11. Anticoagulants Flashcards
Prothrombin complex concentrates (PCC)
Use
Derived from
Contain
Prothrombin complex concentrates (PCC) are recommended for rapid reversal of vitamin K anticoagulants. They are derived from human plasma and contain the vitamin K dependent clotting factors II, VII, IX and X. As they normalise levels of vitamin K dependent clotting factors and re-establish haemostasis, they may also be used as adjunctive therapy in patients with major bleeding.
Fresh frozen plasma (FFP)
for INR - problems
Fresh frozen plasma (FFP) and vitamin K are most frequently administered. Because of the variable content of vitamin K-dependent clotting factors in FFP, and the effects of dilution, the efficacy of this approach is open to doubt. Other potential problems include significant intravascular volume challenge, and the possibility of rare complications such as transfusion-associated lung injury or blood-borne infection.
Vitamin K
admin
time taken for reversal
Vitamin K should be administered by slow intravenous infusion over 30 minutes to avoid potential anaphylactic reactions. The reversal of INRs with vitamin K can take 24 hours to exert its maximal effect regardless of route of administration.
Dyprimadole
S/E
Catuion
DD interaction
Antiplatletet
Severe bronchospasm
Antagonise xanthine deriv
Catuion in asthamtics
Exacerb - MG, Migraine
Myalgia hypotension
tachycardia
D-D interaciton - block adenosie @avn enhanced
anticoag heparin enanced
Dabigatran
Competitive thrombin inhibitor blocking both free and bound thrombin - Diffce vs other`
Prodrug - converted by hydrolysis
potent, synthetic, reversible, non-peptide thrombin inhibito
LMWH
binding to antithrombin complex inactivates factor Xa.
LMWH binds less to platelets, endothelium and von Willebrand factor, hence less risk of bleeding.
less likely to bind both antithrombin and thrombin (LMW binds Xa more readily).
xcreted in the urine
efficacious, safer and have improved inpatient stay and hospital cost. VS heparin
Plaminogen -
Mechanism
t
Plasminogen is an inactive precursor and it is converted into the active plasmin through the action of endogenous tissue plasminogen activator and thrombin.
It lyses fibrin and fibrinogen resulting in the formation of fibrin degredation products (FDP) that inhibit thrombin. Epsilon-aminocaproic acid inhibits thrombolysis by antagonising plasminogen activation.
Streptokinase prouduced
Bind forms
prob
Streptokinase is produced by Lancefield group C (not A) beta-haemolytic Streptococci.
It binds to plasminogen forming a streptokinase-plasminogen complex which converts additional circulating plasminogen and fibrin-bound plasminogen into plasmin.
It is associated with allergic and anaphylactic reactions and has a plasma half life of approximately 20 minutes. However, studies with radioactive streptokinase indicate two disappearance rates:
Heparin is a
Effects monitored
How does it work
which inhibits what
Heparin is an anticoagulant and its effects are monitored by measuring the activated partial thromboplastin time (APTT), although thrombin and clotting times are also prolonged (not INR). It accelerates the action of antithrombin III, which inhibits activated factors XII, XI, X, IX and thrombin.
Plasma binds antithrombn III
albumin protease + fibrongen
Metab - hepatic heparinise - excrete urine
low dose inhib Xa
High dose - plt aggreg XIIa, XI, IXa
Decrease plasma tubidity - reduction TG
HIT -abod med 3% pop
5-10 days after initiating
plt bound + removed circ - render tcytopaenic
Warfarin is -
Inhibt ____ which are
Enzymatics inducers cause
Warfarin is an oral anticoagulant and it inhibits the synthesis of vitamin K dependant factors II, VII, IX and X.
