Hematology and Oncology Disorders Flashcards
1
Q
recent RCTs comparing the use of fresh or “young” RBC transfusion w/ “older” units w/ longer storage time in critically ill adults have shown what?
A
more febrile, nonhemolytic transfusion reactions in patients receiving younger units
2
Q
systemic autoimmune d/o characterized by the presence of antiphospholipid Abs
A
APS (antiphospholipid syndrome)
3
Q
one of the most commonly acquired thrombophilias and is unique from most genetic thrombophilias because of it a/w BOTH arterial AND venous thromboses
A
APS (antiphospholipid syndrome)
4
Q
what are the most common venous and arterial sites of involvement of thrombosis in APS (antiphospholipid syndrome)?
A
- DVT of the lower extremities
- cerebral arterial circulation
5
Q
thrombosis in unusual sites such as, hepatic veins, visceral veins, cerebral venous circulation, should prompt consideration for
A
APS (antiphospholipid syndrome)
6
Q
is a/w significant obstetric morbidity
- should be considered in the setting of an unexplained death of ≥ 1 morphologically normal fetuses ≥ 10 weeks of gestation
- premature birth of ≥ 1 neonates before 34 weeks of gestation because of eclampsia or severe preeclampsia
- or ≥ 3 unexplained, consecutive spontaneous abortions before the tenth week of gestation
A
APS (antiphospholipid syndrome)
7
Q
other manifestations of APS (antiphospholipid syndrome)
A
- thrombocytopenia
- autoimmune hemolytic anemia
- nonbacterial cardiac valve thickening or vegetations
- livedo reticularis
- skin ulcers
- TIAs
8
Q
aPTT and mixing study in APS (antiphospholipid syndrome)
A
- often prolonged
- does NOT correct w/ mixing study
9
Q
clinical criteria for diagnosis of APS (antiphospholipid syndrome)
A
- confirmed thrombotic event, or
- confirmed obstetric morbidity
- combined w/ presence of a lupus anticoagulant (IgM or IgG isotype anticardiolipin Abs (medium-high titer), or IgM or IgG subtype anti-β2-glycoprotein I antibodies (titer >99th percentile))
- confirmed on ≥ 2 occasions at least 12 weeks apart
10
Q
rare complication of APS defined as small vessel thrombosis in ≥ 3 organs in < 1 week
A
catastrophic APS (CAPS)
11
Q
catastrophic APS (CAPS) is often triggered by
A
- infection
- malignancy
- another acute precipitating event
12
Q
- most commonly affects women in their 30s
- a/w mortality rates of 40-50% d/t cerebral and cardiac thrombosis, infection a/w treatment, and multiorgan failure
A
catastrophic APS (CAPS)
13
Q
diagnosis of catastrophic APS (CAPS)
A
requires objective demonstration of microvascular thrombosis w/o vessel inflammation to suggest an underlying vasculitis
14
Q
PBS of catastrophic APS (CAPS) often demonstrates
A
- microangiopathic hemolytic anemia (MAHA)
- schistocytes
15
Q
current guidelines for management of catastrophic APS (CAPS)
A
- heparin gtt
- corticosteroids to reduce proinflammatory cytokine production
- IVIG or plasma exchange in severe cases
16
Q
treatment of catastrophic APS (CAPS) a/w SLE
A
- cyclophosphamide
- rituximab or eculizumab in refractory cases
17
Q
long-term AC for catastrophic APS (CAPS) in patients who respond to initial treatment
A
warfarin
18
Q
what conditions are a/w higher mortality in catastrophic APS (CAPS)?
A
- older patients
- underlying SLE
- higher Charlson Comorbidity Index (CCI)
- higher day 0 Simplified Acute Physiology Score II (SAPS)
- higher SOFA score
- renal and neurological involvement
- hemorrhagic events
- macrovascular arterial thrombosis
- low hb
- persistently low thrombocytopenia (likely indicating diffuse, ongoing microangiopathy)
19
Q
what is the Charlson Comorbidity Index (CCI)?
A
predicts 10-year survival in patients w/ multiple comorbidities
20
Q
what is the Simplified Acute Physiology Score (SAPS)?
A
estimates mortality in ICU patients; comparable to APACHE II
21
Q
what is the Sequential Organ Failure Assessment (SOFA) score?
A
predicts ICU mortality based on lab results and clinical data
22
Q
- mild, transient drop in platelet count
- typically occurs w/i the first 2 days of heparin exposure
A
heparin-induced thrombocytopenia type 1 (HIT 1)
23
Q
mechanism of HIT 1
A
direct effect of heparin on platelets, causing non-immune platelet aggregation
24
Q
clinically significant syndrome d/t Abs to platelet factor 4 (PF4) complexed to heparin, referred to as “HIT Abs” or “PF4/heparin Abs”
A
heparin-induced thrombocytopenia type 2 (HIT 2)
25
HIT 2 is aka
heparin-induced thrombocytopenia and thrombosis (HITT)
26
the risk of thrombosis, including life-threatening limb gangrene, from HIT 2 persists until what measures are taken?
