6PD deficiency
genetic mutation leads to reduced half-life of G6PD
x-linked recessive disorder --> males at higher risk for symptomatic disease
associated with extravascular (an intravascular-rare) hemolysis
113
G6PD enzyme
important in maintaining RBC integrity
protects against oxidative stress
114
G6PD deficiency can lead to a wide variety of hemolytic syndromes based on severity of the enzyme deficiency
there are class I, class II, class III, and class IV variants
115
G6PD deficiency class I variants
most severe
chronic hemolysis
congenital non-spheocytic hemolytic anemia
116
G6PD deficiency class II variants
severe
intermittent episodes of hemolysis
G6PD Mediterranean (prevalent in Middle East)
117
G6PD deficiency Class III variants
mild-moderate severity
intermittent episodes of hemolysis
G6PD A- (present in ~10% of American blacks)
118
G6PD class IV variants
not associated with hemolysis
G6PD B
119
G6PD deficiency triggers for hemolysis
infections (bacterial, viral, fungal)
medications (anti-infectives, analgesics)
foods (fresh fava beans, bitter melon)
DKA
120
G6PD deficiency clinical presentation- neonatal hyperbilirubinemia
may develop with all variants (more likely to occur with more severe variants)
yellowing of skin, sclera, mucous membranes
encephalopathy may occur in severe cases
121
G6PD deficiency clinical presentation class I variants
anemia and jaundice usually observed in newborn period
after infancy: chronic hemolytic manifestations subtle and variable- pallor uncommon, scleral icterus intermittent, splenomegaly rare
periods of increased hemolysis in association with triggers (drugs, infections, metabolic abnormalities)
122
G6PD deficiency clinical presentation class II, III variants
asymptomatic in steady state
periods of hemolysis in association with triggers (drugs, infections, metabolic abnormalities)
123
G6PD deficiency diagnostic evaluation class I variants
mild to moderate anemia at baseline (Hgb 8-10 g/dL)
increased MCV
increased reticulocyte count as baseline (10-15%)
124
G6PD deficiency diagnostic evaluation
acute hemolysis characterized by:
decreased Hgb/Hct
increased reticulocyte response
evidence of hemolysis (increased bilirubin, decreased haptoglobin, increased LDH)
if intravascular hemolysis occurs hemoglobinemia/hemoglobinuria may be present
peripheral blood smear
125
G6PD deficiency diagnostic evaluation peripheral blood smear
```
red cell fragments (schistocytes)
microspherocytes
eccentrocytes/bite cells
anisocytosis
poikilocytosis
polychromasia
Heinz bodies
```
126
G6PD deficiency treatment
```
neonatal hyperbilirubinemia treated similarly to other cases or neonatal jaundice
avoid exposure known to trigger hemolysis
supportive care for acute hemolytic events
class I variants: folic acid supplementation
```
127
G6PD deficiency prognosis
associated with protective effect against malaria
acute renal failure can develop during times of acute hemolysis
class II variants: hemolysis will continue well after trigger is discontinued
class III variants: even with continued exposure to trigger, acute hemolytic process ends after ~1 week (with the reversal of anemia)
128
G6PD deficiency screening
all personnel being deployed to malaria endemic regions must be screened
all personnel entering military service
universal newborn screening in many malaria-endemic regions
newborn screening in US state dependent (MI not involved)
129
hereditary spherocytosis/elliptocytosis
inherited forms of hemolytic anemia with presence of spherocytes or elliptocytes in peripheral circulation
heterogenous genetic pattern and clinical manifestations (presentations vary greatly)
130
hereditary spherocytosis/elliptocytosis diagnostic evaluation
presence of spherocytes or elliptocytes on peripheral smear
characteristic feature is increased MCHC
131
hereditary spherocytosis/elliptocytosis treatment
includes splenectomy in severe cases
132
acquired hemolytic anemias
```
autoimmune hemolytic anemia
gold agglutinin disease
paroxysmal nocturnal hemoglobinuria
drug-induced hemolytic anemia
infection
mechanical RBC destruction
thrombotic microangiopathy
```
133
acquired hemolytic anemia caused by presence of IgG auto antibodies
autoimmune hemolytic anemia
134
autoimmune hemolytic anemia
50% of cases are idiopathic; can also develop in association with SLE, CLL, lymphoma
auto-antibodies bind RBC membrane most avidly at body temperature
auto-antibody coated RBC leads to extravascular hemolysis in spleen and liver
occasionally intravascular hemolysis may occur due to complement activation
135
autoimmune hemolytic anemia clinical presentation
generally rapid onset
symptoms of anemia (fatigue, dyspnea, etc.)
