presentation 22ndmay

Anesthesia for Patients on Anticoagulant Therapy

Moderator – Prof.M.P KhanPresentors-Dr.Ritu Singh

Dr.Yadunath Vishwakarma

Introduction

• Haemostasis comprises of cellular and biochemical process that limit blood loss resulting from injury, maintain intravascular blood fluidity and promote re vascularization of thrombosed vessels after injury.

• There are 2 types of haemostasis-Primary haemostasis- immediately after injury

platelets eposit at the site.

Secondary Haemostasis- later a stable clot is formed by activation of plasma clotting factors.

Platelets and Hemostasis

• Imp role in haemostasis• Derived from bone marrow megakaryocytes and

circulate in blood as inactive precursor.• Platetets have 2 types of granules- Alpha granules- fibrinogen,factor 5 and 8,vwf,platelet

derived growth factor. Dense granules-

ADP,ATP,Calcium,serotinin,histamine,epinephrine

• There are two separate systems of coagulation (i) the intrinsic or the intravascular (ii) the extrinsic or the extravascular system.

• Activation of either system leads to a common pathway which generates thrombin which converts fibrinogen to fibrin.

Plasma mediated Hemostasis

Clotting factors 1 - Fibrinogen2 – Prothrombin3 – Thromboplastin4 – Calcium5 – Proaccelerin7 – Proconvertin8 - Anti-haemophilic factor9 - Christmas factor10 – Stuart Prower Factor11- Anti hemophilic factor C12 – Hageman factor13 - Fibrin stabilizing factor

oThe blood coagulation process can be activated by one of

two pathways, the Tissue factor pathway (formerly known

as the extrinsic pathway) and the Contact activation

pathway (known as the intrinsic pathway).

oTissue factor binds to and activates Factor VII and the

Tissue Factor/VIIa complex then activates Factor X and

Factor IX to Xa and IXa respectively.

oFactor X can also be converted to Xa by IXa (in the presence

of Factor VIII).

The intrinsic pathway is activated when Factor XII

comes in contact with a foreign surface.

The resulting Factor XIIa then activates Factor XI, which

in turn activates Factor IX.

Factor Ixa then activates Factor X.

Thus Factor Xa can be generated by activation of the

tissue factor or contact activation pathways. Factor Xa

then cleaves prothrombin and the resulting thrombin

converts fibrinogen to fibrin.

Four of these clotting factors (Factors II, VII, IX, X) are Vitamin K dependent

and therefore their activity is decreased by the Vitamin K antagonist,

warfarin.

Factor VII has the shortest half life of the Vitamin K dependent coagulation

factors.

However, for adequate anticoagulation, one needs to reduce the other

coagulation factors appropriately, including Factor II (prothrombin) which has

a 60 hour half life.

It takes several days after initiation of warfarin therapy to reduce Factor II and

thus warfarin and heparin need to overlap for approximately 4–5 days when

starting therapy.

Laboratory tests for haemostasis (A) Test of platelet function.

• Platelet count – Standard component in screening of cogulation

abnormality.

• Normal value 1.5 lakh to 4 lakh. Values above 1 lakh assosiated with

normal hemostasis

• Automated platelet count preferable. Low platelet count merits

further assessment by visual platelet count by using blood smear.

• False low platelet count can be due to haemodilution and platelet

clumping due to EDTA. This can be avoided using citrate as anti

coagulant or manual counting.

Laboratory tests for haemostasis

• Bleeding time(<11 min.):- To calculate bleeding time an incision 9 mm long and 1 mm deep is made on volar surface of the forearm with back pressure maintained by inflating a blood pressure cuff on the upper part of the arm to 40mm Hg of pressure excess bloods blotted away every 30 seconds with filter paper – this is best predictor of functional platelet disorder. Bleeding time is prolonged with platelet count less than 100,000 cell /L.


(B) Tests of coagulation • Prothrombin time – Integrity of extrinsic and common

pathway.

Time required in seconds for clot formation to occur after

mixing a sample of patient plasma with tissue fator

(thromboplastin) and ca2+. Low levels of factor VII, X, V and

prothrombin and fibrin prolongs PT.

Normal Prothrombin time – 11.5 - 14.5 sec.

