Miscellaneous Flashcards
Lab features of factor XI deficiency and diagnosis
- Prolonged aPTT, which corrects with mixing study
- confirmation by factor XI activity
Factor XI clinical features
- Bleeding phenotype highly variable
- NO spontaneous bleeding, hemarthrosis, or muslce hematomas
- Bleeding typically in setting of trauma or surgery - “injury-related bleeding disorder”
Factor XI deficiency management
- if significant bleeding history, factor XI replacement
- IF significant bleeding and inhibitor present, recombinant factor VIIa
PCH diagnosis
clinical/laboratory
- clinical context of hemolysis precipitated by the cold
- Coombs/DAT + complement (C3) (but can be negative in kids), negative for IgG or IgM
- ideally Donath-landsteiner antibody (But insensitive and can rapidly become negative)
Deauville X meaning
New areas of uptake unlikely to be related to lymphoma
Deauville 5 meaning
Uptake markedly higher than liver (2-3x) and/or new lesions
Deauville 4 meaning
Uptake moderately more than liver uptake, at any site
Deauville 3 meaning
Uptake greater than mediastinal blood pool but less than liver
Deauville 1 meaning
No uptake
Deauville 2 meaning
Uptake less than mediastinal blood pool
Morphine IV to PO conversion
1 mg IV = 3 mg PO
Niraparib dosing based on weight and plt count
Patients <77 kg or with a platelet count <150,000/mm3: Oral: 200 mg once daily
Patients ≥77 kg and with a platelet count ≥150,000/mm3: Oral: 300 mg once daily
Cryoprecipitate components
- Fibrinogen
- Factor XIII
- Von willebrand factor
- Fibronectin
VITT presentation
*Strongly mimics HIT
1) vaccine type – J&J, Astra Zeneca
2) timeframe – typically in a narrow window 5 to 10 days post-vaccination, leading to identification of cases typically between 5 to 30 days post-vaccination (so 5-30 currently used as interval)
3) thrombosis – (most commonly in cerebral veins (including intracranial hemorrhage), deep veins of the leg, pulmonary arteries, and splanchnic vessels). Both arterial + venous.
*But can have thrombosis without thrombocytopenia or thrombocytopenia without thrombosis.
4) Platelet count nadir – between 10,000 and 100,000/microL, with a median platelet count of 47k
5) High frequency of DIC.
VITT diagnosis
Positive PF4 antibody + appropriate clinical context (post-COVID vaccine thrombosis and/or thrombocytopenia)
VITT management
- ***High dose IVIG 1 gm/kg (based on actual body weight) daily for 2 days (reduce VITT antibody-induced platelet activation)
- anticoagulation (DOAC preferred)
Duration of anticoagulation for VITT
IF thrombosis → Anticoagulation for minimum 3 months after normalization of the platelet count, as long as no further thrombosis occurs
IF NO thrombosis –> anticoagulation until platelet count recovery and perhaps longer if tolerated (four to six weeks after platelet count recovery)
Porphyria mechanism generally
- Porphyrias are caused by alterations in the enzymes of heme biosynthesis. Heme is essential in the function of many hemoproteins, including hemoglobin and hepatic cytochrome P450 enzymes.
