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Pharmacology N929 > Afibrinolytics, Protamine, and DDAVP > Flashcards

Afibrinolytics, Protamine, and DDAVP Flashcards

1
Q

afibrinolytic medications uses

A

prevent lysis of fibrin, promotes clot formation (think spine surgeries)
-used to prevent and treat excessive bleeding as inhibitors or fibrinolysis.
interfere with formation of fibrinolytic enzyme plasmin from its precursor plasminogen by plasminogen activators (primarily t-PA and u-PA) which takes place mainly in lysine rich areas on surface of fibrin

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2
Q

2 types of afibrinolytic medications

A

lysine analogs: (tranaxamic acid, aminocaproic acid)

serine protease inhibitor: aprotinin, no longer avail

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3
Q

Epsilon Aminocaproic Acid (Amicar) MOA, uses

A

FDA approved for the use in the treatment of acute bleeding due to elevated fibrinolytic activity. inhibits proteolytic enzyme plasmin, enzyme responsible for fibrinolysis
-clinical uses include trauma, CPB, spinal infusions

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4
Q

Amicar Dosing Ranges

A

bolus followed by infusion
bolus 5-15g (pedes 75-150mg/kg)
infusions 1-2g/hr (pedes 5-30mg/kg/h)

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5
Q

Tranexamic Acid (TXA, cylokapron) MOA, uses

A

synthetic analog of amino acid lysine, inhibits fibrinolysis by competitively binding to lysine receptor sites on plasminogen. this prevents plasmin from binding to and degrading fibrin which preserves fibrin matrix struvture
parenteral TXA is effective in treating bleeding from multiple causes such as GI, surgical, and trauma

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6
Q

TXA t1/2, potency, route of admin, cases

A

t1/2 2 hours
8-10 times more potent than aminocaproic acid
given IV
ortho cases, bolus then redose versus spine cases- continuous gtt

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7
Q

TXA dosage/cost

A

10-15mg/kg IV (up to 1g) following infusion of 1-5mg/kg/h

cost of 1g is approx $50

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8
Q

TXA clinical uses (5 types of surgeries/populations)

A

non cerebral trauma (suggested to be beneficial within first 3 hours)
pedes (spine fusions, craniosynostosis)
ortho procedures (common in joint procedures)
cardiac (including with and without CPB)
obstetrics: in massive transfusion algorithm for this and trauma

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9
Q

CRASH 2 trial

A

20,011 adults with traumatic bleeding- showed TXA reduces death due to bleeding with no increase in vascular occlusive events.
in patients treated within 3h of injury, TXA reduced death due to bleeding by 1/3 but when given after 3h, it seemed to increase the risk.

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10
Q

WOMAN trial

A

world maternal antifibrinolytic trial (2017), death due to bleeding was significantly reduced in women given TXA, especially in women given tx within 3 hours of giving birth

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11
Q

TXA contraindications

A

active intravascular clotting (PE, DVT, embolic cerebral CVA)
anaphylaxis
SAH

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12
Q

TXA precautions

A

eliminated unchanged in urine, requires decreased dosing in patients with renal function impairment (change from 1g to .5g)
UTI- ureteral obstructions due to clot formation has been reported
hypotension with rapid IV injection
color vision defect- visual changes is an indicator of toxicity (1st sx)
seizure disorders with high dose
concomitant admin with factor concentrates

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13
Q

protamine

A

simple proteins obtained from sperm of salmon and certain other species of fish
positively charge alkaline protamine combines with negatively charged acidic heparin to form a stable complex void of anticoagulant activity
hematin-protamine complex is removed by reticuloendothelial system

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14
Q

protamine dosage

A

1-1.5mg for every 100U of heparin given

-guided also by last ACT and estimated amount of total IV heparin administered within last 2 hours

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15
Q

protamine adverse responses

A

hypotension (esp with rapid IV injection or whole 15mg)
pulmonary HTN (protamine heparin complex can result in complement activation and thromboxane release=pulmonary constriction)
-allergic reactions

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16
Q

allergic reactions to protamine: how to handle it

A

options are limited in a patient with a true known allergy
pretreatment with histamine receptor antagonists, followed by a slow trial
completely avoid protamine, and allow heparin effect to dissipate (take hours, risk for bleeding and blood transfusion)
administer alternative to heparin (ex bivalirudin)

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17
Q

patients at risk for true allergy to protamine

A

prior reaction to protamine
allergy to vertebrae fish (24.5x risk)
exposure to NPH insulin (8.2x risk)

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18
Q

DDAVP

A

d amino d arginine vasopressin (synthetic analogue of natural hormone arginine vasopressin)
causes release of endogenous store of FVIII and vWf

