HEMATO-ONCOLOGY Flashcards
What are the vWF and Fibrinogen receptors?
GpIb
GpIIb/IIIa
Which cytokine activate macrophages?
Gamma-interferon
What is the first step to septic shock activation by macrophages?
Lipid A From bacteria LPS binds CD14
Causes of eosinophilia (5) NAACP
Neoplasia
Asthma
Allergic processes
Chronic adrenal insufficiency
Parasites (invasive)
What substances are in basophils (3)
Heparin
Histamine
Leukotrienes
What type of Igs can be bind by Mast cells and what substances can release (3)?
Fc portion of Ig E
Causing degranulation of
Histamine
Heparin
Eosinophilic Hemotactic factor
What type of cell proliferate most in Multiple Myeloma?
Plasma cells
What agents activate intrinsic and extrinsic coagulation pathways?
Intrinsic : collagen, basement membrane,activated platelets
Extrinsic : thromboplastin (tissue factor)
What are Xa factor inhibitors?
LMWH☑️
Heparin
Apixaban, rivaroxaban
Fondaparinux
What are IIa factor (thrombin) inhibitors (3)
Heparin☑️
LMWH (deltaparin-enoxaparin)
Argatroban,bivalirudin,dabigatran
What enzyme is inhibited by warfarin?
Vitamin K epoxied reductase
Which factors are inhibit by protein C and S
V factor
VIII factor
What factors are inhibited by antythrombin ( enhanced by heparin)(6)?
II VII IX X XII
What’s factor V Leiden mutation ?
Factor V resistant to inhibition by protein C
When you see target cells(4)?
HbC disease
Asplenia
Liver disease
Thalassemia
When you see Heinz bodies?
G6PD deficiency
When you see Howell-jolly bodies?
Hyposplenia
Asplenia
What are normocytic anemias extravascular hemolysis (5)?
Hereditary espherocitosis G6PDH deficiency Piruvate kinase deficiency Paroxysmal nocturnal hemoglobinuria Sickle cell anemia
What are microcytic anemias(5)?
Iron deficiency (late) ACDa Thalassemias Lead poisoning Sideroblastic anemia
What’s Plummer-Vinson syndrome triad?
iron deficiency anemia
esophageal webs
atrophic glossitis
What’s Hb Barts and Hb H?
4 allele deletion: No α-globin. Excess γ-globin forms γ4 (Hb Barts). Incompatible with life (causes hydrops fetalis).
3 allele deletion: HbH disease. Very little
X-Ray finding of beta thalassemia major
Crew cut
Tile of hemoglobin , skeletal deformities and infeciosus risk in beta thalassemia mejor?
Hb F ( alfa2 gamma2)
Chipmunk facies
Parvovirus B19
Managment of lead poisoning (3)
Dimercaprol
EDTA
Succimer (kids)
Which enzymes are impaired in lead poisoning(2).
ferrochelatase
ALA dehydratase
Enzyme defect in hemosiderosis
δ-ALA synthase
Causes of sideroblastic anemia (5)
alcohol is most common lead vitamin B6 deficiency (TREATMENT) copper deficiency isoniazid
Big differences between folate and B12 deficiency(3)
FOLATE
⬆️homocysteine
↔️Methylmalonic acid
❎Neurological symptoms
B12
️⬆️homocysteine
⬆️Methylmalonic acid
✅Neurological symptoms
How chronic diseases cause anemia?
Liver secretes hepcidin
Which inhibit intestinal iron absorption
Cause of paroxysmal nocturnal hemoglobinuria
impaired synthesis of GPI anchor for decay-accelerating factor that protects RBC membrane from complement
Symptoms and treatment for paroxysmal nocturnal hemoglobinuria
Triad: Coombs ⊝ hemolytic anemia, pancytopenia, and venous thrombosis.
Labs: CD55/59 ⊝ RBCs on flow cytometry.
Treatment: eculizumab (terminal complement inhibitor).
