Hemostasis Pharmacology and transfusion therapy Flashcards
What kind of blood transfusion would an anemia pt receive?
packed red blood cells
What kind of transfusion would a clotting factor deficiency pt need to receive?
fresh frozen plasma (coag factors)
If a pt donates their own blood ahead of a major surgery, this is _____ transfusion
autologous
____ is the universal recipient
AB+
____ is the universal donor
O-
Type vs screen: What does the type of blood mean?
Determines the ABO and Rh phenotype of the RECIPIENT’s blood
Type vs screen: What does the screen mean?
Identifies antibodies directed against other antigens by Mixes recipient’s blood with type O RBCs that contains major antigens of other blood group systems and observe for clumping
Pre-transfusion testing what does cross matching mean? When it is usually ordered?
Takes donor blood and mixes with recipient blood to make sure it is a “match”
Only ordered when there is a high likelihood that patient will receive PRBCs (packed red blood cells)
What type of blood is used in an emergency setting?
O-
Name 3 reasons why we would transfuse someone.
Replace acute blood loss
Oxygen delivery
Morbidity and mortality
When is a transfusion usually indicated?
in a pt with a Hbg less than 6 g/dL
1 unit of PRBCs should increase ____ in average sized adults without active bleeding or hemolysis; usually given over ____
Hgb 1 g/dL
1-2 hours
Does transfusion therapy require signed informed consent?
YES! Requires signed informed consent prior to non-emergency transfusions
When do transfusion reactions typically occur? What are the s/s?
during the transfusion or within 24 hours
fever, chills, pruritus, urticaria
**What is the most common risk of transfusions? What is one way to prevent it? What is the best treatment?
Febrile Non-hemolytic Rxn - MC
used leukocyte reduced PRBC
stop transfusion, Tylenol
**What is the most common cause of death associated with transfusion risks? Associated s/s?
Circulatory overload
swelling, SOB, decreased O2, difficulty breathing
What kind of pts are most at risk for circulatory overload?
renal failure, CHF, increased age, decreased ejection fraction or acute cardio syndrome (recent heart attack)
What is the treatment for circulatory overload?
diuretics
What is urticaria?
hives
Name some risks associated with transfusions?
Hemolytic Transfusion Reactions (incompatible blood 1/14,000)
Allergic Reactions ranging from urticaria to anaphylaxis
Infectious Complications
Septic Reactions
Viral Transmission
Transfusion Associated Graft Versus Host Disease
Post Transfusion Purpura
Iron overload
Hyperkalemia or other Electrolyte Toxicity
Hypothermia
When would you want to give a transfusion of whole blood?
Only in setting of massive hemorrhage, provides O2-carrying capacity and volume expansion
PRBCs increases the _____ in the anemic patient. Each unit has a total volume of approx. ____
oxygen-carrying capacity
200mL
What modifications can be made to a unit of PRBCs
Leukocyte reduced
Irradiated
Washed
What type of PRBCs: _______ used to reduce risk of immunologically-mediated effects, infectious disease transmission, reperfusion injury
Leukocyte reduced
What type of PRBCs: _______ to avoid the occurrence of graft-versus-host disease (GVHD) in patients who have immune deficiency states
Irradiated
What type of PRBCs: _______ to prevent or eliminate complications associated with infusion of proteins present in the small amount of residual plasma in red cell concentrates
washed
Whole blood is separated into ____ and ____
PRBCs
plasma
Plasma contains ____ and ____
platelets and proteins
The plasma is then centrifuged to give one unit of ____ and one unit of ____
platelets
fresh frozen plasma
____ is the universal plasma donor
AB
____ is the universal plasma recipient
O
FFP is separated from freshly drawn blood by removing the ____, _____ and _____
red blood cells
white blood cells
platelets
Name 6 things you can find in FFP
coagulation factors, fibrinogen, antithrombin, albumin, protein C and protein S
Once FFP has thawed, the plasma must be transfused within ____ hours or the concentrations of factor V and factor VIII begin to decline.
24 hours
____ is the most commonly used plasma product, in part because it can correct deficiencies of any of the circulating coagulation factors
FFP
What is cryoprecipitate made up of?
just clotting factors
von Willebrand factor, factor VIII, factor XIII, and fibrinogen.
What is the chief advantage to using cryoprecipitate vs FFP?
that it allows von Willebrand factor, factor VIII, factor XIII, and fibrinogen to be replaced using a much smaller volume than if those factors were replaced by transfusing FFP
A _____ contains a large amount of a specific clotting factor that has been produced with recombinant technology or collected from thousands of donors and pooled into a highly concentrated product.
factor concentrate
What is the major indication for factor concentrates?
to replace specific factor deficiencies (eg, hemophilia A and B) with minimal volume and without supplying extraneous proteins
** What are the four indications for platelet transfusion products?
-Patients with a platelet count <10,000 to prevent spontaneous hemorrhage.
