Hematology/Oncology Flashcards
In which hemolytic disease we see Heinz bodies and bite cells?
G6PD deficiency
What are Heinz bodies?
These are oxidized or precipitated hemoglobin.
What is the role of G6PD?
G6PD is an enzyme that generates NADPH. NADPH is a cofactor for production of Glutathione. Without Glutathione, oxidative metabolites accumulate in the erythrocytes and precipitate DNA into Heinz bodies.
Why G6PD activity level can be normal during the acute hemolytic crises in a G6PD deficient patient?
During the acute hemolytic crises, the newer erythrocytes will have disproportionately higher activity of G6PD as compared to older erythrocytes.
What type of hemolytic anemia is associated with Chronic Lymphocytic leukaemia (CLL)?
Extravascular autoimmune hemolytic anemia due to IgG (Warm agglutinin) antibodies.
What is Hereditary Hemorrhagic Telangiectasis?
Osler-Weber-Rendu syndrome characterized by diffuse telangiectasias, recurrent epistaxis, and widespread AV malformations.
Lung hemorrhagic AV malformations can result in hypoxemia resulting in reactive polycythemia.
What are the important clinical sxs of paroxysmal nocturnal hemoglobinuria?
it is an autoimmune intravascular and extravascular hemolytic anemia due to abscess of CD 55 and CD59 proteins resulting in complement activation of WBCs.
SXS are hemolysis, cytopenia, and venous thrombosis due to hypercoagulability.
Is coombs test positive or negative for Autoimmune hemolytic anemia?
Positive
Is Coombs test positive or negative in hereditary spherocytosis?
It is negative
What are the causes of intravascular hemolysis? What does lab show?
MAHA, transfusion reactions, infections, PNH, IV Rho(D) immunoglobin infusion.
Decreased haptoglobin, Increased (LDH, Indirect bilirubin)
What are the causes of extravascular hemolysis? What does lab show?
Intrinsic RBC enzyme deficiencies (eg G6PD), Hemoglobinopathies (eg SCD, Thalassemia), Membrane defects (eg hereditary spherocytosis), warm or cold agglutinins anemias, infections
Mild decreased or normal Haptoglibin, Increased indirect bilirubin, Mildly increased LDH
What does Hb electrophoresis for beta thal minor shows?
increase in hemoglobin A2
What is the pentad of thrombotic thrombocytopenic purpura?
Microangiopathic hemolytic anemia, thrombocytopenic purpura, Neurologic complications (headaches, seizures), renal disease, Fever
What enzyme is deficient in TTP?
ADMATS13 - an enzyme that cleaves large mutimers of vWFs
What is S1Q3T3 sign on ECG?
It is McGinn-White sign indicating right heart strain.
It is seen in PE.
Which is the drug of choice for post-polycythemia vera myelofibrosis?
Ruxolitinib, the Janus kinase inhibitor
What needs to be avoided in TTP?
Plasma transfusion needs to be avoided because it can contribute to formation of platelet thrombi.
What would normalize first after starting plasmapharesis for TTP?
Neurologic deficits
What is the treatment for transfusion related hemosiderosis?
Treatment is with iron chelators such as deferoxamine.
Physical examination will show grey skin and lung crepitation.
What is Budd-Chiari syndrome?
It is due to hepatic venous outflow obstruction that could be caused by myeloproliferative disorder (P vera), Malignancy (hepatacellular cancer), oral contraception/pregnancy.
Sxs are manifestation of hepatic vein obstruction. Liver injury (jaundice, LFTs), abdominal pain, ascites, venous pooling, varices
Diagnosis with abdominal doppler ultrasound. JAK2 mutation for P vera
Common meds that disrupt dihydrofolate reductase and result in megaloblastic anemia?
phenytoin, methotrexate, trimethoprim, and pyrimethamine
What are common side effects of phenytoin?
gingival hyperplasia and Folic acid deficiency
What supplementations are recommended with phenytoin?
Folic acid, vitamin D and calcium
Why there is increased risk of non HL in SLE?
patients with chronic autoimmune disease are at increased risk for lymphoproliferative disorders such as NHL due to chronic B cell stimulation, immune dysregulation, use of immunosuppressive agents.
