Heme Flashcards
Ipilimumab/Yervoy
CTLA-4 immune checkpoint inhibitor
Nivolumab/Opdivo
PD-1 immune checkpoint inhibitor
Axicabtagene/Yescarta
anti-CD19 CAR-T (CD28 construct)
Brexucabtagene/Tecartus
anti-CD19 CAR-T (CD28 construct)
Tisagenlecleucel/Kymriah
anti-CD19 CAR-T (41BB construct)
Lisocabtagene/Breyanzi
anti-CD19 CAR-T (41BB construct)
Ciltacabtagene/Carvykti
anti-BCMA CAR-T (41BB construct)
Idecabtagene /Abecma
anti-BCMA CAR-T (41BB construct)
What does CTLA-4 bind to?
Dendritic cell ligand B7 (CD80), which would otherwise bind to CD28; this results in immune suppression
Which is more serious - PD-1 or CTLA-4 inhibition?
CTLA-4 has more severe side effects
Combined Research:
Cornell - Supplemental Application needed
UPenn - no supplemental needed
Mount Sinai - separate residency number
NYU - physician scientist track on website but link broken; clinical investigator track also exists
Yale - separate residency number
Beth Israel - direct ABIM
Mass Gen - Stanbury direct (fellowship not automatically coupled); will not automatically consider for categorical
Brigham - apply internally
Johns Hopkins - apply internally during intern year
Boston University - yes
Columbia - nothing
Montefiore/Einstein - not cancer specialty
Dabrafenib
BRAF inhibitor
Used in combination with trametinib, a MEK inhibitor, for melanoma and glioma
Cytarabine
Pyrimidine analog - competes with cytidine and incorporates into DNA, inhibiting DNA replication and inhibiting DNA polymerase
Nelarabine
Purine analog - metabolized into ara-GTP, which competes with guanosine
Anamnestic antibody response
Delayed hemolytic transfusion reaction to RBC antigen to which patient was previously sensitized (e.g. pregnancy)
Occurs days to weeks after transfusion
ABO incompatibility would cause what key features?
- Fever, flank pain, hemoglobinuria
- DIC
- Positive Coombs test
What does capillary refill assess?
Volume status/hypovolemia
Also look at dry mucous membranes, low skin turgor
What does pallor assess?
Anemia
Also look at mucous membranes, coarseness of hair, puffiness of face, nail defects
Potential exacerbations of sickle cell trait that can lead to intravascular hemolysis, tissue ischemia, and/or pain
- Flying at high altitude
- Dehydration due to alcohol
common cancers associated with malignant pericardial effusion
Breast
Lung
Lymphoma
Kerr sign
Referred pain from diaphragm and phrenic nerve to left shoulder - from splenic rupture
How is heparin-induced thrombocytopenia diagnosed?
Immunoassay (only if high titer)
Functional assay (serotonin release assay; gold standard)
Argatroban
Direct thrombin inhibitor
Used for HIT
Fondaparinux
Indirect inhibitor of Factor Xa (similar to LMWH), does not inhibit thrombin at all
Synthetic pentasaccharide sequence
Used for HIT
Chylothorax - signs and treatment
When lymphatic flow through thoracic duct is disrupted, leading to direct leakage of chyle into pleural cavity
Pleural fluid will contain T cells, Ig, and triglycerides (chylomicrons)
Treat with thoracentesis or chest tube, limiting dietary fat, and possible thoracic duct ligation
Sickle cell priapism treatment
Aspiration from corpora cavernosa, then intracavernous injection of phenylephrine
Who most often develops inhibitors of coagulation?
- Malignancy
- Rheumatic disease
- Postpartum period
Primary symptom of drug-induced thrombocytopenia
Oropharyngeal mucositis (sore throat, erythema, ulcers)
Smudge cells
Chronic lymphocytic leukemia
Waldenstrom macroglonulinemia - symptoms
- Hyperviscosity (diploma, hearing, headache)
- Neuropathy
- Hepatosplenomegaly, LAD
> 10% clonal B cells
Cyclophosphamide
Alkylating agent
Lupus with significant renal or CNS problems, vasculitis, cancer
Hemorrhagic cystitis, bladder cancer caused by acrolein metabolite - reduce risk with fluids, frequent voiding, mesna
Sterility, myelosuppression
What is a lung consequence of sickle cell disease?
Pulmonary hypertension due to vascular remodeling
Intravascular hemolysis releases heme, which consumes nitric oxide resulting in vasoconstriction; there is also inflammation and injury
Why is acute promyelocytic leukemia an emergency?
Tumor-induced consumptive coagulopathy - via activation of tissue factor (DIC) and increased generation of plasmin (fibrinolysis)
Tumor lysis syndrome - prophylaxis and treatment
Prophylaxis: IV fluids + xanthine oxidase inhibitor (allopurinol or febuxostat) or rasburicase
Treatment: IV fluids + rasburicase
Hydroxyurea main side effect
Myelosuppression
How can CML be differentiated from leukemoid reaction?