-Patients with a platelet count <50,000 who are actively bleeding, are scheduled to undergo an invasive procedure, or have a qualitative intrinsic platelet disorder.
-Patients with a platelet count <100,000 who have a central nervous system injury, have multisystem trauma, or are undergoing neurosurgery
-Patients with a normal platelet count who have ongoing active bleeding and a reason for platelet dysfunction, such as a congenital platelet disorder, chronic aspirin therapy, or uremia
Each unit of transfused platelets should increase the platelet count by _____
5,000 to 10,000.
A patient develops an acute onset of shaking chills 10 minutes into a random donor platelet transfusion. Other than a mild fever, vital signs are normal and there is no evidence of rash, urticaria, or respiratory distress. What is the best course of action?
stop transfusion and administer acetaminophen
What are the four hemostasis promoting agents?
1) Protamine Sulfate
2) Vit K
3) Desmopressin
4) Thrombin
**______ neutralizes heparin and is the antidote for heparin overdose
Protamine sulfate
**How is protamine sulfate administered?
administered IV only
** What is the black box warning associated with protamine sulfate?
May result in severe hypotensive or anaphylactoid-like reactions
____ is the reversal agent for warfarin
Vit K
What is another name for Vit K?
phytonadione
____ Prevention and treatment of hypoprothrombinemia caused by vitamin K antagonist (VKA)-induced (warfarin) or other drug-induced vitamin K deficiency
Vit K
What is one cause of hypoprothrombinemia?
caused by malabsorption or inability to synthesize vitamin K
Where is Vit K metabolized?
in the liver
_____ increases plasma levels of von Willebrand factor, factor VIII, and t-PA contributing to a shortened activated partial thromboplastin time (aPTT) and bleeding time
Desmopressin (DDAVP)
____ is used for hemostasis may rarely lead to hyponatremia and extreme decreases in plasma osmolality, resulting in seizures, coma, and death
Desmopressin (DDAVP)
____ converts fibrinogen to fibrin directly at the site of bleeding.
topical thrombin
____ is used in various types of surgery to aid in hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible.
topical thrombin
What are the contraindications of topical thrombin?
patients with a known sensitivity to components of bovine origin
not for use in massive bleeding.
Must not be injected or allowed to enter large vessels.
What are the general contraindications for all anticoagulants?
Bleeding – current or past (not an absolute contraindication)
Most are cleared by kidneys so renal function is important to assess (Not Unfrac Heparin)
Allergic reaction to the drug
What are the 4 parenteral anticoagulants on the market?
(Unfractionated) Heparin
Low-molecular-weight heparin (LMWH) (Enoxaparin/Lovenox)
Bivalirudin (Angiomax)
Argatroban (Acova)
**____ Binds to anti-thrombin (III) and enhances its inactivation of factor Xa and thrombin.
Unfractionated Heparin
In what clinical setting do you usually find unfractionated heparin?
only given INpatient setting
What routes is unfractionated heparin given?
Sq or continious IV only
**_____ lab you must monitor for a pt on unfractionated heparin
activated partial thromboplastin time (aPTT)
What are the adverse effects of unfractionated heparin?
bleeding, thrombocytopenia, osteoporosis, elevated levels of transaminases (LFTS, aka liver function)
For Unfractionated Heparin, as the dose increases, the ????
risk of bleeding increases
For Unfractionated Heparin pts, _____ and _____ are more prone to hemorrhage
Elderly women and renal insufficiency patients
Osteoporosis caused by unfractionated heparin affects the activity of both ___ and _____
osteoblasts and osteoclasts
What are the contraindications to unfractionated heparin?
HIT, hypersensitivity, active bleeding, hemophilia, significant thrombocytopenia (<50,000), purpura, severe hypertension
Heparin-Induced Thrombocytopenia (HIT) affects ____ of those exposed to heparin and ___ of those exposed to LMWH
3%
0.6%
Heparin-Induced Thrombocytopenia (HIT) is caused when ????
Heparin + PF4 form a neoantigen on the PLT surface, induces an immune antibody response resulting in PLT clearance
Why is HIT particularly dangerous?
because it decreases PLT counts, but may also induce a hypercoagulable state
**HIT can occur with ____ dose, ____ schedule, and _____ administration route
Any dose
any schedule
any administration route
HIT is more common with ____ and _____
UFH, especially in surgical patients
females
_____ is the most common manifestation of HIT, platelet count drops ____ of baseline
Thrombocytopenia
greater than 50% of baseline
the typical onset of thrombocytopenia occurs ____ after the initiation of heparin therapy
5 to 10 days
When does early onset of HIT occur?
may be seen if the patient has been exposed to heparin in the last few months and has circulating HIT antibodies
How long does it take for the baseline platelets to return to normal?
