Final Flashcards
Where can you see neutrophilia
CML, leukemia, sickle cell
Secondary disosrders: infection, inflammation, smoking, stress, asplenia and medications (corticosteroids lithium and exogenous growth factors), CSF secreting tumors (bronchogenic carcinoma)
How do neutrophils change with infection
Increase in marginated pool, decrease in circulating, increase in tissue
How do neutrophils change with epi
Increased circulating pool, decreased marginated pool, decreased in tissue
How do neutrophils change with steroids
Equal circulating and marginated pool
How does leukocyte adhesion deficiency affect neutrophils
Increase in circulating pool, low marginated pool, low in tissues
What are causes of acute vs chronic neutrophilia
Acute: physical stimuli, emotional stimuli, infection (localized or systemic, bacterial, mycotic, rickettsial, some viral), inflammation or necrosis (burns, trauma, gout, vasculitis), drugs
Chronic: heme disorders (chronic hemolysis, asplenia*, myeloproliferative disorders), endocrine disorders (thyroid storm, ACTH overproduction), drugs, malignancy (gastric or bronchogenic), inflammation and infection
What is the workflow for evaluation of neutrophilia
Repeat counts; if persistent examine smear for leukocrythroblastosis -> if yes, BM exam for tumor, granulomas, CML; if no -> look for signs of fever or infection -> if no, serological for AID, peripheral blood for BCR-ABL and JAK2, potential drugs, smoking
What are the causes of eosinophilia
Parasite infections (trichinella), allergic rhinitis, atopic dermatitis, urticaria, fungal allergy, asthma, meds (abx, NSAIDs, antipsychotics), bronchiectasis/cardiac failure
What should basophilia always trigger evaluation for
CML and PV
What drugs cause neutropenia
Cephalosporins, clindamycin, gentamicin, sulfonamides, tetracyclines, vancomycin, carbamazepine, mephenytoin, phenytoin, anti depressants (amitriptylene), H2 blockers (ranitidine), antimalarials, antithyroid, CV drugs (hydralazine, captopril, propranolol), diuretics (thiazides), antipsychotics (chlorpromazine), allopurinol
What is the suggested workup for neutropenia
If fever and ANC <500 give abx; if new -> see if isolated or pancytopenia -> if isolated do BM exam, if pan measure B12; if BM exam reveals abnormal cytogenetics, myelodysplasic, if LGL by flow then LGL if normal then idiopathic; if not new see if FH -> check for ELANE mutation (cyclic neutropenia)
What is lymphopenia
Lymphocyte count <1500
What are the causes of lymphopenia
Congenital immunodeficiency diseases (SCID, CVID, ATM, wiskott-Aldrich), aplastic anemia, infections, iatrogenic (chemo, glucocorticoids)
What is monocytopenia seen in
Hairy cell leukemia even in absence of hair cells on smear, do flow cytometry for markers (CD11c and CD103)
What conditions have low hemoglobin but normal hematocrit
Thalassemia
What is the definition of anemia
Hemoglobin <12 in females and <13 in males
How do you calculate mea corpuscular hemoglobin and mean corpuscular hemoglobin concentration
MCH: hemoglobin/red cell count
MCHC: hemoglobin/hct
What does increased reticulocyte count suggest in terms of anemia
Either blood loss or response to therapy; low reticulocyte count indicates iron deficiency or folate/b1 efficiency or low. EPO
What are acanthocytes associated with
Liver disease
What are echinocytes associated with
End stage renal dz
What is the evaluation of someone with anemia
Look at reticulocyte count; if high and bleeding, due to blood loss, if high and no bleeding do a smear - if schistocytes (microangiopathy), spherocytes (hereditary spherocytosis or warm abs), sickle cell, bite cells (G6PD), target (thalassemia), inclusions (malaria); if reticulocyte count low do peripheral smear - if microcytic (iron def, thalassemia, sideroblastic), normocytic (aplasia, marrow infiltration, Renal dz, inflammation, chronic dz), if macrocytic (B12 def, folate def, Myelodysplasia, drug toxicity, alcohol)
What is the treatment for aplastic anemia
Offer HSC transplant for <40; if not eligible, immunosuppressive therapy with antithymocyte globulin and cyclosporine
What drugs can cause microcytic anemia
Alcohol, lead, chloramphenicol, isoniazid - via reducing heme synthesis
What is pagophagia
Craving for ice seen with iron deficiency
