Hematology / Oncology Flashcards
True or false: you should order antiplatelet antibody testing to evaluate ITP.
False
While there is such a test, it has low sensitivity and is not available at many hospitals. As such, ITP is still a diagnosis of exclusion. You must exclude the following things:
- Infections: HIV, HCV, HBV, H. pylori
- Autoimmune: SLE, vasculitides
- Nutrient deficiencies: B12, folate
- Malignancy: MDS, leukemia
If a patient has a thrombocytopenia-like bleeding pattern (e.g., epistaxis, gum bleeding, and petechiae) but there platelet levels are normal, you should consider ordering a ___________________.
platelet function analyzer 100
This test passes anticoagulated platelets through a collagen network and measures the speed at which the filter clogs up. Prolonged closure time indicates platelet dysfunction.
What is paraprotein?
A type of protein that inhibits clotting factors
True or false: all DOACs can be started without heparin bridging.
False
Apixaban and rivaroxaban can be started without bridging.
Dabigatran and edoxaban require heparin bridging.
Describe the utility of the pulmonary embolism severity index.
PESI is a score that predicts the 30-day mortality of pulmonary emboli using several criteria (age, sex, cancer status, CHF status, AMS, and vitals among other things). Those with PESI < 65 have a near 0% risk of 30-day mortality and can be managed outpatient. Those 65-85 have a near 1% risk and can go either way for disposition. Greater than 85 is considered higher risk and should be managed inpatient initially.
What is the mechanism behind inflammatory anemia?
IL-6 leads to proteolysis of the membrane protein ferroportin which is the protein that absorbs iron from the gut, thus lowering the serum iron without affecting iron stores already within cells.
Inflammatory anemia usually has what iron panel profile?
High ferritin
Low TIBC
Low serum iron
Discuss the different treatment options for MDS based on risk status.
In patients with high risk disease (which is determined by genetic analysis), allogenic stem cell transplantation is pursued if the patient is young and healthy enough to tolerate it. In patients with low-risk disease, therapy is aimed at limiting the need for transfusions. Specifically, lenalidomide can help delay progression and limit transfusion need.
Lenalidomide works by _______________.
affecting both the humoral and cellular immune system
Describe hypereosinophilic syndromes.
High levels of eosinophils (>1.5) can cause organ damage regardless of why they are elevated. The most common organs involved are the skin (eczema, erythroderma, urticaria, and angioedema), lungs (parenchymal infiltrates, pleural effusion, lymphadenopathy, and pulmonary emboli), gastrointestinal tract (eosinophilic gastritis, enteritis, colitis, chronic active hepatitis, focal hepatic lesions, eosinophilic cholangitis, Budd-Chiari syndrome), and heart (mitral or tricuspid regurgitation, cardiomegaly, restrictive cardiomyopathy).
Describe the management of anemia in people with hereditary spherocytosis.
Those with HS usually just have a mild anemia that warrants no intervention. There are some instances where they do need interventions, though:
- Chronic severe hemolytic anemia: rarely, those with HS will have more severe anemia and require splenectomy to limit hemolysis.
- Aplastic anemia: those with HS are at increased risk of virally induced aplastic anemia and can require transfusion.
Prednisone treats what kind of anemia?
AHA
D-dimer is only useful in _____________________.
evaluating those with a low probability of PE
It isn’t perfectly sensitive, so if someone has a high probability of PE then you would need to do additional imaging regardless of what the D-dimer is.
How should you diagnose PE in pregnant women?
- First, do PVLs. If they have DVTs you can presume their pulmonary symptoms are from PE.
- Second, if PVLs are negative do a V/Q scan.
- Third, only do a CTA if the V/Q is equivocal.
Why is it important to deal with anemia preoperatively?
Preoperative anemia has been associated with increased perioperative mortality, particularly when it is IDA. Addressing iron deficiency before a surgery can boost survival and limit intervention.
True or false: the preferred agent (per the boards) to reverse warfarin toxicity urgently is FFP.
False
It is Kcentra (4-factor prothrombin complex concentrate). This is preferred because it is quicker to give than FFP and saves volume for those in whom volume is a concern. Of note, Kcentra costs $5k per dose.
