Leukopenia Dr. Bossaer EXAM 4 Flashcards
What is the MOA of G-CSF?
activation of the JAK-STAT pathway -> transcription of factors stimulating differentiation of Granulocytes (Neutrophils)
What are the G-CSF agents?
Filgrastim
tbo-filgrastim
filgrastim-sndz (biosimilar)
What is the brand name of Filgrastim and pegfilgrastim?
What is difference in dosing between the two?
Filgrastim: Neupogen
pegfilgrastim: Neulasta (PEG G-CSF)
pegfilgrastim is PEGylated and lasts longer (1x dosing)
When do we start giving CSF drugs?
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
What are the common side effects of CSF drugs?
Bone pain -> give Tylenol, not NSAIDs bc of thrombocytopenia (bleeding risk) and GI bleeding risk
Flu-like symptoms
When would we use CSF agents as primary prophylaxis?
-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)
When would we use CSF agents as secondary prophylaxis?
-if they had neutropenia before -> prevent delay of future cycles
What factor triggers the intrinsic and which one triggers the extrinsic pathway?
Intrinsic: Exposed collagen (endothelial lining disruption)
Extrinsic: Trauma and Tissue factor
Match the pathway that is more affected by INR and PT tests.
Intrinsic: INR
Extrinsic: PT
What is the function of Plasmin in the fibrinolytic pathway?
breaks down blood clots
-> increase in D-Dimer (seen in DVT)
What are the Platelet disorders that cause increased Bleeding?
-Thrombocytopenia (low platelets)
-Platelet dysfunction
Drugs (Aspirin, Clopidogrel)
Platelet defects
vWF disease (initiates platelet aggregation)
example: nose bleeds
What are diseases that can cause Coagulation disorders leading to increased Bleeding?
patients are not producing enough coagulation factors
-Hemophilia (F8 and F9), Liver disease (Factor deficiency)
-Anticoagulation drugs
example: joint bleeds, GI bleeds
Which drug can cause Fibrinolysis disorders leading to increased Bleeding?
tPA (alteplase, reteplase)
too much breakdown of blood clots
the bleeding could be anywhere (example CNS bleeds)
Which test is used to identify Thrombocytopenia and vWF disease?
Platelet function assay (bleeding time)
-assess platelet function and number
-also abnormal when using antiplatelets
Which lab test is affected by Warfarin?
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
Which lab test is affected by Heparin and aragtroban?
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)
What platelet level is associated with a high risk of spontaneous intracranial bleeding?
<10 -> need a platelet transfusion
What disease states can cause low platelet levels?
-liver disease (thrombopoietin release is decreased)
-alcoholism
-splenomegaly
-ITP: Idiopathic (Immune) Thrombocytopenia Purpura -> autoimmune cells destroy platelets
-TTP: Thrombogenic Thrombocytopenia Purpura
Microangipathich hemolysis
Which of the Thrombocytopenia Purpura disorders is ideal for platelet transfusion?
ITP
avoid in TTP bc it is a thrombogenic (clotting) disease, platelet transfusion would increase the risk of blood clots
MOA of Thrombopoietin Mimetics
bind to Thrombopoietin receptors and activate the JAK-STAT pathway -> platelet production
-Romiplostim
-Eltrombopag
-Avatrombopag
Which drugs can cause Thrombocytopenia?
-chemotherapy
-Herapin-induced-thrombocytopenia (hapten-type immune reaction) !!!
-LMWH !!!
-anticonvulsants (Carbamezapine, Phenytoin, Phenobarbital, Primidone)
-anti-infectives (Linezolid)
How does ITP cause thrombocytopenia?
-antibodies that destroy platelets
-decreased thrombopoietin (TPO)
->can use thrombopoietin mimetics
How does ITP present in adults VS children?
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
What is the treatment for ITP?
-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
What needs to be done before a Splenectomy?
vaccination against encapsulated organisms bc we need the complement system for them, 2 weeks before Splenectomy
-Strep pneumo
-Neisseria meningitis
-Haemophilus influenzae
How do Anti Rh antibodies work in treating ITP?
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
How does IV immune globulin work in treating ITP?
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
What is a possible side effect when using IV IG 2g/kg over 2 days?
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
How are infusion reactions associated with IV IG managed?
begin infusion at a low rate (0.5 ml/kg/hr)
-increase slowly every 30 min to 5 ml/kg/hr
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
-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
What are the premeds for Rituximab?
Tylenol, diphenhydramine, slow infusion rate
-risk for Hypogamaglobinemia (decreased response to vaccines with long-term use)
-risk for HepB reactivation
What is a class side effect of Thrombopoietin mimetics?
Bone marrow reticulin formation (bone marrow fibrosis)
-> the bone marrow will not be able to produce RBCs, and WBCs
What is the dosage form of the different thrombopoietin mimetics?
What DDI is associated with orals?
!!!
Romiplostim (Nplate) - SC
Eltrombopag and Avatrombopag - oral
DDI with orals: increases AUC of Rosuvastatin and hepatoxic
Which factor is enalrged in Thrombotic Thrombocytopenia purpura (TTP)?
von Willebrand Factors (vWF)
-leads to thrombus formation and end-organ dysfunction
-avoid platelet transfusion (making it worse)
Which drugs can cause TTP?
!!!
-Quinine (malaria treatment)
-injected ER oxymorphone
-Chemotherapy (Gemcitabine, cisplatin, Mitomycin C)
-oral contraceptives
-Ticlopidine»_space; Clopidogrel
What is the treatment for TTP?
transfusing plasma that provides ADAMSTS13
-ADAMSTS13 cleaves multimers of vWF (vWF is enlarged and causes platelets to form small clots)
Which drugs can cause Aplastic Anemia (anemia, thrombocytopenia, neutropenia)?
Anticonvulsant: Carbamazepine, Phenobarbital, Phenytoin
Drugs for hyperthyroidism: Methimazole, Propylthiouracil
Chloramphenicol
Which drugs can cause Agranulocytosis?
-Clozapine !!!
-Anticonvulsant: Carbamazepine, Phenobarbital, Phenytoin
-Drugs for hyperthyroidism: Methimazole, Propylthiouracil
-Anti-infectives: Sulfonamide, Chloramphenicol. Macrolides
Which coagulation factors need Vitamin K for activation?
Which foods are rich in Vitamin K?
Factor 2, 7, 9, 10
Vit K is found in leafy greens and produced by gut bacteria (antibiotics increase INR)
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
RBC transfusion
-she lost a lot of blood after the accident
IV Dextran only replaces her iron (the body’s material to make RBCs)
Why don’t we give a Blood transfusion to every patient who is anemic?
FYI
Iron overload in the heart and liver (Ferritin storage)
-heart failure
-liver failure
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.
Decreased Cipro effectiveness
due to chelation of the Iron with Cipro
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
Refer to MD for evaluation
if she has anemia, must find out what the cause of the blood loss is !!!
-rule out colon cancer
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
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
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?
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
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
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
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?
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
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
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
