hematology Flashcards
pathophys of immune thrombocytponeic purpura?
autoimmune production of IgG against platelet antigens, ->consumed by splenic macrophages -> thrombocytopenia
which cells produce the antibodies in ITP?
splenic plasma cells
Lab findings in ITP
Decreased platelet count
Normal PT/PTT
Increased megakaryocytes on bone marrow biopsy
Treatment for ITP?
Corticosteroids, IVIG
-splenectomy for refractory cases - eliminates the site of the antibody production
Name two types of microangiopathic hemolytic anemia
- HUS
- TTP
thrombotic thrombocytopenic purpura pathophs (TTP)?
Decreased ADAMTS13 - ADAMST13 normally cleaves vWF multimers into smaller monomers for degradation. With decreased ADAMTS13, uncleaved monomers lead ot abnormal platelet adhesion - > microthrombi -> sheering of rbcs
Decreased ADAMTS13 is usually due to…
an acquired autoantibody
who usually gets HUS?
children with e coli O157:H7 infection
Clinical findings of microangiopathic hemolytic anemia (HUS and TTP)?
- skin and mucosal bleeding
- hemolytic anemia
- fever
- renal insufficiency (HUS)
- CNS abnormalities (TTP)
lab findings of microangiopathic hemolytic anemia (HUS and TTP)?
- thrombocytopenia with increased bleeding time
- normal PT/PTT
- anemia with schitocytes
- increased megakaryocytes on biopsy
uremia disrupts which parts of platelet function?
both adhesion and aggregation
bernard-soulier syndrome is due to a genetic deficiency of…
GPIb
what is the cause of glanzmann thrombasthenia?
genetic GPIIb/IIIa deficiency
Hemophilia A is a X linked deficiency of…
factor VIII
Hemophilia B =
Christmas Disease
Hemophilia B is a deficiency of…
factor IX
What is the most common coagulation factor inhibitor?
anti-FVIII
How can you differentiate hemophilia A from a coagulation factor inhibitor (autoantibody against factor VIII)
Upon mixing the patients plasma with normal plasma, the PTT will not correct due to the presence of the antibody (whereas it would correct with hemophilia A)
Most commonly inherited coag disorder?
Von Willebrand disease- genetic vWF deficiency
inheritance of most common type of vWF defieincy?
AD
lab findings of vWF disease?
- increased bleeding time
- increased PTT, normal PT
- abnormal ristocetin test
why is PTT increased in vWF disease?
VWF normally stabilizes factor VIII
treatment of vWF disease?
desmopressin
function of alpha 2 antiplasmin?
inactivates plasmin
why may an alcohol have decreased alpha 2 antiplasmin?
liver cirhossis - not produced
plasmin function
cleaves serum fibrinogen
presentation of disorder of fibrinolysis?
- increased PT/PTT (plasmin destroys coag factors)
- increased bleedining time (blocks aggregation)
- increased fibrinogen split products with NORMAL D-dimer
why is d-dimer normal in disorders of fibrinolysis
Fibrin thrombi are absent in the case of disorder of fibrinolysis therefore D-dimers are not formed
treatment for disorders of fibrinolysis?
aminocaproic acid — blocks activation of plasminogen
A deficiency of cystathione beta synthase results in high levels of…
homocysteine
estrogen induces increased production of…
coagulation factors
name the microcytic anemias
- iron deficiency
- anemia of chronic disease
- sideroblastic anemia
- thalasemmia
what is the cofactor needed for ALAS?
B6
How does lead poisoning cause sideroblastic anemia?
-lead inhibits ALAD and ferrochelatase - needed for heme synthesis
if you have alpha thalasemia with 3 genes deleted, what will your Beta chains for?
tetramers - HbH - will damage RBCs
if you have alpha thalasemia with 4 genes deleted, what will form?
Hbarts - tetramers of gamma chains
How does alpha thalesemia with 4 genes deleted present?
Death in utero via hydrops fetalis
if you have alpha thalasemia with two genes deleted how will you present?
mild anemia with increased RBC count
alpha thalassemia is usually due to a gene…
deletion
beta thalassemia is usualy due to a gene…
mutation (point mutation)
what is the genotype of someone with beta thalasemia minor?
One normal beta globin gene, one mutated gene with diminished production
B/B+
hemoglobin electrophoresis findings wiht beta thalasemmia minor?
- Slightly decreased HbA
- Increased HbA2 and HbF
what is the most severe form of beta thalesemia? and genotype?
Beta thalassemia major - Bo/Bo
Both mutations yeild absent production
explain the pathophys of beta thalasemia major?
No production of Beta chains — alpha chains precipitate and damage RBC membranes causing ineffective erytrhopoiesis and extravascular hemolysis
-Massive erythroid hyperplasia
presentation of beta thalasemia major?
- crewcut appearance on xray
- chipmunk facies
- extramedullary hematopoiesis with hepatosplenomegaly
- risk of aplastic crisis with parvovirus B19
electrophoresis findings of someone with beta thalasemia major?
