Hematology Flashcards
What kind of cell is this and what disease state is it associated with?
Burr cell
Disease: uremia
What kind of cell is this and what diseases is it associated with?
Spur cell
Disease: liver diseases
What kind of cell is this and what diseases is it associated with?
Target cell
Diseases: significant liver disease, thalassemia syndromes, sickle cell disease, homozygous hemoglobin C, other hemoglobinopathies
What kind of cell is this and what diseases is it associated with?
Sickle cell
Disease: sickle cell disease (HbSS), HbS beta-thalassemia; less common in HbSC
What kind of cell is this and what diseases is it associated with?
Teardrop cell (dacrocytes)
Disease: myelofibrosis and other infiltrating bone marrow processes, thalassemia
What kind of cell is this and what diseases is it associated with?
Elliptocyte
Disease: hereditary elliptocytosis, severe iron-deficiency anemia
What kind of cell is this and what diseases is it associated with?
Spherocyte
Disease: hereditary spherocytosis, autoimmune hemolytic anemia
What kind of cell is this and what diseases is it associated with?
Schistocyte
Disease: microangiopathic hemolytic anemia (TTP, HUS, HELLP syndrome, DIC, occasionally vasculitis), severe burns, valve hemolysis
What kind of cell is this and what diseases is it associated with?
Howell-Jolly Bodies (nuclear remnants)
Disease: splenectomy or functional asplenia
What kind of cell is this and what diseases is it associated with?
Basophilic Stippling (indicates ineffective erythropoeisis)
Disease: lead poisoning, thalassemia, pyrimidine 5’-nucleotidase deficiency
What kind of cell is this and what diseases is it associated with?
Hypersegmented polymorphonuclear leukocytes (neutrophils)
Disease: megaloblastic anemia (pernicious anemia/vit B12 deficiency, folate deficiency)
What are the three types of B-thalassemias and what kinds of Hb are associated with them?
B-thal minor
- heterozygous - one normal and one thalassemia allele (either B+/B0)
- mild anemia with lots of microcytes, asymptomatic
- RDW nml
- HbA2 > 3.5% is diagnostic
B-thal intermedia
- homozygous (B+/B+)
- some normal B-globin and some abnormal
- mild sxs and no required transfusions
- increased HbA2 and HbF
B-thal major
- B0/B0 or B+/B0
- essentially NO B-globin production
- by 6-12 mo pallor, irritability, hepatosplenomegaly, sig anemia, jaundice, bone marrow expansion; transfusion dependent and often develop iron overload
- HbF only
What are the 4 types of alpha-thalassemia?
the more loci affected, the worse the symptoms
- a-thal trait: 1 locus, asymptomatic, no heme abnormalities (silent carrier)
- a-thal minor: 2 loci, asymptomatic, low MCV, mild anemia
- Hemoglobin H disease (HbH): 3 loci, moderate to severe hemolysis
- hydrops fetalis: 4 loci, death in utero due to mainly Hb Bart (tetramer of gamma chains)
What is the most common cause of chronic GI blood loss worldwide?
Hookworm infection (Necator americanus or ancylostoma duodenale)
What is the most common cause of iron-deficiency anemia in pediatric population?
inadequate iron intake
How can you differentiate between iron-deficiency anemia and B/A-thalassemias?
- RDW is normal in patients with thalassemias but increased in IDA patients
- Mentzer Index: MCV/RDW
- IDA: index > 13
- thalassemia: index < 13
How can you differentiate iron-deficiency anemia vs. anemia of chronic disease?
- Hepcidin = small protein released from hepatocytes that block Fe absorption in gut and iron release by hepatocytes and macrophages
- IDA: low hepcidin levels (body wants to collect/release as much Fe as possible)
- ACD: hepcidin nml
- IDA: low Fe, high TIBC, low transferrin saturation, usually low ferritin
- ACD: low Fe, low TIBC, low to nml transferrin sat, nml to high ferritin
What are the 2 types of pernicious anemia?
IF = intrinsic factor; produced by parietal cells of stomach
- congenital pernicious anemia:
- occurs <3 yrs old
- consanguinity w/ AR inheritance
- IF absent so no antibodies against it; otherwise nml gastric secretion
- juvenile pernicious anemia
- older children
- autoimmune-mediated decrease in gastric IF
- commonly assoc w/ gastric atrophy and decreased gastric fxn
- commonly assoc with other AI conditions (i.e. vitiligo, thyroiditis)
What is the mutation that causes sickle cell disease?
point mutation on 6th codon of B-globin gene → adenine replaced by thymidine → valine encoded instead of glutamic acid → HbS polymerization and sickling
What is the average lifespan of RBC in HbSS disease compared to normal?
