fcps anticoagulants

7/31/2019 FCPS Anticoagulants

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8/29/2012MEDC 604 Anti-coagulants1


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DR MUHAMMAD ASHRAF ZIA

MCPS;FCPS:ASSTT.PROFESSOR

SIMS/SERVICES HOSPITAL LAHORE

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Anticoagulants


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8/29/2012MEDC 604 Anti-coagulants 3

Chemical Process of Clotting


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QUESTION ?

8/29/2012MEDC 604 Anti-coagulants

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LIST THE CLASSES & EXAMPLES OF

ANTICOAGULANTS ?


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Direct Thrombin (II) Inhibitors asAnticoagulant Drugs


Bivalent: Hirudin (Bivalirudin, Lepirudin, Desirudin)

Univalent:

Argatroban Dabigatran Melagatran Ximelagatran


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Other Anticoagulant Drugs:


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Defibrotide Ramatroban Antithrombin III Protein C (Drotrecogin alfa)


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8/29/2012 10


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Warfarin

Acenocoumarole

Phenindione Factor Xa inhibitors Rivaroxaban

Thrombin inhibitors Ximelagatran

(Exanta) Dabigatran (Pradaxa)



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Antiplatelet drugs


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Aspirin(loprin)

Dipyridamole(persantin)

Thienopyridines Clopidogrel(plavex)

Ticlopidine(ticlid) GP IIb/IIIa antagonists Abciximab(rheopro)

Eptafibatide(integrilin)


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Heparin

unfractionated heparin, a highly sulfatedglycosaminoglycan The name heparin

comes from the Greek hepar, meaning liver as

the molecule was originally derived from canine

liver cells.

http://en.wikipedia.org/wiki/Glycosaminoglycanhttp://en.wikipedia.org/wiki/Glycosaminoglycan


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INDICATIONS

Acute coronary syndrome,

Atrial fibrillation

Deep-vein thrombosis and pulmonary embolism

Cardiopulmonary bypass forheart surgery.

ECMO circuit forextracorporeal life support

Hemofiltration

Indwelling central or peripheral venous catheters

http://en.wikipedia.org/wiki/Acute_coronary_syndromehttp://en.wikipedia.org/wiki/Atrial_fibrillationhttp://en.wikipedia.org/wiki/Deep-vein_thrombosishttp://en.wikipedia.org/wiki/Pulmonary_embolismhttp://en.wikipedia.org/wiki/Cardiopulmonary_bypasshttp://en.wikipedia.org/wiki/Heart_surgeryhttp://en.wikipedia.org/wiki/ECMOhttp://en.wikipedia.org/wiki/Extracorporeal_life_supporthttp://en.wikipedia.org/wiki/Hemofiltrationhttp://en.wikipedia.org/wiki/Cathetershttp://en.wikipedia.org/wiki/Cathetershttp://en.wikipedia.org/wiki/Hemofiltrationhttp://en.wikipedia.org/wiki/Extracorporeal_life_supporthttp://en.wikipedia.org/wiki/ECMOhttp://en.wikipedia.org/wiki/Heart_surgeryhttp://en.wikipedia.org/wiki/Cardiopulmonary_bypasshttp://en.wikipedia.org/wiki/Pulmonary_embolismhttp://en.wikipedia.org/wiki/Deep-vein_thrombosishttp://en.wikipedia.org/wiki/Deep-vein_thrombosishttp://en.wikipedia.org/wiki/Deep-vein_thrombosishttp://en.wikipedia.org/wiki/Atrial_fibrillationhttp://en.wikipedia.org/wiki/Atrial_fibrillationhttp://en.wikipedia.org/wiki/Atrial_fibrillationhttp://en.wikipedia.org/wiki/Acute_coronary_syndrome


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Mechanism of Action

Heparin binds to the enzyme inhibitor

antithrombin III (AT

results in its activation through an increase in the

flexibility of its reactive site loop.

activated AT then inactivates thrombin and other

proteases involved in blood clotting, most notably

factor Xa.

