Hematology Flashcards
1
Q
What is the definition of anemia?
A
A reduction in RBC number or in hgb concentration to a level that is more than two standard deviations below the mean
2
Q
The Hgb is ______ at birth and reaches the physiologic lowest point between _ and _ months of age in the term infant (between _ and _ months in the preterm infant)
A
The Hgb is high at birth and reaches the physiologic lowest point between 3 and 4 months of age in the term infant (between 1 and 2 months in the preterm infant)
3
Q
What is a major constitutent of Hgb during fetal and early postnatal life? When does it disappear?
A
Fetal hemoglobin (Hgb F); Disappears by 6-9 months of age
4
Q
Classificaiton of anemia is based on what two parameters?
A
Mean corpuscular volume
Morphologic appearance of the RBC (size, color, shape)
5
Q
What is the meaning of microcytic, hypochromic anemia?
A
Small, pale RBCs; low MCV
6
Q
Why is the reticulocyte count helpful?
A
Reticulocyte count reflects the number of immature RBCs in circulation; Low reticulocyte counts indicate bone marrow failure or diminished hematopoiesis
7
Q
What are the two most common causes of microcytic hypochromic anemias during childhood?
A
Iron deficiency anemia and ß-thalassemia trait
8
Q
What causes the majority of iron deficiency anemia?
A
Inadequate iron intake
9
Q
In what two age groups is nutritional iron deficiency most common? Why?
A
9-24 months of age: owing to inadequate intake and inadequate iron stores
Adolescent girls: because of poor diet, rapid growth, and loss of iron in menstrual blood
10
Q
What are some clinical features of moderate anemia?
A
- Weakness and fatigue
- Decreased exercise tolerance
- Irritability
- Tachycardia
- Tachypnea
- Anorexia
- Systolic heart murumur
11
Q
What types of occult blood loss can lead to iron deficiency anemia?
A
Secondary to polyps, Meckel’s diverticulum, IBD, PUD, and early digestion of whole cow’s milk (iron-poor) beore age 1
12
Q
Describe the mechanism leading to increased tranferrin in iron deficiency anema?
A
Iron stores disappear first leading to low serum ferritin; As serum iron decreases iron binding capacity increases manifested as increased transferrin and decreased transferrin saturation
13
Q
Why is ferritin not always a reliable marker of iron deficiency anemia?
A
Because ferritin is also an acute-phase reactant, it may be increased in infection, disease states, and stress
14
Q
In management of iron deficiency anemia, iron is given with ______ to enhance intestinal absorption
A
Vitamin C (orange juice)
15
Q
What is the major Hgb in RBCs? What is it made up of?
A
Hemoglobin A1; A tetramer of two α chains and two ß chians
16
Q
α-thalassemia results from…
ß-thalassemia results from…
A
Defective α-globin chain synthesis
Defective ß-globin chain synthesis
17
Q
Why do thalessemias lead to increased size of bones in the face and skull?
A
Both types of thalassemia result in hemolysis that elads to increased bone marrow activity; as marrow activity increases, the marrow spaces enlarge, increasing the size of bones
18
Q
What are the four disease states of α-thalassemia?
A
- Silent carrier: only one α-globin gene is deleted
- α-thalasssemia minor: Two α-globin genes are deleted; patients have mild anemia
- Hgb H disease (Bart’s): Three α-globin genes are deleted and patients have severe anemia at birth with an an elevated Hgb Bart’s
- Fetal hydrops: Four α-globin genes are deleted; infant dies in utero
19
Q
What is ß-thalassemia major?
A
May be caused by either total absence of the ß-globin chains or deficient ß-globin chain production
20
Q
α-thalassemia is most common in…
ß-thalassemia is most common in
A
α-thalassemia: Southeast Asians
ß-thalassemia: Mediterranean background
21
Q
What are the clinical features of ß-thalassemia?
A
- Hemolytic anemia beginning in infancy
- Hepatosplenomegaly
- Bone marrow hyperplasia (thalassemia facies)
- Delayed growth and puberty may be present
22
Q
What are the laboratory findings of ß-thalassemia?
A
- Severe hypochromia and microcytosis
- Target cells and poikilocytes
- Elevated unconjugated bilirubin, serum iron, and LDH
- Low or absent Hgb A and elevated Hgb F
23
Q
How does ß-thalassemia lead to hemochromatosis? How can this be delayed?