- heparin is eliminated, AND
- non-heparin anticoagulant is initiated
27
what are HIT variants?
clinical HIT d/t HIT Abs that activate platelets in the ABSENCE of heparin
- delayed-onset HIT
- refractory (persistent) HIT
- spontaneous HIT
- VITT (vaccine-induced immune thrombotic thrombocytopenia)
28
delayed-onset HIT is defined by
thrombocytopenia and/or thrombosis occurring ≥ 5 days after heparin has been withdrawn
29
why might delayed-onset HIT occur?
high-titer Abs to PF4/heparin
30
refractory (persistent) HIT is defined as
- persistent thrombocytopenia and/or thrombosis that last for weeks AFTER stopping heparin
- the presence of HIT Abs alone does NOT define this condition
31
spontaneous HIT is described as
- RARELY, HIT has been described in the absence of recent heparin exposure
- most affected patients have a preceding infection or have undergone a major surgical procedure
32
what diagnostic criteria have been proposed for spontaneous HIT?
- otherwise UNEXPLAINED thrombocytopenia and/or thrombosis w/o recent heparin exposure
- demonstration of anti-PF4 Abs of IgG subclass that cause strong in vitro platelet activation in the absence of heparin
- occurring in the setting of exposure to minimal amount of heparin
33
VITT (vaccine-induced immune thrombotic thrombocytopenia) is described as
a condition that may occur in individuals vaccinated w/ certain covid-19 vaccines (AstraZeneca, University of Oxford, and Serum Institute of India, and Janssen; Johnson & Johnson)
34
some patients produce Abs that react in laboratory assays for HIT but do NOT cause thrombocytopenia or thrombosis
heparin-induced Abs (HIA)
35
although there are similarities in clinical presentation between TMA (thrombotic microangiopathies) and CAPS, what are some key differences that may help differentiate them?
- no schistocytes seen on PBS w/ TMA
- likely underlying diagnosis of APS makes CAPS much more likely
36
- aka typhlitis
- necrotizing enterocolitis
- typically develops in neutropenic patients, < 500 cells/µL
- most commonly occurs following chemotherapy for acute hematologic malignancies (leukemia, lymphoma, MM), or immunosuppressive therapy for solid tumor malignancies and transplants
neutropenic enterocolitis
37
initial management of neutropenic enterocolitis
- abx
- supportive care
38
neutropenic enterocolitis has been reported in what infection?
HIV
39
pathophysiology of neutropenic enterocolitis
damage of gut mucosal barrier, necrosis, and hemorrhagic transmural inflammation of multiple layers of the bowel wall, resulting in impaired host defenses, and bacterial translocation
40
sepsis, bacteremia, and fungemia often develop in neutropenic enterocolitis; what are the organisms typically isolated?
- Pseudomonas aeruginosa
- Escherichia coli
- Klebsiella spp
- Bacteroides spp
- Clostridium spp
- Candida
41
clinical diagnosis of neutropenic enterocolitis
- neutropenic host
- fever (93%)
- abdominal pain
- characteristic abdominal CT findings
42
what are the characteristic CT abdominal findings in neutropenic enterocolitis?
bowel wall thickening; > 4 mm of the cecum and terminal ileum
- mesenteric fat stranding
- bowel dilation
- mucosal enhancement
- pneumatosis
43
ddx for neutropenic enterocolitis
- CDI
- colonic pseudo-obstruction (aka Ogilvie syndrome)
- CMV colitis
- GVHD in the setting of BMT
44
GVHD presentation
- rash
- diarrhea
- abnormal liver function
45
treatment for colonic pseudo-obstruction (Ogilvie syndrome)
- conservative; decompression w/ NGT
- neostigmine if cecal diameter > 12 cm or 48-72 hours of conservative therapy has failed
46
subtype of acute myeloid leukemia (AML) that differs from other forms of AML because of its propensity to cause coagulopathy w/ DIC
acute promyelocytic leukemia (APL)
47
subtype of leukemia that mimics DIC w/ the following clotting tests abnormalities;
- low fibrinogen level
- thrombocytopenia
- elevated PT
- elevated thrombin time
- elevated PTT
- elevated fibrinogen degradation products
acute promyelocytic leukemia (APL)
48
what is a distinguishing feature in the diagnosis of acute promyelocytic leukemia (APL)?
Auer rods on PBS
49
leukemia subtype w/ translocation between chromosomes 15 and 17
acute promyelocytic leukemia (APL)
50
targeted therapy for acute promyelocytic leukemia (APL)
all-trans retinoic acid (ATRA)
51
what activates endothelial cells in CAPS?
anti-β2-glycoprotein
52
rare d/o characterized by overstimulation of the immune system, leading to systemic inflammation and multisystem organ failure
hemophagocytic syndromes (HPSs)
53
what are the poor prognostic factors of hemophagocytic syndromes (HPSs)?
- a/w lymphoma
- > 30 yoa
- higher ferritin elevation
- marked thrombocytopenia
- male sex
- low albumin
54
- d/o infancy and childhood
- caused by genetic mutations that impair the cytotoxic function of NK and cytotoxic T cells
primary hemophagocytic lymphohistiocytosis (HLH)
55
- often a/w predisposing condition, malignancy (lymphoma), immunodeficiency, or infection (EBV)
- can be referred to as macrophage activation syndrome when it occurs in a/w AI disease, such as juvenile idiopathic arthritis, adult-onset Still's disease, and SLE
secondary hemophagocytic syndrome (HPS)
56
the diagnostic HLH guidelines proposed by the Histiocyte Society remain the most widely used criteria, but are poorly validated and exclude a number of manifestations, which are?
- neurological involvement
- rash
- coagulopathy
- hyponatremia
- elevated transaminases
- elevated LDH
- low CRP
57
treatment for hemophagocytic syndromes (HPSs) is extrapolated from the pediatric literature which includes what?
