Leukopenia Dr. Bossaer EXAM 4

Question 1

What is the MOA of G-CSF?

Answer 1

activation of the JAK-STAT pathway -> transcription of factors stimulating differentiation of Granulocytes (Neutrophils)

Question 2

What are the G-CSF agents?

Answer 2

Filgrastim
tbo-filgrastim
filgrastim-sndz (biosimilar)

Question 3

What is the brand name of Filgrastim and pegfilgrastim?

What is difference in dosing between the two?

Answer 3

Filgrastim: Neupogen

pegfilgrastim: Neulasta (PEG G-CSF)

pegfilgrastim is PEGylated and lasts longer (1x dosing)

Question 4

When do we start giving CSF drugs?

Answer 4

24-48h after chemotherapy (if given too early it can make neutropenia worse bc chemotherapy targets rapidly dividing cells - bone marrow is growing faster with CSF)

-it decreases the duration of neutropenia and the likelihood of neutropenic fever
-also we can start chemo faster and at higher doses, less time for the cancer to grow back

Question 5

What are the common side effects of CSF drugs?

Answer 5

Bone pain -> give Tylenol, not NSAIDs bc of thrombocytopenia (bleeding risk) and GI bleeding risk
Flu-like symptoms

Question 6

When would we use CSF agents as primary prophylaxis?

Answer 6

-always in high-risk patients
>20% risk of febrile neutropenia

-sometimes with 10-20% risk or when there are other risk factors (COPD, older age)

-with myeloid cancer (AML) or Myelodysplastic syndromes (MDS) only after remission bc these are myeloid growth factors making leukemia (AML) worse

-if they have life-threatening infections (neutropenia)

-bone marrow transplantation (donor produces more stem cells, neutrophils to be donated)

Question 7

When would we use CSF agents as secondary prophylaxis?

Answer 7

-if they had neutropenia before -> prevent delay of future cycles

Question 8

What factor triggers the intrinsic and which one triggers the extrinsic pathway?

Answer 8

Intrinsic: Exposed collagen (endothelial lining disruption)

Extrinsic: Trauma and Tissue factor

Question 9

Match the pathway that is more affected by INR and PT tests.

Answer 9

Intrinsic: INR
Extrinsic: PT

Question 10

What is the function of Plasmin in the fibrinolytic pathway?

Answer 10

breaks down blood clots
-> increase in D-Dimer (seen in DVT)

Question 11

What are the Platelet disorders that cause increased Bleeding?

Answer 11

-Thrombocytopenia (low platelets)
-Platelet dysfunction
Drugs (Aspirin, Clopidogrel)
Platelet defects
vWF disease (initiates platelet aggregation)

example: nose bleeds

Question 12

What are diseases that can cause Coagulation disorders leading to increased Bleeding?

Answer 12

patients are not producing enough coagulation factors

-Hemophilia (F8 and F9), Liver disease (Factor deficiency)

-Anticoagulation drugs

example: joint bleeds, GI bleeds

Question 13

Which drug can cause Fibrinolysis disorders leading to increased Bleeding?

Answer 13

tPA (alteplase, reteplase)

too much breakdown of blood clots

the bleeding could be anywhere (example CNS bleeds)

Question 14

Which test is used to identify Thrombocytopenia and vWF disease?

Answer 14

Platelet function assay (bleeding time)

-assess platelet function and number
-also abnormal when using antiplatelets

Question 15

Which lab test is affected by Warfarin?

Answer 15

PT and INR (PT is used to calculate INR)

-also affected to some extent by DOACs
-increased in
Vitamin K deficiency (also in newborns), liver disease

Question 16

Which lab test is affected by Heparin and aragtroban?

Answer 16

aPTT (activated partial thromboplastin time)
-> also measures Hemophilia or liver disease

we use anti-Xa activity more for heparin now (if they were on a DOAC -> go with aPTT bc DOACs interact with the anit-Xa test)

Question 17

What platelet level is associated with a high risk of spontaneous intracranial bleeding?

Answer 17

<10 -> need a platelet transfusion

Question 18

What disease states can cause low platelet levels?

Answer 18

-liver disease (thrombopoietin release is decreased)
-alcoholism
-splenomegaly

-ITP: Idiopathic (Immune) Thrombocytopenia Purpura -> autoimmune cells destroy platelets

-TTP: Thrombogenic Thrombocytopenia Purpura
Microangipathich hemolysis

Question 19

Which of the Thrombocytopenia Purpura disorders is ideal for platelet transfusion?

Answer 19

ITP

avoid in TTP bc it is a thrombogenic (clotting) disease, platelet transfusion would increase the risk of blood clots

Question 20

MOA of Thrombopoietin Mimetics

Answer 20

bind to Thrombopoietin receptors and activate the JAK-STAT pathway -> platelet production

-Romiplostim
-Eltrombopag
-Avatrombopag

Question 21

Which drugs can cause Thrombocytopenia?