- No HbA (or little)
- HbA2 and HbF
target cells are characteristic of which disease?
beta thalasemmias and sickle cell
inheritance of paroxysmal nocturnal hemoglobinuria?
NOT inherited - its AQUIRED
what is defective in paroxysmal nocturnal hemoglobinuria?
GPI - the protein that anchors decay accelerating factor to the surface of RBCs, preventing C3 convertase activity
decay accelerating factor =
CD55
what is the main cause of death in patients with paroxysmal nocturnal hemoglobinuria?
thrombosis - destroyed platelets release cytoplasmic contents -> thrombosis
how do blasts (immature cells) appear on blood smear?
Large immature cells often with punched out nuceloili
what do lymphoblasts stain for?
Tdt - a DNA polymerase
is Tdt postive in myeloid blasts or mature lymphocytes?
no - specific to lymphoblasts
what do myeloblasts stain positive for?
MPO (in the cytoplasmi) - may crystalize and be seen as auer rods
what translocation characterizes acute promyelocytic leukemia?
t(15:17) -translocation of retinoic acid receptors (RAR) on chromosome 17 to chromosome 15 ; blocks maturation and promyelocytes accumulate
Abnormal promyelocytes increase your risk…
DIC, as they contain granules
CLL is a proliferation of what?
Naive B cells
what do the naive B cells of CLL express?
both CD5 and CD20
What will be seen on blood smear of someone with CLL?
increased lymphocytes and smudge cells
complications of CLL?
- Hypogammaglobulinemia - may lead to infection
- autoimmune hemolytic anemia
- transformation to diffuse large B-cell lymphoma (richter transformation)
what is hairy cell leukemia a proliferation of?
mature B cells
how do the mature B cells in hairy cell leukemia appear?
they have hairy cytoplasmic processes
what do the mature B cells in hairy cell leukemia stain for?
TRAP
clinical features of hairy cell leukemia
- splenomegaly - cells accumulate in red pulp
- dry tap on bone marrow due to fibrosis
what is adult t-cell leukemia/lymphoma a proliferation of?
mature CD4 t cells
adult t-cell leukemia/lymphoma is associated with which virus?
HTLV-1
what is mycosis fungoides a proliferation of?
mature CD4 t cells
mycosis fungoides clinical features
the CD4 t cells infiltrate the skin, leading to rashes, plaques, etc. Pautrier microabscesses.
-may spread to involve the blood = sezary syndrome
where do B cell proliferate in the lymph node?
cortex
where do t cells proliferate in th elymph node?
paracortex
hyperplasia of the sinus histiocytes is seen…
in lymph nodes that are draining a tissue with cancer
which lymphomas arise from small B cells?
- follicular lymphoma
- mantle cell lymphoma
- marginal cell lymphoma
- small lymphocytic lympoma (CLL that involes tissue)
which lymphomas arise from intermediate B cells
burkitt lymphoma
which lymphomas arise from large B cells
large B cell lympoma
follicular lympoma is a neoplasitc proliferation of…
small b cells (CD20+)
what translocation drives follicular lympoma?
t(14:18)
what does the t(14:18) result in?
BCL2 on chromosome 18 translocates to the ig heavy chain locus on chromosome 14- > overexpression of Bcl2 which inhibits apoptosis
which treatment is useful in follicular lymphoma?
rituximab
what is mantle cell lymphoma a proliferation of?
small b cells (CD20+)
what transcolation drives mantel cell lymphoma?
t(11:14)
what does the t(11:14) result in?
cyclin D1 from chromosme 11 gets translocated to ig heavy chian on chromsome 14 -> overexpression of cyclin D1 which promotes G1/S transition
what is marginal zone lymphoma a proliferation of?
small b cells (CD20+)
what translocation drives mantle cell lymphoma?
t(11:18)
what is MALToma?
a marginal zone lymphoma in mucosal sites
what conditions is marginal zone lymphoma associated with?
Hashimoto thryoiditis, Sjogren syndrome, and H pylori
which translocation drives burkitts lymphoma?
t(8:14)
what does the t(8:14) result in?
c-myc translocation onto the Ig heavy chain locus on chromosome 14 -> overexpression of c-myc oncogene
what is the most common type of hodgkins lymphoma?
nodular sclerosis
how will a lymph node with the nodular sclerosis type of hodgkins lymphoma appear?
divided by bands of sclerosis, with reed sternberg cells in lake like spaces
what cytokine do RS cells produce?
IL-5
which cytokine may be increased in multiple myeloma?
IL6
what does the M spike seen in multiple myeloma represent?
monoclonal IgG or igA produced by malignant plasma cells
why does the rouleaux formation occur in multiple myeloma?
-the elavated serum protein (from the neoplastic plasma cells producing immunoglobulins) decrease the charge between RBCs
which type of amyloid is found in multiple myeloma?
primary AL amyloidosis
what is waldenstrom macroglobulinemia?
b-cell lymphoma with monoclonal igM production
what do the langherhans cells of langerhans cell histiocytosis stain + for?
CD1a+ and S-100
presentation of hand-schuller-christain disease?
scalp rash, lytic skull defects, diabetes insipidus, exopthalamus in a child