Treatment for AIP
hemin
1) Diagnosis of AIP 2) confirmatory testing specific for AIP
1) elevated plasma and urinary ALA and PGB above baseline (>10 mg/L or >10mg/g)
2) normal or slightly elevated total plasma porphyrins
3) normal or slightly increased stool porphyrins
Confirmatory testing:
1) ***low erythrocyte PBGD activity (deficient enzyme in AIP)
2) genetic testing
AIP clinical features
- develop over hours to days + insomnia as early symptom + persist for days to weeks + unexplained acute abdominal pain (85-95%, poorly localized) + unexplained psychiatric symptoms + peripheral neuropathy + vomiting + muscle weakness + pain in limbs/head/neck/chest + bladder dysfunction + dark or reddish-brown urine
AIP pathophysiology
Inherited deficiency of porphobilinogen deaminase (PBGD; also called hydroxymethylbilane synthase [HMBS]), the third enzyme in the heme biosynthetic pathway
Chronic granulomatous disease diagnosis
- undergo neutrophil-function testing (cytochrome c reduction assay, chemiluminescence, nitroblue tetrazolium (NBT) reduction test, and dihydrorhodamine (DHR) 123 oxidation test (preferred))
- Positive findings should be confirmed by genotyping
CGD clinical features
- recurrent, life-threatening bacterial and fungal infections + granuloma formation
CGD mechanism
defects in the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex
MBL diagnostic criteria
1) monoclonal B cell population (flow cytometry preferred)
2) <5000 cells/microL
3) >3 months
4) no other features of a b cell lymphoproliferative disorder (lymphadenopathy, organomegaly, cytopenias, or extramedullary involvement) or autoimmune disorder or infectious disease
X-linked sideroblastic anemia (XLSA) clinical features
- young boy presenting with hgb of 7 with microcytosis and no evidence of iron deficiency
XLSA treatment
B6
1) 2 categories of sideroblastic anemias 2) causes in second category
1) clonal sideroblastic anemias, which are stem cell disorders (MDS, MPN)
2) sideroblastic anemia attributed to copper deficiency, certain medications, or excessive alcohol use
Settings in which copper deficiency develops
1) malabsorption
2) prolonged parenteral nutrition
3) zinc ingestion
Work up for ring sideroblast detected on bone marrow aspirate
Review for history of excessive alcohol use
Test for copper deficiency
Review medications for drug-induced sideroblastic anemia
IF above nondiagnostic, genetic testing: ALAS2 (female only), SF3B1 and JAK2
Primary complication of sideroblastic anemia to be aware of
- iron overload (ineffective erythropoiesis leads to increased iron absorption)
What is Heyde syndrome?
VWF is thought to suppress angiogenesis. Patients with aortic stenosis or severe MR have been found to have increased GI angiodysplasia (Heyde syndrome) thought secondary to acquired VWS and VWF deficiency
Brodifacoum is
superwarfarin, used as rodenticide, common cause of toxic ingestion leading to coagulopathy
1) Management of toxic ingestion of anticoagulant rodenticides 2) management of associated severe bleeding
- Activated charcoal (assuming normal mental status and no aspiration risk and can be given within 2 hrs)
- IF normal coags 48h after ingestion, no treatment
- IF INR less than 4.5 and no bleeding, monitor
- IF INR greater than 4.5 and no bleeding, oral vitamin K with INR monitoring
- IF minor bleeding, oral vitamin K
- IF life threatening bleeding, 4-factor PCC, then FFP by rapid infusion + IV vitamin K
Presentation of brodifacoum/superwarfarin toxicity - 1) timeframe 2) sources of rodenticide
- Spontaneous bleeding following toxic ingestion of rodenticide (in cereal bait, pellets, loose grain, paste)
- usually 24h delay until bleeding starts
- lasts for months (much longer half life)
Management of supratherapeutic INR
- Given INR 4.5-10 and no evidence bleeding, no indication for vitamin k (per American Society of Hematology guidelines)
- Given INR >10 and patient has no evidence of bleeding, recommend vitamin K 2.5 mg or 5 mg PO (per American Society of Hematology guidelines)
- Given bleeding OR urgent surgery/procedure needed, recommend
Vitamin K IV 10 mg once, slow infusion
4 Factor-prothrombin complex concentrate (PCC or Kcentra)
Management of low or intermediate risk MDS
- essentially observation until they become transfusion dependent
Factor dosing calculation in hemophilia B
*Goal is to raise factor levels to 100% initially and then maintain factor levels above 50% by bolus q8-12h or continuous infusion
- 1 U/kg raises factor level by 1% (More like 0.75% but can fudge)
100 U/kg raises factor level by 100%
venetoclax mechanism
BH3-mimetic.[10] Venetoclax blocks the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein, leading to programmed cell death of CLL cells.