What is the next best treatment option in patients with hemochromatosis if they cannot tolerate weekly phlebotomy?
Iron chelation therapy. eg is Defarasirox PO qd
Which is the most important investigation in suspected cases of lymphoid malignancies?
CBC
Which test would be best to confirm Vit B12 deficiency?
Methylmalonic acid (MMA)
What is common link between hereditary hemochromatosis and porphyria cutanea tarda?
C282Y mutation
Increase in Hemoglobin A2 supports what diagnosis?
Beta thalassemia minor;
HbA2 consists of 2 alpha and 2 delta units
Which diagnostic study would be most helpful in confirming diagnosis of AML-M3?
cytogenetic studies performed on bone marrow are the best way to confirm a diagnosis of acute promyelocytic leukemia, which carries the t(15:17) chromosome abnormality. A faster way to perform cytogenetic abnormalities studies is by Fluorescence in Situ hybridization.
What is the differentiation syndrome?
it is a fatal complication that is seen in acute promyelocytic leukemia patient (AML-M3) after treatment with ATRA. There is a massive release of cytokines that results in system wide inflammation. Sxs such as fever, weight gain, hypotension, pleural and pericardial effusion and ARDS.
Tx is Dexamethasone.
What is the WHO criteria for polycythemia vera?
Major criteria:
1) Hb >165g/L in Men and >160g/L in Women; Hct >49% in men and >48% in women; RBC mass >25% more than normal predicted value.
2) Bone marrow biopsy showing increase in all 3 cell lines (trilineage growth)
3) JAK2 mutation
Minor criteria:
Decreased EPO levels (<25U/L)
In order to diagnose for Factor V leiden, what is the screening test?
activated Protein C resistance assay; mutation in the Factor V gene makes it resistance to proteolytic effect of protein C
Currently, which is the best screening test for hereditary hemochromatosis?
serum Transferrin saturation; calculated by ratio serum Fe/TIBC
Is thrombotic thrombocytopenic purpura a medical emergency?
Yes
Is acute promyelocytic leukemia (APL/AML-M3) a medical emergency and why?
Yes, It results in pancytopenia and promotes consumptive coagulopathy. There is high risk for pulmonary/cerebrovascular hemorrhage due to consumptive coagulopathy. There is increased risk for DIC.
Immediate treatment with ATRA
What is the crucial diagnostic step in diagnosis of TTP?
Peripheral blood smear which will show signs of intravascular hemolysis (schistocytes, helmet cells, triangle cells).
What is the positive rapid fluorescent spot test?
This test detects the generation of NADPH from NADP and is positive if the blood spot fails to fluoresce under UV light.
What is the treatment of Diphyllobothrium latum?
single oral dose of Praziquental 5-10mg/kg
Which finding most reliably indicates a diagnosis of iron deficiency anemia?
low serum Ferritin
In which condition we seen basophilic stipplings?
sideroblastic anemia; Lead poisoning can cause sideroblastic anemia by interfering with the synthesis of heme.
Which is the most common type of thyroid cancer?
papillary thyroid cancer
What is the treatment of choice in patients with nasopharyngeal carcinoma?
Concurrent chemotherapy and radiotherapy
What is the treatment of choice for the pt with prostatic cancer that has metastasized?
Androgen deprivation therapy with a combination of radiation therapy as an option.
What enzyme is involved in the congenital sideroblastic anemia?
Aminolevulinic acid synthase (rate limiting step in the production of protoporphyrin)
What 2 enzymes are affected by lead poisoning in sideroblastic anemia?
Aminolevulinic acid (ALA) dehydrogenase and Ferrochelatase
When do we see HbH?
it is a tetramer of Betaglobin seen in alpha thalassemia major when 3 alpha genes are deleted resulting in severe anemia
What is HbF?
fetal hemoglobin; 2 alpha and 2 gamma
what is HbA2?
seen in minor Beta thalassemia; 2 alpha and 2 delta
When do we see Howell-Jolly bodies?
in patients who have undergone splenectomy. Spleen destroys RBCs with nuclear remnants inside their cells.
What is hemoglobin barts?
it is a tetramer of 4 gamma globins seen in alpha thalassemia major when all 4 genes are deleted.