Why is ferritin not useful in diagnosing inflammation related anemia
Ferritin is an acute phase reactant
Where is intramedullary hemolysis seen
Thalassemia
What is characteristic of methemoglobinuria
Contains ferric ions which causes pO2 values higher than expected in relation to percent oxygen saturation
What drugs should not be used in patients with G6PD deficiency
Dapsone, methylene blue, nitrofurantoin, phenylhydrazine, primaquine, sulfamethoxazole, sulfapyridine
What is nonmegaloblastic macrocytosis associated with
Liver disease
What does inflammation do to erythropoeisis
Decreases it; hepcidin increases which decreases iron
What do you treat babies who test positive for sickle cell with
5 years of prophylactic penicillin (or macrolide if allergy)
What are the risks assoc with sickle cell trait
Sudden death with extreme exercise
What is the anemia seen with sickle cell
Normocytic normochromic; increased reticulocyte count; if microcytic suggests sickle cell beta thalassemia or coninherited alpha thalassemia
What kind of murmur can be caused by anemia
Systolic
What are the effects of hydroxyurea
Increases HbF, lowers neutrophils, hydrates erythrocytes, macrocytosis, lower reticulocyte count
When should exchange transfusions be used in sickle cell
To manage acute complications; reduces iron overload (rather than transfusion)
What are ACE inhibitors used for in sickle cell
Prevent kidney dz by lowering intraglomerular pressure; also lowers protein excretion (used in patients with sickle cell and albuminuria even in abscence of HTN)
What vitamins supplement must be given to sickle cell patient
Folic acid
What drugs are linked to ITP
Quinidine, rifampin, TMP-SMX, phenytoin, gold
What screening is required for all patients with ITP
HIV
What is the treatment for ITP
Glucocorticoids and IV immune globulin
If there are schistocytes on a peripheral blood smear, can ITP be a diagnosis
No; will be TTP, DIC or HELLP; when measuring platelets make sure to exclude clumpin
What should be administered if patient has HIT
Direct thrombin inhibitors (lepirudin or argatroban)
What is the 4T score for diagnosis of HIT
-thrombocytopenia:2 points (platelet count fall >50%), 1 point (platelet count fall 30-50% or nadir 10k-19k)), 0 points (platelet fall <30% or nadir <10,000)
-timing of fall: onset btw 5-10 das 2 points, onset after 10 days 1 point, <4 days 0 points
-thrombosis: new thrombosis, skin necrosis 2 points, progressive or recurrent thrombosis, nonnecrotizing skin lesions 1 point, no thrombosis 0 points
-other causes for thrombocytopenia: none 2 points, possible 1 point, definite 0 points
Score 0-3: low probability, 4-5 intermediate, 6-8 high
Should you transfuse platelets in untreated TTP-HUS
No; associated with stroke and acute kidney injury
What is the treatment for essential thrombocythemia
If <60 with no hx of thromboembolic event, and platelet count <1 million follow without therapy; those not in this category treated with hydroxyurea and low dose aspirin (if need greater platelet reaction, give pegylated IFN-alpha or anagrelide)
What are causes of reactive thrombocytosis
Iron deficiency, inflammation, cancer, infection
What is the Ann Arbor staging system for lymphoma
- stage I: involvement of single LN region or single extranodal organ
- stage II: involvement of 2 or more LN regions or lymphatic structures on same side of diaphragm; or involvement of limited contiguous extranodal sites (IIE)
- STage III: involvement of LN regions or lymphoid structures on both sides of the diaphragm (if involves spleen IIIS)
- Stage IV: diffuse or disseminated involvement of one or more extranodal Organs with or without LN involvement
What should patients with HL receive before starting treatment
EKG and pulm function; women should receive fertility preservation counseling
What are prognostic risk factors for HL therapy
Increased ESR, male, >40, stage IV dz, bulky mediastinal LAD
What is the treatment for Hodgkin
ABVD
What is patient management after treatment of HL
For first 3 years, seen every 3-6 months; in 4th and 5th year every 6 months and annually thereafter
What should be included in follow up for HL survivors