Management of low risk myelofibrosis
- IF asymptomatic, observation
- IF symptomatic, start JAKinhibitor
*UMass BMT providers had very low threshold to start JAK inhibitors but for boards and by the books, low risk asymptomatic observation is indicated
Precipitants of CRS
- CAR-T
- BiTe
- *post-transplant cytoxan used for prophylaxis of GVHD
- *post haplo-HCT
Definition of mild CRS
Fever without other systemic symptoms
Management of mild CRS
- antihistamines, antipyretics, IV fluids, close monitoring
Initial management of severe CRS
STAT tocilizumab one dose (Start w/ toci since you don’t want to theoretically ablate product with steroids - UMass, UTD argues for toci + steroids given more rapid and complete CRS control and ablation is theoretical)
Initial management of patient w/ severe CRS and ICANS
- steroids (toci not effective for ICANS)
Management of severe bite associated CRS
1) Stop infusion
2) dexamethasone 10 mg up to 4 times/daily (toci less effective than steroids in this setting)
Precipitants of atypical HUS
**pregnancy →
surgery →
autoimmunity →
congenital
Risk factors for hemolysis with IVIG
- high-dose infusions (1 to 2 grams per kg per day)
- high IVIG doses (eg, >100 grams)
- female sex,
- non-O blood group
Presentation of CM TMA postpartum
All CM-TMA features + can see severe AKI postpartum
Lab features of immune TTP
(median plt count (10k) almost always <30K) + low grade anemia w/ median hematocrit 21% + reticulocytosis + hemolysis labs (extremely high LDH (around 1000 typically) + indirect hyperbilirubinemia + low haptoglobin) + negative DAT + normal coags + ADAMTS13 <10% (low specificity - many diseases can cause low ADAMTS13)
Clinical features of immune TTP
Initial symptoms (fatigue, dyspnea, petechia, abdominal pain/ nausea/vomiting (45%), headache/confusion (20%) - typically mild symptoms at onset) + abnormal or normal (more commonly) kidney function (AKI uncommon), often comorbid autoimmune disorders + typically previously healthy person + median age 40 + females more commonly (75%) + increased frequency in pregnancy
Major RF’s for recurrent VTE
1),Major surgery >30 minutes
2) hospitalization or confined to bed with “bathroom privileges” for ≥3 days due to acute illness
3) CS
4) trauma with fractures
5) high estrogen states - estrogen therapy, pregnancy or puerperium
Minor RF’s for recurrent VTE
Minor surgery <30 minutes, hospitalization <3 days, reduced mobility at home ≥3 days due to acute illness, lower extremity injury without fracture with reduced mobility ≥3 days, long-haul flight
When is it appropriate to measure D-dimer to determine risk of recurrent VTE?
female patients with VTE in whom there is uncertainty regarding the appropriateness of extended anticoagulant therapy
Paraneoplastic syndromes associated with Hodgkin Lymphoma
1) nephrotic syndrome (minimal change disease or FSGS)
2) Subacute motor neuropathy (Guillain-Barré) (subacute, progressive, painless, and often asymmetric lower motor neuron weakness)
Sweet syndrome presentation
abrupt appearance of painful, edematous, and erythematous papules, plaques, or nodules on the skin
Paraneoplastic syndromes associated with AML
- Sweet syndrome
- erythroderma
What is the function of irradiating PRBCs?
Inactivating lymphocytes (Thus, used to prevent ta-GVHD in at-risk individuals)
Indications for irradiating PRBCs
1) Congenital immunodeficiencies
2) potent immunosuppressive therapies (*purine analogs, ATG, certain monoclonal antibodies)
3) auto or allo transplant recipients
4) Hodgkin Lymphoma
5) Individuals at risk for partial HLA matching with the donor due to directed donations, HLA-matched products, or genetically homogeneous populations
How leukoreduction works
- Each unit of whole blood or packed RBCs contains approximately two to five billion (2 to 5 x 109) leukocytes (white blood cells [WBCs]), which are collected along with the other cellular elements. These leukocytes are thought to contribute to a number of adverse effects including febrile nonhemolytic transfusion reactions (FNHTRs), human leukocyte antigen (HLA) alloimmunization, and transmission of cytomegalovirus