It used to be that guidelines recommended searching for _____________ in those with unprovoked DVT.
malignancy
Studies have shown mixed results in looking for occult malignancy, so currently guidelines recommend only being up to date on standard cancer screens like Pap smears, mammograms, and colonoscopies.
B2 microglobulin is used to risk stratify ______________.
MM
Patients with multiple myeloma will sometimes get ppx ______________.
IVIG (because of hypogammaglobulinemia)
A patient who has evidence of hemolysis (e.g., elevated indirect bilirubin and low hgb) as well as low-grade fever a few days after receiving a blood transfusion may have _______________.
delayed hemolytic transfusion reaction
In this syndrome, a person has low-level antibodies to a non-ABO antigen on RBCs (say, from a past transfusion or pregnancy). When they get blood that may have that antigen, they won’t hemolyze as aggressively as frank ABO mismatch, but slowly the will lyze the cells and may present days later like the stem described.
__________________ should be supplemented in DIC to limit bleeding.
Cryoprecipitate
True or false: most adult Parvovirus infections entail arthralgias and rash.
False
Most are actually asymptomatic, which is why you need to have a high index of suspicion in a person presenting in aplastic crisis.
True or false: aplastic anemia most commonly presents with pure red cell aplasia.
False
Aplastic anemia most commonly involves all cell lines.
When should essential thrombocytosis be treated?
In patients > 60 years old who have had thromboembolic events.
Treat with hydroxyurea.
List some causes of secondary thrombocytosis.
- Iron deficiency
- JAK2 kinase mutations
- Malignancy
- Bleeding
- Collagen vascular diseases
Benign neutropenia is a condition in which ______________________.
ethnic minorities can have persistent neutropenia to 1.0-1.5 range; it is not associated with increased risk of infection
G6PD levels should not be measured _____________.
during an acute hemolytic crisis; it will be falsely normal because the newly made RBCs will raise G6PD serum levels even when the absolute levels are low
How can the iron panel help differentiate anemia of kidney disease vs inflammation?
In inflammation, serum iron and TIBC is low whereas in CKD it is usually normal.
______________ is diagnosed by abdominal fat pad biopsy.
Amyloidosis
Review the presentation of Waldenstrom macroglobulinemia.
WM is an indolent B-cell lymphoma that presents with B symptoms, anemia, hepatosplenomegaly, and an elevated IgM spike. Bone marrow biopsy is needed to confirm the diagnosis.
Atypical presentations of rheumatoid arthritis might be _______________.
hemochromatosis
Particularly look out for the “hook-like osteophytes” of the 2nd and 3rd MCP joints.
The best initial test for hemochromatosis are _________________.
transferrin and ferritin
High transferrin and high ferritin are classic. Normal of both has a good negative predictive value.
When is tPA indicated in the treatment of DVTs?
When limb ischemia is suspected (e.g., absent pulses, cyanosis, etc.)
In what situation can you give blood that doesn’t crossmatch?
In severe autoimmune hemolytic anemia, even correctly ABO-matched blood will often fail to crossmatch. If a person is having anemia-related symptoms or is severely anemic, you should give them blood that fails to crossmatch because it will still survive for several days during which you can immunosuppress them.
True or false: the most common problem after autologous bone marrow transplant is GVHD.
False
With autologous transplants you do not get GVHD. The most common complication is infection.
What workup is needed when a polyclonal M spike is noted?
- BMP: renal function, Ca
- CBC: anemia
- Whole body MRI: looking for lytic lesions (more sensitive than x-ray)
At which level should you consider iron removal therapy?
Ferritin > 1000 in a patient with no concern for inflammatory elevation of ferritin
Use deferoxamine (IV) or deferasirox (PO)
What hgb target is usually used when giving EPO agents to those with anemia of CKD?
11-12
This helps to limit some of the risks of EPO (HTN, strokes).
______________ is the reversing agent for dabigatran.
Idarucizumab
Those with sickle cell are at increased risk of perioperative complications. A landmark trial in 1994 showed that ___________________ helped to decrease the risk substantially.
simple transfusion to >10
What thrombophilia is associated with an increased risk for warfarin-induced skin necrosis?