5-7 days after the withdrawal of heparin
____ occurs in up to 50% of individuals with HIT. Where is it most common?
Thrombosis
venous, leg veins, cardiac vessels, and small venules of the skin
Where are arterial thrombosis due to HIT most likely to occur?
heart, central nervous system, limbs, and internal organs
What are some common complications due to HIT induces thrombosis.
skin necrosis, limb gangrene (sometimes requiring amputation), and organ infarction
When would you want to consult hematology if you suspect HIT?
New onset of thrombocytopenia (platelet count <150,000/microL)
A drop in platelet count of ≥50% from a prior value, even if absolute thrombocytopenia is not present
Venous or arterial thrombosis
Necrotic skin lesions at heparin injection sites
Acute systemic reactions (fever/chills, tachycardia, hypertension, dyspnea, cardiopulmonary arrest) occurring after IV heparin bolus administration
What are the 4 Ts scoring system for assessing HIT
If you suspect HIT, _____ is the most specific test. What other tests can you also order?
Serotonin release assay
HIPA
Heparin-PF4 Ab ELISA
What is the HIT management plan?
- STOP HEPARIN
- begin immediate anticoagulation therapy
-DO NOT GIVE PLATELETS - long term oral anticoag therapy is needed
- must list “Heparin” allergy in the patient’s chart moving forward
_____ is recommended following a HIT event, once the pt is stable and platelet count is higher than 150K
Warfarin (coumadin)
______ enhance inhibition of factor Xa by AT III, has less direct inhibition of Xa and virtually no direct inhibition of thrombin.
Lovenox
_____ must reduce dosing with CrCl <30; CONTRAINDICATED with ESRD
Lovenox
**What is the best way to monitor Low-Molecular Weight Heparin (LMWH)?
anti–factor Xa levels must be measured because little effect on the aPTT
______ is recommended in preg pts over heparin
Lovenox
Under what 4 conditions would you want to use a levenox bridge?
Embolic stroke within past 3 months
Previous embolic stroke or VTE during interruption of chronic anticoagulation
Mechanical heart valve
Atrial fibrillation in pt with high stroke risk
What are the 2 non-heparin thrombin inhibitor
Argatroban (Acova)
Bivalirudin (Angiomax)
____ A direct, highly-selective thrombin inhibitor.
Reversibly binds to the active thrombin site of free and clot-associated thrombin.
Inhibits fibrin formation; activation of coagulation factors V, VIII, and XIII; activation of protein C; and platelet aggregation
Argatroban (Acova)
What do you order on a pt, in order to adjust a Argatroban (Acova) dose?
measure aPTT to adjust dose
______ A direct, highly-selective thrombin inhibitor.
Reversibly binds to the active thrombin site of free and clot-associated thrombin.
Bivalirudin (Angiomax)
_____ alternative to heparin in patient undergoing percutaneous coronary intervention (PCI), especially if history of HIT
Bivalirudin (Angiomax)
you order _____ on heparin pts, and _____ on warfarin pts
ptt
PT/INR
______ is a Vitamin K antagonists
Warfarin (Coumadin)
______ inhibits vit K oxide reductase complex subunit I, this inhibits factors II, VII, IX and X.
Warfarin (Coumadin)
_____ kinetics are metabolized in the liver, primarily via CYP2C9, circulates bound to albumin.
Warfarin (Coumadin)
What pregnancy category is Warfarin?
Preg category D
______ is indicated prophylaxis and treatment of thromboembolic disorders (DVT/PE) and embolic complications arising from atrial fibrillation or cardiac valve replacement
Warfarin (Coumadin)
______ No dosage adjustments with renal impairment
Warfarin (Coumadin)
_____ Necrosis or gangrene of the skin and other tissue can occur (rarely, <0.1%) due to paradoxical local thrombosis; onset is usually within the first few days of therapy and is frequently localized to the limbs, breast, or penis
Warfarin (Coumadin)
How does Warfarin interact with alcohol?
binge drinking) decreases the metabolism of oral anticoagulants and increases PT/INR.
Chronic daily ethanol use increases the metabolism of oral anticoagulants and decreases PT/INR.
Warfarin and Vit E _____ warfarin effect
increase
Warfarin and Cranberry juice may _____ warfarin effect.
increase
What is an additional point to educate pts on Warfarin?
Take warfarin at the same time each day
Maintain a consistent diet
What are the 4 direct oral anticoagulants?
Dabigatran (Pradaxa) – inhibits thrombin
Rivaroxaban (Xarelto) – inhibits factor Xa
Apixaban (Eliquis) – inhibits factor Xa
Edoxaban (Savaysa) – inhibits factor Xa
_____, _____ and ______ all inhibits factor Xa
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Edoxaban (Savaysa)
______ is a DOAC that inhibits thrombin
Dabigatran (Pradaxa)
______ : Stroke prevention in nonvalvular atrial fibrillation, DVT/PE, and DVT/PE prophylaxis after hip or knee arthroplasty
Dabigatran (Pradaxa)
Rivaroxaban (Xarelto)
What is the reversal agent for Dabigatran (Pradaxa)?