- Leukoreduction refers to the selective removal of leukocytes by passing the blood through a leukocyte reduction filter
Indications for leukoreduction (by the books)
*essentially all PRBCs are leukoreduced now
1) Chronically transfused patients
2) Previous febrile nonhemolytic transfusion reaction
3) Patients undergoing cardiac surgery
4) All recipients (or potential recipients) of solid organ or hematopoietic cell transplants
5) All individuals with acute leukemia, and probably individuals with other malignancies
6) CMV seronegative at-risk patients for whom seronegative components are not supplied
Malignant heme pathologies associated with HTLV-1
Adult T cell leukemia-lymphoma (ATL) (including CTCL)
NCCN recommendation for low emetic risk chemo
- single agent:
Decadron vs. reglan vs. compazine vs. 5-HT3
Blastic plasmacytoid dendritic cell neoplasm clinical features
aggressive + Lymphadenopathy + cutaneous involvement
Blastic plasmacytoid dendritic cell neoplasm immunophenotype
CD123 + CD4 + CD56 + TdT + BDCA-2/CD303
*count from 1-6
Transplant criteria for amyloidosis
1) Age <70 2) SBP >90 3) NYHA <3 4) No more than 2 organs involved (liver, heart, kidney, or autonomic nerve) 5) Troponin T level <0.06 (high sensitivity troponin T <75 ng/ml) 6) NTproBNP <5 ng/L 7) ECOG 0-1 8) CrCl ?30 mL/minute
Difference between 3 and 4 factor PCC
- 3 does not have factor VII
What is the mechanism of action of FC fusion protein
Alprolix Coagulation Factor IX (Recombinant), Fc Fusion Protein, is a recombinant DNA derived, coagulation Factor IX concentrate. It temporarily replaces the missing coagulation Factor IX needed for effective hemostasis. Alprolix contains the Fc region of human IgG1, which binds to the neonatal Fc receptor (FcRn). FcRn is part of a naturally occurring pathway that delays lysosomal degradation of immunoglobulins by cycling them back into circulation, and prolonging their plasma half-life.
SVT management
IF no VTE RF’s but close to deep vein system (within 5 cm), prophylactic NOAC for 45 days
IF VTE RF’s, then need therapeutic dosing
Next step after PVT diagnosed in a young, healthy person
JAK2 mutational analysis
High leukocyte alkaline phosphatase score suggests what
Leukemoid reaction
Bone marrow findings in CMML
- <20% blasts by definition
- dysplasia
Key criteria for CMML
***monocytosis accounting for >10% of WBC
Avapritinib SE to know
diarrhea
HDAC inhibitors
- romidepsin
- vorinostat
- panobinostat
- belinostat
Donor type for patients with familial AML
Matched unrelated donor
Xa reversal agenet
andexanet alfa
benefit of exchange over simple transfusion
less alloimmunization
ICANS treatment
- Prophylactic AED w/ keppra 500 mg BID
- Dex 10 mg q8h
Required prophylaxis with campath
PJP
Belzutifan SE’s
anemia + hypoxia
caplacizumab mechanism
Binds VWD and blocks its interaction with plt glycoprotein Ib-IX-V
Drugs known to cause immune TTP
- bactrim
- Quetiapine
- gemcitabine
- oxaliplatin
- Quinine
Drugs known to cause non-immune TTP
- valproic acid
- avastin
- velcade
- carfilzomib
- dasatinib
- docetaxel
- imatinib
- ixazomib
- mitomycin
- palbociclib
- pentostatin
- ponatinib
- sunitinib
- cocaine
- oxycontin
- cyclosporine
- everolimus
- inflixmab
- sirolimus
- tacrolimus
Revlimid mechanism of action
- Modulates CRL4 E3 ubiquitin ligase
- Induces the ubiquitination of IKZF1 and IKZF3 by CRL4
Immunophenotype of Langerhans cell histiocytosis
CD1a+
CD207+
angiosarcoma immunophenotype
- CD31+
- CD34+
Monomorphic PTLD treatment
Anti-CD20 (rituxan)
+ CHOP
morphology of cells in LGL
large granular lymphocytes
Virus associated with ATL
HTLV-1
Paraneoplastic syndrome associated with ATL
hypercalcemia
mutations to know for T-LGL
STAT3 and STAT5b
Relevance of cresyl blue staining
G6PD + Hgh H disease
Blood to transfuse HCT recipient that is A+ with a B+ donor
O+ (they will have the blood type of the donor after engraftment BUT a type O pt may have anti-A in their plasma produced by residual lymphocytes either transiently or persistently despite converting to blood type A.