- dexamethasone
- etoposide w/ or w/o cyclosporine A
- doxorubicin
- IVIG
- ruxolitinib
- anakinra
- allogeneic SCT
58
treatment that be used for HLH when a/w lymphoma and EBV
- cyclophosphamide, adriamycin, vincristine, prednisone (CHOP), and rituximab
59
what treatment can be considered in patients w/ HLH that have marked elevations in ferritin and LDH?
plasma exchange
60
treatment consideration for relapsed cases of HLH
splenectomy
61
a fall in platelet count after cardiopulmonary bypass (CPB) is expected to drop by how much and for how long?
- 1/2
- can persist for 4 to 6 days following surgery
62
anti-PF4 heparin ELISA testing is positive in what percentage of patient between post-op days 3 to 10 of CPB? and what percentage are confirmed to have HIT?
- 25-50%
- 1-4%
63
the risk-benefit ratio and timing of initiation of DVT chemoprophylaxis following cardiac surgery and CPB is controversial, but chemoprophylaxis can be safely initiated once post-op bleeding risk has declined which is usually by post-op day?
1 or 2
64
treatment of HIT consists of what?
- d/c heparin
- removal of heparin-coated intravascular devices (important! and easy to forget)
- avoidance of warfarin (d/t enhanced prothrombotic activity early in warfarin therapy)
- AC w/ alternative agents
65
what is the only AC agent currently approved by the FDA for HIT?
argatroban
66
what adjunct therapy may be used for refractory HIT, but w/ limited evidence to support its use?
IVIG
67
TEG (thromboelastometry) has been proposed to assist in guidance of factor replacement in patients w/ hemorrhage; RCTs in which patient populations have supported the utility of TEG?
- traumatic hemorrhagic shock
- liver transplant
68
a visual guide depicted as a graph that helps answer questions about the components of clot formation, stability, and lysis
TEG (thromboelastometry)
69
in TEG, the clotting time (R, or activated clotting time, ACT) is what?
the time from reagent addition to the sample until FIBRIN forms
70
what is the most common cause of a prolonged R or ACT time?
coagulation factor deficiency
71
in TEG, clot kinetics are measured by the K time, which is?
the time to achieve a clot amplitude of 20 mm; a measure of clot STRENGTH
72
in TEG, clot kinetics are also measured by the α angle, which is?
the rate of clot formation d/t fibrin accumulation and cross-linking
73
in TEG, maximum amplitude (MA) is what?
a measure of the maximum dynamic properties of fibrin and platelet bonding through glycoprotein 2b/3a receptors
74
the maximum amplitude (MA) reflects what?
the OVERALL strength of the fibrin clot and is most impacted by platelet numbers and function
75
in TEG, LY30 and LY60 are what?
a measure of clot stability and breakdown by the percentage decrease at 30 and 60 minutes after MA
76
LY30 and LY60, basically, provides what information?
the degree of fibrinolysis
77
an increase in LY30 and/or LY60 might prompt consideration of treatment w/ what?
tranexamic acid (TXA)
78
when administered w/i the first 8 hours (especially the first 3 hours), what treatment has been shown to decrease all-cause mortality in patients p/w or at risk for traumatic hemorrhage?
tranexamic acid (TXA)
79
the 4T scoring system is best studied in the ICU population to help stratify the risk of HIT; what are the citeria?
- degree of thrombocytopenia
- change and timing of platelet count from baseline
- presence of thrombosis
- other possible causes of thrombocytopenia
80
HIT Ab testing should ONLY be performed in patients at what risk?
intermediate or high risk
81
the initial screening ELISA for HIT has what test characteristics?
very sensitive but not specific
82
an intermediate or high 4T score and positive ELISA should prompt what management?
- d/c heparin
- remove heparin-bound devices
- confirmatory testing w/ a functional assay (either 14C-serotonin release assay or heparin-induced platelet activation assay)
- initiation of an alternate form of AC
- lower extremity doppler US
83
what is the most common complication of HIT?
lower extremity DVT
84
in patients w/ HIT, current guidelines support treatment w/ what agents?
- direct thrombin inhibitors; argatroban or bivalirudin
- indirect factor Xa inhibitors; danaparoid or fondaparinux
85
current guidelines recommend the use of what AC agent ONLY for HIT in pregnant patients when danaparoid is NOT available?
fondaparinux
86
what AC agent has a long half-life making it less preferred in critically ill patients, the elderly, AKI or CKD, or significant bleeding risk?
fondaparinux
87
there is emerging evidence suggesting that non-vitamin K antagonists, such as what AC agent, may be effective in treating critically ill patients w/ HIT?
rivaroxaban
88
what are the only IV direct thrombin inhibitors available for use in HIT?
- argatroban
- bivalirudin
89
argatroban is the recommended first-line agent and only drug approved by the FDA for HIT, but should be used w/ caution in which patients?
- HF
- liver disease
- severe anasarca
- after cardiac surgery
90
which medication is recommended for patients w/ HIT requiring emergent cardiac surgery or PCI, but requires significant dose adjustments in both hepatic and renal dysfunction?
bivalirudin
91
tranexamic acid, a lysine analogue that acts as an inhibitor of fibrinolysis, has been shown to reduce mortality in patient populations?
- postpartum hemorrhage
- trauma
- selected patients w/ traumatic brain injury (TBI)
92
the use of tranexamic acid in what patient population has NOT been shown to reduce mortality?
patients undergoing coronary artery bypass grafting (CABG)
93
what is another practical use of TEG (thromboelastometry)?
can measure functional impact of hypothermia and acidosis
94
trauma-induced coagulopathy following massive hemorrhage is multifactorial; what are these factors?