CBC, thyroid function, annual infuenza shot if received bleomycin or chest radiation; breast cancer screening beginning 8-10 years post radiation or at age 40
What should all patients with NHL be tested for
HIV and hep C
What is the prognosis of 8;21 AML
Good in adults, poor in kids; RUNX1/AML1 gene
What is the abnormality seen in AMML
Inversion 16 or translocation 16;16; abnormal eosinophils with large and irregular basophilic granules and positivity for chloroacetate esterase; KIT mutation confers poor prognosis; RUNX1/CBFB
Where is translocations involving 11q seen
Acute monocytic leukemia ; poor prognosis unless have 9;11 mutation; involves KMTA/MLL
What are the most common mutations seen in AML
FLT3(most common in APL and AML with normal karyotype) - assoc with poor prognosis
NPM1 - favorable
CEBPA - favorable
What is the standard chemo induction for AML
3 days of daunorubicin or idarubicin, and 7 days of continuous infusion of cytarabine; can cause tumor lysis syndrome; if neutropenic fever, give abx, if persists, give antifungals
What is the definition of remission for AML
Normalized blood counts, <5% BM blasts, normalization of karytoype
what are the treatments for AML and ALL
- AML: induction = 3+7 anthracyclin and ara-c; consolidation: high dose ara-c (HDAC); maintenance: promyelocytic leukemia only - ATRA
- ALL: induction - vincristine/prednisone + others; consolidation: multiple agents plus CNS prophylaxis (MTX or ara-c), maintenance: 6MP and MTX
What is IKZF1 alterations seen in
ALL with Ph chrom; poor prognosis
What are the 2 groups of ALL with hyperdiploidy
A group with 1-4 extra chrom (47-50) and more commonly more than 50 chrom - more common in kids (X, 21, 10, 14, 17,18, 4, 6); gain of 5 and 17q is poor prognosis; 4 10 17 good prognosis
What is the 1;19 translocation seen in
Kids with B cell ALL; CD10, CD19, CD34-, CD9
What is 8;14 seen in besides burkitt
Mature B cell ALL: high incidence of CNS involvement or abndominal LN involvement
What is the follow up for CML
1-2 weeks during initiation of imatinib; once stable blood counts, every month
What is the Rai staging system for CLL
Stage 0 - asymptomatic with lymphocytosis
Stage I: lymphocytosis with LAD
Stage II: lymphocytosis, LAD and HSM
Stage III: anemia
Stage IV: thrombocytopenia ; last 2 have mean survival of <2 years
What is the Binet staging system for CLL
Based on # of LN sites involved
Stage A: fewer than 3 sites
Stage B:3 or more sites - survival of 7 years
Stage C: anemia or thrombocytopenia; survival < 2 years
What can complicate CLL
Prone to autoimmune disease development; autoimmune thrombocytopenia or hemolytic anemia
What are the markers for hairy cell
CD22, 25, 103; also express tartrate resistant acid phosphatase
What is the treatment for hairy cell leukemia
Splenectomy; cladribine and deoxycoformycin; chemo refractory responds to vemurafenib (BRAF inhibitor)
What drugs can cause myelodysplastic syndromes
Alkylating agents (busulfan, nitrosurea, procarbazine) - latency 5-7 years Topoisomerase inhibitors: 2 year latency
What alterations are seen in myelodysplastic syndromes
Euploidy mostly; loss of 5,7, 20 or trisomy 8
What mutation is seen specifically in MDS (not AML)
SF3B1 (RNA splicing machinery) - favorable outcome
What causes diamond Blackfan anemia
5q deletion
What is the treatment for MDS
If asymptomatic, nothing; if anemic, transfusion, azacitidine(hypomethylating agent) can prolong survival and delay time of formation to leukemia - give to patients with poor prognosis and symptomatic
What is lenalidomide used for
Thalidomide derivative; reversing anemia in MDS with 5q deletion; side effect: mylosuppresion and increased risk of thrombosis
What treatment can be given for MDS in patients with HLA-DR15
ATG, cyclosporine and anti-CD52 mab (alemtuzumab)
What is primary myelofibrosis
Proliferation of dysplastic megakaryocytes that produce factors that stimulate collagen formation leading to BM fibrosis
What mutations are seen in primary myelofibrosis
JAK2, MPL (thrombopoietin receptor), CAL
What factors are overproduced in primary myelofibrosis
TGFeta, tissue inhibitors of metalloproteinases; osteoprotegrin (osteoclasts inhibitor)
What can the extramedullary hematopoeisis of primary myelofibrosis cause
