Hematology/Hematopathology Flashcards
What (2) infections produce lymphocytic leukocytosis?
- Viral infections (CD8+ cells increase)
- Bordetella pertussis infection (bacteria produces lymphocytosis promoting factor which blocks lymphocytes from leaving the blood)
Mutations in the Myeloproliferative neoplasms (4)
CML = Philidelphia chromosome t(9;22) -> BCR-ABL fusion protein PV = JAK2 mutation ET = JAK2 mutation Myelofibrosis = JAK2 mutation
all of these (+) tyrosine kinase -> proliferation of cell production
“starry sky” appearance
Burkitt Lymphoma
presentation: rapidly enlarging LN in an adult
Diffuse Large B Cell Lymphoma
adult from Japan + IV drug user + rash + lytic bone lesions
Adult T Cell Lymphoma
Cerebriform nuclei
Mycosis fungoides/Sezary syndrome
Anisocytosis definition
variation in RBC size
Poikilocytosis definition
variation in RBC shape
What do the hepcidin levels indicate?
Hepcidin sequesters iron in its storage places and suppresses Epo production. Overall goal is to reduce iron in circulation.
Increased hepcidin = Decreased circulating iron (decreased TIBC, decreased serum iron) Increased ferritin (because iron is stuck in storage)
Corrected reticulocyte count (%) equation
(% Retics observed x Hct)/ normal Hct
normal Hct = 45
Normal reticulocyte count =
1-2%
normal reticulocyte count response to anemia =
what does that indicate?
> 3%
indicates good marrow response and thus peripheral destruction
When do you need to correct the reticulocyte count?
Anemia = decrease in total RBCs can falsely elevate reticulocyte count
What does anemia + corrected reticulocyte count of less than 3%
poor marrow response to anemia and thus this is an underproduction problem
Indirect BR = unconjugated or conjugated
Indirect BR = Unconjugated BR
Direct BR = unconjugated or conjugated
Direct BR = Conjugated BR
- Normocytic
- Shistocytes
- hemoglobinuria
- jaundice
- low serum haptoglobin
- corrected Retic count > 3%
Intravascular hemolysis -> normocytic anemia
- Normocytic
- Jaundice
- Spherocytes
- BR gallstones
- corrected Retic count > 3%
Extravascular hemolysi -> normocytic anemia
Cause of a corrected reticulocyte less than 3%
Aplastic anemia = failure of bone marrow therefore it cannot produce the needed cells (including reticulocytes)
Corticosteroids ->
- neutrophils?
- lymphocytes?
- eosinophils?
- neutrophilis: neutrophilia due to the decreased activation of neutrophil adhesion molecules therefore locking the neutrophils in the blood
- lymphocytes: lymphopenia due to increased apoptosis of lymphocytes
- eosinophils: eosinopenia due to sequestration of eosinophils in the lymph nodes
Intrinsic clotting cascade players =
What test measures activity?
XII
XI
IX
VIII
Measured by aPTT
Extrinsic clotting cascade players =
What test measures activity?
VII
Measured by PT
IgG to the heparin-platelet factor 4 complex found in?
thrombosis or bleeding?
Heparin-induced thrombocytopenia
Promotes thrombosis in the setting of thrombocytopenia -> makes the thrombcytopenia worse!
adult female + numbness and tingling on left arm and face + hematuria + proteinuria + shistocytes on peripheral blood + thrombocytopenia + fever =
pathogenesis?
Thrombotic thrombocytopenic purpura (TTP)
Pathogenesis: Deficiency in vWF protease (ADAMTS13) -> large multimers of vWF accumulate and stimulate platelet aggregation
Deficiency of platelet glycoprotein Ib (GPIb) -> disorder of platelet function
What disease?
Normal function of GPIb
Bernard-Soulier Syndrome
GPIb adheres vWF to the exposed subendothelial collagen. If not present, platelets cannot adhere.
Deficiency of platelet glycoprotein IIb/IIIa (GPIIb/IIIa) -> disorder of platelet function
What disease?
Normal function of GPIIb/IIIa
Glanzmann Thrombasthenia
GPIIb/IIIa normally aggregates the platelets to one another. If not present, platelets cannot aggregate.
Budd-Chiari syndrome =
What (2) neoplasms is it seen in?