Laboratory tests for haemostasis`• Partial thromboplastin time – integrity of intrinsic and

common pathway.

Time in seconds for clot formation to occur after mixing

patient plasma with phospholipid ,calcium and

activators(celite,kaolin,silica)

Low levels of factor VIII, IX, XI, XII prolong PTT.

Partial thromboplastin time – 24.5 – 35.2 sec


INR- International Normalized Ratio• A mathematical correction of the PT ratio for difference in

sensitivity of thromboplastin reagent.• The prothrombin time (PT) is the test most commonly

used to monitor warfarin dosing. The reliability of the result of the PT is influenced adversely by the variability in the sensitivity of thromboplastin reagents used by different laboratories

• Relies upon reference thromboplstin with known sensitivity to anti thrombotic effect of anti –coagulant

• Allows comparison of test results between labs and standardized reporting of PT


INR- International Normalized Ratio

INR = (Patients PT in sec/Mean PT in Sec)ISIISI-International Sensitivity Index

Each thromboplastin is assigned an ISI which reflects the sensitivity of the thromboplastin to Warfarin-mediated reduction of the Vitamin K dependent clotting factors. By convention, the ISI of the reference thromboplastin is 1.0.

Laboratory tests for haemostasis• Thrombin time :-

This test measure thrombin fibrinogen interaction and is

prolonged with low levels of fibrinogen (<100mg/dl) in

pressure of abnormal fibrinogen and in presence of

circulating anticoagulants such as heparin.

Thrombin time – 22.1 – 31.2 sec.


• Activated clotting time (ACT)- Functional measure of cogulation

It is the time required for the whole blood to clot in the test tube at 37c.

It is usually 107+ 13 seconds. It is simple,low cost and linear operating

response at high concentration. Limitations include poor reproducibility

and lack of senstivity and prolangation during hypothermia and

hemodilution.

Thromboelastography- Unique feature is that it measures the entire

spectrum of clot formation from early fibrin strand generation through

clot retraction and fibrinolysis.

Measures include: (1) the time until initial clot formation (r value),which is dependent on the clotting factor concentration and sensitive to anticoagulant medication;

(2) the time until clot formation (a-angle), which is dependent on fibrinogen and platelets;

(3) the absolute clot strength(maximum amplitude [MA]), for which sufficient platelets and normal platelet aggregation are needed; and

(4) the degree of clot lysis (the amplitude 60 minutes after MA or A60), with abnormal A60 being indicative of hyperfibrinolysis or antifibrinolytic therapy.

Like other tests operating in low shaer stress environments, thromboelastography models venous rather than arterial coagulation.

Thromboelastography assesses platelet aggregation but not platelet adhesion, nor the effects of aspirin, uremia, or von Willebrand’s disease.

Laboratory tests for haemostasis • Protamine titration- M.c point of care method for

determining heparin concentration in peri operative setting. Protamine a strongly basic polycationic protein 1 mg of which neutralizes 100 IU of Heparin. A series of blood sample with incremental doses can be used for analysis. Advantages include sestivity for low heparin concentration as well as insenstivity to hemodilution and hypothermia and un affected by aprotinin.


Tests for fibrinolysis:

(i) Thrombin time 22.1 – 31.2 sec.

(ii) Fibrinogen – fibrin degradation products > 5

g/dl.

(iii) Fibrin D dimer assay – (<250 g/ml).

Anticoagulants

• Are medications that helps prevent existing

blood clots from growing larger and the

formation of new blood clots by increasing the

amount of time it takes a blood to clot.

Anti coagulants may be classified into

(A) Used invitro • (i) Heparin – 150IU of heparin prevents

clotting of 100ml of blood. • (ii) Calcium complexing agents.

• Sodium citrate – 1.65mg for 350ml of blood• Sodium oxalate – 10mg for 1ml of blood. • Sodium edentate – 2 mg for 1ml of blood.

Anti coagulants may be classified into

(B) Used in Vivo – • (i) Heparin, LMWH• (ii) Oral anticoagulants – 1. Coumarin derivatives – Bishydroxy coumarin,

warfarin sodium. 2. Indandione derivatives – Phenindion

When are anticoagulants indicated Prophylactic

AF (Atrial fibrillation)

Artificial valve replacement

Deep vein thrombosis

Pulmonary hypertension.