rate of inactivation of these proteases by AT canincrease by up to 1000-fold due to the binding of

heparin:

http://en.wikipedia.org/wiki/Antithrombinhttp://en.wikipedia.org/wiki/Thrombinhttp://en.wikipedia.org/wiki/Factor_Xahttp://en.wikipedia.org/wiki/Factor_Xahttp://en.wikipedia.org/wiki/Thrombinhttp://en.wikipedia.org/wiki/Antithrombin


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Heparin

Heparin dosage is measured in units; one unit is the quantity of heparin required to

keep 1ml of cats blood fluid for 24 hours at zero

degrees Celsius.

UFH is not absorbed orally and must beadministered intravenous infusion or

subcutaneous bolus.

Once in plasma, heparin binds to plasma proteins

endothelial cells and macrophages.



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Heparin

Clearance is non-linear, depending on a rapid,saturatable mechanism and slower renal

clearance.

Due to the variable binding and clearance of

UFH, monitoring neded activated partialthromboplastin time (APTT). An APTT ratio of1.5-2.5 is often used as a target



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Antidote to Heparin Overdose

Protamine sulfate (1 mg per 100 units of heparinthat had been given over the past four hours) has

been given to counteract the anticoagulant effect

of heparin

http://en.wikipedia.org/wiki/Protamine_sulfatehttp://en.wikipedia.org/wiki/Protamine_sulfate


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Fondaparinux Sodium..



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Fondaparinux Sodium synthetic analogue of the pentasacharide

fragment of heparin responsible for binding AT.

By modifying the structure, the affinity offondaparinux sodium for AT is increased, thus

increasing the half-life and specific activity.

Fondaparinux sodium has a molecular weight of

1.7kDa and is more specific for inhibition of factor

Xa than the LMWH, with no effect on thrombin

inhibition.


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Fondaparinux Sodium.Absorption is via the subcutaneous route and

half-life is around 17 hours.

A fixed dosing regime for VTE prophylaxis of

2.5mg once daily is not adjusted for body weight.

No monitoring is advised

fondaparinux sodium can be monitored with an

anti-Xa assay.

contraindicated in patients with a creatinineclearance of less than 30ml/min as it is excreted

unchanged in the urine


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Fondaparinux Sodium. Fondaparinux can not be reversed with protamine

sulphate, but as with LMWH, recombinant factor

VIIa may be effective.



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Dosage Forms And Strengths

Single-dose, prefilled syringes containing either2.5 mg , 5 mg , 7.5 mg , or 10 mg of

fondaparinux.



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QUESTION ?


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HOW TO MINIMISE THE INCIDENCE OFBLEEDING & HAEMATOMA FORMATIONASSOCIATED WITH EPIDURAL ANAESTHESIA INPATIENTS TAKING THESE DRUGS ?


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SPINAL/EPIDURAL HEMATOMAS

FACTORS RESPONSBLE

use of indwelling epidural catheters

concomitant use of other drugs that affect

hemostasis, such as non-steroidal anti-inflammatorydrugs (NSAIDs), platelet inhibitors, or otheranticoagulants

a history of traumatic or repeated epidural or spinal

puncture a history of spinal deformity or spinal surgery

that can increase the risk


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Monitor patients frequently for signs and symptomsof neurologic impairment. If neurologic compromiseis noted, urgent treatment is necessary


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WARFARIN

PROLONGED USE; stop for three days,Repeat PT,INR

LESS THAN 24 HRS USE; proceed with block

MORE THAN 24 HRS/MULTIPLE DOSES;

Stop wafarin check PT/INR


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ANTICOAGULANTS&HAEMATOMA


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ANTIPLATELETS&HAEMATOMA.