Budd-Chiari Syndrome = splenic or hepatic vein thrombosis
Seen in:
- Polycythemia vera (PV)
- Essential thrombocythemia (ET)
Both types of myeloproliferative neoplasms that have a JAK2 gene mutation
- Lymphoblast cells >20% of bone marrow
- age less than 15 years old
Acute Lymphoblastic Leukemia (ALL)
- B cell type in young kids
- T cell type in older kids/adolescents and more of a mass (lymphoma)
t(8;14)
what genes are involved?
Burkitt lymphoma
c-myc (chr 8) and heavy chain Ig (chr 14)
t(14;18)
what genes are involved?
Follicular lymphoma
heavy chain Ig (chr 14) and BCL-2 (chr 18)
t(11;14)
what genes are involved?
Mantle cell lymphoma (MALToma)
cyclin D1 (chr 11) and heavy chain Ig (chr 14)
t(15;17)
what genes are involved?
Acute promyelocytic leukemia
produces a PML/RARA -> abnormal retinoic acid receptor
Microcytic anemias (4)
- Iron deficiency
- Thalassemia
- Sideroblatsic/lead poisoning
- Anemia of chronic disease
Macrocytic anemias
- megaloblastic (2)
- non-megaloblastic (3)
Megaloblastic:
- Folate deficiency
- Vitamin B12 deficiency
Non-megaloblastic:
- Alcohol
- Liver disease
- Bone marrow failure
autologous hematopoetic stem cell transplant =
patient is his/her own donor
allogenic hematopoetic stem cell transplant =
donor is related or unrelated but they are HLA-matched
syngenic hematopoetic stem cell transplant =
donor is the healthy identical twin
where are bone marrow transplants taken from?
posterior iliac crests
marker for the pluripotent hematopoetic stem cell
CD34+
Prophylaxis of acute GVHD?
Calcineruin inhibitor (cyclosporin, tacrolimus) + Methrotrexate
calcineurin inhibitor = decreases action of IL2 + block IL2 synthesis = induce apoptosis of CD4 T cells and inhibit T cell clonal expansion
What is a langerin?
protein found inside the Birbeck granules which are found in Langerhans Cell Histiocytoses
HLA-DR+, S100+, CD1+
Langerhans Cell
Differential diagnosis for an anterior mediastinal mass?
4 T’s:
- Thymus - thymoma, thymic cyst
- Thyroid mass
- Teratoma (germ cell tumor)
- “Terrible” lymphoma - B (Hodgkin) or T cell (acute T cell)
What test monitors warfarin therapy?
PT
What test monitors heparin therapy?
PTT
3 year old + epistaxis + petechiae + upper respiratory infection last week + sudden onset of symptoms =
Treatment?
Acute immune thrombocytopenic purpura (ITP)
Treatment:
- self limiting in 6 months
- restriction of activity
What is platelet satelliteism?
Platelets clump around WBC and therefore the machine indicates thrombocytopenia even though there isn’t. There is no risk of bleeding in the patient.
Occurs due to the EDTA anti-coagulant in the collection tubes.
Re-draw blood in a different type of tube (Citrate anti-coagulant).
What type of bleeding is: menorrhagia?
Platelet-type
What type of bleeding is: epistaxis?
Platelet-type
To dx sickle cell disease (2)
- Hemoglobin electrophoresis
- Metabisulfite screen
Antithrombin (AT) inhibits factors _
II VII IX X XI XII
(main effect is via inhibition of II and X)
APC + PS complex inhibits factors _
V
VIII
30 year old Cacusaian female with multiple DVTs and a PE.
Patient’s blood has normal PTT.
Add APC+PS to patient’s blood and PTT does not change.
What mutation does the patient have?
Factor V Leiden mutation
Adding APC+PS to the patient’s blood should have caused resulted in an increase in PTT due to the inhibition of factor V. If the patient has a resistant Factor V, then APC+PS will have no effect on it.
Vitamin K dependent factors =
II VII IX X protein C protein S
a lack of CD59 + CD55 is indicated in?
Paroxysmal Nocturnal Hemoglobinuria
They are the markers that protect the RBC from compliment mediated lysis.
Where is factor VIII synthesized?
Endothelial cells
Along with VWF
Ristocetin aggregation test measures what?
vWF and GPIb adhesion/aggregation
Ristocetin aggregation test is negative/abnormal. What two diseases are indicated and how to tell them apart?
Abnormal ristocetin aggregation tests implicate vWF deficiency and Bernard-Souiler Syndrome.
vWF deficiency: aggregation will normalize when mixed with normal blood, patients will also have symptoms that indicate factor VIII deficiency
Bernard-Souiler Syndrome: aggregation will not normalize when mixed with normal blood, peripheral smear will also show large platelets
Diagnostic blood smear for malaria shows what two things?
