Hematopathology & Hematology Flashcards
Which AML does FLT3-ITD mutation play a prognostic role?
AML with t(6;9)
Aggressive disease with poor prognosis
Myelomonocytic differentiation
What is true regarding genetic abnormalities in T-ALL?
• ~1/3 of T-ALL have translocations involving the TCR
– 14q11.2—alpha and delta
– 7q35—beta
– 7p14-15—gamma
*most issues involve Chr 14 or 7 because this is where the TCR is located
What are the three patterns of HIV related lymphadenopathy?
• Follicular hyperplasia
– Irregular GCs, naked GCs, follicle lysis, monocytoid Bcells
*will see follicles throughout the LN and they will be large with weird shapes
• Follicular involution
– Regressed GCs, thin mantle zones, histiocytes,
immunoblasts
*often mistaken for lymphoma but work up will show these are not monoclonal B cells
• Lymphocyte depletion
– Small lymph nodes, no follicles, increased histiocytes, follicular dendritic cells, erythrophagocytosis
Which type of bacteremia can cause increased sulfhemoglobin?
Clostridium perfringens bacteremia
What is the pattern of different hemoglobins on alkaline electrophoresis?
HbA α2β2 globin chains, 97% in normal adult
Hb A2 α2δ2 globin chains, 3% in normal adult
HbF α2ϒ2 globin chains, not in normal adult
Alkaline gel run on cellulose acetate at pH 8.5 runs from neg to pos
From cathode (+) to anode (-), remember “A Frozen Section Conundrum”
Fast moving (next to +): N, I, H, Barts
A
F
S, D, G, Lepore, India and Hasharon
A2, C, E, O
Slow moving (next to -): Constant spring
What is the anomaly seen here and what word should you associate it with?
Alder Reilly Anomaly
Patients lack lysozymal enzymes to break down
mucopolysaccharides (see this word and think this anomaly)
– Mucopolysaccharidoses
(Hurlers, Hunters syndromes)
Dense metachromatic azurophilic granules in all
WBCs, normal neutrophil function, autosomal recessive
Based on this cell, what type of Hodgkin’s lymphoma is this and what is this cell called?
Nodular sclerosis with the characteristic lacunar cell
A lacunar cell is a formalin fixation induced retraction artifact
Synctial NS variant is an aggressive form of CHL that often presents at a high stage with bulky mediastinal disease composed of sheets of RS cells and lacunar cells; may undergo focal necrosis
What are the good and bad cytogenetic prognostic factors in MDS?
- Good: Normal, -Y, del(5q), del(20q), TET2 mutations: Acquired somatic mutation, Favorable prognosis
- Intermediate: Other abnormalities
- Poor: Complex (>3 abnormalities) or chr 7 abnormalities
Most common cytogenetic abn: complex karyotype (2 or more clonal abnormalities)
2nd most common: 7 or 7q-
3rd most common: isolated 5q
What are the lab findings with mast cell neoplasms?
- Elevated serum tryptase
- Elevated urine N-methylhistamine (NMH)
- Elevated urine prostaglandin D2 (PGD2)
- Histamine levels elevated but nonspecific; hypereosinophilic states also raise histamine
Unlike benign mast cells, express CD25 and CD2 with diminished expression of CD117
Expression of CD25 correlates with the presence of CKIT mutation (most commonly D816V)
What is the percentage of hemoglobins seen in sickle cell trait?
- 35-45% HbS (if not in this range, something else with it!)
- 50-65% HbA
- <3% HbA2
What are the three types of hereditary elliptocytosis?
HE is AD disease with mutation in spectrin alpha chain so there is a problem with horizontal interactions
1) Common type (most commonly in African Americans)
*Hereditary pyropoikilocytosis is the transient neonatal expression of HE
2) Spherocytic type (double heterozygosity of HS and HE)
3) Stomatocytic type
Common in southeast Asia and caused by specific band 3 protein defect so there is a defect in sodium/potassium permeability of the RBC membrane (confers protection against P vivax)
Also think about Rh null phenotype if you see stomatocytes!
