RBC path Flashcards
1
Q
Anemia
A
reduction of total circulating red cell mass below normal limits
2
Q
Major mechanisms of anemia
A
blood loss, increased red cell destruction, decreased red cell production
3
Q
Most useful lab values for anemia eval
A
mean cell volume, mean cell hgb, mean cell hgb concentration, RDW
4
Q
Common clinical findings in anemia
A
pale, weakness, malaise, easy fatigability, dyspnea, SOB; chronic hypoxia can lead to fatty change in liver, myocardium, and kidney
5
Q
What does HCT measure?
A
relative concentration of red cells, not the total red cell mass
6
Q
How quickly are reticulocytes produced
A
5 days
7
Q
Common features of hemolytic anemia
A
shortened red cell life span, elevated EPO levels and compensatory increase in EPO, accumulation of hgb degradation products
8
Q
Where are senescent RBC destroyed?
A
macrophages in spleen, liver, bone marrow
9
Q
Extravascular hemolysis
A
caused by alterations that render red cell less deformable, makes it more difficult for cells to go through spleen
10
Q
Sxs of extravascular hemolysis
A
anemia, splenomegaly, jaundice
11
Q
Intravascular hemolysis
A
caused by mechanical injury, complement fixation, intracellular parasites, exogenous toxic factors
12
Q
Manifestations of intravascular hemolysis
A
anemia, hemoglobinemia, hemoglobinuria, hemosidonuria, jaundice
13
Q
Role of haptoglobin
A
binds free hemoglobin, produces a complex that is cleared by phagocytes
14
Q
Is bilirubin in uncomplicated hemolytic anemias conjugate or unconjugated?
A
unconjugated
15
Q
Hereditary Spherocytosis
A
inherited disorder caused by intrinsic defects in red cell membrane skeleton that render red cells spheroid, less deformable, and vulnerable to splenic sequestration and destruction
16
Q
Inheritance pattern of HS
A
autosomal dominant
17
Q
Potential proteins affected by HS
A
spectrin a or b, ankyrin, band 3, protein 4.1 and band 4.2
18
Q
G6PD deficiency
A
abnormalities reduce the ability of red cells to protect themselves from oxidative injury
19
Q
What may cause episodic hemolysis characteristic of G60D?
A
infections such as viral hepatitis, pneumonia, typhoid fever; drugs; foods
20
Q
Heinz bodies
A
denatured globin chains that appear as dark inclusions within red cells stained with crystal violet; will be plucked out by macrophages and produce bite cells
21
Q
When will acute hemolysis begin following exposure of G6PD-deficient individuals to oxidants?
A
2 to 3 days
22
Q
Most prominent form of Hgb in adults
A
A (alpha 2, beta 2)
23
Q
Most prominent form of Hgb in newborns
A
HbF
24
Q
Genetic aberration in sickle cell disease
A
point mutation in B globin, resulting in red cell distortion; glutamate replaced by valine
25
Vaso-occlusive crises
episodes of hypoxic injury and infarction that often cause severe pain
26
Acute chest syndrome
fever, cough, chest pain, pulmonary infiltrates and inflammation
27
Priapism
affects males after puberty and may lead to hypoxic damage and erectile dysfunction
28
Sequestration crises
entrapment of sickled red cells leading to rapid splenic enlargement, hypovolemia, shock
29
hyposthenuria
inability to concentrate urine
30
What types of organisms are children with sickle cell at increased susceptibility for?
encapsulated - S. pneumoniae, H. influenzae meningitis and septicemia
31
Thalassemia syndromes
group of disorders caused by inherited mutations that decrease synthesis of alpha or beta globin chains leading to anemia, tissue hypoxia, and red cell hemolysis
32
What chromosome codes for alpha globin
Chromosome 16
33
What chromosome codes for beta globin
chromosome 11
34
What do globin defects in thalassemia cause?
anemia via decreased red cell production and decreased red cell lifespan
35
Types of B-Thalassemia mutations
B0 mutation (absent synthesis), B+ mutations (reduced synthesis)
36
Two ways B-thalassemia causes anemia
deficit in HbA synthesis produces hypochromic, microcytic red cell; diminished survival of red cells and their precursors
37
Hemolysis in B-thalassemia and cause
extravascular hemolysis due to membrane damage from imbalance of alpha and beta globin chains
38
Which areas is B-thalassemia major most common in?