- SCD lifespan: 15-50 days
- Normal lifespan: 120 days
What part of body does the first SCD pain crisis typically involve?
hands/feet symmetrically (dactylitis)
What is the leading cause of death in children and adults w/ SCD?
acute chest syndrome
How is acute chest syndrome defined?
Development of new pulmonary infiltrate with one of the below:
- fever
- chest pain
- tachypnea
- hypoxia
What is the typical treatment for acute chest syndrome?
- antibiotics that cover pneumococcus, mycoplasma, and chlamydia (usually 3rd gen cephalosporin for routine bacterial cvg + macrolide such as azithromycin for atypical cvg)
- respiratory support
- hydration
What kinds of bacterial infections are SCD patients highest risk for?
- encapsulated organisms (s. pneumoniae, n. meningitidis, h. influenzae)
- salmonella (bacteremia, osteomyelitis)
- patients should start PCN ppx once diagnosed
What is a common cause of aplastic crisis in SCD patients?
- Parvo B19 infection
- destroys early RBC precursors in bone marrow → BAD because SCD Hb lifespan only 15-50 days → can cause life-threatening anemia
- low retic count
- elevated Parvo IgM = acute infection
What is HbCC disease?
- Homozygous for HbC
- mild hemolytic anemia, splenomegaly
- no VOC issues
What is HbSC disease?
- equal amounts HbC and HbS
- less anemic w/ less severe hemolysis than patients w/ HbSS
Describe G6PD disease
- X-lined recessive (Males > females)
- reduced glutathione → less protection for RBC against oxidation stress
- must avoid oxidant stress (fava beans, dapsone, primaquine, systemic infxn)
- hemolytic crisis sxs = sudden onset pallor, fatigue, dark urine
- peripheral smear = Heinz bodies (denatured globin), bite cells (macrophages removing heinz bodies)
- cannot test for it during acute crisis b/c all messed up cells will be gone, must wait a couple months
Describe Hereditary Spherocytosis
- Autosomal Dominant (75%) or de novo mutation (10-25%)
- structural or functional abnormality of cytoskeleton proteins (spectrin, ankyrin, band 3, protein 4.2)
- normal shape RBC → goes through spleen and b/c cytoskeleton more rigid cannot easily pass thru → RBC membrane loss → cell becomes spherical and less deformable → increased risk for splenic lysis with each subsequent pass thru
- diagnosis: anemia, reticulocytosis, increased MCHC, spherocytes on smear, positive osmotic fragility test
Warm AIHA vs. Cold Agglutinin Disease
- warm AIHA:
- IgG Abs to Rh group antigen bind at body temp → macrophages and monocytes attack them → hemolysis
- acute onset pallor, jaundice, dark urine
- primary vs. secondary (infection, meds, lymphoproligerative and collagen vascular disorders)
- positive direct Coombs
- tx = steroids
- cold disease
- mycoplasma and EBV: IgM-RBC complexes activate complement → intravasc hemolysis
- paroxysmal cold hemoglobinuria: keep patient warm and use blood warmer for transfusions; steroids NOT helpful
How does aplastic anemia present, how is it diagnosed, what causes it, how is it treated, what are the types?
- presents w/ pancytopenia
- diagnosed via bone marrow exam (hypocellular or acellular bm)
- cause: unknown in >50% cases; drugs (sulfa drugs), toxins (benzene, insecticides), infection, radiation
- treatment for severe aplastic anemia: matched sibling stem cell transplant and immunosuppressive therapy
What is Fanconi Anemia (inheritance pattern, mechanism, clinic manifestations, diagnosis, treatment)?
- Autosomal Recessive
- Poor DNA repair mechanisms
- short stature, skeletal abnormalities (absent or abnml thumbs, abnml radii, microcephaly, vertebral abnml), cafe au lait spots, hyperpigmentation or hypopigmentation, renal anomalies
- diagnosis: identification of DNA repair issues
- 40-50% risk of myelodysplastic syndrome, 15% risk of AML by age 50, increased risk of hepatic malignancy and squamous cell carcinoma
- cure: HSCT; however does NOT decrease risk for cancers
- FANCONI SYNDROME IS A DIFFERENT PROBLEM
What is Red Cell Aplasia and what are there different types?
- red cell aplasia = anemia in setting of reticulocytopenia
- Types:
- Parvovirus (B19)
- transient erythroblastopenia of childhood (TEC)
- congenital hypoplastic anemia (Diamond-Blackfan)
- can also have idiopathic cause or 2/2 drugs or immune disorders
How does Parvovirus B19 cause anemia, how does it present, what is the typical time course, and how to diagnose and treat?