Protein C deficiency
Remember that warfarin-induced skin necrosis is caused by a transient hypercoagulable state when proteins C and S, which are both anticoagulant factors, are knocked out by warfin before the procoagulant factors 10, 9, 7, znd 2. Those with protein C deficiency are at increased risk because they already have low levels of C.
Side note, protein C deficiency is an autosomal dominant disorder. One missing copy leads to 50% of the level of protein C and thus the increased risk. (I’m guessing a homozygous mutation would be fatal because you would not be able to anticoagulate at all, but I’m not sure.)
Describe the utility of the PE screening scores.
• PERC (PE Rule-out Criteria): a series of questions designed to screen-out PE. If all answers are no, then the probability of PE is so low that no imaging or further workup are needed. If any are positive, then the clinician should consider imaging.
• Wells: This stratifies people into low-, medium-, and high-risk categories. Low-risk patients can be screened out with no further testing. Medium-risk patients should get a D-dimer; if the D-dimer is negative then no further testing need be done. Lastly, high-risk patients should go straight to imaging because a negative DD does not rule-out PE in high-risk pts.
Paroxysmal nocturnal hematuria leads to low levels of which cell lines?
RBCs, WBCs, and platelets
This happens because the CD55 and CD59 receptor that prevents the activation of complement is present on all blood cells.
If a patient has clear hemolyis by their labs but a completely normal smear (i.e., no spherocytes, schistocytes), then think ____________.
PNH
In PNH, you have transient hemolysis so the smear can normalize but the labs won’t.
Diagnose PNH with ______________.
flow cytometry
Coagulopathy of liver disease can look like DIC. What lab can distinguish the two?
Factor VIII level
Because VIII is produced in endothelial cells, it is not affected by the liver. Moreover, it will often be high in liver disease because the body senses the hypocoagulable state.
Those with sickle cell anemia can have baseline hgb in the _______ range.
5-7
Review the types of alpha thalassemia by genotype.
Remember that there are four alpha hemoglobin genes:
•One gene broken: silent carrier, no symptoms
• Two genes broken: alpha thal trait, mild anemia
•Three genes broken: hemoglobin H disease, severe, transfusion-dependent anemia
• Four genes broken: hydrops fetalis
Increased levels of A2 is a sign of __________.
beta-thalassemia minor (Barts)
Review the INR ranges and their interventions.
*Elevated INR and any major bleeding: give prothrombin complex concentrate
*INR 3-10 and no bleeding: withhold warfarin and recheck
*INR > 10 and no bleeding: withhold warfarin and give vitamin K
Also, anticipated surgical procedures can also indicate vitamin K.
True or false: TTP-HUS in a pregnant woman typically presents with schistocytes.
False
_____________ is the treatment for atypical HUS.
Eculizumab
True or false: those with SS disease will have about 60% HgB A.
False
Those with SS form of SCD will have no hemoglobin A.
Those with sickle trait can have pain crises if ______________.
They also have beta minor.
What are indications for hydroyxurea therapy in those with SCD?
Frequent pain crises or vaso-occlusive events like ACS and CVA
Hydroxyurea increases fetal hemoglobin and decreases vasospasm and platelet activation, all of which decrease the likelihood of vaso-occluisive events
True or false: ADAMTS13 is needed to confirm the diagnosis of TTP.
False
That test can take a while and TTP has such a high mortality (90% if untreated) that you need to begin treatment sooner than that. When you have clinical findings (fever, AMS) and lab findings (hemolytic anemia, AKI) with no concern for competing diagnoses like HUS or DIC, then start PLEX.
Describe the diagnosis of ACS in those with SCD.
It is essentially like PNA that evolves quickly: fever, respiratory distress, infiltrates on imaging, and rapid progression. You treat it like PNA (abx, fluids, O2 support), then when it progresses you intubate and do exchange transfusion.
Review the management of thromboembolism as presented in Moll’s article “How I Treat: Unexplained Arterial Thrombosis.”
1) First, clearly define the clot. Obtain whatever imaging you need to in order to know where it is (i.e., venous or arterial), how big it is, and what watershed areas it is affecting.
2) When you know the areas that it is affecting, then consider a consultation to that organ’s specialist (e.g., if it is a hepatic thrombosis, then consult a hepatologist to evaluate the extent of liver damage.).