- consumption of platelets and coagulation factors during clot formation in damaged blood vessels
- plasma dilution from ivf or excessive prbc administration
- dysregulated activation of the thrombomodulin-protein C system d/t tissue injury and hypoperfusion
- hypoxemia
- acidosis
- hypothermia
95
what are the concerns surrounding the 1:1:1 ratio (1 unit of pooled platelets approximating 6 units, followed by alternating units of prbcs and plasma) approach based on the PROPPR trial fallen out of favor to a more targeted approach as w/ the use of TEG?
- TRALI
- transfusion-associated circulatory overload
- infection
- immunomodulation risk
96
preferred initial therapeutic option for splenic rupture
embolization; either proximal splenic artery or selective distal embolization
97
dasatinib, a second-generation tyrosine kinase inhibitor, is a/w adverse effects?
- cytopenias
- pleural effusions
- bleeding (decreases platelet function)
98
criteria for hyperleukocytosis
total leukemic blood count of 50,000-100,000/μL
99
leukostasis, when WBCs coalesce in the microvasculature, typically occurs in AML and CML during a myeloid blast crisis w/ very blast counts, and most commonly p/w
respiratory distress and/or neurological symptoms
100
pulmonary signs/symptoms of leukostasis
- dyspnea
- hypoxia
- variable interstitial or alveolar infiltrates on cxr
- decreased PO2 on abg measurement d/t increased O2 uptake by the large numbers of blast cells (hallmark sign)
101
since a hallmark sign of leukostasis is a decreased PO2 on abg measurement d/t increased O2 uptake by the large numbers of blast cells, how should O2 levels be monitored?
pulse oximetry
102
neurological signs/symptoms of leukostasis
- visual changes
- headache
- dizziness
- tinnitus
- gait instability
- decreased levels of consciousness
103
patients w/ hyperleukocytosis have an increased risk of what? and that risk may persist for at least a week after reduction of the WBC count, possibly from reperfusion injury
intracranial hemorrhage
104
what is the initial therapy for leukostasis?
leukapheresis
105
specificity of US for the detection of splenic rupture
> 90%
106
- h/o blood product transfusion
- skin rash
- diarrhea
- elevated bilirubin
transfusion-associated graft-vs-host disease (TA-GVHD)
107
classic skin lesion a/w GVHD
erythematous maculopapular morbilliform eruption that starts on the face, ears, palms, and soles
108
what are the important predispositions to developing TA-GVHD?
- lymphoproliferative malignancies (in particular, Hodgkin's lymphoma)
- prior receipt of certain chemotherapeutic medications
109
use of what may prevent TA-GVHD?
irradiated blood products
110
PPIs have been a/w w/ what severe delayed-type hypersensitivity reactions?
- SJS
- TEN
- drug rash w/ eosinophilia and systemic symptoms (DRESS)
111
characteristic skin lesion of Pseudomonas aeruginosa
ecthyma gangrenosum (bullous hemorrhagic lesions)
112
contamination of platelet concentrates predominantly transmit what pathogen?
gram-positive bacteria from skin flora
113
contamination of prbc products predominantly transmit what pathogen?
gram-negative organisms, usually Enterobacteriaceae w/ Yersinia enterocolitica being the most characteristic organism
114
contaminated blood transfusion reactions are 2/2 either the organism itself or toxin produced by the organism; the clinical result is
severe sepsis or septic shock
115
DOAC that inhibits thrombin (factor IIa)
dabigatran
116
DOACs that inhibit factor Xa
"-Xabans" --> they "ban" factor Xa
- rivaroxaban
- apixaban
- edoxaban
- betrixaban
117
FDA-approved reversal agent for coagulation deficit a/w factor Xa inhibitors
andexanet
118
what is the dosing for andexanet?
- depends on dosing of factor Xa inhibitor
- if lower dose then andexanet 400 mg iv then 4 mg/min x 120 minutes
- if higher dose then andexanet 800 mg iv then 8 mg/min x 120 minutes
119
management if andexanet is unavailable
4 factor prothrombin complex concentrate (PCC) 50 to 100 units/kg
120
3 factor prothrombin complex concentrate includes concentrates of what?
- factor II
- factor IX
- factor X
121
4 factor prothrombin complex concentrate includes concentrates of what?
- factor II
- factor IX
- factor X
AND
- factor VII
122
monoclonal Ab directed to dabigatran and its metabolites
idarucizumab
123
hemophagocytic lymphohistiocytosis (HLH) mimics severe sepsis and septic shock because of
massive, unchecked release of inflammatory cytokines, often referred to as cytokine storm
124
by consensus, the diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH) are
- known HLH-associated genetic mutation (usually of genes PRF I, UNC 13D, or STX 11)
OR
at least 5 of 8 criteria:
- fever, temperature ≥ 38.5°C
- splenomegaly
- cytopenias of at ≥ 2 blood cell lines (hb < 9, ANC < 1,000, platelet < 100,000)
- hypertriglyceridemia (fasting TG > 265 mg/dL), and/or hypofibrinogenemia (fibrinogen < 150 mg/dL)
- hemophagocytosis in BM, spleen, LN, or liver
- low or absent NK cell activity
- ferritin > 500 ng/mL; greater specificity when > 3,000 ng/mL
- increased soluble CD25 (soluble interleukin-2 receptor alpha)
125
why might TGs be elevated and is one of the diagnostic criteria in HLH?
inflammatory cytokines inhibit lipoprotein lipase (LPL)
126
why might ferritin be elevated and is one of the diagnostic criteria in HLH?
macrophages are a major repository of ferritin
127
treatment of patients w/ HLH-induced acute organ dysfunction, including hypotension
administration of etoposide (aka VP-16), and dexamethasone
128
- tick-borne protozoan
- in USA
- may cause hepatosplenomegaly
babesiosis (Babesia microti)
129
severe disease from this protozoan, Babesia microti, is a/w
- abdominal pain
- vomiting
- diarrhea
- hemolytic anemia
- thrombocytopenia
130
how is babesiosis diagnosed?