Cardiomyopathy.

Unstable angina

Congenital haert disease.

Therapeutic Pulmonary embolism.

Ischemic stroke.

Coronary artery bypass graft

surgery.

Angioplasty and stenting

Coronary artery disease.

Peripherial arterial disease.

Retinal vessel thrombosis.

Warfarin

• Vitamin K antagonists such as warfarin (Coumadin) inhibit vitamin K epoxide

reductase, an intracellular enzyme that recycles vitamin K.

• Oral warfarin reaches effective plasma concentrations in 90 minutes, with the full

anticoagulant effect developing over a period of several days.• Initiation of the anticoagulant and antithrombotic effects of warfarin depends on the

plasma factor VII concentration because factor VII has the shortest half-life (3 to 6

hours).However for effective anti coagulation factor 2 should be inhibited which

requires at least 7 days

• Warfarin effect is monitored in the laboratory by using the PT (INR standardized).

Because pharmacokinetic and pharmacodynamic factors vary widely from patient to

patient, frequent PT determination is necessary.

• Heparin is the most commonly used anticoagulant drug in the operating room.

• It is a highly negatively charged sugar that is extracted from mast cells, pig intestinal

mucosa, or bovine lung.

• Saccharide units of very different size are stripped from the proteoglycan skeleton,

which accounts for the large variation in size of unfractionated heparin (5000 to

30,000 kd).

• Advantages of unfractionated heparin over LMWH or pentasaccharide drugs are its

immediate onset, efficacy against thrombin, short half-time of 30 to 60 minutes, and

reversibility with protamine, a highly positively charged protein isolated from salmon.

• .

Heparin:

• Most vascular and percutaneous interventional procedures require lower levels of anticoagulation, and intravenous doses of 3000 to 5000 units of heparin are administered to achieve an ACT of twice baseline or less.

The major complications of heparin therapy include heparin-induced

thrombocytopenia (HIT) types 1 and 2 and osteopenia . HIT type 1 is

not mediated by immunoglobulin G (IgG), is self-limited, and does not require

intervention. HIT type 2 is the most feared nonhemorrhagic complication of

heparin treatment and is usually due to antiplatelet factor 4 antibodies causing

platelet aggregation.

Protamine reversal of anticoagulation is not usually required. Bolus heparin

can cause a moderate decrease in systemic vascular resistance and systemic

blood pressure, for unclear reasons. Protamine at approximately 1 mg to

100 units of heparin is commonly used to reverse the activity of

heparin .

LMWH is produced by cleaving heparin into shorter fragments. The

pentasaccharide unit binds to and activates antithrombin, but the shorter

saccharide units make LMWH ineffective in inhibiting thrombin directly.

Instead, the LMWH/antithrombin complex binds to and inactivates factor Xa

and indirectly inhibits thrombin production. LMWH has a delayed onset of 20

to 60 minutes and a longer half-time than heparin and can be administered

subcutaneously either once or twice daily and require less monitoring(anti-Xa

levels) or no monitoring. Have predictable pharmokinetics and fewer effect on

platelet function.Disadvantages of LMWH include less reliable reversal with protamine and

increased risk of bleeding during long-term use compared to unfractionated

heparin.

LOW MOLECULAR WEIGHT HEPARIN

Pentasaccharide (fondaparinux) contains only the

pentasaccharide unit necessary for binding and activation of

antithrombin.Like LMWH the length of the saccharide chain is insufficient for

antithrombin to effectively bind and inhibit thrombin. Therefore, antithrombin-

mediated anti-Xa activity confers the therapeutic

efficacy of pentasaccharide.

Its longer half-life as compared with LMWH allows once-daily

subcutaneous administration. Like LMWH, therapy does not

require laboratory monitoring.

Pentasaccharides do not cause HIT. The risk of bleeding during long-term

therapy with pentasaccharide exceeds that of LMWH.

Others

Direct thrombin inhibitors are the most important alternative to heparin.