A
Hemochromatosis is caused by increased iron absorption from the intestine and from iron transfused in transfused RBCs; Chelation of iron with deferoxamine promotes iron excretion and may help delay hemochromatosis
24
Q
How do you treat ß-thalassemia minor?
What misdiagnosis can lead to harmful treatment of ß-thalassemia minor?
A
No treatment is required
Iron deficiency anemia (may be treated inappropriately with iron when iron level in ß-thalassemia minor is normal or elevated)
25
What leads to ring sideroblasts in sideroblastic anemia?
Ring sideroblasts result from the accumulation of iron in the mitochondria of RBC precursors
26
What aside from iron deficiency anemia, thalassemia and sideroblastic anemia can cause microcytic hypochromic anemia?
Lead toxicity and anemia of chronic disease
27
Macrocytic (megaloblastic) anemias are characterized by MCV \> \_\_
What are the two major causes in children?
95
Folic acid and Vitamin B12 deficiencies
28
What can lead to folic acid deficiency?
* Diet lacking uncooked fresh fruits and vegetables
* Exclusive feedings with goat's milk
* Decreased intestinal absorption due to celiac disease, enteritis, chron's disease...
29
What medications can lead to folic acid deficiency?
Anticonvulsants and oral contraceptives
30
To be absorbed, dietary vitamin B12 must first combine with _______ secreted by _____ \_\_\_\_\_\_\_ cells; Absorption occurs in the _______ \_\_\_\_\_\_
To be absorbed, dietary vitamin B12 must first combine with **glycoprotein** (intrinsic factor) secreted by **gastric pariet**al cells; Absorption occurs in the **terminal ileum**
31
What is the management of folic acid deficiency?
What is the management of vitamin B12 deficiency?
Folic acid: Dietary folic acid
B12: Monthly intramuscular vitamin B12 injections
32
What are some common causes of normocytic, normochromic anemias?
Hemolytic anemias, red cell aplasias, and sickle cell anemia
33
How are normocytic, normochromic anemias differentiated (name the lab and the significance of the lab values)?
Reticulocyte count
* Low reticuloyte count: Reflects bone marrow suppression or failure and is consistent with red cell aplsias, pancytopenia, and malignancy
* High reticulocyte count: reflects bone marrow production of RBCs as seen in hemolytic anemias and sickle cell anemia
34
What are the intrinsic hemolytic anemias that cause normocytic normochromic anemia?
* Hereditary spherocytosis
* Hereditary eliptocytosis
* Glycolytic enzyme defects
* Pyruvate kinase deficiency
* Glucose-6-phosphate dehydrogenase deficiency
35
WHat is the most common inherited abnormality of the RBC membrane?
Hereditary spherocytosis
36
What protein is abnormal in hereditary spherocytosis? What is the inheritance patterns?
Abnormality of the structural RBC membrane protein spectrin
Usually autosomal dominant
37
What are the signs and symptoms of hereditary spherocytosis?
* Splenomegaly by 2-3 years of age
* Pigmentary gallstones
* Aplastic crises (associated with parvovirus infection)
* Jaundice and anemia
38
What studies can be used to diagnose hereditary spherocytosis?
Blood smear and osmotic fragility studies (spherocytes are more fragile)
39
What "cures" hereditary spherocytosis?
Why is this procedure delayed until after 5 years of age?
Splenectomy
Delayed to decreased the incidence of invasive disease caused by encapsulated bacteria
40
Hereditary elliptocytosis is autosomal _______ defect in the structure of \_\_\_\_\_\_\_
dominant; spectrin
41
What are the symptoms of patients with hereditary elliptocytosis?
Majority of patients are asymptomatic
42
Pyruvate kinase deficiency is an autosomal _______ disorder
recessive
43
What becomes depleted in PK deficiency? What is there decreased production of?
ATP depletion
Decreased production of PK isoenzyme
44
What is seen on blood smear of patients with Pyruvate kinase (PK) deficiency?
Polychromatic RBCs
45
What is the management for pyruvate kinase deficiency?
Transfusions and splenectomy for severe disease
46
What is the msot common RBC enzymatic defect?