ASPIRIN&NSAID

No risk for haematoma,in otherwise normal patients

DRUGS TO BE STOPPED

TICLIDOPINE, 14 days CLOPEDOGRIL 7 days

ABCIXIMAB 48 hrs

EPTIFIBATIDE, 8 hrs


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HEPARIN&HAEMATOMA

MINIDOSE s/c prophylaxis

(5000 u s/c tds)

No contraindication

PTS NEEDING HEPARIN I/OP APPLY BLOCK 1 hr be fore dose

REMOVAL OF CATH

1 hr before dose

4 hrs after dose


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THERAPEUTIC DOSE

1000 U I/V PER HR

MONITOR APTT 6 HRLY

AVOID BLOCK REMOVAL ;stop dose & repeat aptt


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LMWH

ENOXAPRIN

MANY INCIDENCS OF HAEMATOMA REPORTED

IF BLEEDING ON BLOCK HOLD DOSE FOR NEXT24 HRS

REMOVAL OF CATH; 2 HRS BEFORE DOSE

IF DOSE ALREADY GIVEN

REMOVE CATH AFTER 10 HRS


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FIBRINOLYTIC /THROMBOLYTICS

AVOID N BLOCK

(UROKINASE,STREPTOKINASE)


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WHAT IS CONCENTATION OF V111 INFFP,CRYOPRECIPITATE & FACTOR V111 CONC..?



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liquid portion ofhuman blood that has been

frozen and preserved after a blood donationand will be used for blood transfusion

centrifuged, separated, and frozen solid at18 C (0 F) or colder within eight hours ofcollection. "FFP" is often used to mean any

transfused plasma product.

http://en.wikipedia.org/wiki/Human_bloodhttp://en.wikipedia.org/wiki/Blood_donationhttp://en.wikipedia.org/wiki/Blood_transfusionhttp://en.wikipedia.org/wiki/Blood_transfusionhttp://en.wikipedia.org/wiki/Blood_donationhttp://en.wikipedia.org/wiki/Human_blood


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FACTOR VIII&FFP.

ONE ML OF FFP CONTAINS 1 U OF FACTOR 8

most common inherited defect in secondaryhemostasis is factor VIII deficiency(hemophilia

A).

Symptomatic patients generally have less than 5% ofnormal factor VIII activity.

Classically, patients present with a prolonged aPTT

but a normal PT and bleeding time


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contains the labile as well as stable components coagulation,

fibrinolytic

complement systems; proteins that maintain oncotic pressure

In addition,

fats,

carbohydrates

minerals similar to those in circulation.

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http://en.wikipedia.org/wiki/Coagulationhttp://en.wikipedia.org/wiki/Fibrinolysishttp://en.wikipedia.org/wiki/Complement_systemhttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Oncotic_pressurehttp://en.wikipedia.org/wiki/Fathttp://en.wikipedia.org/wiki/Carbohydratehttp://en.wikipedia.org/wiki/Mineralhttp://en.wikipedia.org/wiki/Mineralhttp://en.wikipedia.org/wiki/Carbohydratehttp://en.wikipedia.org/wiki/Fathttp://en.wikipedia.org/wiki/Oncotic_pressurehttp://en.wikipedia.org/wiki/Oncotic_pressurehttp://en.wikipedia.org/wiki/Oncotic_pressurehttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Complement_systemhttp://en.wikipedia.org/wiki/Fibrinolysishttp://en.wikipedia.org/wiki/Coagulation


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INDICATION

Replacement of isolated factor deficiencies

Reversal of warfarin effect

Massive blood transfusion (>1 blood volume withinseveral hours)

Use in antithrombin III deficiency

Treatment of immunodeficiencies

Treatment of thrombotic thrombocytopenic purpura


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Hypofibrinogenaemia (low fibrinogen levels), ascan occur with massive transfusions

Bleeding from excessive anticoagulation - Fresh

frozen plasma contains most of the coagulationfactors and is a much better choice whenanticoagulation has to be reversed quickly.

http://en.wikipedia.org/wiki/Hypofibrinogenaemiahttp://en.wikipedia.org/wiki/Fibrinogenhttp://en.wikipedia.org/wiki/Anticoagulationhttp://en.wikipedia.org/wiki/Anticoagulationhttp://en.wikipedia.org/wiki/Fibrinogenhttp://en.wikipedia.org/wiki/Hypofibrinogenaemia