- presence of organisms in RBCs on thick PBS
- serologically, or
- PCR
131
- tick-borne bacteria
- can cause hepatic and multisystem organ failure
ehrlichiosis (Ehrlichia)
(genus under the Rickettsiales order)
132
common laboratory features of ehrlichiosis
- thrombocytopenia
- increased liver enzymes
- anemia
- AKI
133
how is ehrlichiosis diagnosed?
- presence of inclusions, called morulae, in neutrophils or monocytes on PBS or buffy coat
- serology, or
- PCR
134
what is the buffy coat?
the fraction of an anticoagulated blood sample that contains most of the WBCs and platelets following centrifugation that sits between the plasma and erythrocytes
135
hematologic disease induced by acquired deficiency of von Willebrand factor cleaving protease ADAMTS13
thrombotic thrombocytopenic purpura (TTP)
136
measure activity level of ADAMTS13 in thrombotic thrombocytopenic purpura (TTP)
< 10%
137
thrombotic thrombocytopenic purpura (TTP) is characterized clinically by
- microangiopathic hemolytic anemia (MAHA)
- thrombocytopenia
- purpura or bleeding
- major or minor neurologic symptoms
138
- anti-β2 glycoprotein I antibody positive
- histopathological evidence of vessel occlusion
catastrophic antiphospholipid Ab syndrome
139
mainstays of treatment for catastrophic antiphospholipid Ab syndrome (CAPS)
- AC (in the absence of bleeding)
- corticosteroids
- plasma exchange
140
there is NO consensus on absolute criteria needed for the diagnosis of disseminated intravascular coagulation (DIC), but what are the common laboratory criteria?
- thrombocytopenia
- prolonged PT
- prolonged aPTT
- low plasma fibrinogen
- elevated plasma D-dimer
141
disseminated intravascular coagulation (DIC) can present under what circumstances?
- trauma
- sepsis
- malignancy
142
disseminated intravascular coagulation (DIC) often manifests how?
oozing from sites of trauma, catheters, or drains
143
what is the Coombs test result in TTP and why
- negative
- the hemolytic anemia is NOT from an immune process; is d/t mechanical shear stress
144
most common etiology of pulmonary-renal syndromes
microscopic polyangiitis
145
- fever
- elevated ESR
- elevated CRP
- AKI
- anemia
- usually MPO-ANCA positive
microscopic polyangiitis
146
aPTT measures activity of what?
- contact activation clotting pathway (factors VIII, IX, XI, XII)
AND
- common pathway (factors I (fibrin), II (thrombin), V, X)
147
PT measures activity of what?
- tissue factor clotting pathway (factor VII)
AND
- common pathway (factors I (fibrin), II (thrombin), V, X)
148
because the INR is a part of the measurement of both aPTT and PT, conditions that affect factors in the common pathway can result in both being elevated; what are those conditions?
- disseminated intravascular coagulation (DIC)
- supratherapeutic heparin
- direct thrombin inhibitors
- warfarin
- vitamin K deficiency
- hepatic insufficiency
149
what might accidentally happen in an emergency situation in an ESRD patient w/ a TDC that might lead to severe coagulopathy?
administration of medications via the TDC w/o removing the heparin "lock" which might be as much as 20,000 units
150
treatment for DIC
- treat underlying condition if possible
- cryoprecipitate if low fibrinogen levels
151
protamine dosing
- 1 mg per 100 units of heparin (max single dose 50 mg)
- may repeat 0.5 mg per 100 units of heparin if aPTT remains elevated
- but also depends on time elapsed since heparin overdose or if on gtt (heparin half-life 60-90 minutes)
152
the supernatant of cryoprecipitate from pooled plasma used to purify and concentrate relevant clotting factors generates what?
prothrombin complex concentrates (PCC)
153
what must be administered in conjunction w/ PCC and why?
- vitamin K 10 mg iv
- factors II, VII, IX, X are vitamin K dependent factors!
154
generally, how long does vitamin K take to reverse supratherapeutic warfarin?
8-24 hours
155
what are the most common adverse effects of checkpoint inhibitors (anti-PD1 and CTLA-4 Ab therapy)?
- skin reactions; rash
- GI problems; colitis
156
what are the most common severe complications of checkpoint inhibitors?
- myocarditis
- pneumonitis
- enteritis
- neurological dysfunction
157
- rotary nystagmus on upward gaze
- peripheral sensory neuropathy (lack of any movement to stimulation and decreased DTRs)
- anti-Ma2 Abs against both central and peripheral neurons
- a/w RCC
paraneoplastic syndrome
158
what is the grading scale for complications from checkpoint inhibitors?
- grade 1 = mild
- grade 2 = moderate
- grade 3 = severe
- grade 4 = life-threatening
159
typically, patients w/ grade 3 or 4 complications from checkpoint inhibitors should be admitted where?
ICU
160
treatment for complications from checkpoint inhibitors grades 2 to 4
- d/c checkpoint inhibitor
- diagnosis of the syndrome
- initiation of treatment specific for the diagnosed syndrome
161
in some cases d/c'ing the checkpoint inhibitor is sufficient to improve the patient; in patients who continue to progress, what treatment options should be considered?