Praxbind (idarucizumab)
Avoid taking ______ with taking grapefruit juice
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
What is the Rivaroxaban (Xarelto) reversal agent?
AndexXa (andexanet alfa)
_____ Inhibits platelet activation and fibrin clot formation via direct, selective and reversible inhibition of free and clot-bound factor Xa
Apixaban (Eliquis)
What is the reversal agent of Apixaban (Eliquis)?
AndexXa (andexanet alfa)
_____ Factor Xa (FXa) inhibitor; inhibits platelet activation by selectively and reversibly blocking the active site of FXa without requiring a cofactor (antithrombin III) for activity
Edoxaban (Savaysa)
Cannot use _____ if CrCl > 95 mL/min
Edoxaban (Savaysa)
What is the reversal agent for Edoxaban (Savaysa)?
there is none :)
What is the reversal of Heparin?
Protamine
What is the reversal for Warfarin?
Vit K
For DOACs, need to monitor _____ and possible reduce dose
kidney function
_____ Inhibits COX-1 production, which is a critical enzyme in the biosynthesis of thromboxane A2.
Aspirin
_____ Irreversibly acetylates COX enzymes (lasts the life of the platelet)
Aspirin
When taking ASA and NSAIDs together, what is the dosing schedule?
ASA should be taken at least 60 minutes before or 8 hours after NSAIDs
_____ inhibit ADP pathway of platelets. Irreversibly blocks the ADP receptor (P2y12).
Clopidogrel (Plavix)
What drugs should be avoided while also taking Plavix?
Other drugs that inhibit CYP 2C19 (omeprazole, esomeprazole) should be avoided concurrently, as may reduce effectiveness of clopidogrel
_____ the active metabolite irreversibly blocks the P2Y12 component of ADP receptors on the platelet
Prasugrel (Effient)
Due to increased risk of CVA _____ is contraindicated if hx of TIA or CVA
Prasugrel (Effient)
____ irreversibly blocks the P2Y12 component of ADP receptors, which prevents activation of the GPIIb/IIIa receptor complex, thereby reducing platelet aggregation
Ticlopidine (Ticlid)
_____ may cause life-threatening hematologic reactions, including neutropenia, agranulocytosis, thrombotic thrombocytopenia purpura (TTP), and aplastic anemia.
Ticlopidine (Ticlid)
What is the recommended monitoring for Ticlopidine (Ticlid)?
CBC with diff every 2 weeks starting the second week through the third month of treatment.
____ reversibly and noncompetitively binds the adenosine diphosphate (ADP) P2Y12 receptor on the platelet surface which prevents ADP-mediated activation of the GPIIb/IIIa receptor complex thereby reducing platelet aggregation
Ticagrelor (Brilinta)
The most common SE in clinical trials of _____ was dyspnea
Ticagrelor (Brilinta)
What is the black box warning for Ticagrelor (Brilinta)?
Black box warning regarding reduced effectiveness with concomitant use of ASA above 100 mg daily
_____ : reversibly and noncompetitively binds the adenosine diphosphate (ADP) P2Y12 receptor on the platelet surface which prevents ADP-mediated activation of the GPIIb/IIIa receptor complex thereby reducing platelet aggregation
Cangrelor (Kengreal)
Where is the most common place you would find Cangrelor (Kengreal)?
in the cath lab
IV only
____ and ____ work by Gp IIB/IIIA receptor inhibitor. Where would you find them?
Eptifibatide (Integrilin)
Abciximab (Reopro)
in the cath lab
What is the goal of fibrinolytics?
to breakdown thrombi in the setting of life-threatening or massive thrombi
The goal of therapy is to produce rapid thrombus dissolution, thereby restoring blood flow.
_______ act by converting plasminogen to plasmin, which then degrades the fibrin matrix of thrombi and produces soluble fibrin degradation products.
Fibrinolytics
______ preferentially activate plasminogen that is bound to fibrin, which in theory confines fibrinolysis to the formed thrombus (thus avoiding systemic activation).
Alteplase (tPA)
_____ is given IV for PE with hemodynamic instability, acute STEMI, severe DVT, and ascending thrombophlebitis.
Alteplase (tPA)
____ a protein produced by streptococci that combines with the proactivator plasminogen. This enzyme complex catalyzes the conversion of inactive plasminogen to active plasmin.
Streptokinase
_____ is given to heart attack pts only, NOT stroke pt (will increase bleeding)
Streptokinase
Heparin binds to _____ in order to exert its anticoagulant effect
antithrombin III