What constitutional hematopoietic deficiency is caused by:
ELA2 mutations (neutrophil elastase) located at 19p12
Is responsible for TWO syndromes
Cyclic neutropenia (benign familial neutropenia)
Neutrophil count varies from normal to essentially none in a roughly 21 day cycle
Kostmann Syndrome
Autosomal dominant, may present in neonatal period with omphalitis but progresses to pancytopenia and or leukemia
They can ask you to identify stain in a normal lymph node based on pattern. What stain is this in a normal lymph node?
Bcl6
What is the grading system for follicular lymphoma?
2008 WHO does not require distinction of grade 1 and 2, considered together to be low grade
- Grade 1: 0-5 centroblasts/hpf
- Grade 2: 6-15 centroblasts/hpf
- Grade 3: >15 centroblasts/hpf
Grade 3A = some residual centrocytes
Grade 3B = no residual centrocytes
*Ki67 may be used as an adjunct in grading (<20% in grades 1-2, >20% in grade 3
What is the diagnostic criteria for diagnosing Acute Myelomonocytic Leukemia?
Both myeloid & monocyte precursors
- >20% blasts
- Blast count includes promonocytes
- >20% neutrophils and myeloid precursors
- >20% monocytes and promonocytes
What is the molecular alteration seen in hepatosplenic T cell lymphoma?
Isochromosome 7q
Two variants of hepatosplenic T cell lymphomas are known:
Alpha-beta variant expresses T cell receptors alpha-beta and shows f_emale preponderance_ (younger than 13 yrs. and older than 50 yrs).
Gamma-delta variant expresses T cell receptor gamma-delta chains and is more common in young males. Both variants carry poor prognosis.
What are the EBV positive large B cell neoplasms?
Plasmablastic lymphoma–found in HIV people MOSTLY oral cavity and if arising from multicentric Castleman’s, it is also HHV8 positive. Negative for CD56 in contrast to plasmacytoma.
Primary effusion lymphoma–co infection with HHV8; usually immunocompromised
Lymphomatoid granulomatosis
DLBCL associated with chronic inflammation–classically arising in longstanding pyothorax
EBV+ DLBCL of the elderly–usually extranodal; by definition >50 years old
EBV+ DLBCL, NOS–usually in immunodeficiency; if no immunodeficiency by definition under 50yrs old
What is Gaisbock syndrome?
Spurious erythrocytosis of dehydration
What RBC morphologic finding is seen in pyrimidine 5’ nucleotidase deficiency?
Basophilic stippling
Autosomal recessive disorder characterized by chronic hemolytic anemia associated with prominent RBC basophilic stippling, which is very useful in diagnosing this enzyme deficiency. P5’N-1 deficiency is also implicated in the anemia of lead poisoning and thalassemia with basophilic stippling.
What is Felty syndrome?
Triad of RA, splenomegaly and neutropenia
What is the technique for how hemoglobin is usually measured?
Commonly measured by cyanohemoglobin/hemoglobin cyanide (HiCN) method
- Lysed blood dissolved in solution of potassium ferricyanide and potassium cyanide
- Oxidizes Hb to hemiglobin cyanide (HiCN)
- Concentration of HiCN measured by spectrophotometry
- Absorbance at 540nm reflects the amount of Hb
Detects all forms of Hb except sulfhemoglobin (SHb)
Lipidemia and paraproteinemia can falsely raise the hemoglobin measurement
BQ! What additional cytogenetic abnormalities are commonly seen in CML, BLAST PHASE?
+ Ph, i(17q), +8, +19
BQ SLIDE!
Name this lesion of the spleen.
