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What is a contraindication to a blood transfusion?
any pt whose Hb is >10g/dl
What is the indication for a blood transfusion?
any pt whose Hb is <7 g/dl. it is better to wait til their Hb is lower such as this to give a transfusion (maintain Hb at 7-9)
What is the leading cause of fatal transfusion reactions?
accidental transfusion with ABO incompatible RBCs
***What is transfusion-related acute lung injury (TRALI)?
- leading cause of transfusion-related death
- serious pulmonary reaction possibly associated with leukocyte antibodies/cytokines in donor blood, and recipient’s neutrophil priming and activation
- almost always occurs within 6hrs of transfusion
- Symptoms include bilateral pulmonary edema, dyspnea, hypoxemia, fever, and hypotension
What is transfusion-associated graft-vs-host disease?
- occurs when immunosupressed/deficient pt is given cellular blood products that possess immunologically competent lymphocytes
- it can be prevented by gamma irradiation og the blood to innactivate the donor lymphocytes
Indications for platelet transfusion.
- used to prevent bleeding in pts with thrombocytopenia
- the cut off is:
- 10x10^3 for pts with no other complications
- 20x10^3 with bleeding risk factors
- 50x10^3 if uncomplicated surgery is planned
- 100x10^3 if CNS surgery is planned
Contraindications for platelet transfusion.
Platelet transfusions are no helpful in pts with hemolytic syndromes such as ITP, TTP, HUS, HIS
What are the indications for fresh frozen plasma (FFP) transfusion?
- must ABO compatible
- coagulation deficiencies
- reversal of warfarin od
- replacement of single congenital factor def when specific concentrates are not available
When is fresh frozen plasma (FFP) contraindicated?
intravascular volume expansion, correction/prevention of protein malnutrition, and when specific concentrates are available
What are some adverse effects/complications of FFP transfusion?
- pathogen transmission
- adverse immune responses
What is cryoprecipitate?
it is precipitate from FFP that contains concentrated levels of factor VIII, factor XIII, vWF, fibronectin, and fibrinogen
Indications for the use of cryoprecipitate.
- pts with vWF disease who require vWF multimer replacement
- acute bleeding in pts with fibrogenemias
What should cryoprecipitate not be considered a first line tx for and why?
- it is not first line for Hemophilia A or B or vWF dz
- this is because there is no standard concentration of factors in it
- there are better commercial factor concentrates
What are plasma derivatives?
concentrates of plasma proteins (clotting factors) prepared from large donor pools of plasma or cryoprecipitate--> the specific protein is purified
What are human-plasma derived and recombinant factor VIII and factor IX preperations used for?
they are used for tx of hemophilia A or B
What is human-dervied factor VIII preparations used for?
significant bleeding in vWF dz
What is recombinant factor VIIa used for?
it is used to tx acute bleeding and prohilaxis in hemophilia A and B
What is albumin used for?
it is used for volume expansion but the results of tx with this showed poorer outcomes than using just nml saline
What is hemacord?
it contains hematopoietic progenitor cells (CD34+) from humancord blood
What are the indications for hemacord?
For use in hematopoietic stem cell transplantation procedures in patients with disorders affecting the hematopoietic (blood forming) system. For example, cord blood transplants have been used to treat patients with certain blood cancers and some inherited metabolic and immune system disorders.
How does hemacord work?
Once these HPCs are infused into patients, the cells migrate to the bone marrow where they divide and mature. When the mature cells move into the bloodstream they can partially or fully restore the number and function of many blood cells, including immune function.
What are warnings assoc with hamacord?
- graft-vs-host dz
- engraftment syndrome
- graft failure
- infusion rxns
What is sargromastim, its MOA, and adverse effects?
- it is a GM-CSF (granulocyte monocyte conlony-stimulating factor)
- it stimulates neutrophil production and enhances neutrophil action
- often used for pts receiving bone marrow or stem cell transplantation
- adverse effects: fever,arthralgias, myalgias, peripheral edema, pleural & pericardial effusion
What are the indications for drugs such as filgastrim, pegfilgastrim, and sargramostim?
- CA chemo-associated neutropenia
- congenital neutropenia, aplastic anemia
- mobilization of hematopoetic stem cells (G-CSF)
What is oprelvekin?
- it is a recombinant IL-11
- it used to stimulate platelet production
- often used to prevent thrombocytopenia secondary to CA chemo
- adverse effects: fatigue, fluid retention, A-fib
What is Eltrombopag and Romiplostim?
- they are TPO (thrombopoetin) receptor agonists
- used to treat refractory idiopathic thrombocytopenia purpura (ITP)***
- eltrombopag can cause hepatoxicity and increased risk of hematologic malgnancies
What is filgrastim and what is its mechanism of action and adverse effects?
- it is a granulocyte colony-stimulating factor
- pegfilgastrim is a pegylated version of filgrastim that has a longer 1/2 life
- it stimulates neutrophil production and enhances neutrophil function (phagocytic activity)
- bone pain is an adverse effect
What are the indications for epoetin-alpha and darbepoetin-alpha?
- certain forms of anemia
- chronic renal failure
- cancer: relative resistance to endogenous EPO, bleeding, poor nutrition, and infiltration of bone marrow by tumor cells)
- zidovudine (for HIV)
- Fe supplementation (and sometimes folic acid) may be required with EPO tx
What is Epoietin-alpha and what is its mechanism of action?