Answer 21

-chemotherapy
-Herapin-induced-thrombocytopenia (hapten-type immune reaction) !!!
-LMWH !!!

-anticonvulsants (Carbamezapine, Phenytoin, Phenobarbital, Primidone)
-anti-infectives (Linezolid)

Question 22

How does ITP cause thrombocytopenia?

Answer 22

-antibodies that destroy platelets

-decreased thrombopoietin (TPO)
->can use thrombopoietin mimetics

Question 23

How does ITP present in adults VS children?

Answer 23

in kids it is acute onset and duration following viral illness (immune system overreacts), treated once and it is fine

in adults, it is chronic (comes and goes)

-both present with severe thrombocytopenia, epistaxis, GI bleeding, Petichiae (purple spots), heavy menses in adults

Question 24

What is the treatment for ITP?

Answer 24

-1st line: immunosuppressant: prednisone, dexamethasone
-Splenectomy (source of auto-antibodies, and site where platelets are removed)

-IV immune globulin
-Anti Rh factor globulin (WhinRho)
-Rituximab
-Mycophenolate mofetil

-Stimulate platelet production with romiplostim and eltrombopag

Question 25

What needs to be done before a Splenectomy?

Answer 25

vaccination against encapsulated organisms bc we need the complement system for them, 2 weeks before Splenectomy -Strep pneumo -Neisseria meningitis -Haemophilus influenzae

Question 26

How do Anti Rh antibodies work in treating ITP?

Answer 26

it only works in patients with the Rh (+), A (+), B (+), AB (+) blood type the anti-Rh-D antibodies (drug) bind to the D-antigen on the RBCs -> which stimulates macrophages to destroy them (causes hemolytic anemia though) -> target the immune system to target RBC and keep it away from platelets -only used in children, they can tolerate it

Question 27

How does IV immune globulin work in treating ITP?

Answer 27

the goal is to flood the blood with IgG antibodies and bind them to the Fc-receptors of macrophages -so that macrophages don't target platelets

Question 28

What is a possible side effect when using IV IG 2g/kg over 2 days?

Answer 28

Fluid retention (pulmonary edema) adjust the dose to 2g/kg over 5 days especially for patients with heart failure other side effects: -fever, chills, infusion reactions

Question 29

How are infusion reactions associated with IV IG managed?

Answer 29

begin infusion at a low rate (0.5 ml/kg/hr) -increase slowly every 30 min to 5 ml/kg/hr

Question 30

How long does it usually take for patients to respond to corticosteroid therapy for ITP treatment? How should it be discontinued? What do we consider after prolonged corticosteroid therapy? EXAM Q

Answer 30

-1-2 weeks -> Platelets back at >30-50 -then taper -if they are on more than 20mg of prednisone per day for more than a month -> PJP prophylaxis - Bactrim MWF

Question 31

What are the premeds for Rituximab?

Answer 31

Tylenol, diphenhydramine, slow infusion rate -risk for Hypogamaglobinemia (decreased response to vaccines with long-term use) -risk for HepB reactivation

Question 32

What is a class side effect of Thrombopoietin mimetics?

Answer 32

Bone marrow reticulin formation (bone marrow fibrosis) -> the bone marrow will not be able to produce RBCs, and WBCs

Question 33

What is the dosage form of the different thrombopoietin mimetics? What DDI is associated with orals? !!!

Answer 33

Romiplostim (Nplate) - SC Eltrombopag and Avatrombopag - oral DDI with orals: increases AUC of Rosuvastatin and hepatoxic

Question 34

Which factor is enalrged in Thrombotic Thrombocytopenia purpura (TTP)?

Answer 34

von Willebrand Factors (vWF) -leads to thrombus formation and end-organ dysfunction -avoid platelet transfusion (making it worse)

Question 35

Which drugs can cause TTP? !!!

Answer 35

-Quinine (malaria treatment) -injected ER oxymorphone -Chemotherapy (Gemcitabine, cisplatin, Mitomycin C) -oral contraceptives -Ticlopidine >> Clopidogrel

Question 36

What is the treatment for TTP?

Answer 36

transfusing plasma that provides ADAMSTS13 -ADAMSTS13 cleaves multimers of vWF (vWF is enlarged and causes platelets to form small clots)

Question 37

Which drugs can cause Aplastic Anemia (anemia, thrombocytopenia, neutropenia)?

Answer 37

Anticonvulsant: Carbamazepine, Phenobarbital, Phenytoin Drugs for hyperthyroidism: Methimazole, Propylthiouracil Chloramphenicol

Question 38

Which drugs can cause Agranulocytosis?

Answer 38

-Clozapine !!! -Anticonvulsant: Carbamazepine, Phenobarbital, Phenytoin -Drugs for hyperthyroidism: Methimazole, Propylthiouracil -Anti-infectives: Sulfonamide, Chloramphenicol. Macrolides

Question 39

Which coagulation factors need Vitamin K for activation? Which foods are rich in Vitamin K?