Bivalent ones are Hirudin(natural) and Bivalurudin and univalent

areargatroban, melagatran (and its oral precursor, ximelagatran), and

dabigatran. Used during percutaneous coronary intervention and as an

adjunct to thrombolytics in patients with acute myocardial infarction.

Direct Factor Xa Inhibitors-Rivaroxaban is an oral, reversible, direct

factor Xa inhibitor that is rapidly absorbed. Howerer apixaban also has

the same Moa but irreversible.

Others

Thrombolytics are classified as native tissue plasminogen activators,

streptokinase and urokinase, or as exogenous tissue plasminogen activator

formulations, alteplase and tenecteplase.

Tissue plasminogen activators are both thrombolytics and anticoagulants

because fibrinolysis generates increased amounts of circulating fibrin

degradation products, which inhibit platelet aggregation by binding to

platelet surfaces without participating in the process of coagulation. Surgery

or puncture of noncompressible vessels is contraindicated within a 10-day

period after the use of thrombolytic drugs.

Others

Antiplatelet drugs include cyclooxygenase (COX) inhibitors, thienopyridine

derivatives, and platelet GPIIb/ IIIa antagonists.

CYCLOOXYGENASE INHIBITORSCOX inhibitors include:

(1) nonselective inhibitors (aspirin and NSAIDs) and

(2) selective agents inhibiting only COX-2.

Aspirin irreversibly inhibits COX-1-mediated platelet granule release over the platelet’s

lifetime.

NSAIDs (naproxen, piroxicam, and ibuprofen) reversibly inhibit platelet COX and

prevent thromboxane A2 synthesis. Platelet function normalizes 3 days after

discontinuing the use of NSAIDs. Platelet function is not affected by COX-2- specific

inhibitors because platelets do not express COX-2.

THIENOPYRIDINE DERIVATIVESThe thienopyridine derivatives ticlopidine and clopidogrel interfere with

platelet function by interfering with fibrinogen binding to platelets and thus

inhibiting ADPinduced primary and secondary platelet aggregation. Platelet

functions normalize 7 days after discontinuing clopidogrel and 14 to 21 days after

discontinuing ticlopidine.

GPIIb/IIIa ANTAGONISTSAvailable GPIIb/IIIa platelet receptor antagonists include abciximab,

eptifibatide, and tirofiban.

These drugs are potent inhibitors of platelet aggregation because binding of

fibrinogen and vWF to platelet GPIIb/IIIa receptors is blocked.

Platelet aggregation normalizes 8 hours after discontinuing eptifibatide and tirofiban

and 24 to 48 hours after discontinuing abciximab.

Peri- Operative Preperation

Evaluation of patients on anticoagulants –(A) History :- Ensures if the bleeding problem is present

or not and if present whether it is acquired or congenital.

• Any blood relatives with known problems or need blood transfusion for bleeding?

• Any personal history of prolong bleeding (>60 min) after minor injury such as biting lips or cheek ?

• Any personal history of unprovoked recurrent epistaxis (>4 times/year), gingival bleeding, excessive menorrhogia?

• Any personal history of easy, widespread brusing larger than 4-5 cm or palpable brusing? Any extensive brusing after minor surgery or injury?

• Any personal history of bleeding following surgical procedure

especially minor surgery like circumcision, dental extraction or skin

biopsies especially lasting 12 hours or more?

• Has bleeding recurred (6-12 hours) after initial cessation of

haemorrhage?

• Any personal history of spontaneous or minor injury deep muscle or

joint hemotomas, hematuria, or retroperitoneal haemorrhage?

• Medication taken by the patient for last 10-14 days?

• Any history of medical disease associated with haemostasis defects

(SLE, Cancer, liver, kidney).

(B) Haematological Investigation

• Assessment of clotting status is of great importance during surgery, and

also in specific situations such as patient with inherent disorders of

clotting, those with massive blood transfusion, those receiving

anticoagulant therapy and those suspected of developing disseminated

intravascular coagulation (DIC).

• Tests lack the senstivity to predict the abnormalities of cogulation

routinely and should be weighed against the cost benefit ratio. A carefully

performed history is the most effective predictor.