Littoral Cell Angioma
In therapy related AML, which agents cause:
- AML 2-3 years after txmt
- Not assoc with MDS
- Translocation with 11q23 (MLL) or 21q22 (RUNX1)
- Better response to therapy
- Often monocytic
Topoisomerase II inhibitors
• Epipodophillotoxins, anthracyclins
What is the formula to calculate MCHC?
MCHC = (Hgb/Hct) x 100
What are the acute leukemias that have BETTER prognosis?
- t(15;17) PML/RARalpha
- t(8;21) RUNX1/RUNX1T1–can aberrantly express CD19
- inv16 MYH11/CBFbeta–increased abnormal eos
If you see these genetic abnormalities, you can call acute leukemia even if there are less than 20% blasts
1) What disease causes the finding seen and is due to a defect in lysosome formation which causes decreased phagocytosis and
defective microtubule polymerization?
2) What gene in mutated in this disease?
3) What are the manifestations of this disease?
1) Chediak-Higashi Syndrome
2) CHS1 (LYST) gene mutations which leads to defect in lysosome formation which causes decreased phagocytosis and defective microtubule polymerization
3) Defect in cells with granules
- Abnormal WBC & LGL cause infections
- Melanosomes cause occulocutaneous albinism
- Neurons cause neuropathy
- Platelets cause bleeding
- Accelerated phase, hemophagocytic-like syndrome triggered by viral infection (EBV)
-
PB and BM with large WBC inclusions
- Made of primary and secondary granules
A hemoglobin electrophoresis with HbS, F and A2 has two possible causes. What are they?
1) Combined sickle cell and hereditary persistence of fetal hemoglobin (clinically mild)
2) Combined sickle cell and beta thal (clinically severe)
What is the most common structural abnormality in B-ALL?
t(9;22)
Unfavorable finding
190kd most common
What type of tetramers form in alpha thal and beta thal?
Alpha thal: β4 (HbH) and ϒ4 (HbBarts) tetramers form
Beta thal: α4 tetramers form
What is the pattern of different hemoglobins on acid electrophoresis?
HbA α2β2 globin chains, 97% in normal adult
Hb A2 α2δ2 globin chains, 3% in normal adult
HbF α2ϒ2 globin chains, not in normal adult
Acid gel run on citrate agar at pH 6.0 runs from middle out both directions but remember from cathode (+) to anode (-), remember “Call Surgeon Ask Forgiveness”
![](https://s3.amazonaws.com/brainscape-prod/system/cm/255/676/254/a_image_thumb.jpg?1464210778)
O is in the center of the gel
C
S
O
A, A2, D, G, E, Lepore, N, I, H
F, Barts
What is the formula for calculating MCV?
MCV = Hct x 10/RBC
What leukemia is commonly associated with leukemia cutis often described as “blueberry muffin babies”?
Congenital acute leukemia
Defined as acute leukemia presenting before the age of 4 weeks
Must be distinguished from transient myeloproliferative disorder and leukemoid reaction
Most commonly myeloblastic (65%)
~10% have abnormalities of 11q23 (MLL gene)
What autosomal recessive disorder is characterized by severe thrombocytopenia in neonates secondary to absent megakaryocytes in marrow? What is the mutation?
Congenital amegakaryocytic thrombocytopenia (CAMT)
Mutation of the thrombopoietin receptor (MPL) gene
What translocation is associated with B-ALL that is CD10 negative and CD15 positive?
t(4;11)
This is the MLL translocation on 11q23 and is very characteristic so need to know for boards!
Usually seen in infants
It is CD10 neg, CD15 pos, POOR prognosis and an association with TOPOISOMERASE INHIBITORS
MLL translocations can occur in AML as well
FLT3+
What are some labs values that are elevated in iron deficiency anemia (other than the usual) that might be helpful to know for boards? Also what is the GOLD STANDARD for dx IDA?