Glucose-6-phosphate dehydrogenase deficiency
47
What is the pathosphysiology of G6PD deficiency and what triggers its symptoms?
G6PD enzyme is critical for protecting the RBC from oxidative stress; deficiency results in RBC damage when RBC exposed to oxidants
Triggers: Infection, Fava beans, sulfa drugs
48
\_\_\_\_\_\_\_ is not beneficial in G6PD deficiency
splenectomy
49
What are some extrinsic causes of hemolytic anemia?
* Autoimmune hemolytic anemia
* Alloimmune hemolytic anemia
* Microangiopathic hemolytic anemia
50
What is autoimmune hemolytic anemia (AIHA)?
Occurs when antibodies are misdirected against the RBCs
51
What are the two types of AIHA?
* Primary: Generally idiopathic in which no underlying disease is identified; viral infections and drugs may be causal
* Secondary: associated with udnerlying disease process, such as lymphoma, SLE, or immunodeficiency disease
52
What are the clinical features of fulminant acute type AIHA? In what population does this occur?
Preceded by respiratory infection; features include acute onset of pallor, jaundice, hemoglobinuria, and splenomegaly
Occurs in infants and young children; complete recovery is expected
53
What are the laboratory findings in AIHA?
Severe anemia, spherocytes on blood smear, prominent reticulocytosis, and leukocytosis; **Direct coombs test is positive**
54
What is the management of AIHA?
* Transfusions may provide transient benefit
* Corticosteroids are used for severe anemia
55
Alloimmune hemolytic commonly involves newborn __ and ___ hemolytic diseases
Rh and ABO
56
When does Rh disease occur?
Rh hemolytic disese occurs when the mother (who has no Rh antigen) produces antibodies to the Rh antigen on her fetus's RBCs; In subsequent pregnancies antibodies pass from the mother to the fetus causing hemolysis and hydrops fetalis
57
In Rh hemolytic disease, what test is strongly positive?
Direct Coombs
58
In ABO hemolytic disease, what are the results and strength of a direct coombs test?
Weakly positive
59
What is microangiopathic hemolytic anemia?
This form of anemia results from mechanical damage to RBCs caused by passage through an injured vascular endothelium
60
What are some causes of microangiopathic hemolytic anemia?
Hypertension, hemolytic uremic syndrome, artificial heart valves, a giant hemangioma, and DIC
61
What are the laboratory findings in microhangiopathic hemolytic anemia?
Studies show RBC fragmentation seen as "burr/helmet" cells, "target" cells, and irregularly shaped cells on blood smear, and thrombocytpenia
62
What is the genetic cause of Sickle cell (SS) disease?
SS disease is caused by a single amino acid substitution of valine for gluamic acid on position 6 of the ß-globin chain of Hgb
63
What effect on the RBC occurs with the mutation in SS disease?
Mutation results in polymerization of Hgb within the RBC membrane when the RBC is exposed to low oxygen or acidosis
64
What is the difference between SS disease and SS trait?
SS disease: result of having 2 genes for Hgb S
SS trait: result of having only one gene for Hgb S; patients are usually asymptomatic without anemia
65
How is SS disease diagnosed?
Usually diagnosed at brth through state newborn screening programs; Hgb Electrophoresis is a highly sensitive and specific test
66
When are there clinical features of SS disease?
Not until after Hgb F declines (protective until 6 months of age)
67
What types of crieses occur in SS disease?
* Vasoocclusive crisis
* Painful bone crisis
* Acute abdominal crisis (sickling in mesenteric artery)
* Stroke
* Priapism
* Acute chest syndrome (pulmonary infiltrate)
* Sequestration crisis (accumulation of blood in spleen)
* Aplastic crisis (parvovirus B19 or other infection)
* Hyperhemolytic crisis
68
How is a painful bone crisis managed?
* Pain control
* IV fluids at 1.5-2x maintenance
* Incentive spirometry to decrease risk of Acute chest syndrome
* May respond to partial exchange transfusion
69
Which crises is treated with splenectomy?
Which are treated with supportive care and transfusion of RBCs?
Splenectomy: Sequestration crisis
Supportive care + RBCs: Aplastic crisis and hyperhemolytic crisis (rapid hemolysis)
70
What is the leading cause of death from SS disease?
Infection
71
What type of bacteria are patients with SS at risk for? Why?