Treatment for sickle cell anemia
Hydroxyurea ⬆️HbF
Actions of corticosteroids in lymphocytes and eosinophils
lymphocytes APOPTOSIS
eosinophils SEQUESTERING IN LYMPHNODES
Symptoms of acute intermittent porphyria (5Ps)
Painful abdomen
Port wine–colored urine
Polyneuropathy
Psychological disturbances
Precipitated by drugs (e.g., cytochrome
P-450 inducers), alcohol, starvation
Enzyme impaired in Acute intermittent porphyria
Porphobilinogen deaminase
Enzyme impaired in Porphyria cutanea tarda
Uroporphyrinogen decarboxylase
Bernard-Soulier syndrome
Cause And how differentiate it from other
⬇️ GpIb
No agglutination on ristocetin
Glanzmann thrombasthenia
Cause And how differentiate it from other
⬇️GpIIb/IIIa
no platelet clumping. Agglutination with ristocetin
Immune thrombocytopenia
Cause and Dx
Anti-GpIIb/IIIa antibodies
⬆️ megacaryocytes in bone marrow
Cause and diagnosis of Thrombotic thrombocytopenic purpura
Inhibition or deficiency of ADAMTS 13 (vWF metalloprotease)
Labs: schistocytes, LDH.
Symptoms: pentad of
1. neurologic
2.renal symptoms
3. fever
4. thrombocytopenia,
5. microangiopathic hemolytic anemia.
Diagnosis and treatment of Von Willerbrand disease
Dx ristocetin cofactor assay
( agglutination is diagnostic).
Treatment: desmopressin, which releases vWF stored in endothelium.
Which factors are affected ind antythrombin deficiency?
IIa
Xa
Which disease cause thrombotic skin necrosis with hemorrhage after warfarin administration?
Protein C or S deficiency
Which contains cryoprecipitate?(5)
fibrinogen
factor VIII
factor XIII
vWF
fibronectin
Difference between leukemoid reaction and CML
leukemoid reaction ⬆️ leukocyte alkaline phosphatase (LAP)
CML ⬇️leukocyte alkaline phosphatase (LAP)
Principal characteristics of Hodgkin lymphoma (4)
Localized, single group of nodes;
Reed-Sternberg cells.
young adulthood and> 55 years;
associated with EBV.
Principal characteristics of no Hodgkin lymphoma (4)
extranodal involvement common
Majority involve B cells
20–40 years old.
associated with HIV and autoimmune diseases.
Cell markers of reed-sternberg cells (3)
CD15+
CD30+
B-cell origin
Causes and findings in Burkina lymphoma (1-3)
t(8;14)—translocation of c-myc (8) and heavy-chain Ig (14)
“Starry sky” appearance
Associated with EBV.
Jaw lesion
Age of patients and Genetics of mantle cell lymphoma
Older males
t(11;14)—translocation of cyclin D1 (11) and heavy-chain Ig (14)
Multiple myeloma findings (5)
Monoclonal plasma cell (“fried egg” appearance)
Punched-out lytic bone lesions on x-ray A
M spike on serum protein electrophoresis (IgG IgA)
Ig light chains in urine (Bence Jones
protein)
Rouleaux formation B
What’s Pseudo–Pelger-Huet anomaly—
neutrophils with bilobed nuclei. Typically seen after chemotherapy.
Markers to ALL
TdT+ (marker of pre-T and pre-B cells)
CD10+ (pre-B cells only).
Markers to SLL and CLL
And characteristic cell
CD20+, CD5+ B-cell neoplasm
Smudge cell
Diagnosis and treatment of Hairy cell leukemia
Stains TRAP (tartrate-resistant acid phosphatase ⊕) flow cytometry. Treatment: cladribine, pentostatin.
Acute myelogenus leukemia findings (2)
Auer rods
peroxidase ⊕ cytoplasmic inclusions
Markers and typical cells in langerhans cell histiocytosis
S-100 and CD1-a
Bribeck granules “tennis rackets”
Lytic bone lesions
Which mutation is implied in chronic myeloproliferative disorders?
JAK 2
In Polycythemia vera
Essential thrombocytosis
Myelofibrosis
Findings in CML
⬇️ RBCs ⬆️ WBCs ⬆️ Platelets ✅ Philadelphia chromosome ❎JAK mutation
What’s heparin-induced thrombocytopenia?
IgG antibodies against heparin- bound platelet factor 4 (PF4). platelets thrombosis and thrombocytopenia.
ALTERNATIVE Bivalirudin!!!!
What are Direct factor Xa inhibitors?