- glucocorticoids
- plasmapheresis
- immunosuppressants
162
it is believed that treatment w/ a checkpoint inhibitor does not initiate a paraneoplastic response, but amplifies it, and d/c'ing the checkpoint inhibitor has little effect to ameliorate symptoms; in a few isolated cases what medication has been initiated w/o d/c'ing the checkpoint inhibitor?
natalizumab (α4 integrin blocker that prevents the entry of immune cells into the brain)
- has NOT been tested in a clinical trial!
163
- patient that is highly likely to have type 2 HIT
- hypotensive
think of what?
adrenal insufficiency d/t adrenal vein thrombosis and hemorrhage 2/2 hypercoagulable state
164
what infections are known to produce adrenal insufficiency?
- disseminated TB
- fungal disease
- meningococcal sepsis
165
- fever
- leukocytosis
- pain localized to RUQ
- CT a/p showing enlarged GB w/ intraluminal gas and/or surrounding fluid
acalculous cholecystitis
166
- back and flank pain
- subsequent hypotension
- receiving full-dose AC
- drop in hb
retroperitoneal hemorrhage
167
to determine if a patient should be considered for reversal of their DOAC, what are the 2 main factors?
- determine if it's a major bleed
- assess the AC status
168
when considering DOAC reversal, a major bleed is defined by
- location (critical sites)
- volume of blood loss
169
when considering DOAC reversal, a AC status is based on
- the specific agent
- time of last dose
- renal function
170
- major complication of chimeric Ag receptor (CAR)-T cell therapy
- fever
- hypotension
- hypoxemic respiratory failure
cytokine release syndrome (CRS)
171
cytokine release syndrome (CRS) is in part mediated by
cytokine IL-6
172
treatment for cytokine release syndrome (CRS)
- supportive treatment
- empiric abx
- corticosteroids
- tocilizumab
173
cytokine release syndrome (CRS) may affect any organ, but in some patients it can manifest as a predominant neurologic syndrome called
immune effector cell-associated neurotoxicity syndrome
174
when do signs/symptoms of cytokine release syndrome (CRS) occur?
2-14 days after initiating CAR-T cell therapy
175
severity of cytokine release syndrome (CRS) is graded which helps guide treatment;
- grade 1
- fever
- no hypotension
- no hypoxia
- flu-like symptoms
176
severity of cytokine release syndrome (CRS) is graded which helps guide treatment;
- grade 2
- fever
- hypotension
- no vasopressors required, and/or
- hypoxia requiring < 6 L/min NC
177
severity of cytokine release syndrome (CRS) is graded which helps guide treatment;
- grade 3
- fever
- hypotension
- 1 vasopressor required, and/or
- higher supplemental O2 support required
178
severity of cytokine release syndrome (CRS) is graded which helps guide treatment;
- grade 4
- fever
- hypotension
- multiple vasopressors required, and/or
- positive pressure ventilation required
179
treatment for grade 2 CRS
tocilizumab alone
180
treatment for grades 3 and 4 CRS
both corticosteroids and tocilizumab
181
mechanism of tumor lysis syndrome (TLS)
rapid release of intracellular K+, PO4, and NAs into the bloodstream
182
TLS is most commonly seen when?
- after induction cytotoxic chemotherapy for acute leukemias and lymphomas
183
can TLS happen spontaneously?
yes
184
TLS is defined as
≥ 2 of the following during a 24-hour period w/i 3 days before the start of cytotoxic therapy OR up to 7 days afterward:
- hyperkalemia
- hyperphosphatemia
- hypocalcemia
- hyperuricemia
- oliguria
(nb, electrolyte disturbances are absolute values or relative to baseline)
185
complications of TLS
- cardiac arrhythmias
- AKI
- seizures
- death
186
enzyme responsible for metabolism of nucleic acids to uric acid
xanthine oxidase
187
uric acid can crystallize and precipitate in the renal tubules; this is enhanced in the presence of what?
calcium phosphate
188
initial treatment for TLS if oliguria is not already present
judicious ivf to maintain renal tubular flow
189
a form of recombinant urate oxidase that metabolizes uric acid to nontoxic allantoin thus preventing uric acid nephropathy and renal failure
rasburicase
190
xanthine oxidase inhibitor
allopurinol
191
what are the data in support of alkalization of urine to prevent or abort TLS-induced kidney injury?
mixed; most experts suggest avoiding
192
criteria for emergent hemodialysis for TLS
usual criteria
- life-threatening hyperkalemia
- diuretic-refractory volume overload
- uremic symptoms
- severe metabolic acidosis
- intoxication w/ a dialyzable toxin
193
has prophylactic HD in the absence of usual criteria shown to improve clinical outcomes of patients w/ TLS?
no
194
tumor embolization or surgical procedures in patients w/ neuroendocrine tumors can release large amounts of what?
serotonin and other small-molecule neurotransmitters
195
most common clinical features of carcinoid crisis
- flushing
- diarrhea
- bronchospasm
- tachycardia
196
prevention of carcinoid crisis prior to tumor embolization or surgery
long-acting somatostatin analogue
197
treatment for carcinoid syndrome intraoperatively
- octreotide iv prn
- should not be given preemptively if already on long-acting somatostatin analogue
198
thrombotic thrombocytopenic purpura (TTP) is a medical emergency caused by
reduced von Willebrand factor-cleaving protease, ADAMTS13
199
- small-vessel platelet-rich thrombi
- thrombocytopenia
- microangiopathic hemolytic anemia (MAHA)
- organ damage
thrombotic thrombocytopenic purpura (TTP)
200
what are the 2 different forms of thrombotic thrombocytopenic purpura (TTP)?