- bananna shaped gametocytes
- intraerythrocyte ring forms
Heterophile antibodies are found in =
EBV-induced infectious mononucleosis
Monospot test is looking for heterophile antibodies
anaplastic cells definition and features (5)
neoplastic cells that demonstrate a complete lack of differentiation
features:
- loss of cell polarity and architecture
- cellular pleomorphism
- nucleus variations
- mitotic figures
- giant multinucleated tumor cells
CD14 =
surface marker of monocyte-macrophage lineage
Mutation in BRAF oncogene leads to what 2 cancers?
What is BRAF?
Hairy Cell Leukemia
Melanoma
BRAF = Ras signal transduction
HIV+ patient + large mass surrounding small intestine + uniform round basophilic cells with proliferation fraction (Ki-67) > 99% =
Burkitt Lymphoma
Proliferation fraction (Ki-67) indicates =
mitotic index
Genetics of sickle cell disease?
AR
Both parents have to have sickle cell trait (heterozygous carrier).
What does JAK2 gain of function mutation do?
Renders the Hematopoetic stem cells more sensitive to growth factors.
Waxing and waning painless lymphadenopathy + indolent =
Follicular lymphoma
hospitalized patient + prolonged PT + prolonged PTT + decreased # platelets + decreased fibrinogen + bleeding =
Disseminated Intravascular Coagulation
- consumption of coagulation factors and platelets and fibrinogen
- symptoms of bleeding due to the consumption
Trisomy 21 patients are likely to develop which leukemia (2 types)
- AML
- ALL
what bug is likely to induce an aplastic crisis in a sickle cell patient?
Parvovirus B19
Aplastic crisis definition
massive reduction in RBC synthesis
Mechanism of warfarin induced skin necrosis?
Decreased production of protein C -> prothrombotic state -> thromboses in the skin -> necrosis
“dewdrops on a rose petal” skin condition on a child
Varicella zoster - chicken pox
diagnosis of antiphospholipid antibody syndrome =
- 2 findings of antiphospholipid antibody in the serum 12 weeks apart
- at least one clinical feature of the disease - thrombosis (arterial or venous), pregnancy morbidity
Iron deficiency anemia + Esophageal webs + Atrophic glossitis =
Plummer Vinson Syndrome
Dry tap (3)
- Hairy cell leukemia
- Aplastic anemia
- Myeloproliferative disorder - myelofibrosis
Leukemia with splenomegaly, dry tap, no lymphadenopathy =
Hairy cell leukemia
Blue color on Wright-Giemsa stain in reticulocytes is
residual rRNA
PECAM-1 is expressed on endotheial cells during
WBC transmigration
DIC in pregnancy is caused by =
placental injury leading to the release of tissue factor into maternal circulation
Decreased LAP vs Increased LAP
LAP = leukocyte alkaline phosphatase
decreased LAP = CML
(increased WBC with left shift)
increased LAP = leukemoid reaction (increased WBC with increased neutrophils + left shift)
Decreased haptoglobin indicates
intravascular hemolysis
RBC breaks -> releases hemoglobin -> hemoglobin + haptoglobin travel to the spleen
Increased MCHC =
hereditary spherocytosis
increased TT indicates =
direct or indirect thrombin inhibition
Increased PTT, PT, and TT indicates =
Direct Xa inhibitor
- Rivaroxaban
- Apixaban
Patients with ALL have an increased risk for (3)
- Down syndrome
- Ataxia telagiectasia
- Neurofibromatosis 1
65 year old man, neutrophils with two lobes, hypercellular bone marrow =
Myelodysplastic syndrome
Pseudo-Pelger-Huet anomaly = neutrophils with two lobes
Blood transfusion risks (3)
- Iron overload -> hemochromatosis
- Hypocalcemia due to citrate chelation (the lack of Ca is also the reason why the blood packets do not clot)
- Hyperkalemia due to RBCs lysing over time
Sideroblastic anemia inhibits what enzyme?
ALA Synthase or decreases the concentration of its cofactor (vitamin B6/pyridoxine)
Porphyria cutanea tarda inhibits what enzyme?
Uroporphyrinogen decarboxylase
Acute intermittent porphyria inhibits what enzyme?
PBG deaminase with a subsequent upregulation of activity of ALA synthase (because no product is made)
Lead poisoning inhibits what two enzymes?
- Ferrochelatase
- ALA dehydratase
Basophilic stippling
Lead poisoning
Patient with blisters on backs of hands and forearms that heal with hyperpigmentation after rupturing. What enzyme is deficient?