- Parvovirus infects erythroid progenitors → acute or chronic red cell aplasia
- red cell aplasia + fever, rash (slapped cheek), and/or arthropathy
- Time course:
- in healthy patient is transient
- in immunocompromised patients can become chronic
- in SCD patients can cause aplastic crisis
- Diagnosis: Parvovirus B19 DNA and/or IgM
- treatment: supportive in healthy patients, IVIG in complicated cases among immunocompromised patients
What is Transient Erythroblastopenia of Childhood (TEC)?
- red cell aplasia
- acquired, self-limited (resolves in 1-2 mo)
- children 1-3 yo
- pallor + decreased activity
- normocytic anemia + reticulocytopenia
- treatment = supportive
What is Congenital Hypoplastic Anemia (Diamond-Blackfan), how does it present, how is it treated?
- red cell aplasia
- macrocytic anemia + reticulocytopenia
- diagnosed < 1 yo
- presentation: thumb anomalies, dysmorphic features (snub nose, thickened upper lip, wide-set eyes), short stature, glaucoma, renal anomalies, hypogonadism, short webbed neck, congenital heart disease, intellectual disability
-
management: transfuse until 6 mo - 1 yo → steroids after 12 mo (not earlier because of bone growth)
- anemia responds to steroids in 80% of cases, spontaneous remission in 25%
- if steroid refractory or dependent → chronic transfusions and possibly stem cell transplant
How to differentiate Pure Red Cell Aplasias?
- anemia + low reticulocytes = red cell aplasia (Parvo B19, TEC, Diamond Blackfan)
- Parvo: school-aged children, associated fever/rash/arthropathy
- TEC: children between 1-4 yo, normocytic RBCs, no fever/rash/arthropathy
- DBA: usually diagnosed < 1 yo, macrocytic RBCs, congenital deformities
How is severe neutropenia vs. mild neutropenia defined?
- Severe neutropenia: ANC < 500
- Mild neutropenia: ANC between 1000-1500
What are different etiologies of Neutropenia?
-
Inherited:
- cyclic neutropenia
- severe congenital neutropenia (Kostmann syndrome)
- Shwachman-Diamond syndrome
-
Acquired:
- neonatal isoimmune neutropenia
- chronic benign neutropenia (autoimmune)
- virus- or drug- induced
What is Cyclic Neutropenia?
- inherited neutropenia
- neutropenia occurs at regular interval (every 21 +/- 3d)
- defective maturation of uncommitted stem cells
- during neutropenic period: fever, aphthous stomatitis, pharyngitis, cervical lymphadenitis, rectal/vaginal ulcers
- at risk for sepsis caused by clostridium septicum
- ⅓ of patients get it via AD inheritance
- management: G-CSF and antibiotics, excellent oral hygiene
What is Severe Congenital Neutropenia (Kostmann Syndrome)?
- inherited neutropenia
- rare, AR disorder
- ANC typically < 200
- also with monocytosis + eosinophilia
- at risk for SBI and death
- management: G-CSF, BMT
What is Shwachman-Diamond Syndrome?
- inherited neutropenia
- AR inheritance mutation in SBDS gene
-
present similar to CF patients: FTT, steatorrhea due to pancreatic exocrine deficiency, recurrent infections
- NORMAL SWEAT TEST
- diagnostic eval: CBC, BM aspirate and biopsy, serum isoamylase, serum pancreatic trypsinogen, fecal elastase levels, SBDS gene analysis
- treatment: supportive w/ pancreatic enzyme replacement, G-CSF, BMT
- increased risk for AML and myelodysplastic syndrome
What is Neonatal Isoimmune Neutropenia (NIN)?
- acquired neutropenia
- self-limited disease that occurs in newborns
-
similar to Rh disease (except mother sensitized to fetal neutrophil antigens of paternal origin)
- mother does not have these antigens →produce maternal Abs → IgG Abs cross placenta and destroy fetal neutrophils → neutropenia
- ANC recovers in 6-12 weeks
- subsequent siblings at risk as well
What is Chronic Benign Neutropenia?
- acquired neutropenia
- also known as autoimmune neutropenia
- ANC persistently < 1000 due to autoantibodies to granulocytes
- most common kind of neutropenia in healthy kids
- AD inheritance or sporadic
- median diagnosis age 8-11 mo; resolves after ~ 2 yrs
- usually mild; if severe give G-CSF