- autoantibodies against ADAMTS13
- hereditary defect in the ADAMTS13 gene
201
- microangiopathic hemolytic anemia (MAHA), hb < 10 g/dL
- thrombocytopenia, platelets < 30,000/μL
- AMS
- TIA or stroke
- seizures
thrombotic thrombocytopenic purpura (TTP)
202
should therapy be withheld or delayed while waiting for ADAMTS13 activity?
no!
203
what is the mechanism of microangiopathic hemolytic anemia (MAHA) in thrombotic thrombocytopenic purpura (TTP)?
mechanical shearing (fragmentation) of RBCs as they pass through the microvasculature full of platelet-rich microthrombi
204
PBS findings in thrombotic thrombocytopenic purpura (TTP)
- schistocytes
- thrombocytopenia
205
standard therapy for thrombotic thrombocytopenic purpura (TTP)
- therapeutic plasma exchange (TPE)
- glucocorticoids
- rituximab
206
what medication should be added if standard therapy for thrombotic thrombocytopenic purpura (TTP) doesn't work?
caplacizumab
207
caplacizumab MOA
MAB that binds to von Willebrand factor and blocks its interaction w/ platelet glycoprotein 1b-IX-V
208
what is the leading preventable cause of maternal death globally and accounts for 20% of maternal deaths in developing countries?
postpartum hemorrhage (PPH)
209
what is the most common cause of postpartum hemorrhage (PPH) and accounts for 70% of cases?
uterine atony
210
what is the current definition of postpartum hemorrhage (PPH)?
blood loss > 1,000 mL, regardless of method of delivery
211
what are the "four T's" of postpartum hemorrhage (PPH)?
- tone (uterine atony)
- trauma (lacerations and rupture)
- tissue (retained placenta or clots), and
- thrombin (clotting d/o's)
212
postpartum hemorrhage (PPH) d/t atony is often a/w a number of risk factors which are
- chorioamnionitis
- therapeutic use of magnesium
- prolonged labor
- fetal macrosomia
- advanced maternal age
- labor induction or augmentation
- multiple gestation
213
what agents may be used for uterine atony to restore tone?
- oxytocin
- methylergonovine
- misoprostol
214
what mechanical approaches are used for uterine atony?
- uterine massage
- uterine balloon tamponade
- uterine compression suturing
- uterine and vaginal packing
215
if pharmacological agents and mechanical approaches fail to control PPH, what is the next best step?
emergent hysterectomy
216
- a rare but serious complication of bone marrow and hematopoietic SCT
- risk factors include;
- calcineurin inhibitors
- mammalian target of rapamycin inhibitors
- GVHD
- multiple previous transplants
- HLA mismatch
- opportunistic infection
- certain conditioning regimens (especially those including total body irradiation)
transplant-associated thrombotic microangiopathy (TMA)
217
what are the clinical features of transplant-associated TMA?
- new or worsening HTN
- progressive AKI
- worsening thrombocytopenia
- MAHA
- pHTN
- progressive neurologic dysfunction
218
- a/w systemic inflammation and characterized by fever, rash, and diffuse capillary leak
- pulmonary edema
- end-organ dysfunction
engraftment syndrome
219
- pathologic lesion in arterioles and capillaries resulting in microvascular thrombosis
- microangiopathic hemolytic anemia (MAHA)
- schistocytes and thrombocytopenia on PBS
thrombotic microangiopathy (TMA)
220
there are several different types of TMAs; what are they?
- immune-mediated TTP (autoantibody against ADAMTS13)
- hereditary-mediated TTP (defect in ADAMTS13 gene)
- HUS from Shiga toxin
- acquired, complement-mediated TMA
- hereditary, complement-mediated TMA
- drug-mediated TMA
- metabolism-mediated TMA
- coagulation-mediated TMA
221
TMAs can be broadly categorized how?
- hereditary d/o's
- acquired d/o's
222
aside from the TMAs, what are other causes of MAHA and thrombocytopenia?
- DIC
- infection
- some malignancies
- preeclampsia
- HELLP syndrome
- severe HTN
- collagen vascular disease
- s/p organ and hematopoietic cell transplant
223
TTP treatment continues until when?
thrombocytopenia has resolved w/ a platelet count of ≥ 150,000/µL
224
- can occur between 2 to 24 months of administration of medication
- main clinical symptoms include, dyspnea, cough, fever, and chest pain
- radiographic features are nonspecific; traction bronchiectasis, consolidation, reticular opacities, GGO, centrilobular nodularity, honeycombing
checkpoint inhibitor pneumonitis (CIP)
225
therapy w/ immune checkpoint inhibitors has been a/w what adverse effects?
- enteritis
- dermatitis
- encephalitis
- pneumonitis
226
acute radiation pneumonitis typically occurs after what time period?