Mediterranean countries, parts of Africa, and Southeast Asia
39
Predominant type of Hb in B-thalassemia major individuals
HbF
40
Clinical course of B-thalassemia major
brief unless blood transfusions are given, growth retardation, bony prominences, hepatosplenomegaly; cardiac disease resulting from progressive iron overload and secondary hemochromatosis
41
Morphology of B-Thalassemia major
marked variation in size and shape, microcytosis, hypochromia
42
B-thalassemia minor
patients typically asymptomatic but may experience mild anemia
43
B-thalassemia minor blood smear
red cell abnormalities including hypochromia, microcytosis, basophilic stippling and target cells
44
HbF levels in B-thalassemia minor
normal or slightly increased
45
Why is it important to recognize B-thalassemia minor
superficially resembles hypochromic microcytic anemia of iron deficiency, important for genetic counseling
46
alpha thalassemia caused by...
inherited deletions that result in reduced or absent synthesis of a-globin chains
47
hemoglobin Barts
excess unpaired gamma globin chains that form gamma tetramers, seen in newborns with a-thalassemia
48
HbH
excess B-globin chains form tetramers, seen in older children and adults with a-thalassemia
49
Clinical syndromes of a-thalassemia
silent carrier state, a-thalassemia trait, HbH disease, hydrops fetalis
50
Paroxysmal nocturnal hemoglobinuria
acquired mutations in PIGA gene, essential for membrane associated complement regulatory proteins
51
What type of hemolysis is manifested in PNH?
intravascular hemolysis
52
Leading cause of death in PNH patients
thrombosis
53
CAs developed by PNH syndrome
acute myeloid leukemia, myelodysplastic syndrome
54
What GPI-linked proteins are deficient in patients with PNH?
CD55 (decay-accelerating factor), CD59 (membrane inhibitor of reactive lysis), C8 binding protein
55
Immunohemolytic anemias
caused by abs that bind to red cells leading to premature destruction
56
Warm antibody type immunohemolytic anemia
most common form, idiopathic or caused by drugs; IgG abs active at 37C
57
Cold agglutinin type immunohemolytic anemia
IgM abs bind below 37C, appear following an acute infection (Mycoplasma pneumoniae, EBV, CMV, influenza, HIV) or may be chronic
58
Clinical manifestations of cold agglutinin immunohemolytic anemia
pallor, cyanosis, Raynaud phenomenon
59
Cold hemolysin type immunohemolytic anemia
IgG abs bind below 37C, occurs in children following viral infections
60
Direct Coombs antiglobulin test
patient's red cells mixed with sera containing abs specific for human immunoglobulin or complement, abs will cause agglutination if immunoglobulin or complement is present
61
Indirect Coombs antiglobulin test
patient's serum tested for ability to agglutinate commercially available red cells bearing defined ags, used to characterize ag target and temp dependence of ab
62
Most significant hemolysis caused by trauma to red cells is in seen in individuals with...
cardiac valve prostheses, microangiopathic disorders, shear forces produced by turbulent blood flow and pressure gradients
63
Megaloblastic anemia
impairment of DNA synthesis leading to ineffective hematopoiesis
64
Macrocytic changes/morphology
peripheral blood has pokilocytic red cells, macrocytic red cells, hypersegmented polys, MCHC "normal," low reticulocyte count; bone marrow is hypercellular with bands and dysplastic metamyelocytes
65
Neurologic complications of B12 deficiency
spastic paraparesis, sensory ataxia, severe paresthesias of lower limb.
66
Pernicious anemia
form of megaloblastic anemia caused by autoimmune gastritis that impairs production of IF, required for vitamin B12 uptake
67
Diagnostic values of pernicious anemia
moderate to severe megaloblastic anemia, autoantibodies to IF, leukopenia with hypersegmented granulocytes, low serum B12, elevated serum levels of homocysteine and methylmalonic acid
68
Primary cause of gastric pathology in pernicious anemia
autoreactive T-cell response initiates gastric mucosal injury and triggers formation of autoantibodies
69
B12 deficiency due to loss of pepsin secretion and achlorydria
vitamin B12 not released from proteins in food
70
Vitamin B 12 deficiency due to loss of exocrine pancreatic function
Vitamin B12 not released from haptocorrin-vitaminB12 complexes
71
Folic acid deficiency
megaloblastic anemia due to suppressed DNA synthesis
72
Homocysteine and MMA levels in folate deficiency
homocysteine elevated, MMA normal
73
Homocysteine and MMA levels in vitamin B12 deficiency
homocysteine and MMA elevated
74
Porphyrins
pigments involved in formation of heme
75
Clinical manifestation of porphyria
abnormal reactions to sunlight, staining of teeth, nervous system issues such as referred pain, seizures, hallucinations, and general psychosis
76
Most common nutritional disorder in the world
iron deficiency anemia
77
Most common populations to develop IDA
toddlers, adolescent girls, women of child bearing age
78
What protein transports iron throughout the body?