Increased labs:
Serum soluble transferrin receptor (SSTR)
*also elevated in erythroid hyperplasia caused by hemolytic anemia, hemorrhage or polycythemia
Zinc protoporphyrin (ZPP)
Free erythrocyte protoporphyrin (FEP)
*Both ZPP and FEP also elevated in lead poisoning and anemia of chronic disease
Gold Standard: Bone marrow biopsy
According to Osler lecture, the boards like to show a gross photo of this spleen. What is this?
CLL/SLL
CLL/SLL and large granular cell lymphomas grow in miliary pattern in spleen (white pulp)
What marker in flow cytometry can be used to detect hereditary spherocytosis?
eosin-5-maleimade
*HS is AD disease with affected ANK1 (ankyrin) so there is a problem with vertical interactions
Increased MCHC
Which hemoglobinopathy has thalassemic red cell indices and results from mutation in the alpha globin gene stop codon which producing an abnormally long transcript that is easily degraded?
Hb Constant spring
*slow moving Hb that is by the negative end in alkaline gel
What is this structure made of?
Ribosomes/RNA
showing basophilic stippling
What are the variant translocations in APML that are usually resistant to ATRA?
t(5;17)(q23;q12)
• 5 – nucleophosmin gene
t(11;17)(q13;q21)
• 11- nuclear matrix association gene
t(11;17)(q23;q21)
• 11 – ZBTB16 (previously PLZF)
What is the expression of Bcl2 on germinal center B cells in follicular lymphoma due to?
BCL2-IGH translocation which is t(14;18)
What lymphoma characteristically involves young men with hepatosplenomegaly and neoplastic cells are most commonly gamma/delta T cells?
Hepatosplenic T cell lymphoma
sinusoidal involvement of neoplastic T cells, doesn’t form mass
Usually negative for both CD4 and CD8
Iso7q (non specific also seen in NK/T CL and ALCL) and Trisomy 8
Pics show sinusoids of liver and red pulp of spleen involved by malignant T cells
What is the most common enzyme deficiency in hereditary erythrocyte disorders of the glycolytic pathway?
Pyruvate Kinase Deficiency–ECHINOCYTES (BURR CELLS)
Impaired Embden Hofmeyer pathway
– Cannot make ATP, NAD, but increased 2,3 DPG, so there is good O2
carrying
– Fluorescent spot test, screening test
– Quantitative pyruvate kinase assay, confirmatory test
– Autosomal recessive
Many MALT lymphomas have an antigenic stimulation. What infectious etiologies are associated with the following MALTs?
1) Gastric MALT
2) Ocular MALT
3) Immunoproliferative Small Intestine Disease (IPSID)–alpha chain disease)
4) Cutaneous MALT
5) Salivary MALT
6) Thyroid MALT
7) Splenic MZL
1) Helicobacter pylori
2) Chlamydophila psittaci
3) Campylobacter jejuni
4) Borrelia burgdorferi
5) Sjogren’s disease
6) Hashimoto’s
7) Hepatitis C
BQ! What hemoglobinopathy should you think of if you have thalassemic indices, increased HbF, and ~15% HbS on alkaline gel?
Hemoglobin Lepore
*actual HbS is rarely present in that low of a quantity so think about Lepore
Result of fusion between β and δ chains
What hemoglonins can a co-oximeter measure?
4 wavelengths
Can directly measure:
Carboxyhemoglobin (HbCO)–ABG and pulse ox can’t detect
Methemoglobin (Hi)–ABG and pulse ox can’t detect
Oxyhemoglobin
Deoxyhemoglobin
They can ask you to identify stain in a normal lymph node based on pattern. What stain is this in a normal lymph node?
CD10
What AML translocation is this:
- DEK-NUP214
- Basophilia and multilineage dysplasia
- Poor prognosis
t(6;9) DEK/NUP214
Lymphoproliferative process that presents as spontaneously regressing papules typically isolated to the extremities and has a benign clinical course?