- recombinant human EPO
- binds to EPO receptors on red cell progenitors and stimulates erythroid proliferation and differentiation
How do hematopoietic growth factor analogues such as darbepoetin and PEG-filgrastim differ from endogenous, natural hematopoietic growth factors?
they are modified or pegylated to have a longer than normal 1/2 life
What are the important side effects of Epoetin-alpha?
increased risk of HTN, stroke, MI, and heart failure
What are the essential nutrients for hematopoeisis?
Fe, vit B12, folic acid
What are the essential hematopoeitic growth factors?
EPO, GM-CSF, G-CSF, TPO, interleukins (IL-11), others
What are some oral supplements are used to tx Fe def anemia and what are their side effects?
- iron sulfate, iron fumarate, and iron gluconate
- mainly cause GI sx such as epigastric pain, n/v, diarrhea and consitpation
What are some perenteral Fe solutions used to tx Fe deficiency and what are their indications?
- iron dextran, iron-sucrose complex, iron sodium gluconate complex
- these should only be used for pts that cannot tolerate oral Fe, or absorb oral Fe, or extensive chronic blood loss that cannot be maintained with oral Fe
- it is common for pts with chronic renal dz on dialysis to need this
What are the drugs that are used to tx a vit B12 def (megaloblastic macrocytic anemia)?
- cyanocobalamin and hydroxocobalamin (has longer 1/2 life)
- these can be given IM
- folate can also help correct anemia caused by B12 def but only B12 def causes neurological problems
What is hydroxyurea?
- it is used to tx sickle cell anemia
- it works by increasing HbF to almost 20%
What is 5-azacytidine and butyrates?
- 5-azacytidine is a demethylating agent
- and they both increase HbF
What is the MOA and indications of glucocorticoids?
- down regulates the expression of many inflammatory cytokines (TNF-alpha, IL-1, and IL-2)
- blocks the synthesis of araihadonic acid metabolites (prostaglandins, leukotrienes, and thromboxanes)
- indicated to prevent solid organ rejection and chronic graft-vs-host dz
What are the adverse effects of glucocorticoids?
- hyperglycemia, diabetes
- adrenal suppression
- susceptibility to infection
- muscle wasting
What is cyclosporine A and tacrolimus?
- calcineurin inhibitors
- this stops activation of NFATc which leads to IL-2 not being transcribed***
- they are used to prevent rejection in kidney, liver and cardiac transplants
- CsA: also used for RA, psoriasis, and chronic dry eyes
- they are metabolized by the CYP3A4 enzyme***
What is the most common adverse reaction to calcineurin inhibitors (CsA and TAC)?
What are sirolimus and everolimus?
- mTOR inhibitors (mammalian target of Rapamycin)
- blocks T cell proliferation (does not effect IL-2 but inhibits cellular response to IL-2)
- used for prophylaxis of organ transplant rejection (everolimus esp for kidney)
- also used for drug-eluting stents in CAD
- metabolized by CYP 3A4
What are the adverse effects of mTOR inhibitors (sirolimus and everolimus)?
- anemia, leukopenia, thrombocytopenia
- HA, nausea, diarrhea
What is azothioprine?
- anti-metabolite-->prodrug of purine analog 6-mercaptopurine
- used to prevent transplant rejection with glucocorticoids and calcineurin inhibitors
- major adverse effect is bone marrow suppression
- metabolism inhibited by allopurinol so must be reduced by 60-75% when used together
What is methotrexate?
- antimetabolite--> inhibits dihydrofolate reductase which inhibits pruine and thymidine synthesis
- indicated for graft-vs-host dz in bone marrow/stem cell transplantations and some inflammatory dz such as RA, crohn's and psoriasis
- major adverse effects = myelosupression, gut disorders, hepatotoxicity, and renal toxicity
What is mycophenolic acid/mycophenolate mefotil?
- inhibitor of inosine monophosphate dehydrogenase (IMPDH), the rate limiting enzyme in the formation of guanosine
- indicated for prevention of rejection in kidney, heart, and liver transplants and some autoimmune dz
- adverse effects: leukopenia, diarrhea, vomiting
- these are very specific to lymphocytes!
What is cytokine release syndrome?
- caused by activation of T cells by antibody binding and release of T cell cytokines
- symptoms: Fever, chills, headache, myalgias, tremor, weakness
- more serious ones include--pulmonary edema, hypotension with CV collapse, cardiac arrhythmia
- prevent with premedication of glucorticoids and acetominophen
What is antithyomocyte globulin (ATG)?
- targets all T cells resulting in broad immunosupression
- indications are acute renal transplant rejection and severe rejection episodes
- adverse effects inslude cytokine release syndrome and susceptibility to infection
What is Muromonab-CD3 (OKT3)?
- monoclonal antibody to human T cell CD3
- binds to CD3 antigen which results in disruption of T cell function and depletion of T cells
- indications are acute renal transplant rejection and glucocorticoid resistant acute rejection
- adverse reactions include cytokine release syndrome
What are daclizumad and basiliximab?
- monoclonal antibodies to CD25 receptor (IL-2 receptor) on activated T cells
- blocks proliferation of T cells mediated by IL-2
- indicated for acute organ rejection
- NOT used for ongoing rejection
- adverse effects include GI sx
What is belatacept?
- MOA: binds to B7 molecules on APCs and blocks interaction between B7 and CD28 (costimulatory)
- indicated in prevention of kidney transplant rejection
- adverse effects include anemia, n/v, diarrhea, constipation, peripheral edema, UTI, HTN