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19
Q

DDAVP dose

A

.3mcg/kg IV infusion over 15-30 minutes

  • platelet adhesion increases within 30 minutes.
  • give slowly, causes hypotension
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20
Q

DDAVP pharmacology, t1/2, SE

A

shown to be more potent than arginine vasopressin in increasing plasma levels of factor VIII activity in patients with vWF

  • change in structure of arginine vasopressin to DDAVP results in decrease in ADH and vasopressor action on smooth muscle
  • excreted in urine, t1/2 3h in health patients and up to 9h in severe renal impairment
  • hypotension is most commonly reported SE
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21
Q

DDAVP contraindications

A

hypersensitivity
patients with moderate to severe renal impairment
patients with hyponatremia (desmopressin may create a more dilution hyponatremia)

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22
Q

reversal agents: antiplatelets

A

platelet transfusion

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23
Q

reversal agents: heparin

A

protamine

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24
Q

reversal agents: vitamin K antagonists aka warfarin

A

3 and 4 factor PCC’s if emergent

vitamin K if urgent

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25
Q

reversal agents: direct thrombin inhibitors

A 
Idarucizumab (reverses dabigatran)
andexanet alfa (reverse apixaban or rivaroxaban)
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26
Q

reversal agents: emerging agent to know

A

ciraparangtag (reverses UFH, LMWH, fondaparinux, dabigatran, FXa)

27
Q 
Antithrombotic Agent: antiplatelets
drug name(s)
stop before procedure (days)
monitoring 
reversal agents
A 
drug names:
ASA, 7 days
P2Y12 receptor antagonists 7-14 days
GPIIb/IIIa antagonists 24-72h
monitoring: none
reversal agents: platelet transfusion
28
Q 
Antithrombotic Agent: vitamin K antagonists
drug name(s)
stop before procedure (days)
monitoring 
reversal agents
A

warfarin
2-5d
PT, INR
PCC, FFP, vitk

29
Q 
Antithrombotic Agent: heparins 
drug name(s)
stop before procedure (days)
monitoring 
reversal agents
A

unfractionated heparin, 6h, aPTT, protamine

LMWH, 12-24h, none required but fXA can be pulled, partially reversed by protamine

30
Q 
Antithrombotic Agent: pentasaccharide
drug name(s)
stop before procedure (days)
monitoring 
reversal agents
A

fondaparinux
3 days (prophylactic dosing)
none required, but fXa levels can monitor
no reversal

31
Q 
Antithrombotic Agent: direct thrombin inhibitors
drug name(s)
stop before procedure (days)
monitoring 
reversal agents
A 
drug name: 
argatroban, 4-6h
bivalirudin 3h
monitoring: aPTT of ACT
no reversal

dabigatran: 2-4d (longer if renal impairment), no required monitoring but thrombin time can be monitored, idarucizumab can reverse this.

32
Q 
Antithrombotic Agent: FXa inhibitors
drug name(s)
stop before procedure (days)
monitoring 
reversal agents
A

rivaroxaban, apixaban, edoxaban
2-3d
none required, but fXa levels can be monitored
andexanet alfa for rivaroxaban and apixaban

33
Q

what FFP contains

A

variable but near normal levels of coagulation factors, coagulation inhibitors, albumin, immunoglobulins

34
Q

what cryoprecipitate contains

A

slowly thawing FFP leaves being a cold insoluble precipitate which contains fibrinogen, FVIII, vWF, and FXIII

35
Q

factor concentrates can either be (2)

A

plasma derived or

recombinant

36
Q

assessing efficacy of FFP transfusion

A

commonly via PT/INR, PTT, fibrinogen, platelet count, viscoelastic tests which range in turn around times of 30-90m

37
Q

with what products do you use a filter and warmer

A

PRBC’s, FFP, cryo

38
Q

with what products do you use a filter only and NO warmer

A

platelets

39
Q

plasma derived factor concentrates (8)

4 standalone factors

A

Factor VII, vWF, factor IX, factor XIII
Riastap fibrinogen concentrate (factor I)
FEIBA (factor eight inhibitor bypassing activity, mainly contains non activated II and IX, and X and mainly activated VII)
Profilnine (factors of II, IX, X)
Kcentra (factors II, VII, IX, X)

40
Q

recombinant factor concentrates

A

factor VIIa, factor IX

41
Q 
Riastap
how long it can be stored
does it require crossmatch
what makes it different than cryo/ffp
effectiveness
A

human plasma derived fibrinogen concentrate
fractionated from blood and stored up to 30 months
can be quickly reconstituted and administered IV with no thawing of blood type matching required
fibrinogen concentrate is standardized in each vial (900-1300mg/50mL vial) versus cryo/ffp is variable.
should be as effective as cryo and superior to FFP