Lymphomatoid papulosis aka pseudolymphoma
Primary cutaneous CD30+ T cell lymphoproliferative disorder with wedge shaped dermal infiltrate of atypical lymphocytes and a background of polymorphic inflammatory cells
What drug associated cause of thrombocytopenia is associated with an autoantibody against GPIX component of GPIb/V/IX complex?
Quinidine
What hemoglobin chains are defective in Hb D and G?
HbD is a BETA chain defect
HbG is an ALPHA chain defect
*D looks like a B and G looks like an A
Clinically normal
Both run with HbS on alklaine gel
CD30 is generally a marker we think about with embryonal carcinoma and ALCL but it can also be positive in what subset of DLBCL and what does CD30 positivity mean when seen in mycosis fungoides?
CD30+ in EBV related DLBCL
In MF, CD30+ is associated with transformation
How are aplastic anemias usually treated and what are the causes?
70% of cases are idiopathic
10% are due to a medication or toxin
5% are related to viral hepatitis (especially HCV)
Many causes but are mostly T cell mediated autoimmune diseases so most treatment is anti-T cell (ie cyclosporin)
What flow expression of the blasts can help differentiate between acute leukemia in Downs syndrome and transient myeloproliferative disorder (TMD) in Downs?
AML Downs: Positive for CD13 and CD11b, negative for CD34
TMD: Negative for CD13 and CD11b, positive for CD34
Somatic mutations in the GATA1 gene in blasts of both TMD and DS associated AML
Who is at highest/lowest risk for developing post transplant lymphoproliferative disorder?
PTLD usually within 1st year post transplant, EBV implicated in most
Late (>5 years) post transplant lymphomas are EBV negative and more aggressive
Renal and bone marrow transplants have lowest risk
Heart, lung, liver and bowel have highest risk
Recipient age: children at highest risk
Pretransplant status: EBV negative at highest risk
PTLD clone usually of recipient origin
Often involves the allograft itself
What are the flow cytometry findings in paroxysmal nocturnal hemoglobinuria (PNH)?
This disease is a deficiency of the GPI anchored proteins which is best detected by flow.
GPI anchors function to deflect complement mediated destruction
Red blood cells: loss of CD59 (preferred) and CD55
Monocytes: loss of CD14 and CD55; failure to bind FLAER
Granulocytes: loss of CD16 and CD24; failure to bind FLAER
*FLAER (fluorescent aerolysin) is a protein that binds specifically to the GPI anchor. Absence of FLAER binding to WBCs is the most sensitive measure of PNH and can be detected with flow.
What lymphoma has the following ODD immunophenotype?
Negative: B/T/myeloid antigens (CD20, CD79, CD19, CD10, CD3, CD5, CD13, CD14, CD33)
Positive: CD45, CD30, CD38, CD138, EMA, HHV8
Primary effusion lymphoma
What is the only ACQUIRED intrinsic hemolytic anemia (all others are hereditary)?
PNH
Acquired mutation of the PIG-A gene on the X chromosome which causes decreased GPI anchors.
GPI anchors function to deflect complement mediated destruction so without them there is unchecked complement mediated destruction taking place
*LAP SCORE IS DECREASED! This is one situation other than CML where the LAP score is decreased
What are the hemoglobin percentages in the alpha thals?
Silent carriers and alpha thal trait: Normal
HbH (3 missing α chains- β4 tetramers): 20% HbH, 80% HbA
HbBarts (4 missing α chains-ϒ4 tetramers): 100% HbBarts
What chains comprise HbA, HbA2 and HbF?
HbA α2β2 globin chains, 97% in normal adult
Hb A2 α2δ2 globin chains, 3% in normal adult
HbF α2ϒ2 globin chains, not in normal adult
They can ask you to identify stain in a normal lymph node based on pattern. What stain is this in a normal lymph node?
CD3
This lymphoma usually consists of small lymphocytes with an abundance of clear cytoplasm (“fried eggs”) many of which have bilobed or indented nuclei (“monocytoid”). What is it?