It is acidic
Hepatic enzyme inducing agents,for example, carbamazepine and phenobarbitone, reduce its effect. Enzyme inhibitors such as valproate enhance the effect of warfarin. If the enzyme-inducing drug is withdrawn without reducing the dose of warfarin, haemorrhage may occur.
binds albumin pref
Warfarin prevents vit k returning to reduced form
Aprotonin is a
Aprotinin is an enzyme inhibitor acting on plasmin and kallikrein and is classed as an antifibrinolytic (not fibrinolytic), thus inhibiting fibrinolysis. It is indicated in patients at high risk of blood loss.
Alteplase
is what
how act
Alteplase (tissue type plasminogen activator) is a thrombolytic and acts by activating plasminogen to form plasmin, which degrades fibrin and so breaks up thrombi. It is used in the treatment of myocardial infarction and life-threatening venous thrombosis.
Factor VIIa
Factor VIIa (recombinant) is a purified coagulation factor used to treat patients with inhibitors to factors VIII and IX. It has been used successfully in patients with serious trauma in whom haemorrhage has been difficult to control surgically. Thus it can be classed as a procoagulant (not anticoagulant).
Warfarin
Prot bind
How does it work
t 1/2
Reduced by
Increased by
Safe pregn?
Skin necrosis worse in
Warfarin is an oral anticoagulant which is rapidly absorbed by mouth and is almost totally protein bound.
It competes with vitamin K in the synthesis of hepatic coagulation factors II, VII, IX and X.
It has a half life of about 30 hours (not 20).
Hepatic enzyme inducing drugs like phenytoin reduce its effects, whereas drugs that displace it from protein binding enhance its effects, for example, sulphonamides and NSAIDs.
Warfarin is teratogenic and is contraindicated in the first trimester of pregnancy.
Patients with protein S or protein C deficiency appear to be particularly prone to skin necrosis.
What are anticoagulants + how classify
Reduce/ prevent coagulation - itnerfering process of fibrin plug
1 Antiplateler
2 Heparin
3 OAC
4 Fibrinolytic
Stucture of heparin
Anionic muco polsaccharride glycosaminglycan organic acid
Sphlate reside
Naturally oucc in lug liver mast cell and arterail wall
Unfractionated heparin mol mass 5000 25000 Da
How does heparin act
4 main effects
- Inhibition of coagulation - enhancing formation anti throib III - thrombin complex =
Inhib factors IIa Xa XIIa XIa IXa
2 Inhib platelet aggrergation
- Release lipoprotein liase
Uses heparin
How admin
Prophylaxis & rx DVT, PE, Unstab Angina, Crit peripheral art occlusion, priming extra corp circuits
IV /SC
Dose thrombo propy - 5000IU SC 8-12hrly
Full anticoag -CPB run
-> 300 IU/ Kg or 3mg/kg
Infusion
T1/2 40-90 min
What are the LMWH
Framgnet derived depolymerisation hpearin
Mol Mass 2000-8000Da
Compared w/ IFH - more effect inhib Xa
Less effective anti thrmobin III
Admin s/c
Advant Single daily dose - longer t1/2 Reuire less monitor Less fx plt & red HITTS Redcue affin VwB
Hpearin monitored
Activated partial thromboplastin time
& Thromibn time
APTT - Intrisnic - VIII, IX, X, XII
& common pathway - II X fib
On CPB antioag w/ hpearin - monitor ACT
LMWH _ mor epred plasma level - not req routine montitoring
If essential - Factor Xa assay
Side fx Heparin
- Haemorrhage
HITTS
hypotension following rapid infusion
osteoporsos
Alopecia
HITTS
type 1 - non immune tcyopenia <4 day - plt reqtun normal without stop - non signif
Tpye II - immune med
more sever 5-14days start
Half - serious thormbosis & mortality high (pe_
Formation complex heparin, plt factor 5 & igG - plat aggreg & htormbo
How hpearin reversed
Protamine -
Basic cationic protein obtain fish sperm -
1mg reverse effect 100IU heparin
How does warfarin act
Coumarin deriv oac
Inhib gamma carobyl - vit k depend clott
II VII IX X
prevent rturn vit k to red form
No effect cirulating clotting factor - takes 3 days exert effect