Apixaban
Rivaroxaban
Mechanism of action of clopidogrel ,ticagrelor (reversible)
Inhibit platelet aggregation by irreversibly blocking ADP receptors. Prevent expression of glycoproteins IIb/IIIa on platelet surface.
Mechanism of action of Cilostazol and dipyridamole?
Phosphodiesterase III inhibitor; cAMP in platelets, resulting in inhibition of platelet aggregation; vasodilators.
Which anti metabolites have ⬆️ toxicity whit de use of allopurinol or febuxotat?
Azathioprine
6-MP
Which drug is an folic acid which inhibit competitively dihydrofolate reductase?
Methotrexate
What pharmac can rescue the myelosuppression caused by methotrexate ?
Leucovorin
Pharma used to prevent cardio toxicity by doxorubicin daunorubicin
Dexrazoxane
Which Pharma prevents myelosuppression caused by cyclophosphamide ?
Mesna
Which anti cancer drugs do not cause bone marrow suppression(3)?
Bleomycin. Pulmonary fibrosis
Cisplatin. Nephrotoxicity
Vincristine Neurotoxicity
How can avoid cisplatin and carboplatin nephrotocixyty?
Amifostine
Mechanism of action of Hydroxyurea ?
Inhibit ribonucleotide reductase
Cause SEVERE MYELOSUPRESSION
Mechanism of action of bevacizumab
Monoclonal antibody against VEGF
Mechanism of action of erlotinib
EGFR tyrosine kinase inhibitor
Mechanism of action of imatinib
Tyrosine kinase inhibitor of BCR-ABL and c-KIT
Mechanism of action of rituximab
Monoclonal antibody against CD20
Mechanism of action of TAMOXIFEN RALOXIFENE
Tamoxifen estrogen receptors ❎ breast ✅endometrium✅bone
Reloxifene estrogen receceptors ❎breast ❎endometrium ✅bone
Mechanism of action of trastuzumab ?
Monoclonal antibody against HER-2 human epidermal grow factor 2
Is a tyrosine kinase exceptor which promotes apoptosis
Mechanism of action of vemurafenib
Inhibitor of BRAF oncogene melanoma
What are sequences of changes in iron deficiency anemia?(6)
⬇️ferritin hemosiderin bone marrow ⬇️serum ferritin ⬆️TIBC, transferrin ⬇️serum iron ⬇️blood hemoglobin Microcytic, hypo chromic
What are contraindications of fibrinolytic use (5)
Hemorrhagic stroke 180/110
Suspect of dissecting aneurism
What’s the most common repercussion arrhythmia?
Accelerated idioventricular rhythm
How aTPT is in hemophilia type A and B
Increased
Functions of vWF(2)?
Platelet adhesion
Carrier protein for factor VIII
Functions of prostacilcina (2)
Anti platelet aggregator
Vasodilator
Which events occurs in cellular the 5 cellular phases ?
G0 resting G1. RNA protein lipids carbohydrates synthesis S DNA replication G2 ATP synthesis M mitosis
Function of retinoblastoma protein
Hypophosphorilated ACTIVE cell cannot go G1⏩S
Hyperphosphorilated INACTIVE cell can go G1⏩S
Neoplasias linked whit dermatomyositis (4)
Ovarian
Lung
Colorrectal
Non-Hodgkin lymphoma
Clinical sings of whipple disease (3)
Arthritis
Diarrhea
Fever
Why ⬆️ACTH produces hyper pigmentation?
BECAUSE HAS A SIGNIFICANT SEQUENCE HOMOLOGY WITH ALFA-MSH!!!!!!!! PERROS HPSSSS
What type of hormones are secreted by lung small cell carcinoma?(2)
ACTH
Vasopressin
What type of hormones are secreted by squamous cell carcinoma lung (1)?
PTHrP
How high doses of folate can precipitate seizures?
Folate is an antagonist of phenytoin
Vasopressin is used to treat what hematologist disease (2)?
vWD
Hemophilia type A
Mechanism of action of aminocaproic acid?
Inhibition of breakdown of fibrin in blood clots
How HBV. DNA virus can produce cancer?
HBx an oncogen viral protein
Inactivate P53
What’s the protein product of c-myc implied in Burkitt lypmphoma?
Transcription factor nuclear phosphoprotein
What’s BCL2 protein implied in follicular lymphoma?