Marginal zone lymphoma
Clonal plasma cells are often present; rare intranuclear Dutcher bodies (shown here)
This is a rare finding but when it is seen (neutrophilic erythrophagocytosis), what disease should you think about?
Paroxysmal cold hemoglobinuria (PCH)
*IgG biphasic hemolysin (Donath Landsteiner antibody) with Anti-P specificity that causes intravascular hemolysis
DAT is positive with C3 and antibody panel is negative
Occurs in the setting following viral infection or syphilis
If you see stomatocytes, what 3 things should be in the differential?
Hereditary stomatocytosis
Alcohol and liver disease
Rh Null phenotype
Others: dilantin and artifact
What is the most common cause of Budd Chiari?
Polycythemia vera
What serum marker is elevated in Castleman’s and what are two disease associations that should be remembered for boards?
Serum IL6 is elevated
Associated with with Kaposi sarcoma and
POEMS (polyneurophathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin abnormalities)–multicentric Castleman’s
What is Lennert’s lymphoma?
Peripheral T-cell Lymphoma : Lymphoepithelioid variant
A distinct morphologic variant of Peripheral T-cell Lymphoma that has numerous epithelioid histiocytes. They are seen in first image as lighter pink areas in between clusters of small lymphocytes. usually occurs in adults and is often at advanced stage at presentation. Prognosis is poor. The neoplastic cells are usually small and lack significant atypia. Occasionally, large atypical lymphocytes may be present. Epithelioid histiocytes can be better appreciated in this high magnification view.
What is this structure made of?
Denatured/oxidized hemoglobin
showing Heinz body
Bite cells are sharp bitelike defects in RBCs where a Heinz body has been removed in the spleen
Heinz bodies seen in: G6PD def or unstable hemoglobins (HbH and HbBarts), sulfhemoglobinemia
This type of AML shown accounts for 8-10% of all de novo cases of AML affecting young adults, it HIGHLY chemosensitive, has blasts with pronounced azurophilic granularity sometimes have large (pseudo Chediak-Higashi) granules and Auer rods and has a high rate of activating KIT mutations in relapsed cases.
![](https://s3.amazonaws.com/brainscape-prod/system/cm/255/676/298/q_image_thumb.jpg?1464303277)
AML with t(8;21) AML1 (RUNX1) and ETO (RUNX1T1) genes
AML1 encodes the alpha chain of core binding factor (CBFalpha)
Immunophenotype: CD34, CD13, CD33, CD56, HLADR and CD19
What stain helps distinguish systemic from cutaneous anaplastic large cell lymphoma?
MUC1
Distinguishes systemic anaplastic large cell lymphoma (MUC1+) from cutaneous anaplastic large cell lymphoma (usually MUC1-)
What hemoglobinopathy is the 2nd most common in the world after sickle cell, the CBC shows thalassemic indices and is from a beta 26 glu–>lys mutation?
Hemoglobin E
For board purposes, what type of leukemia should be considered in a patient with gingival hyperplasia?
Monocytic leukemias
What are the two prognostic groups of CLL/SLL?
1) Pre-GC (naive) B-cell type
-unmutated IgVH, CD38+, ZAP70+, associated with 17p (10%) or 11q (25%) deletions, poor prognosis
CD38 and ZAP70 expressed by over 30% of cells correlates with unmutated status
2) Post-GC center type
- mutated IgVH, CD38-, ZAP70-, associated with isolated 13q deletion, good prognosis
If you have 80% erythroid cells, and 10% blasts, is it erythroleukemia?
YES!
Confusing criteria! The criteria says you need >50% of nucleated cells should be erythroid and then >20% of THE REMAINING NUCLEATED CELLS should be blasts. In this example, there are only 20% of non-erythroid cells and 10% of them are blast meaning that 50% of the non-erythroid cells are blasts which meets criteria
What is the definition of:
1) AML, NOS minimally differentiated
2) AML, NOS without maturation
3) AML, NOS with maturation
1) <3% blasts stain with SBB, MPO and NSE
2) 3-10% of blasts stain with SBB, MPO and NSE
3) >10% of blasts stain with SBB, MPO and NSE
AML, NOS by definition does not have any of the recurrent genetic abnormalities
What neoplasm is positive for cyclin D1 (bcl1) correlating with a t(11;14) translocation other than mantle cell lymphoma?