Infection is a result of decreased splenic function so patients are at risk for infection with encapsulated bacteria (Hib, Strep pneumo, Salmonella, N. meningitidis)
72
What other disease associated with SS disease may mimic a painful bone crisis? What is the most common cause?
Osteomyelitis, most commonly caused by salmonella (although S. Aureus may also cause osteomylitis)
73
What is seen on blood smear in SS disease?
Sickled cells, target cells, Howell-Jolly bodies
74
What increases Hgb F and has been shown to decrease vasoocclusive crises in SS disease?
Hydroxyurea
75
What is started in SS disease patients within the first few months of life and why?
Daily oral penicillin prophylaxis to decrease the risk of S. pneumoniae infection
76
What follow up is recommended beginning at 2 years of age for SS disease patients and why?
Serial transcranial Doppler ultrasound or magnetic resonance angiography to identify patients at risk for stroke
77
What are red blood cell aplasias?
A group of congenital or acquired blood disorders characterized by anemia, reticulocytopenia, and a paucity of RBC precursors in the bone marrow
78
What are the three most common red blood cell aplasias?
* Congenital hypoplastic anemia (Diamond-Blackfan anemia)
* Transient erythroblastopenia of childhood
* Parvovirus B19 associated red cell aplasia
79
Name the RBC aplasia:
Anemia within the first year of life, rapid onset
One fourth to one third have physical findings: craniofacial, renal, cardiac anomalies
Short stature; triphalangeal thumbs
Diamond Blackfan anemia
80
What is Fanconi anemia? What is the inheritance pattern?
Congenital aplastic anemia; Autosomal recessive
81
When is the onset of bone marrow failure in fanconi anemia? How does it present?
Mean age of 7 years; typical presentation is with ecchymosis and petechiae
82
What are the skeletal abnormalities associated with Fanconi anemia?
Short stature in almost all patients with the absence of hypoplasia or the thumb and radius
83
What laboratory values are seen in Fanconi anemia?
* Pancytopenia
* RBC macrocytosis
* Low reticulocyte count
* Elevated Hgb F
* Bone marrow hypocellularity
84
What is the management for Fanconi anemia?
Treatment includes transfusions of RBCs and platelets as needed, and bone marrow transplant from an HLA-compatible donor
85
What is polycythemia?
An increase in RBCs relative to total blood volume or hematocrit \> 60%
86
What is polycythemia vera?
A malignancy involving the RBC precursor that occurs during childhood
87
What is the most common cause of appropriate polycythemia in childhood? What can cause Inappropriate polycythemia?
Appropriate: Hypoxemia as a result of cyanotic congenital heart disease
Inappropriate: Benign and malignant tumors of the kidney, cerebellum, ovary, liver, and adrenal gland; excess hormone production and kidney abnormalities
88
What is the management for polycythemia?
Treatment of underlying cause; phlebotomy is also used to keep Hct \< 60%
89
Possible complications of polycythemia are...
Thrombosis and bleeding
90
The function of what three elements are required for hemostasis?
Blood vessels, platelets, and soluble cloting factors
91
What clinical features suggest abnormal hemostasis in children?
* Cutaneous bleeding (ecchymoses)
* Spontaneous epistaxis
* Prolonged bleeding after simple surgical procedures
* Recurrent hemarthroses
* Deep venous thrombosis
92
What are the diagnostic studies for evaluation of clotting abnormalities?
* CBC
* Platelet count
* Blood smear
* aPTT and PT
* Platelet function assay (less common)
93
What are two inherited disorders involving factor VIII of the clotting cascade?
Hemophilia A and von Willebrand's disease
94
What is the difference between hemophilia A and von Wilebrand's disease?
Hemophilia A: Defect in factor VIII procoagulant activity; platelet function is normal
von Willebrand's disease: Factor VIII procoagulant activity is variable but platelet function is defective because of a decrease or defect in vW factor which is necessary for platelet adhesion to blood vessel walls
95
What is the inheritance pattern of hemophilia A?
X-linked
96
What are the hallmark clinical features of Hemophila A? What are the features of severe, moderate, and mild forms of the disease?
* Hallmarks: Hemarthroses and deep soft tissue bleeding
* Severe: spontaneous bleeding
* Moderate: Bleeding only with trauma
* Mild: Bleeding only after surgery or major trauma
97
What is the most dreaded complication of hemophila A?