Apoptosis inhibitor
What are BRCA1 BRCA2 enzymes implicated in many tumor diseases?
DNA repair Enzymes
What is cyclin D1 product mutation in mantle cell lymphoma?
Promote G1 to S phase
What’s the product of fusion gene in CML (Philadelphia chromosome>
Increase tyrosine kinase
Promote mitosis
Inhibit apoptosis
Effect of use of rivaroxaban an in times of coagulation
⬆️aPTT
⬆️PT
↔️ TT
Effect of use of NON fractionated heparin an in times of coagulation
⬆️ aPTT
⬆️ TT
↔️ PT
Effect of use of davigatran an in times of coagulation
⬆️ aPTT
⬆️ PT
⬆️ TT
What is the net effect of heparin-induced thrombocytopenia?
PARADOXICAL THROMBOSIS
Treatment of heparin induced thrombocytopenia?(3)
Hirudin
Lepirudin
Argabatran
DIRECT THROMBIN INHIBITORS
How increase hemoglobins after iron replacement in iron deficiency anemia?
2gr/Dl per week the first three weeks
Hat is the problem in factor V Leiden mutation?
Factor V is resistant to the action anticoagulant of protein C
Creating an procoagulant state.
Which time of coagulation is increase in anti phospholipid antibody?
⬆️aPTT
What’s the action of folinic acid (leucovorin) to overcome leukopenia by methotrexate?
Folinic acid compete by DHF reductase against MTX
What’s the action of sulfonamide?
Inhibit the conversion of PABA to folic acid
ONLY IN PROKARYOTES
What’s chromosomes are implicated in acute promyelocytic leukemia?( a typo of Acute myelogenus leukemia)
t15-17
Etiology of black Vs brown biliary stones
Black stones chronic hemolysis or ileal disease
Brown stones biliary tract infection
What’s the worst picture for hemorrhage by low Vit k factors dependent (4) ?
Newborn
Refusal to Vit K prophylaxis
Exclusive Breastfeeding
Cystic fibrosis
Treatment for multiple myeloma
Proteasome inhibitors
Bortexomib
Boronic-acid contain dipeptide
Clinical findings of Multiple Myeloma (5)
Bone pain Fatigue Anemia Kidney disease Hypercalcemia
Which proteins of extra celular spa con interact with integrines ?
Collagen
Fibronectin
Laminin
Most important clinical findings in polycythemia Vera (3)
Aquagenic pruritus
Facial plethora
Splenomegaly
What type of red cells are typical in abetalipoproteinemia?
Acanthocytes
Mechanism of action of infliximab and uses (3)
Antibody to TNF-alpha
Rheumatoid arthritis
Ankylosing spondylitis
Crohn disease
Function of BCL 2 gene
It is an oncogene which inhibit cell death cascade
Genes implicated in follicular lymphoma
t14-18 bcl-2 oncogene
Mechanism of action of drug resistance of tumors like cells
P- glycoproteins an ATP dependent efflux protein
Cytokeratin is a cell marker for…
Epithelial cells!!!!!!
What type of cancer is linked whit EBV?
Nasopharyngeal carcinoma
What’s pure red cell aplasia?
IgG antibodies and T citotoxic cells
Produced in thymoma and lymphoma
Parvovirus B19
What is the effect of hepcidin?
⬇️iron absorption in the gut by causing degradation of ferroportin (transmembrane protein responsible for take the iron from the enterocyte to blood circulation)
What protein takes the iron from gut lumen to the enterocyte?
Divalent metal transporter-1
DMT-1
Mechanism of action of raltegravir ?
Integrase inhibitor!!!
Mechanism of action of enfuvirtide?
Fusion inhibitor
Ending word for protease inhibitor?
NAVIR!!!!!
What kind of antibodies are generated in immune thrombocytopenic purpura?
GP IIb/IIIa IgG
Common causes of aplastic anemia?(4)
Parvovirus
Epstein-Barr
⬆️Chemotherapy
Radiation
What drug can overcome the toxicity of methotrexate?
LEUCOVORIN!! (Folinic acid)
What association is used to enhance the effect of 5-fluorouracil?