transferrin
79
What protein stores iron?
ferritin
80
Most functional iron in humans is found in what protein?
hemoglobin
81
Ferritin levels in IDA
<12ug/L
82
Ferritin levels in iron overload
5000 ug/L
83
What molecule regulates iron absorption
hepcidin
84
Most common cause of iron deficiency in the western world
chronic blood loss, like a GI bleed
85
Plummer-Vinson syndrome
esophageal webs, microcytic hypochromic anemia, atrophic glossitis
86
Anemia of chronic disease
impaired red cell production associated with chronic diseases that produce systemic inflammation
87
How does chronic inflammation suppress erythropoiesis?
stimulating hepcidin
88
Ferritin and TIBC in IDA
low ferritin, high TIBC
89
Ferritin and TIBC in anemia of chronic disease
high ferritin, low TIBC
90
Aplastic anemia
exhibits pancytopenia and can be acquired, inherited or triggered by chemical or physical agents
91
Two major etiologies of aplastic anemia
extrinsic, immune-mediated suppression of marrow precursors, stem-cell abnormalities
92
Aplastic anemia morphology
hypocellular bone marrow, fat cells, fibrous stroma, scattered lymphocytes, plasma cells
93
Clinical features of aplastic anemia
pancytopenia, weakness, pallor, dyspnea, thrombocytopenia, neutropenia, reticulopenia
94
Pure red cell aplasia
marrow disorder, only red cell precursors are affected
95
Etiology of pure red cell aplasia
thymoma, large, granular lymphocytic leukemia, drugs, autoimmune disorders, parvovirus infection
96
Myelophthisic anemia
form of marrow failure in which space-occupying lesions replace normal marrow elements most often due to metastatic CAs
97
Polycythemia
abnormally high red cell count, increased Hgb
98
Causes of relative polycythemia
dehydration, Gaisböck syndrome
99
Absolute polycythemia
primary when it results from intrinsic abnormality, secondary when progenitors are responding to a high level of EPO
100
Three main causes of excessive bleeding
increased fragility of vessels, platelet deficiency or dysfunction, derangement of coagulation
101
Primary pathway for initiation of coagulation
extrinsic (TF) pathway
102
Partial thromboplastin time
utilized for detecting abnormalities of blood clotting and to monitor treatment effect of heparin; tests intrinsic and extrinsic pathways; look at factors V, VIII, IX, X, XI, XII, prothrombin, fibrinogen
103
Prothrombin time
tests extrinsic and common clotting pathways; coumadin therapy; look at factors V, VII, X, prothrombin, fibrinogen
104
Bleeding disorders caused by vessel wall abnormalities usually present as....
small hemorrhages in skin and mucous membranes
105
Clinical conditions that cause abnormalities in vessel walls
infections, drug reactions, scurvy and ehlers-danlos, Henoch Schönlein purpura, hereditary hemorrhagic telangiectasia, perivascular amyloidosis
106
Thrombocytopenia
count <100,000/uL, <20,000 associated with spontaneous bleeding
107
PT and PTT in thrombocytopenia
normal, pathways remain intact
108
Thrombocytopenia due to decreased platelet production
results from conditions that depress marrow output or affect megakaryocytes
109
Thrombocytopenia due to decreased platelet survival
destruction caused by deposition of abs or immune complexes on platelets, may also occur via mechanical injury
110
Thrombocytopenia due to sequestration
if spleen is enlarged, it can harbor 80-90% of platelets
111
Thrombocytopenia due to dilution
result from massive transfusions, prolonged blood storage decreases the number of viable platelets
112
Chronic immune thrombocytopenic purpura
caused by autoab mediated destruction of platelets, can be idiopathic or secondary
113
Chronic ITP autoantibodies
directed against platelet membrane glycoproteins, typically IgG abs
114
Major site of platelet removal
spleen
115
Morphological characteristics of chronic ITP
spleen is of normal size, marrow has increased megakaryocytes, abnormally large platelets in peripheral blood
116
Clinical features of Chronic ITP
adult women <40 yo, bleeding into skin and mucosal surfaces, history of easy bruising or nosebleeds, hemorrages into soft tissues; may first present as melena, hematuria ,excessive menstrual flow, subarachnoid hemorrhage, intracerebral hemorrhage
117
Lab findings of chronic ITP
low platelet count, normal or increased megakaryocytes, large platelets in peripheral blood, PT and PTT normal
118
Acute ITP
mainly a disease of childhood, appear abruptly 1-2 weeks after a self-limited viral illness; most will self resolve
119
Drug-induced thrombocytopenia