A subset of myeloma patients
*according to recent articles, these patients have standard risk
What AML translocation is this:
• RPM1-EVI1
• Dysplastic small hypolobated megakaryocytes (shown here)
inv(3)(q21q26.2)
What lymphoma occurs in the mediastinum and usually affects 20-40yr old women? Patients may have superior vena cava syndrome
Mediastinal (thymic) Large B-cell Lymphoma
Immunos/molecular
Lack of surface immunoglobulin by flow
But IgH rearrangement by PCR
CD19 and CD20 +, Bcl-2 and bcl-6 can be +, CD30 + (80%), but weak, CD15 only rarely +, MAL protein +
Alterations in the MAL gene, gains in 9p (the location of JAK2); no rearrangement of BLC2 or BLC6
What conditions decrease osmotic fragility?
- alpha and beta thal trait
- iron def
- chronic liver disease
- hyponatremia
- sickle cell disease
- hb C (target cells)
What cytogenetic abnormality is seen in 80% of T-cell prolymphocytic leukemia cases?
Inv14
What type of leukemia shown is associated with mediastinal germ cell tumors and I(12p)?
Acute Megarkaryoblastic Leukemia (M7)
>50% blasts megakaryocytic either by platelet peroxidase (PPO) technique (electron microscopy with staining for peroxidase) or by flow showing CD41 and CD61.
Note that AML and transient myeloproliferative disorders in Downs syndrome often megakaryoblastic
What hemoglobinopathy shows target cells with crystals and is from a beta 6 glu–>lys mutation?
Hemoglobin C
This is a beta chain variant of hemoglobin
BQ! What is the most common mutation in hairy cell leukemia?
BRAF
Some info on BRAF:
The BRAF gene on chromosome 7 (7q34) encodes the BRAF protein, which participates in the MAP kinase/ERK signalling pathway. This pathway regulates important cell functions including cellular growth, differentiation, proliferation, senescence and apoptosis.
Other than beta thal trait, what other conditions can cause elevated hemoglobin A2?
B12 and folate deficiency
Hyperthyroidism
Antiretroviral therapy
HbC elutes with HbA2 on HPLC so if you have an A2 level >7-8%, should do electrophoresis to see if there is a hemoglobin variant present
What are the different haplotypes in alpha thal?
Categorized as α thal 2 (α+ thal) or α thal 1 (α0 thal)
α thal 2 (α+ thal): TRANS–chr16 has one normal and one deleted α gene (-α/-α). Most common genotype in blacks (better prognosis)
α thal 1 (α0 thal): CIS–chr 16 has two deleted α genes (–/αα). Prevalent in Asians (worse prognosis)
BQ! What is alpha heavy chain disease?
Appears to be more common than gamma heavy chain disease and involves a younger age group. The uniform clinical pattern in most patients is malabsorption and diarrhea following a massive lymphoplasmacytic infiltration of intestinal mucosa or a histiocytic lymphoma of the intestine. In a few patients, the respiratory tract has been involved instead. Bone marrow and other lymphoid organs are not involved.
Usually, routine protein electrophoresis is negative, but small amounts of alpha chain may be detected in the serum and sometimes in the urine with immunoelectrophoresis. The abnormal protein does not contain light chains. It is most common in Mediterranean areas and is associated with poor living conditions in low socioeconomic groups. Similar to MALT lymphoma, many cases may initiate an infectious antigen-driven proliferation. It also has been referred to as Mediterranean abdominal lymphoma and immunoproliferative small intestine disease (IPSID).