LEUCOVORIN!!! (Folinic acid)
What kind of translocation has follicular lymphoma and what gene is overexpresed?
t14;18
BCL2
Direct and indirect Factor Xa inhibitors
DIRECT Rivaroxaban, Apixaban
INDIRECT Fondaparinox
Mechanism of action of Heparin non fractionated and enoxaparin?
Heparin bind to ANTITOMBIN III: f Xa - Thrombin
Enoxaparin bind to ANTITROMBIN III - f Xa
What kind of Basophilic cells (blue) are pathognomonic of MULTIPLE MYELOMA in the bone marrow aspirated?
WAGON WHEEL !!! 🎡
Why sickle cell anemia cause macrocytic anemia?
Deficiency of folic acid Vit B9
Because increased erythrocyte turnover
Which factors cause angiogenesis (2)
Vascular endothelial growth factor (VEGF)
Fibroblast growth factor (FGF)
Cause and clinical features of thrombotic thrombocytopenic purpura?
⬇️ADAMTS13 activity leads to vWF ⬆️⬆️microThrombi
Hemolitic anemia
Thrombocytopenia
Sometimes
Renal failure
Neuro manifestations
Fever
What ⬇️ haptoglobin means ?
Intravascular hemolysis
What RBCs surface markers are absent in paroxysmal nocturnal hemoglobinuria?
CD55
CD59
Because there is an mutation at phosphatidylinositol glycan mutation
⬆️complement- mediated hemolysis
PANCYTOPENIA!!!!
Clinical features of Hemolytic uremic syndrome?(4)
Bloody diarrhea
Hemolytic anemia schistocytes
Thrombocytopenia
Acute kidney injury
Function of Vit B9 folic acid in DNA synthesis
Single carbon donor for purine and pyrimidine synthesis
What kind of anemia is produced in chronic alcoholism whit chronic pancreatitis?
MEGALOBLASTIC ANEMIA!!!!
What is pathognomonic Histologic and clinical finding in follicular lymphoma?
Lymphoma cells whit clefted nuclei t14;18 ⬆️bcl-2
Fluctuating lymphadenopathy
What farmac can prevent the cytotoxicity of acrolein derivative of cyclophosphamide ?
MESNA!!!
Which farmac can prevent the toxicity of doxorubicin?
Dexrazoxane!!!
Histologic finding in glioblastoma multiforme
Central necrosis and vascular proliferation.
Two clinical pathognomonic findings in aplastic anemia?
PANCYTOPENIA
NO SPLENOMEGALY!!!!
Tumors in Lí-Fraumeni syndrome ⬇️TP53 (5)
Sarcoma Breast cancer Brain tumor Adrenocrotical carcinoma Leukemia
What exams are alternated in von Willebrand disease?(2)
⬆️ bleeding time (platelet disfunction)
⬆️ PTT( degradation of VIII factor)
What is the final path in the coagulation cascade
Xa -(Va) ⬇️ Prothrombin --- thombrin IIa ⬇️ Fibrinogen- fibrin Ia
Treatment for hemophilias?
THROMBIN!!!!!
Auer rods are seen in…
ACUTE MYELOGENUC LEUKEMIA !!!!!
AML!!!!!!
t 15;17
Promyelocytic leukemia ➕Retinoic receptor alpha gene
How are the coagulation times in chronic renal failure?
⬆️ bleeding time uremic toxins qualitative platelet disorder
TP, TPT NORMAL
What gene is Overexpressed in Burkit lymphoma and what infectious agent is related?
c-MYC t(8;14)
EBV in HIV patients
How treat warfarin overdoses? (3)
Fresh Frozen Plasma
Prothrombin Complex Concentrates (II,VII,IX,X)
Vitamin K
Which feature differentiate immune thrombocytopenic anemia from hemolytic uremic syndrome?
Would not produce anemia or renal disease
Which cells is infected an which cells proliferated anomaly after Epstein bar virus infection?
Infect B cells
Activation of T cells proliferate anomaly
Where are seen pautrier micro abscesses?
Mucous is fungoides
Sezary sindrome
How MCHC is in spherocytosis?
⬆️MCHC
Complications of espherocitosis ?
Pigment gallstones
Aplastic crises from parvovirus B19 infection
How is haptoglobin in hemolytic anemia?
⬇️haptoglobin
Abnormal cells related whit sideroblastic anemia?
Pappenheimer
Principal findings in hairy cell leukemia ?