CNS bleeding (usually the result of head trauma)
98
What lab findings are seen in hemophilia A?
* **Prolonged aPTT**
* Normal PT, bleeding time, platelet count, and platelet function assay
* **Low factor VIII protein activity**
99
What is the management for hemophilia A?
Treatment includes prevention of trauma and replacement of factor VIII
Desmopressin acetate (DDAVP) may cause the release of stored factor VIII from the patients
100
What is the most common hereditary bleeding disorder?
What is it's inheritance pattern?
von Willebrand's disease
Autosomal dominant
101
What are the 3 categories of von Wilebrand's disease?
* Type I (classic type): Mild quantitative deficiencies of vWf and factor VIII protein - Most common form
* Type II: Qualitative abnormalitiy in vWf
* Type III: Absence of vWf; the most severe type
102
What are the clinical features of von Wilebrand's disease?
* Most patients have mild to moderate bleeding involving mucocutaneous surfaces
* Epistaxis, menorrhagia, bruising, and bleeding after dental extraction or tonsillectomy
* Hemarthroses are **unusual**
103
How is von Willebrand's disease diagnosed?
* Prolonged bleeding time and aPTT may be present but not always
* Quantitative assay for vWf antigen and activity (ristocetin cofactor assay)
104
What is the management for von Wilebrand's disease?
DDAVP - most useful in type I disease and is sometimes effective in type II disease
Cryoprecitpitate (contains intact vWf) - used for serious bleeding, extensive surgeries, or for type III disease
105
What is the management for hemophilia B (Christmas tree disease)?
Factor IX replacement
106
What clotting factors require vitamin K?
Factors II, VII, IX, and X and proteins C and S
107
What can lead to vitamin K deficiency?
* Dietary deficiency if in early infancy
* Pancreatic insufficiency
* Biliary obstruction
* Prolonged diarrhea
* Medications
* Hemorrhagic disease of the newborn
108
What are some clinical manifestations of vitamin K deficiency?
* Bruising
* Oozing from skin puncture wounds
* Bleeding into organs
109
What is the management for vitamin K deficiency?
* Administration of vitamin K
* Intramuscular administration of vitamin K after birth prevents hemorrhagic disease of the newborn
* FFP in severe disease
110
What laboratory findings are seen in DIC and liver disease?
* Prolonged PT and aPTT
* Thrombocytopenia
* Elevated fibrin degradation products
111
What is DIC?
A group of laboratory and clinical features indicative of both accelerated fibrogenesis and fibrinolysis; the initiating event is clotting that leads to consumption of procoagulant factors and resultant hemorrhage
112
What is the management for DIC?
Therapy includes treatment of the underlying cause and transfusions of fibrinogen, FFP, and platelets as needed (same for liver disease); Heparin may be useful if underlying defect cannot be corrected
113
What is Henoch-Schonlein purpura?
An IgA-mediated vasculitis that present with palpable purpura on the lower extremities and buttocks, renal insufficiency, arthritis, and abdominal pain; platelet count normal
114
Hereditary hemorrhagic telangiectasia is an autosomal ________ disorder characterized by....
dominant; locally dilated and tortuous veins and capillaries of the skin and mucous membranes
115
What is deficient in scurvy?
Vitamin C
116
What is thrombocytopenia?
Decreased number of platelets, generally \< 100,000; **most common cause of bleding**
117
What are some congenital disorders leading to decreased platelet function?
* Wiskott-Aldrich syndrome
* Thrombocytopenia-absent radius syndrome (TAR)
118
What X-linked disorder is characterized by thrombocytopenia with unusually small platelets, eczema, and defects in T-and B-cell immunity?
Wiskott-Aldrich syndrome
119
What is TAR (thrombocytopenia-absent radius) syndrome?
Autosomal recessive disorder characterized by thrombocytopenia and limb abnormalities
120
What is the most common acquired platelet abnormality in childhood?
Immune thrombocytopenic purpura (ITP)
121
What are the causes of ITP? Which is most common?
ITP may be viral, drug induced, or idiopathic (most common)
122
What are the clinical features of ITP?
