Heme Onc Flashcards
PTT measures all coagulation factors except which?
VII
PT/INR measures which coagulation factors?
II, VII, IX, X
Which coagulation factors are not synthesized int he liver?
VIII and vWF
What does cryo contain and when should it be used?
- contains FVIII, vWF, fibrinogen
- use for hemophilia A, vWD, and hypofibrinogenemia
What does FFP contain?
all coagulation factors and some fibrinogen
What is the most common congenital bleeding disorder?
von willebrand’s disease
What are the three types of vWD?
- type I: partial quantitative
- type II: qualitative
- type III: complete quantitative
How are the three types of vWD treated?
- type I: desmopressin or cryo
- type II: desmopressin or cryo
- type III: FVIII or cryo
Which type of vWD doesn’t respond to desmopressin?
type III since desmopressin enhances vWF function and type III is the complete absence of the factor
What are hemophilia A and B?
- hemophilia A: FVIII absent
- hemophilia B: FIX absent
How are hemophilias treated?
- A: recombinant FVIII, cryo, desmopressin
- B: recombinant FIX, FFP
What is FVL mutation?
a mutation in factor V, which prevents the binding of protein C, leading to hypercoagulability
How does antithrombin III deficiency present? How is it treated?
- hyper coagulability without response to heparin
- treat with ATIII concentrate or FFP and heparin heparin bridge to therapeutic anticoagulation
How do you treat patients with hyperhomocysteinemia?
folate and B12
Describe the presentation, pathophysiology, and treatment of anti-phospholipid syndrome.
- history of lupus, DVTs, recurrent pregnancy losses
- labs show a prolonged PTT but are hyper-coagulable
- caused by antibodies to cardiolipin and lupus anti-coagulant
- treat with a heparin bridge to lifelong warfarin
What is the specific reversal agent for Xarelto and Eliquis?
andexxa
What is the generic name for praxbind?
idarucizumab
How does heparin work?
it potentiates antithrombin III, making it 1000x more effective
What are the side effects of protamine?
hypotension and bradycardia
How do you test for HIT?
- start with PF4 antibodies
- confirm with a serotonin release assay
How do you monitor the effectiveness of lovenox?
measure factor Xa levels
How does warfarin work?
it inhibits a protein, VKORC, that activates vitamin K, preventing creation of vitamin-K dependent coagulation factors
Which anticoagulation is teratogenic and contraindicated during pregnancy?
warfarin
How does dabigatran work?
it is a direct thrombin (FII) inhibitor
How does andexxa work?
it acts as a decoy receptor for factor Xa inhibitors
How does tPA work?
it activates plasminogen to break down fibrinogen
How is tPA reversed?
with aminocaproic acid
What are absolute contraindications to tPA administration?
- active internal bleeding
- recent CVA or neurosurgery
- intracranial mass/pathology
- recent GI bleed
What are relative contraindications to tPA administration?
- surgery within 10 days
- recent organ biopsy
- recent delivery
- recent major trauma
- uncontrolled hypertension
What is MHC I?
a human leukocyte antigen present on all nucleated cells expresses intra-cellular antigens to active CD8 cytotoxic T cells
How do natural killer cells work?
they recognize and destroy cells that either lack self-MHC or are bound with antibodies
Describe a type I hypersensitivity reaction.
IgE binds to mast cells and basophils, triggering a release of histamine, serotonin, and bradykinin
Describe a type II hypersensitivity reaction. Give two examples.
- antibody mediated
- IgG or IgM binds cell triggering destruction via cytotoxic T cell or complement system
- examples include ABO incompatibility and hyper acute rejection
Describe a type III hypersensitivity. Give two examples.
- immune complex deposition
- antigen-antibody complexes are deposited in tissue leading to complement activation and neutrophil attack
- SLE or serum sickness
Describe a type IV hypersensitivity reaction. Give two examples.
- delayed-type
- APCs present antigen to CD4 cells, activating macrophages
- examples are PPD and contact dermatitis
Describe the four types of hypersensitivity reactions with examples.
- type I: IgE mediated
- type II: antibody mediated (ABO incompatibility or hyper acute rejection)
- type III: immune complex deposition (SLE or serum sickness)
- type IV: delayed/CD4 (PPD or contact dermatitis)
Which HLA classes are most important for recipient/donor matching?
HLA-A, B, and DR
Describe the timing, mechanism, and management of hyperacute rejection.
- less than 1 hr
- mediated by preformed antibodies that activate complement cascade
- treat with emergent re-transplantation
Describe the timing, mechanism, and management of accelerated rejection.
- days
- sensitized T-cells respond to donor HLA, much like a cellular acute rejection
- treat with increased immunosuppression or pulse steroids
Describe the timing, mechanism, and management of acute cellular rejection.
- weeks to months
- T cells respond to donor HLA
- treat with increased immunosuppression or pulse steroids
Describe the timing, mechanism, and management of acute humoral rejection.
- weeks to months
- antibodies form to donor antigens
- treat with pulse steroids, antibodies, or plasmapharesis
Describe the timing, mechanism, and management of chronic rejection.
- months to years
- T cells and antibody formation
- treat with increased immunosuppression or re-transplantation
How does mycophenolate work? What are the side effects?
- inhibits de novo purine synthesis to inhibit T cell growth
- can cause GI upset and pancytopenia
How do the following work:
- cyclosporine
- tacrolimus
- sirolimus
- a calcineurin inhibitor which decreases cytokine production
- inhibits FK binding protein which decreases cytokine production
- inhibits mTOR to limit T and B cell responses to IL-2
Sirolimus is associated with what side effect?
interstitial lung disease
How does thymoglobulin work?
its a polyclonal antibody against T cell antigens
Why do transplant patients get started on Bactrim?
for PJP ppx
What is the treatment for post-transplant lymphoproliferative disorder?
decrease immunosuppressive therapy, rituximab
What is the treatment for CMV in a transplant patient?
ganciclovir
What is the treatment for EBV in a transplant patient?
decrease immunosuppression
Which coagulation factor has the shortest half life?
F VII
What are the main steps of the coagulation cascade?
- FXa activates thrombin (FII)
- thrombin converts fibrinogen to fibrin
How does antithrombin III work?
it binds and inhibits thrombin, preventing conversion of fibrinogen to fibrin and thus activation and cross linking of platelets
What is the most common inherited hypercoagulable disorder?
Factor V Leiden mutation
What is the first immune cell to arrive at the site of an injury?
neutrophils
What is the most common antibody in the spleen?
IgM
Which antibody type can cross the placental barrier and provides immunity to newborns?
IgG
What is the most common malignancy following transplant?
squamous cell carcinoma