Peri- operative management• A growing number of patients are taking oral anticoagulant or antiplatelet

drugs for primary or secondary prevention of ischemic haert disease and arterial or venous thrombosis. The perioperative management of anticoagulation in these patients at the time of elective surgery is contentious yet important. It involves balancing the risks of arterial or venous thromboembolism (such as ischaemic stroke, myocardial infarction, pulmonary embolism or deep vein thrombosis) if the drug is stopped, against the risk of bleeding if the anticoagulant or antiplatelet drug is continued.

Type of Procedure Platelets in /uL

Minimally invasive procedures (central line placement, angiography, thoracentesis, and paracentresis,endoscopy,biopsy)

>30,000

Epidural catheter insertion or removal Ranges from50,000 to 80,000(relative contraindication above 100000)

Operative procedures ordinarily associated with insignificant blood loss

>50,000

Surgery within a closed space such as in neurosurgery and ophthalmic surgery

>100000

Lumbar puncture or spinal or vaginal delivery >50,000

Microvascular bleeding attributed to platelet dysfunction, for example, uremia, a post cardiopulmonary bypass, or in association with massive transfusion

Clinical judgement

Proposed guidelines for platelet transfusion,BCMJ 2005

Caution

• None of the the absolute cut off is more important than clinical judgement .Certain points to be remembered-

1. Clinical evidence of bleeding2. Recent platelet count3. Recent change in platelet count4. Quality of platelet5. Adequacy of cogulation factors 6. The risk benefit ratio

Peri- operative management-Antiplatelet drug

• It is generally considered safe to continue aspirin (dose range from 60mg to 325 daily) throughout the perioperative period, for both cardiac and non-cardiac surgery, unless there is a significant bleeding risk

Mangano DT; Multicenter Study of Perioperative Ischemia Research Group. Aspirin and mortality from coronarybypass surgery. N Engl J Med 2002;347:1309-17.

ASA Practice Advisory 2010

Peri- operative management- Warfarin • The most common indications for oral anticoagulant therapy are atrial

fibrillation, the presence of a mechanical haert valve, and venous thromboembolism.

• For most patients, the therapeutic target for the international normalised ratio (InR) range is 2.0–3.0. For patients with a mechanical haert valve, the recommended InR range is 2.5–3.5.

• When considering how to manage patients on warfarin who require surgery, it is helpful to weigh up the risk of bleeding v ersus the risk of thromboembolism .

This requires consideration of: ■ indication for anticoagulation ■ history of any thrombotic events ■ type of surgery and its associated risks of bleeding and thromboembolism, particularly with respect to postoperative venous thromboembolism.



Peri- operative management- Warfarin • The patient's management is guided by the risk of thromboembolism

The options include: ■ Low risk - stop warfarin five days before surgery (that is, missing four doses before the day of surgery) to allow the INR to drop to less than 1.5, then resume it on the evening of the procedure if there is no evidence of bleeding

■ High risk- stop warfarin and start heparin (unfractionated heparin infusion or low molecular weight heparin) before and after the surgery, during the period when the INR is below the therapeutic range. This option is referred to as 'bridging' anticoagulation. Heparin is usually started on the third morning after the last dose of warfarin when the INR becomes subtherapeutic.


Peri- operative management –Warfarin


Peri- operative management Stopping heparin preoperatively For patients who receive bridging anticoagulation with therapeutic doses of low molecular weight heparin, the last dose should be administered at least 24 hours before the procedure. There is evidence suggesting that there will be a residual anticoagulant effect if low molecular weight heparin is given too close to the time of the procedure.It is recommended that the last preoperative dose be half the usual total daily dose. For unfractionated heparin, it is recommended that the infusion be stopped 4–6 hours before the procedure.


Peri- operative management Resuming heparin postoperatively

The factors that affect the risk of postoperative bleeding include the timing of the anticoagulant dose after surgery, the dose of anticoagulant and the type of surgery along with its associated bleeding risk.The following recommendations take all of these factors into consideration:

■ warfarin can be resumed on the evening of the procedure (regardless of whether the procedure is performed in the morning or afternoon), at the usual maintenance dose (no loading dose)

■ low molecular weight heparin or unfractionated heparin can be resumed 12–24 hours following the procedure for minor surgery. For major surgery, the first dose should be 24–72 hours post surgery. The initial dose will vary from the prophylactic dose (for example, enoxaparin 40 mg daily) to the therapeutic dose (for example, enoxaparin 1 mg/kg twice daily) depending on the risk of thrombosis, and the risk of bleeding. This needs to be individualised for each patient


Neuraxial interventions in patients being treated

with anticoagulant drug • It is adviced not to do any neuraxial intervention

in patient with anticoagulant therapy as they may

lead to paralysis > post epidural haemotoma.