42
Q

factor complex concentrates

A

biological product of pooled human plasma with therapeutic concentrations of factors II, VII, IX, X
4 factor: Kcentra
3 factor: profilnine (low amounts of FVII)

43
Q

clinical uses of FCC’s (3)

A

reverses effects of significant vitamin K antagonism coagulopathy (use Kcentra for this)
emergent or urgent surgery
clotting deficiency (congenital)

44
Q

contraindications of FCC’s

A

DIC and HIT

45
Q

profilnine

A

3 factor complex concentrate originally approved for treatment of patients with hemophilia B (factor IX deficiency). reserved mainly for cardiac cases, not indicated for warfarin or factor Xa reversal

46
Q

Kcentra

A

4 factor complex concentrate which is approved for reversal of vitamin K antagonists

47
Q

which factors are in profilnine

A

IX, II, X, low levels of VII. does not contain heparin or any preservatives

48
Q

profilnine dosing

A

based on temporarily increasing plasma level of factor IX

10-15 units/IBW kg, max dose of 1000 units

49
Q

which factors are in Kcentra

A

antithrombotic proteins C and S and heparin 8-40 units in 500-unit bills in addition to factors II, VII, IX, X

50
Q

when to use Kcentra

A

FDA approved for tx of adult patients treated with vitamin K antagonists with an INR >1.5 and experiencing acute major bleeding

51
Q

do not use Kcentra for

A

patients with INR <1.5 on VKA’s
elective reversal of oral anticoagulant therapy pre invasive procedure
treatment of elevated INR without bleeding or need for surgical intervention
massive transfusion coagulopathy
coagulopathy associated with hepatic dysfunction
patients with DIC and bleeding diathesis
patients with hx of HIT

52
Q

preop INR 2-3.9, kcentra dose, dose max

A

25 units/kg

dont exceed 2500 units of factor IX

53
Q

preop INR 4-6, kcentra dose, dose max

A

35 units/kg

dont exceed 3500 units of factor IX

54
Q

preop INR >6, kcentra dose, dose max

A

50 units/kg

dont exceed 5000 units of factor IX

55
Q 
Recombinant activated factor VII (NovoSeven) (rFVIIa)
chemical makeup
uses 
uses off label
risk associated with factor VII
factors it bypasses
how it promotes hemostasis
A

form of blood factor VII
glycoprotein produced by recombinant DNA technology
used in hemophilia A (deficiency of VIII) or B (deficiency of IX) congenital factor VII deficiency
most of its use is off label for the prevention and tx of coagulopathy and major blood loss (postpartum hemorrhage, trauma, reversal of various anticoagulants, high risk cardiothoracic, spinal, transplant, or vascular surgery)
-can be associated with increased risk of thrombosis in some settings, particularly in patients who do not have hemophilia
-bypasses factors VIII and IX and causes coagulation without the need for these factors
-promotes hemostasis by activating extrinsic pathway of coagulation cascade

56
Q

rFVIIa and extrinsic pathway

A

promotes hemostasis by activating extrinsic pathway of coagulation cascade. forms a complex with TF at the site of injury, thereby activating coagulation factors IX and C which leads to the formation of a hemostatic plug

57
Q

trauma and factor rVIIa: 2 pathways

A

site of tissue injury combine with TF to directly activate factor X
platelet surface

58
Q

factor VIIa dosing
administration instructions
redosing
vial sizes

A

20mcg/kg to over 200mcg/kg range
90mcg/kg IV bolus
reconstitute with specified volume of sterile water for injection, USP
redosing can be every 2 hours as clinically indicated
supplied in 1mg, 2mg, and 5mg vials
expensive

59
Q

factor VII and risk of thrombotic adverse events

A

DIC, advanced atherosclerotic disease, crush injury, septicemia or concomitant tx prothrombin complex concentrates have increased risk of developing thrombotic events due to circulating tissue factor or predisposing coagulatopahy

60
Q

will factor VII stop surgical hemorrhage

A

no, but it will significantly reduce the need for blood transfusions in patients with hemorrhagic shock from blunt trauma

61
Q

should you give factor VII over other blood products?

A

no, you need adequate FFP, cryo, and platelets for full effect of this drug

62
Q

factor VII t1/2

A

2-2.5h for initial dose, may require repeating units bleeding is controlled

63
Q

FCC considerations (6)

A

provide faster correction of coagulopathy (~30 minutes) compared to FFP and vitamin K (>3h).
factors in plasma are relatively dilute and large volume (10-15ml/kg) is required for clinical reversal of oral anticoagulants
less risk of infectious and noninfectious transfusion reactions
action still depends on adequate concentrations of platelets and fibrinogen
concentrated factors have varied half lives with prothrombin remaining active in plasma for up to 60h and factor X present for 30 hours
dosing will require hematology and pharmacy consultations

Pharmacology N929 (11 decks)

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