most common drugs to cause platelet destruction are quinine, quinidine, and vancomycin
120
Type I heparin-induced thrombocytopenia
occurs rapidly after initiation of therapy and generally resolves
121
Type II heparin-induced thrombocytopenia
less common, begins 5-14 days after initiation of therapy; results in severe, sometimes life-threatening venous and arterial thromboses
122
HIV-associated thrombocytopenia
common manifestation of HIV, HIV-infected megakaryocytes (due to CD4 and CXCR4) making them prone to apoptosis, production of autoantibodies also occurs due to B cell hyperplasia
123
Thrombotic microangiopathy
caused by insults that lead to excessive platelet activation and cause the deposition of thrombi in small blood vessels
124
Thrombocytopenic purpura presentation
fever, thrombocytopenia, microangiopathic hemolytic anemia, transient neuro deficits and renal failure
125
Hemolytic-Uremic syndrome presentation
microangiopathic hemolytic anemia and thrombocytopenia, NO neuro sxs, acute renal failure, frequently occurs in children
126
PT and PTT in thrombotic microangiopathies
normal
127
Typical cause of HUS
E. coli strain O157:H7
128
Atypical causes of HUS
alternative complement pathway inhibitor deficiencies
129
Genetic aberration in TTP
deficiency of ADAMTS13
130
Categories of inherited platelet disorders
defects of adhesion, aggregation, secretion
131
Bernard-Soulier syndrome
deficiency of glycoprotein complex Ib-IX, cannot attach to vWF
132
Glanzmann thronbasthenia
failure of platelets to aggregate due to dysfx of glycoprotein IIb-IIIa
133
Causes of disorders of platelet secretion
defective release of certain mediators, storage pool disorders
134
Acquired defects of platelet function
ingestion of aspirin and other NSAIDs, uremia
135
Common bleeding patterns that occur due to coagulation deficiencies
GI and GU tracts, hemarthrosis
136
Hemophilia A deficiency
Factor VIII
137
Hemophilia B deficiency
Factor IX
138
Vitamin K deficiency results in the impaired synthesis of which factors?
II, VII, IX, X, and protein C
139
Major source of factor VIII
sinusoidal endothelial cells and kupfer cells
140
Most common inherited bleeding disorder of humans
von Willebrand disease
141
Type 1 vW disease
autosomal dominant disorder, spectrum of presentations but often mild symptoms
142
Type 2 vW disease
autosomal dominant disorder, qualitative defects in vWF, normal number but missense mutations make it defective
143
Type 3 vW disease
autosomal recessive disorder, low levels of vWF and severe clinical manifestations
144
PTT in Type 1 and Type 3 vW disease
prolonged
145
Inheritance pattern of hemophilia A
X-linked recessive
146
Genetic aberration of most severe hemophilia A
inversion involve X csome that completely abolishes synthesis of factor VIII
147
Hemophilia A symptoms
easy bruising and massive hemorrhage after trauma or operative procedures, hemarthroses, prolonged PTT and normal PT
148
PTT and PT in Hemophilia B
prolonged PTT, normal PT
149
Disseminated Intravascular Coagulation
acute, subacute, or chronic thrombohemorrhagic disorder characterized by excessive activation of coagulation and formation of thrombi in microvasculature of the body
150
Two major mechanisms that trigger DIC
release of tissue factor, widespread injury to endothelial cells
151
Clinical features of DIC
most are obstetric patients, microangiopathic hemolytic anemia, dyspnea, cyanosis, respiratory failure, convulsions, coma, oliguria, acute renal failure
152
Sugar residue on A blood antigen
N-acetylgalactosamine
153
Sugar residue on B blood antigen
galactose
154
Febrile nonhemolytic reaction
fever and chills, mild dyspnea, often occurs within 6 hours of a transfusion
155
Allergic rx in blood transfusion
urticarial reaction, potentially fatal reactions can occur in pts with IgA deficiency
156
Acute hemolytic reaction - blood transfusions
IgM abs against donor red cells that fix complement; fevers, shaking, chills, flank pain rapidly appear; may progress to DIC, shock, acute renal failure, potentially death
157
Delayed hemolytic reaction - blood transfusions
typically caused by IgG abs, induce complement activation and cause severe reactions identical to those reacting to ABO mismatches
158
Transfusion-Related Acute Lung Injury
severe, frequently fatal complication in which factors trigger the activation of neutrophils in lung microvasculature; dramatic onset resp failure during or soon after transfusion, bilateral pulmonary infiltrates, fever, hypotension, hypoxemia