American Association of Regional Anesthesia Guidelines for Neuraxial Anesthesia in Anticoagulated Patients

Medication Recommendation

NSAIDS No contraindication

Asprin No contraindication

Ticlopidine Discontinue 14 days preoperative

Clopridogrel Discontinue 7 days preoperative

GP IIb/IIIa inhibitors

Abciximab Discontinue 7 days preoperative

Eptifibatide Discontinue 4 to 8 hours preoperative

Tirofiban Discontinue 14 days preoperative


Unfractionated Heparin

Sub –Cutaneous

(usually given for prophylaxsis)

Neuraxial intervention

No contraindication, measure platelet count, if more than 4 days of heparin treatment.

After intervention

if more than 4 days of heparin treatment measure platelet count before removing catheter.

Intra venous

Vascular surgery and


Avoid in presence of other coagulopathies. Delay heparin for 1 hour after catheter placement no

restriction before procedure with dosing every 12 hours delay if difficult catheter placement is

anticipated

After intervention

Catheter removal 2 to 4 hours after heparin and normal PTT & ACT


Warfarin


Stop warfarin 4 to 5 days preoperatively normal INR before intervention

After intervention Remove catheter when INR < 1.5

LMWH


Delay 10 – 12 hours after dose. Delay 24 hours after traumatic (bloody) tap or with twice daily dosing.

After intervention

Once daily dosing :Remove catheter 10-12 hours after last dose and start

next dose 2 hours later

Twice daily dosing :Remove catheter 2 hours before 1st dose.

Thrombo lytics

Neuraxial intervention Absolute containdication the first 10 days.

After interventionRemove catheter with fibrinogen level normalize and

should also check neurologically (i.e. sensory and motor)


Coagulation Factor Synthesis and DisordersAssociated with Coagulation Factor Deficiencies

Coagulation factorssynthesized in the liver

Fibrinogen (factor I);factors II, VII, IX, X;protein C; protein S

Coagulation factorssynthesized in endothelial cells

Factor VIII,von Willebrand factor

Coagulation factor with theshortest half-life Factor VII (3-6 hours)

Vitamin K–dependent factors Factors II, VII, IX, X

Most common inheritedbleeding disorder

von Willebrand’sdisease

Level of circulating coagulantfactor below which bleedingoccurs

Plasma levels < 30%

Hemophilia A Factor VIII deficiency

Hemophilia B (ChristmasDisease) Factor IX deficiency

• Thrombin-inhibiting drugs can block the action of thrombin by binding to three domains: the active site or catalytic site and two exosites (Figure 2FIGURE 2Mechanism of Action of Direct Thrombin Inhibitors as Compared with Heparin.). Located next to the active site, exosite 1 acts as a dock for substrates such as fibrin, thereby orienting the appropriate peptide bonds in the active site. Exosite 2 serves as the heparin-binding domain.1 Thrombin is inhibited indirectly by low-molecular-weight heparins, because these drugs strongly catalyze the function of antithrombin. A heparin–thrombin–antithrombin complex is formed in which heparin binds simultaneously to exosite 2 in thrombin and to antithrombin. Furthermore, heparin can act as a bridge between thrombin and fibrin by binding both to fibrin and exosite 2 (Figure 2). Because both thrombin exosites are occupied within this fibrin–heparin–thrombin complex, the enzymatic activity of thrombin is relatively protected from inactivation by the heparin–antithrombin complex.2-4 Thus, heparins have a reduced capacity for the inhibition of fibrin-bound thrombin, which appears to be detrimental, because active thrombin further triggers thrombus growth.