Ascites, portal or intracranial HTN, intestinal or ureteral obstrution, pericardial tamponade, spinal cord compression, skin nodules
What is the treatment for primary myelofibrosis
No definitive therapy; danazol used for anemia; hydroxyurea to control splenomegaly; allopurinol to control hyperuricemia; IFN alpha in early dz; ruxolitinib imrpvoes sx and prolongs survival (JAK2 inhibitor)
What is significant about the pruritis seen with PCV
Worsens after a warm bath
What is the treatment for PCV
Phlebotomy weekly (want Hb <15);if >60 or prior thrombosis - give hydroxyurea; also manage stroke risk ie: tobacco cessation, management of lipids, and BP control
What is does the evaluation of MM begin with
Serum protein electrophoresis and urine protein electrophoresis on 24 hr urine sample
What is the most common CBC abnormality seen in MM
Normochromic anemia
Do you do bone scans for MM
No - use conventional radiography instead
What is used to determine prognosis of MM
Beta 2 microglobin level and serum lactate DH level
What are markers of poor prognosis of MM
Chrom 13 deletion, elevated B2, hypoalbuminemia and >50% plasma cells on BM aspirate
What is the staging for MM
Stage I: low B2 and normal albumin
Stage III B2 >5.5 poor prognosis
When can you not give HSC transplant for people with MM
If progressive kidney dz, decompensated cirrhosis, and class III or IV heart failure
What is the initiation treatment for HSC as a treatment for MM
High dose dexamethasone and thalidomide *require prophylaxis treatment for DVT with spirit, low molecular weight heparin or warfarin
What should be given to prevent complications of MM
Pneumococcal and influenza vaccine, TMP SMX to prevent pneumocystis pneumonia; acyclovir if receiving bortezomib; bisphosphonates to all patients (pamidronate or zoledronate)but limited to 2 years
What do MM patients with back pain need
MRI to rule out spinal cord compression
What mutations are seen in WM
MYD88, CXCR4, ARID1A, CD79
What are the markers for WM
IgM, CD19, CD20 and CD22 positive; CD10 and CD23 neg
What is the presence of CXCR4 associated with
Higher BM dz burden and higher incidence of hyperviscosity
What is the treatment for WM
Plasmapharesis; ibrutinib in patients with sx - targets bruton tyrosine kinase; can also use rituximab, bendamustine, cyclophosphamide, or bortezomib
What is POEMS syndrome
Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes
What is the diagnostic criteria for POEMS
All of the following must be met:
Polyneuropathy, monoclonal plasma cell proliferative disorder, any one off the following (sclerotic bone lesions, castelman’s dz, elevated VEGF), any one off the following (organomegaly -HSM or LAD, extravascular volume overload, endocrinopathy, skin Changes, papilldema, or thrombocytosis/polycythemia)
What is gamma heavy chain dz
Franklin dz; LAD, ever, anemia, malaise, HSM, and weakness, *palatal edema resulting from involvement of waldeyer’s ring; reacts with anti-IgG but not antilight chain; die of infection; usually rapid downhill course
What is alpha heavy chain dz
Seligmann dz; most common heavy chain dz; related to Mediterranean lymphoma (where intestinal parasites are common); infilatration of lymphocytes in lamia propria of small intestine; no hyperviscosity; no light chains; present with chronic diarrhea, weight loss, and malabsorption mesenteric and paraaortic LAD; IPSID assoc with campylobacter
What is mu heavy chain dz
Subset of CLL; presence of vacuoles in malignant lymphocytes; diagnosis required ultracentrifugation or gel filtration to confirm nonreactivity of paraprotein with light chain;; treated same as CLL
What is AA amyloid
Composed of acute phase reactant protein serum amyloid A - occurs chronic inflammation or infection (secondary amyloidosis)
What tissue should you test to confirm diagnosis of systemic amyloidosis
Abdominal fat
How does renal amyloidosis manifest
Proteinuria and hypoalbuminemia, secondary hypercholesterolemia, hypertriglyceridemia, edema, anasarca
What is the leading cause of death of amyloidosis
Cardiac failure
What is raccoon eye sign indicative of
AL amyloidosis
How do you treat AL amyloidosis
Dexamethasone, high dose melphalan followed by HSC transplant
How do you manage nephrotic syndrome caused by amyloidosis
Diuretics, supportive stockings, albumin