1-6 months after completion of external beam radiation
227
checkpoint inhibitor pneumonitis (CIP) is diagnosed how?
diagnosis of exclusion
228
histopathology of checkpoint inhibitor pneumonitis (CIP)
CD8+ lymphocytic alveolitis
229
should a patient be on empiric abx for respiratory pathogens while investigating for checkpoint inhibitor pneumonitis (CIP)?
yes, if indicated
230
in thromboelastography (TEG), what represents the time from reagent activation to onset of clot formation?
reaction time (R-time, aka ACT)
231
the reaction time (R-time, aka ACT) is primary affected by what?
perturbation of the intrinsic clotting cascade (eg, clotting factor depletion, or administration of AC)
232
what is a normal R-time?
varies depending on the reagents used to initiate clotting, so a control sample is used as a reference
233
in thromboelastography (TEG), the K-time is what?
time from onset of clot formation until clot amplitude reaches 20 mm
234
in thromboelastography (TEG), the α-angle is what?
a measure of the rate of rise of clot strength
235
both the K-time and α-angle are primarily affected by what?
deficiencies of fibrinogen
236
both the K-time and α-angle can be corrected by administering what?
cryoprecipitate
237
in thromboelastography (TEG), the maximum amplitude (MA) is what?
a measure of maximal viscoelastic strength of a clot
238
the maximum amplitude (MA) primary depends on what?
platelet number and function
239
what will decrease the maximum amplitude (MA)?
- thrombocytopenia
- impaired platelet function
240
what will increase the maximum amplitude (MA)?
- platelet transfusions
- desmopressin
241
once clot strength has reached its maximum, what is the next step in the process?
counterregulatory process of thrombolysis to begin weakening the clot
242
in thromboelastography (TEG), what is the lysis index (LY-30)?
the percentage of loss of amplitude at 30 minutes after reaching the maximum amplitude (MA)
243
the lysis index (LY-30) is a measure of what?
intensity of fibrinolytic activity
244
overly exuberant fibrinolytic activity can lead to what?
destabilization of fresh clot and recurrent bleeding
245
what therapies can help normalize LY-30?
- tranexamic acid
- aminocaproic acid
246
in the CRASH-2 trial, what reduced bleeding and mortality after major trauma?
tranexamic acid
247
the utility of TEG has been evaluated in subsets of patients at risk of major bleeding including advanced liver disease who were undergoing invasive procedures; what were the take home points?
- significantly lower transfusions of blood products w/o concomitant increase in bleeding complications
- fewer transfusion-related adverse effects
248
TEG has also been shown to reduce unnecessary blood transfusions in which patients?
- patients undergoing cardiac surgery
- perioperative or peripartum bleeding
249
interpret this TEG pattern
normal
250
interpret this TEG pattern
increased thrombolytic activity
251
interpret this TEG pattern
fibrinogen deficiency
252
interpret this TEG pattern
inadequate platelet function
253
interpret this TEG pattern
presence of AC or depletion of clotting factors
254
what are some of the number hematological abnormalities that can occur w/ covid-19 infection?
- lymphopenia
- leukocytosis
- leukopenia
- monocytosis
- reactive lymphocytes
- leukoerythrobastosis
- thrombocytopenia
- hyposegmented neutrophils characteristic of acquired Pelger-Huet anomaly
255
a normal neutrophil has an average of 3.5 nuclei, how many nuclei are seen in Pelger-Huet anomaly (inherited or acquired) and what is the cell called?
- < 3.5, usually 2
- "pince-nez" cell
256
more often, the Pelger-Huet anomaly is acquired, sometimes called "pseudo-Pelger-Huet anomaly," and can result as a consequence of what?
- leukemia
- myelodysplasia
- myxedema
- viral infections
- malaria
- drug toxicity
257
what can cause hypersegmented neutrophil nuclei?
- occasionally iron deficiency
- folate deficiency
- B12 deficiency
258
leukemias manifesting w/ acute hyperleukocytosis are a/w very high risk of early mortality, predominantly d/t what?
- respiratory failure
- intracranial bleeding
259
what is a unique finding that can be seen in patients w/ leukemias manifesting w/ acute hyperleukocytosis?
spurious hypoxemia w/ an artificial decrease in PaO2
260
symptomatic hyperleukostasis is aka
leukostasis
261
hyperleukostasis can be seen w/ what malignancies?
- AML
- ALL
- CLL
- CML
262
hyperleukostasis is most commonly seen in what malignancy?
large, poorly deformable blasts in AML
263
respiratory and neurologic symptoms d/t lung and brain microvascular involvement are most common in a patient w/ symptomatic hyperluekocytosis; what are other findings?
- myocardial ischemia
- bowel ischemia
- renal ischemia
- limb ischemia
- priapism
264
fever is common in hyperleukocytosis, can be d/t what?
- inflammation from leukostasis
- concurrent infection
265
circulating blast fragments in hyperleukocytosis can lead to what lab test result error?
overestimation of platelet count w/ automated blood cell counters
266
use of heparinized tubes will reduce the risk of what lab error in hyperleukocytosis?
erroneous hyperkalemia
267
what other findings can be present on presentation of hyperleukocytosis and may worsen during initial treatment?
- DIC
- TLS
268
what are the treatment options for hyperluekocytosis?
- leukapheresis
- pharmacologic cytoreduction w/ hydroxyurea or chemotherapy
269
what initial chemotherapy is initially started for hyperleukocytosis?
7+3 (cytarabine and idarubicin)
270
what is transfusion strategy is used during the initial treatment of hyperleukocytosis?
- limited prbc transfusion d/t risk of worsening blood viscosity
- continued platelet support to reduce risk of hemorrhage d/t to both thrombocytopenia and DIC
271
the PROPPR trial demonstrated what transfusion strategy reduced exsanguination in hemorrhagic shock patients?
1:1:1 (equal parts plasma, platelets, and prbcs), but this approach has fallen out of favor d/t increased r/o TRALI and TACO; more targeted approach w/ TEG is now preferred
272
the most benefit of plasma-first resuscitation has been shown in which patients?
- transport times > 20 minutes
- cicilian air transports
- blunt injury