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Massive haemorrhage - RBCs andvolume expanders are preferred

therapies. Disseminated intravascular coagulation

http://en.wikipedia.org/wiki/Haemorrhagehttp://en.wikipedia.org/wiki/Red_blood_cellhttp://en.wikipedia.org/wiki/Blood_substituteshttp://en.wikipedia.org/wiki/Disseminated_intravascular_coagulationhttp://en.wikipedia.org/wiki/Disseminated_intravascular_coagulationhttp://en.wikipedia.org/wiki/Blood_substituteshttp://en.wikipedia.org/wiki/Red_blood_cellhttp://en.wikipedia.org/wiki/Haemorrhage


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Each 15 mL unit typically contains 100 IU offactor VIII, and 250 mg of fibrinogen.

also contains von Willebrand factor (vWF)

Individual products may actually have lessthan these amounts as long as the averageremains above these minimums.

http://en.wikipedia.org/wiki/Factor_VIIIhttp://en.wikipedia.org/wiki/Fibrinogenhttp://en.wikipedia.org/wiki/Von_Willebrand_factorhttp://en.wikipedia.org/wiki/Von_Willebrand_factorhttp://en.wikipedia.org/wiki/Fibrinogenhttp://en.wikipedia.org/wiki/Factor_VIII


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Indications

Indications

Haemophilia - Used for emergency back up whenfactor concentrates are not available.

von Willebrands's disease - Not currentlyrecommended unless last reserve.

ddAVP is first line, followed by factor concentrates.


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http://en.wikipedia.org/wiki/Haemophiliahttp://en.wikipedia.org/wiki/Von_Willebrands%27s_diseasehttp://en.wikipedia.org/wiki/Desmopressinhttp://en.wikipedia.org/wiki/Desmopressinhttp://en.wikipedia.org/wiki/Von_Willebrands%27s_diseasehttp://en.wikipedia.org/wiki/Haemophilia


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FFP is considered to have 1 U of factor VIII activityper milliliter.

cryoprecipitate has 510 U/mL,

factor VIII concentrates have approximately 40U/Ml

Each unit of factor VIII transfused is estimated toraise factor VIII levels 2% per kilogram of body

weight.


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Twice-a-day transfusions are generallyrecommended following surgery because of therelatively short half-life of factor VIII (812 h).

Administration of DDAVP can raise factor VIII levels2- to 3-fold in some patients. EACA or tranexamicacid may also be used as adjuncts


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Dosage Calculations

Factor VIII one International Unit (IU) of FVIII per

kilogram body weight (IU/kg) will result in anincrease of recombinant factor VIII concentration inthe recipient's plasma of 1.8-2.0 IU/dL

(sometimes referred to as 1.8-2%). The rise whenusing plasma-derived FVIII is expected to be 2

IU/dL. represented by the formula:

FVIII dose (IU/kg) = (desired rise in FVIII IU/dL) 2


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Example. To increase the factor VIII from 0 to 80IU/dL, as might be required for a surgical procedurein a patient with severe haemophilia A, the factor

VIII dose


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will be 80 2 = 40 IU/kg


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F VIII C i I f i


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Factor VIII Continuous Infusion

Continuous infusions provide improved coagulationfactor cover,

associated with improved bleeding outcomes andmay use less coagulation factor

After an initial bolus injection of FVIII, an infusionis started to maintain coagulation factor levels at 70-100%, according to the following formula:

Infusion rate (IU/kg/h) = clearance (mL/kg/h) xsteady state concentration IU/mL)


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Alternatively, an infusion rate of 4.0-5.0 IU/kg/hwill produce a FVIII level of

approximately 80 IU/dL.


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Monitoring

During surgery, when prolonged courses of therapy

are administered, it is imperative that factor VIII or factor IX levels are

monitored frequently. It is useful

to check pre-operative factor levels and perform an

inhibitor screen.


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QUESTIONS?


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fcps anticoagulants

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