Middle age men Bone marrow fibrosis Pancytopenia Massive Splenomegaly Tartrate-resistant acid phosphatase test
What are the pathognomonic findings in ferropenic anemia? (2)
Disphagia (esophageal webs)
Koilonuchia (spoon nails)
How is the CBCs in paroxysmal hemolytic anemia?
Hemolytic anemia
⬇️ leucocytes
⬇️ platelets
Findings in leukemoid reaction (3)
Left shift
Dohle bodies( MATURE neutrophils whit Basophilic oval inclusions)
⬆️↔️Leukocyte alkaline phosphatase
Drugs and infections which produce Aplastic anemia?(3,2)
Chloramphenicol
Carbamazepine
Sulfonamides
Parvovirus B19
Epstein-Barr virus
Clinical manifestations of carcinoid syndrome?(4) ⬆️5-HIAA urine
SKIN flushing telangectasias cyanosis
GI watery diarrhea cramping
PULMONARY Bronchospasm dyspnea
CARDIAC valvular fibrosis plaques (right>left)
What’s Trousseau syndrome?
Migratory thrombophlebitis by visceral cancer (pancreas,colon, lung)
Adenocarcinomas produce thromboplastin-like substance
HYPERCOAGULABILITY STATE
Presence of immune complex vasculitis associated with IgA and C3 deposition is typical in….
Henoch-Schonlein purpura
Cause of liver fatter change and Hepatocyte necrosis?
FREE RADICAL INJURY!!!!
⬇️
Mithocondrial disfunction
Meaning of presence of Myeloblast, Myelocyte and band In Peripheral blood?
Myeloblast. MALIGNANCY
Myelocyte LEUKEMOID REACTION , PREGNANCY
Band NORMAL INFECTION
Important features of AML acute myelogenus leukemia ( the most common acute leukemia upon adults)? (3)
Around 65 years old
WBCs. 15000-20000
Blasts >20%
Which factors reflects PT?
Tissue factor
Fibrinogen
II , V, VII, X
What measure trombine time TT?
Rate of conversion of fibrinogen to fibrin
If prolonged means liver disease
Explain how high doses of Vit A can cure acute Promyelocytic leukemia an AML?
t(15;17)
🚫Retinoic acid receptor alpha (differentiation of myeloid precursors)
Treatment with all-trains-retinoic acid VIT A!!!! In high quantities
Overcomes this situation
How works LMWH (enoxaparin) and Heparin?
Heparin binds: ANTITROMBIN III+ THROMBIN
ANTITHROMBIN III+ Factor Xa
LMWH binds : ANTITHROMBIN III+ Factor Xa
Rare tumor associated with arsenic and polyvinyl chloride , CD31+?
Liver angiosarcoma
CD31+ = PECAM1
Mechanism of action of Etanercept?
TNF-alpha inhibitor !!!!
What “mab” means in farmac?
Mab. Monoclonal antibody
What “nib” means in farmac?
nib kinase inhibitor
Explain the genetic feature of follicular lymphoma, CML, Burkitt lymphoma , breast cancer, Lí-fraumeni syndrome?
follicular lymphoma Bcl2- Overexpression t14-18
CML Bcr-abl hybrid formation t9-22
Burkitt lymphoma C-myc Overexpression t8-14 t8-22 t8-2
breast cancer Erb-B2 Overexpression
Lí-fraumeni syndrome p53 inactivation
What is the treatment for warfarin-induced skin necrosis?
fresh frozen plasma
to replenich protein C
How patients whit ALL develops dysphagia,stridor and disnea?
30% are T-cells ALL and develope
mediastinal mass compressing the esophagus and trachea.
but the majority 70% are B-cell ALL
whitout mediastinal mass.
How is clasiffied Acute Myelogenous Leukemia? and what is Acute Promyelocytic Leukemia (APML)?
M0-M1-M2-M3 (APML)-M4-M5-M6-M7-M8
APML t(15;17)
abnormal retinoic acid receptor
Auer Rods
PANCYTOPENIA
Disseminated intravascular coagulation
function of EGFR , implied in colo rectal cancer?
EGFR transmembrane receptor
binds KRAS which in turn cause Cell proliferation
What ere the neuroendocrine cells markers?(3)
Neuron-specific enolase
Chromogranine
Synaptophysin