symptoms of hemolysis (jaundice, splenomegaly, dark urine if predominant intravascular hemolysis)
136
autoimmune hemolytic anemia diagnostic evaluation
decreased Hgb/Hct (can be severe with Hct <10%)
decreased platelets (minority of cases)
increased reticulocyte response (takes 3-5 days)
evidence of hemolysis (increased bilirubin and LDH, decreased haptoglobin)
peripheral smear: spherocytes, nucleated RBCs
positive direct antiglobulin test (direct Coombs' test)
137
autoimmune hemolytic anemia treatment
referral to hematologist
transfusions- unlikely that fully compatible blood will be found but transfused RBCs will survive ~as long as patients own RBCs
immune suppression: prednisone 1-2 mg/kg/day
splenectomy
plasmapheresis (in setting of rapid hemolysis)
138
autoimmune hemolytic anemia prognosis
patients generally do well
death due to cardiovascular collapse in setting of rapid hemolysis may occur
139
acquired hemolytic disease (usually extravascular) caused by presence of IgM autoantibodies
cold agglutinin disease
140
cold agglutinin disease etiologies
usually idiopathic
can occur in association with Waldenstorom, macroglobulinemia, lymphoma, CLL
acute post-infectious cold agglutinin disease can develop after mycoplasma pneumonia or viral infection
141
cold agglutinin disease
IgM autoantibodies react with RBCs at low temperatures
IgM attaches to RBC membranes in cooler parts of circulation (fingers, nose, ears) which causes complement binding and fixation
when RBCs return to warmer circulation, IgM dissociates, but complement remains bound
RBCs are sequestered and destroyed in the liver
142
cold agglutinin disease clinical presentation
mottled fingers/toes, acrocyanosis, episodic low BP, dark colored urine in response to cold exposure
anemia rarely severe
143
cold agglutinin disease diagnostic evaluation
decreased Hgb/Hct (usually mild)
increased reticulocyte response
intermittent evidence of hemolysis (increased bilirubin and LDH, decreased haptoglobin)
peripheral smear (made at room temp): agglutinated RBCs
direct antiglobulin test (direct Coombs' test) positive for complement only
serum cold agglutinin titer available
protein electrophoresis often reveals monoclonal IgM
144
cold agglutinin disease treatment- supportive
avoid exposure to cold
transfusions should be administered through an in-line blood warmer
145
cold agglutinin disease treatment- more severe forms
can be difficult to manage
plasmapheresis or IV immunoglobulin may be used until immunosuppressive agents take effect
Rituximab treatment of choice to reduce Ab production
146
paroxysmal nocturnal hemoglobinuria
rare acquired hematopoietic stem cell disorder-may appear de novo or in setting of aplastic anemia
intrinsic RBC abnormality leads to unregulated formation of complement membrane attack complexes and ultimately to intravascular hemolysis
147
paroxysmal nocturnal hemoglobinuria clinical presentation
```
may be asymptomatic
episodic intravascular hemolytic anemia (reddish brown urine-more pronounced in am)
venous thrombosis (especially in hepatic, mesenteric, CNS, and skin veins)
```
148
paroxysmal nocturnal hemoglobinuria diagnostic evaluation
decreased Hgb/Hct (variable severity and frequency)
variable RBC morphology
decreased WB/ decreased platelets may be present
normal to increased reticulocyte response during times of hemolysis
intermittent evidence of hemolysis
decreased iron +/- decreased folate common
peripheral smear: polychromasia
flow cytometry demonstrates decreased CD55 and CD59
may require diagnostic evidence based on symptoms
149
paroxysmal nocturnal hemoglobinuria treatment
usually referred to hematologist
supportive care for mild cases (serum folate and iron supplementation prn)
eculizumab may be used if severe hemolysis or thrombosis present
hematopoietic cell transplant may be required in severe cases
thromboses require anticoagulation
150
paroxysmal nocturnal hemoglobinuria prognosis
life expectancy for severe forms 10-15 yrs
major cause of death is thrombosis
possible progression to myelodysplasia or AML
151
drug-induced hemolytic anemia
drugs can elicit immune reaction resulting in hemolysis- will cause positive Direct Coombs test
drugs with oxidative potential can cause hemolysis
drugs can cause hemolysis via non-oxidative, unknown mechanisms
152
infectious causes of hemolytic anemia
malaria common cause of acquired hemolytic anemia in endemic regions
Shiga toxin-producing E. coli can cause Shiga toxin hemolytic uremic syndrome
Clostridium perfringens sepsis
153
mechanical destruction of RBCs
microangiopathic hemolytic anemia
| March hemoglobinuria
154
microangiopathic hemolytic anemia
descriptive term for non-immune intravascular hemolysis
can occur due to abnormalities in microvasculature, intravasculature devices
155
March hemoglobinuria
acute hemolytic anemia secondary to mechanical RBC damage in marathon runners, prolonged barefoot dancing
156
hemolytic disease of the fetus and newborn
destruction of neonatal or fetal RBCs by maternal IgG Ab
Rh(D) hemolytic disease is the most sever
can also have ABO hemolytic disease and other blood group Abs
157
hemolytic disease of the fetus and newborn clinical presentation
variable
mild-moderate disease: hyperbilirubinemia within 1st 24 hrs of life; +/- symptomatic anemia
hydrops fetalis
158
hemolytic disease of the fetus and newborn diagnostic evaluation antenatal
maternal ABO testing, screening for Ab to RBC antigen
159
hemolytic disease of the fetus and newborn diagnostic evaluation postnatal
demonstration of incompatible blood types between infant and mother
demonstration of hemolysis
positive direct or indirect antiglobulin test (Coombs test)
160
hemolytic disease of the fetus and newborn treatment antenatal
monitoring of Ab titers and fetal condition
fetal RBC transfusions prn
161
hemolytic disease of the fetus and newborn treatment postnatal
treat anemia with supportive care +/- PRBC transfusion, EPO agents
treat hyperbilirubinemia with supportive care +/- phototherapy, exchange transfusion
162
hemolytic disease of the fetus and newborn prevention
Rh(D) typing and Ab screen should be performed at 1st prenatal visit
administration of anti-D immune globulin to Rh(D) negative women exposed, or at high risk of being exposed, to Rh(D) positive RBCs
163
Rh(D) typing and Ab screen should be performed at 1st prenatal visit
mothers with positive screen should be assessed for risk of clinically significant hemolytic disease of fetus/newborn and managed accordingly
Rh(D) negative mothers with negative initial screening should have repeat Ab screen at 28 weeks gestation and delivery
164
administration of anti-D immune globulin to Rh(D) negative women exposed, or at high risk of being exposed, to Rh(D) positive RBCs
routinely administered at 28 weeks gestation and within 72 hours of delivery to Rh(D) positive newborn
administration following any event associated with placental trauma or disruption of fetomaternal interface