http://www.nejm.org/action/showImage?doi=10.1056/NEJMra044440&iid=f02

http://www.nejm.org/doi/full/10.1056/NEJMra044440

http://www.nejm.org/action/showImage?doi=10.1056/NEJMra044440&iid=f02


• Since DTIs act independently of antithrombin, they can inhibit thrombin bound to fibrin or fibrin degradation products.3-5 Bivalent DTIs block thrombin at both the active site and exosite 1, whereas univalent DTIs bind only to the active site. The group of bivalent DTIs includes hirudin and bivalirudin, whereas argatroban, melagatran (and its oral precursor, ximelagatran), and dabigatran are univalent DTIs. Native hirudin and recombinant hirudins (lepirudin and desirudin) form an irreversible 1:1 stoichiometric complex with thrombin.6 In a similar way, bivalirudin, a synthetic hirudin, binds to the active site and exosite 1,7 but once bound, it is cleaved by thrombin, thereby restoring the active-site functions of thrombin.8 Therefore, in contrast to the hirudins, bivalirudin produces only a transient inhibition of thrombin.





Coagulation Factor Deficiency

• Blood loss caused by a low level of one or more coagulation factors (PT or PTT

prolonged to 1.5 times the normal range)

• Is replaced with fresh frozen plasma (10 to 15 mL/kg IV).

• Platelet counts lower than 50,000 to 80,000 cells/mL are increased by administering

concentrated platelets.

• One platelet pheresis unit contains a minimum of 6 x106 cells/mL and generally raises

the platelet count by 30,000 to 60,000 cells/mL in a 70-kg patient.

• Cryoprecipitate (1 concentrate per 10-kg body weight) can be used to augment

fibrinogen levels less than 125 mg/dL.

• Each fresh frozen plasma and platelet pheresis unit has approximately twice the

amount of fibrinogen contained in 1 cryoprecipitate concentrate.

• Cryoprecipitate contains high concentrations of factor VIII and vWF.

Unfractionated Heparin.

1. During subcutaneous 5000U q12h prophylaxis there is no contraindication to the use

of neuraxial techniques. The risk of neuraxial bleeding may be reduced by delaying

the heparin until after the block. Epidural catheters should be removed just prior to

the next dose of heparin and the dose delayed 2 hours.

2. The risk of neuraxial bleeding may be increased in debilitated patients after prolonged

therapy.

3. Since heparin-induced thrombocytopenia may occur during heparin administration,

patients receiving heparin for greater than four days should have a platelet count

assessed prior to neuraxial block and catheter removal.

4. Heparin 5000U sc q8h may lead to increased risk of bleeding. Risks and benefits

should be assessed on an individual basis and avoid other medications that may alter

coagulation (ie nsaids). ASRA advises that patients not receive q8h heparin while

epidural analgesia is maintained, but recognizes that many centers do it.

5. Neuraxial techniques with intra-operative iv heparin during vascular surgery:

• Heparin administration should be delayed for 1 hour after needle placement.

• Avoid if patient has other coagulopathies

• Monitor neurological function postoperatively

• Although the occurrence of a bloody or difficult neuraxial needle placement may

increase risk, there are no data to support mandatory cancellation of a case. Direct

communication with the surgeon and a specific risk-benefit decision about proceeding in

each case is warranted.

Low Molecular Weight Heparin (LMWH)

1. Preoperative LMWH :

• If LMWH has been administered preoperatively LMWH should be held for 24 hrs

prior to a neuraxial technique.

2. Postoperative LMWH:

• Avoid other drugs that affect hemostasis.

• Presence of blood during needle or catheter placement does not necessitate postponement of

surgery. In those cases the first dose of LMWH should be delayed for 24 hrs postoperatively and it is

the responsibility of the anesthesiologist to discuss this with the surgeon

• Twice daily dosing. It is recommended that the first dose of LMWH be administered no earlier than

24 hours postoperatively. Indwelling catheters should be removed prior to initiation of LMWH

thromboprophylaxis.

• Single daily dosing. It is recommended that the first postoperative LMWH dose be administered no

sooner than 6-8 hours postoperatively. The second postoperative dose should occur no sooner than

24 hours after the first dose.

presentation 22ndmay

Health & Medicine

factor xa

factor ixa

christmas factor

hageman factor

presence of factor

otissue factor

tissue factor pathway

resulting factor xiia