CML has low leukocyte alk phos score since they are abnormal neutrophils
CML typical mutation
BCR-ABL t(9;22)
Paroxysmal nocturnal hemoglobinuria
Defect in anchor protein leading to complement-mediated hemolysis
Venous thrombosis, episodic intravascular hemolysis
Eculizumab
Treatment for paroxysmal nocturnal hemoglobinuria
Anti-C5 antibody preventing complement activation
Extravascular hemolysis causes
AIHA, intrinsic RBC enzyme defect (G6PD deficiency) or membrane defect (hereditary spherocytosis)
However, paroxysmal nocturnal hemoglobinuria, DIC, and cold agglutinin IgM are intravascular
CVID comorbidities
- Autoimmune (RA, hemolytic anemia, pernicious anemia)
- IBD-like disease
- Enteropathy with makabsorption and weight loss
- Granulomas
- Increased risk of NHL
What causes TRALI?
Donor anti-HLA or anti-granulocyte Ab cause granulocytes in lungs to agglutinate and degranulate
As opposed to febrile nonhemolytic, which is donor anti-HLA or cytokines
What lab error can cause pseudothrombocytopenia?
Platelet clumping due to anti-EDTA antibodies
Drawing blood in heparin or citrate should resolve
Sideroblastic anemia - effect on iron
Iron, ferritin, and transferrin saturation are all elevated, despite microcytic anemia
Hodgkin treatment long-term adverse effects
Secondary malignancy
Cardiac disease
Radiation-induced hypothyroidism
Folate is important for production of what nucleic acid?
Thymidine
Azacytidine
Impairs DNA methylation
Used in MDS, AML
Asplenic patients with pneumococcal infection are more likely to develop what heme manifestation?
Purpura fulminans:
DIC
Tissue thrombosis
Skin hemorrhage and necrosis
How do neutrophils appear in B12 deficiency?
Hypersegmented
What is the dysplastic appearance of neutrophils and erythrocytes in MDS?
WBC: Hyposegmented, hypogranular
RBC: Ovalomacrocytosis, normal or increased MCV
Why does hereditary spherocytosis lead to gallstone risk?
Chronic hemolysis bilirubin leads to pigment gallstones (as well as jaundice and dark urine)
Can splenectomy lead to platelet elevation in both short and long term?
Yes
Ruxolitinib
Jak1/Jak2 inhibitor used in polycythemia vera, myelofibrosis
Watch out for platelet count
Fludarabine
Purine analog
Heinz bodies, bite cells, blister cells
G6PD deficiency
Heinz bodies are denatured Hgb that may disappear later after episode of oxidative stress
Anticoagulation in case of HIT
Argatroban
Dabigatran reversal agent
Idarucizumab
INR guidelines for warfarin
Bleeding: Discontine, give IV Vit K and PCC
INR >10 without bleeding: Discontinue, give oral Vit K
INR 4.5-10: Hold for few doses; can give low-dose Vit K
INR <4.5: Hold next dose, readjust maintenance
Does cryo require ABO compatibility?
Yes
Which vWD types are autosomal dominant?
Type 1 (mild-moderate quantitative deficiency)
Type 2 (qualitative problem)
Type 3 is complete absence of vWF
What is more effective treatment for antiphospholipid antibody syndrome?
Warfarin
TTP treatment
Plasma exchange
When to treat ITP
Plt <30,000 or significant bleeding
Steroids and IVIG
2nd line: Splenectomy, rituximab, anti-D (Rh) Ig, TPO receptor agonist
Basophilic stippling vs ringed sideroblasts
Basophilic stippling: Lead poisoning inhibits ribosomal RNA degradation
Ringed sideroblasts: Prussian blue-stained, iron-laden mitochondria at periphery
Lead poisoning can have both due to defective heme synthesis
Sideroblastic anemia treatment
If acquired cause, give pyridoxine (cofactor of ALA synthase)
Mentzer index
MCV/RBC: <13 is thalassemia, >13 is IDA
Spherocytes can also be seen in…
AIHA
PNH treatment
Prednisone
Eculizumab (complement C5 inhibitor - must give N. meningitidis vaccine)
BMT
Warm vs cold causes of AIHA
Warm: lupus, CLL, lymphoma, various drugs
Cold: mycoplasma pneumoniae, EBV, Waldenstrom macroglobulinemia
Warm AIHA treatment
Steroids, splenectomy if recurrent, or IVIG if severe and nonresponsive
Blood smear - megaloblastic vs nonmegaloblastic difference
Nonmegaloblastic (alcohol, liver disease) doesn’t have neutrophil hypersegmentation
Tea-colored urine
Porphyria cutanea tarda - caused by buildup of uroporphyrin
Factors that exacerbate ALA synthase in acute intermittent porphyria
CYP450 inducers, alcohol, starvation
Acute intermittent porphyria - signs and treatment
Abdominal pain, port-wine colored urine, polyneuropathy, psych
Treat with hemin and glucose
Acute intermittent porphyria vs porphyria cutanea tarda - diagnosis
AIP: urine porphobilinogen
PCA: plasma or urine porphyrins
What tumor lysis syndrome drug is contraindicated in G6PD deficiency?
Rasburicase
Hairy cell leukemia initial treatment
Cladribine
T15;17
APL
T14;18
Follicular lymphoma - heavy chain Ig;BCL-2
T8;14
Burkitt
T11;14
Mantle cell
Immunosuppressive/cytotoxic therapy fornhemophagocytix lymphohistiocytosis
Dexamethasone, etoposide
Kit stain
Mast cells (mastocytosis); alsslo serum tryptase >20
Langerhans cell histiocytosis - typical mutation
BRAF V600E
Notable Langerhans cell histiocytosis symptoms
Diabetes insipidus and other hypothalamic-pituitary axis involvement, skin/oral brown purplish papules and/or erythematous rash, osteolytic bone lesions, and many others