Illness typically occurs 1-4 weeks after a viral infection
Begins abruptly with cutaneous bleeding or mucous membrane bleeding
Internal bleeding into the brain, kidneys, or GI tract may occur but is rare
123
What is seen on blood smear in ITP?
Few large "sticky" platelets
124
In ITP, very low platelet counts (\<20,000) or active bleeding warrant treatment with...
What is the second line agent?
IVIG or corticosteroids
Anti-D immunoglobulin is a second-line agent that may aslo be effective
125
What percentage of ITP cases resolve spontaneously?
How long must ITP last before it is considered chronic ITP?
70-80% resolve spontaneously
Chronic ITP is diagnosed if ITP lasts \> 6 months
126
What is passive autoimmune thrombocytopenia?
Occurs when **the mother has ITP**, and antibodies against her own platelets cross the placenta and destroy the fetus's platelets
127
What is isoimmune thrombocytopenia?
Occurs when the mother produces antibodies against her fetus's platelets as a result of sensitization to an antigen that her own platelets lack
128
In Kasabach-Merrit syndrome, large __________ may sequester and destroy platelets
hemangiomas
129
What congenital disorders cause **qualitative** platelet dysfunction? What are their inheritance patterns?
Glanzmann's thrombasthenia and Bernard-Soulier syndrome
Both are autosomal recessive
130
What is the difference between Glanzmann's thrombasthenia and Bernard-Soulier syndrome?
GT: Diminished ability of platelets to aggregate and clot as a result of deficient adhesive glycoprotein IIb/IIIa on the platelet cell membrane
BS: Decreased platelet adhesion as a result of absence of platelet membrane glycoproteins
131
What are the types of protein C deficiency?
Homozygous: No protein C activity and detection shortly after birth; **Pulpura fulminans**, a nonthrombocytopenic purpura is often the inital presentation
Heterozygous: Present later with deep venous or CNS thrombosis
132
What is the treatment for protein C deficiency
Treatment may include heparin, FFP, and warfarin; Purified concentrates of protein C have been used
133
What other inherited coagulation abnormalities present similarly to protein C deficiency?
Protein S, antithrombin III, and factor V Leiden deficiencies
134
What are the absolute neutrophil counts for mild, moderate and severe neutropenia?
* Mild: ANC of 1,000-1,500
* Moderate: 500-1,000
* Severe: ANC \< 500
135
Risk of ______ is directly related to ANC
infection
136
What types of infections can result from severe neutropenia?
S. aureus and gram-negative bacteria (Klebsiella, Serratia, Escheria coli, and Pseudomonas) are typical organisms
137
What is the most common cause of neutropenia during childhood?
Infections
138
What is chronic benigin neutropenia of childhood (CBN)?
A common cause of neutropenia in children younger than 4 years of age; refers to a group of acquired and inherited disorders with noncyclic neutropenia as the only abnormality
139
What is shown in lab studies of CBN?
Studies who low ANC with a normal or slightly low WBC; bone marrow demonstrates immature neutrophil precursors
140
What is severe congenital agranulocytosis (Kostmann syndrome?)
An autosomal recessive disorder with frequent and life-threatening pyogenic bacterial infections beginning in infancy; ANC is usually \< 300
141
What are the clinical features of cyclic neutropenia?
Cyclic alterations in neutrophil counts results in regular episodes of neutropenia with resultant infections
142
How is cyclic neutropenia diagnosed? How long are cycles?
Diagnosis is made by obtaining serial neutrophil counts during a 2-3 month period
Cycles last an average of 21 days in 70% of patients
143
What genetic syndromes can cause neutropenia?
* Chediak-Higashi syndrome - occulocutaneous albinism and blond or brown hair with silver streaks
* Cartilage-hair hypoplasia syndrome - short stature, immunodeficiency, fine hair
144
What is Schwachman-Diamond syndrome?
Characterized by exocrine pancreatic insufficiency with malabsorption and short stature caused by metaphyseal chondrodysplasia
145
Describe autoimmune neutropenia and isoimmune neutropenia
Autoimmune: A disorder in which antineutrophil antibodies are produced in response to infection, drugs, SLE, and juvenile rheumatoid arthritis
Isoimmune: Passive transfer of antineutrophil antibodies from the mother to her fetus after maternal sensitization by antigens on the fetal neutrophils