Uroporphyrinogen Decarboxylase deficiency
- Porphyria cutanea tarda
- May also have tea colored urine due to the uroporphyrin build up and urinary excretion
Sickle cell trait has resistance to what infection?
P. falciparum
Only trait! (heterozygotes)
Things that cause warm agglutinins
SLE, CLL, Drugs (alpha-methyldopa)
- Produces IgG
- Positive direct coombs test
- Extravascular hemolysis
Anti-A Ab and Anti-B Ab in a woman with O type blood are what type of antibodies?
IgG - therefore they can cross the placenta and cause fetal RBC hemolysis
Anti-B Ab in a woman with A type blood are what type of antibodies?
IgM - therefore the cannot cross the placenta
Same with anti-A ab in a B type woman
What can be given to help treat the symptoms of folic acid deficiency?
Thymidine supplementation
Decreased folic acid -> decreased dTMP -> decreased DNA synthesis
Thymidine -> increased dTMP (via a different pathway) -> increased DNA synthesis
What receptor in the area postrema can be antagonized to treat chemotherapy-induced vomiting?
Neurokinin-1 (NK-1)
Antagonists block this receptor and therefore decrease substance P release
CYP450 inducers/inhibitors cause warfarin action to be enhanced? (increases risk of bleeding)
inhibitors
CYP450 inducers/inhibitors cause warfarin to be less effective? (decreases INR)
inducers
When does fetal hemoglobin become adult hemoglobin?
Fetal Hb production before at 8 weeks gestation
Major form from 14 weeks through the first few months (6 months?) of life
Fetal hemoglobin =
Alpha2 + Gamma2
53 yo man with frequent headaches, dizziness, sweating, facial plethora, splenomegaly and increased # RBCs
Polycythemia vera
Mutation in JAK2 - cytoplasmic tyrosine kinase (non-receptor tyrosine kinase)
Aplastic anemia + absent thumbs + short stature =
Fanconi anemia
Reddish skin discoloration + tachypnea + tachycardia + headache + dizziness
Cyanide poisoning -> inhibits cytochrome c complex in the ETC
Labs: lactic acidosis, narrowing of venous-arterial PO2 gradient
Treatment: make methemoglobin to soak up the cyanide
Osteoblastic/sclerotic bone metastases (3)
- Prostate cancer
- Small cell lung cancer
- Hodgkin lymphoma
Indicates a more indolent course
Osteolytic/lucent bone metastases (5)
- MM
- Non-small cell lung cancer
- Non-hodgkin lymphoma
- RCC
- Melanoma
Indicates a more aggressive course
G6DP genetics
X linked recessive
Hereditary spherocytosis genetics
Autosomal dominant
Pure red cell aplasia associations/causes (3)
Pure red cell aplasia = anemia (low RBC#) with normal platelet and WBC #
- Thymoma
- Lymphocytic leukemias
- Parvovirus B19
Heavy menstrual periods + increased nosebleeds =
Von WIllebrand disease
Tumor expansion/depth of invasion - stage or grade?
Stage
Microangiopathic hemolytic anemias - form schistocytes (6)
DIC HUS TTP Mechanical damage HELLP syndrome SLE
To make the dx of CML, what cells do you need to see?
- Basophils
- Mature granulocytes
Which leukemia is most responsive to treatment?
ALL
How does uremic platelet dysfunction present?
Increased BT, normal PT, PTT, Platelet count.
Usually occurs in patients with ESRD/uremia. Improved with dialysis
Glutamic acid -> Lysine
in beta globin
HbC defect
- in beta globin gene (chr 11)
- AR
Glutamic acid -> Valine
in beta globin
Sickle cell anemia
- in beta globin gene (chr 11)
- AR
Two things that cause eosinopenia
- Cushings
- Corticosteroids
mechanism of pyruvate kinase deficiency hemolytic anemia
decreased pyruvate kinase -> decreased ATP production -> rigid RBCs -> increased activity of splenic red pulp to increase remove these bad RBCs = splenic hyperplasia
AR
Function of the thymic cortical epithelial cells in T cell maturation?
Positive selection
turns double positive T cells into single positive T cells
Function of the thymic medullary epithelial cells and dendritic cells in T cell maturation?
Negative selection
turns single positive T cells into mature helper or cytotoxic T cells
3 stimuli that cause sickling
- increased acidity
- decreased oxygen (increased altitude)
- decreased blood volume (dehydration)