Answer 39

Factor 2, 7, 9, 10 Vit K is found in leafy greens and produced by gut bacteria (antibiotics increase INR)

Question 40

A patient had a car accident and was found to be Fe deficient. How should this patient be treated for Fe deficiency before starting surgery? A. RBC transfusion B: Ferrous sulfate daily C: IV Dextran 1x dose after a test dose D: Iron sucrose IV 100 mg for 10 weeks

Answer 40

RBC transfusion -she lost a lot of blood after the accident IV Dextran only replaces her iron (the body's material to make RBCs)

Question 41

Why don't we give a Blood transfusion to every patient who is anemic? FYI

Answer 41

Iron overload in the heart and liver (Ferritin storage) -heart failure -liver failure

Question 42

A patient is treated with Ferrous sulfate for Menorrhagia (heavy period) and Ciprofloxacin for a UTI. What is the most concerning DDI? A: Cipro should not be used under the age of 30. B: Decreased Ferrous sulfate exposure due to Cipro. C: Decreased Cipro effectiveness D: Increased GI toxicity due to Cipro and oral iron use.

Answer 42

Decreased Cipro effectiveness due to chelation of the Iron with Cipro

Question 43

A 60 yo patient stated to feel weak and asked for Iron supplements. How should this be managed? A: Ferrous sulfate 325 mg daily B: Ferrous Gluconate 325 mg TID C: Refer to MD for IV ferric gluconate D: Refer to MD for evaluation

Answer 43

Refer to MD for evaluation if she has anemia, must find out what the cause of the blood loss is !!! -rule out colon cancer

Question 44

Which of the following is a candidate for an ESA agent? A: 34yo female receiving neoadjuvant chemotherapy with a Hbg of 10.4 and fatigue. B: 62 yo male receiving palliative chemotherapy with a Hbg of 9.5 C: 57 yo male receiving metastatic pancreatic cancer patient not receiving chemotherapy with a Hbg of 8.9 D: 34 yo with T1DM, CKD and baseline Hbg of 10.5 E: 73 yo with HTN, CKD and baseline Hbg of 12.1 and requiring blood transfusion weekly

Answer 44

A: has cure as the goal due to neoadjuvant therapy (ESA is only for palliative, and Hbg is over 10) B is a candidate 62 yo male receiving palliative chemotherapy with a Hbg of 9.5 C: doesn't receive chemo so the anemia is from the cancer not from chemo, ESA in cancer patients is only for chemo-induced anemia D: would be a candidate due to CKD, but start once Hbg is less than 10 E: not a candidate because Hbg is 12.1

Question 45

A patient with CKD and HTN has low Hbg and Tsat (Fe deficiency). He was started on darbepoetin but his Hbg didn't improve. His meds are: irbesartan, HCTZ, Pantoprazole, and atenolol) Which drug needs to be added? What is the cause of the Fe deficiency?

Answer 45

Add Iron -> EPO needs Iron (raw material) for blood production the cause for Fe deficiency is probably the PPI, Fe absorption needs an acidic environment

Question 46

A patient with low Hbg and Fe deficiency received darbepoetin and IV Fe sulfonate. The patient's Hbg was at 9.8 and improved 4 weeks later it is at 11.7, the Tsat improved to 23% (15% before) What is the next most appropriate step? A: make no changes B: increase the darbepoetin dose C: decrease the darbepoetin dose D: give a blood transfusion

Answer 46

C: decrease the darbepoetin dose or make no changes (close to goal) because the Hbg (11-12 g/dL) and the rate of increase is at goal (1g/dL every 2 weeks) too fast would increase the risk of HTN, MI and stroke

Question 47

A 64-year-old male is admitted to the hospital with healthcare-associated pneumonia. He was treated with Pip/Tazo and Vancomycin. His home meds include Phenytoin, Digoxin, asprin and diazepam. His platelet dropped from 278 to 78. Which of the drugs can cause the reduction of platelets?

Answer 47

Anti-infectives: Pip/tazo or Vancomycin Phenytoin can also reduce platelets, but the drop started when he came to the hospital and was treated with antibiotics, he was fine when he was at home

Question 48

64yo with stage III breast cancer undergoing adjuvant therapy with AC with a 9% risk for neutropenia. After cycle 2 she had a neutropenic fever and cycle 3 had to be delayed. How do we manage this regarding G-CSF use? A: filgrastim daily (10 doses) on day 1 of chemotherapy B: sargramostim for 21 days starting on day 2 of chemo C: pegfilgrastim x1 dose on days of chemo D: no G-CSF, reduce chemotherapy dose

Answer 48

A: is too early, it makes bone marrow grow faster -> chemo drug will target it -> more neutropenia B: 21 days is too long C: is correct D: don't reduce chemo dose, we want to treat the cancer effectively