3) Review for the causes and risk factors for thromboembolism:
- Echo (PFO, aneurysm, valvular problems)
- Carotid Dopplers (if cerebral)
- EKG and telemetry for pAF or other arrhythmia
- Imaging for local atherosclerosis (could be CTA, MRA, or US Doppler)
- Risk of atherosclerosis in history (immobility, obesity, HTN, tobacco use, dyslipidemia, DM, cocaine, amphetamine) or FMH
- Review medications for pro-thrombotic agents (most common ones are OCPs, HRT, anabolic steroids, recent heparin use, and IVIG)
- Look to see if they are up-to-date on malignancy screening (or have signs/symptoms that could potentially be malignancy)
- Consider evaluation for vasculitis or other inflammatory disorders
- Consider imaging the organ in question for anatomic anomalies that could predispose to clot formation (like fibromuscular dysplasia)
- If the above does not illustrate a likely cause, consider a thrombophilia workup — particularly if the patient is young (see the other card)
What malignancy screening is warranted after an unexplained VTE?
Age-related screening, risk-factor-related screening, and symptom-guided screening only
The big picture is don’t go hunting for cancer if the person is otherwise asymptomatic and up-to-date on their screenings (e.g., don’t do PETs on people just because of a clot).
Once you have followed the thorough initial workup of arterial thrombosis and found no secondary cause, what DDx and workup should you consider?
- Primary thrombophilias (FVL, PT 20210, PC, PS, AT, homocystinuria)
- Antiphospholipid syndrome
- Paroxysmal nocturnal hemoglobinuria
- Hyperviscosity syndromes (Waldenstrom, MM, erythrocytosis, thrombocytosis)
- Myeloproliferative neoplasms
- Vasculitis (particularly Behcets, Takayasu, giant cell)
- Sarcoidosis
Review the testing for APLAS.
The diagnosis requires the clinical history of venous or arterial thromboembolism as well as miscarriage in women and lab testing as below:
- Lupus anticoagulant, anti-cardiolipin IgG and IgM, and anti-beta2-glycoprotein 1
- Two sets of the above at least 12 weeks apart
Note: the above antibodies can be positive in the setting of inflammation so be cautious with positive results in someone with signs of inflammation.
What does research suggest about plasminogen mutations in clot risk?
There is no definitive research to suggest that plasminogen and plasminogen activator mutations have clinical syndromes associated with clotting.
What do guidelines say about managing arterial thrombosis in APS?
Trick question, no consensus exists.
Aspirin alone, anticoagulation alone, and combination are all frequently used. There is some data that suggests that warfarin leads to improved outcomes over DOACs and ASA, so you may hear that warfarin is the right choice, but it is far from a complete picture.
How does management of an arterial thrombosis change if a thrombophilia is diagnosed?
All people who have had an arterial thrombosis should be on lifelong baby aspirin because of the documented decrease in risk of arterial thrombosis and their low risk of bleeding. There is some data suggesting that aspirin and anticoagulation decreases the risk of arterial clots in those with a thrombophilia, but the risk of bleeding is higher. Because of this, those with a thrombophilia should have a discussion about the risks and benefits of dual therapy.
One unit of platelets should raise your counts by ____________.
30-50
Review the types of transfusion reactions.
•Febrile non-hemolytic: presents with fever only; is a rule-out diagnosis (meaning you need to assess for acute hemolytic reaction and septic transfusion)
•Hemolytic: presents with hemolysis, flank pain, hypotension; can be delayed or acute
•Allergic: presents with itching and hives
•Septic: presents with fever, rigors, bacteremia
•TRALI: presents with acute respiratory distress that does not respond to diuresis
• TACO: presents with volume overload
What should you do to assess for hemolytic reaction in a person with a fever post-transfusion?
• Get vitals (looking specifically for hypotension)
•UA (look for hemoglobinuria)
•Assess for flank pain
Recurrent allergic reactions to transfusions should prompt evaluation for ______________.
IgA deficiency
List five risks five potential complications of massive transfusion protocol (MTP).
•Coagulopathy (the anticoagulants in blood products can prolong PT)
•Hypocalcemia (the chelating agents in blood products do this)
•TACO
•Hyperkalemia
•Hypothermia (from blood being stored cold)
