PRINCIPLES OF ANTICOAGULANT THERAPY

IN SURGERY.

Klinika cievnej chirurgie

LF UPJŠ a VÚSCH, a.s., Košice

apríl, 2020

INTRODUCTION

Deep venous thrombosis (DVT) and pulmonary

embolism (PE) are a major health problem with two

serious consequences:

PE can be fatal immediately

In the long term, there is a risk of developing

pulmonary hypertension in repeated embolizations of

and

Development of post-thrombotic venous insufficiency.

incidence1-2/1000 persons per year

INCIDENCE AND PREVALENCE

Incidence: 104 - 183 /100 000 / per year

Prevalencia: Age 46 – 69 y. : 4,9% 70y and more: 14,3 %

50-80 r 10.7% more than 80 y 17,8 % overall 5%

Age increases risk 7,5 x after 70 y 5 x increases risk

Obesitas: 9,1% , BMI less than 25 5%( 2,4.. 4,3)

Gender: M: 7,2% Ž: 4,3%

CHVI: 4,78 x vyššie riziko TEN (pod 41 r.)

3,2 x vyššie riziko TEN (48- 69 r.)

Surgery 21x

Injury: 12,7x

M II 8,4 varices: under 45 4,2 over 79 0,5

Active tumor 6,5 x 4

Reccurecy: most often during the first year -10% expected after 1 yearr

30% expected after 10 years

VENOUS TROMBOSIS, DEEP FLEBOTROMBOSIS –

SYMPTOMAS

Phlebothrombosis is a condition where inflammation of the deep

veins of the lower extremities occurs with the formation of a blood

clot - thrombosis.

Situation is dangerous because the thrombus (clot) can be

released and as an embolus can cause pulmonary

embolisation

Pulmonary embolism

Pulmonary embolism occurs when the

arteries and capillaries are closed by

embolus. Embolus usually takes the form of a

blood clot (about 90%) The thrombi are released from the

deep veins of the limbs in thrombosis, from the pelvic veins after surgery or

birth, exceptionally from the right heart. It is particularly dangerous when

lying , immobilizing the legs, in heart failure, thickening of blood or

infusions of hypertonic solutions, in limited blood flow from the vena cava

inferior , surgery in the small pelvis and when is administration of

contraceptive steroids and others. It occurs suddenly when changing

position or defecation. If the thrombi are small, they reach the small

branches of the pulmonary artery at the periphery of the lungs.

The main manifestations of pulmonary embolism

include: blueing of fingers and lips, shortness of breath and collapse of part of the lungs.

VIRCHOW TRIAS

In 1865, Virchow formulated the concept of

thrombosis as a result of:

rheological changes (stasis)

vascular wall damage and

changes in blood clotting

CAUSES OF THROMBOSIS

A: Stasis of venous blood

1. long lying (after op. 3-5 days)

2. in operations - small pelvic and long procedures

3. disadvantageous positions (patient during op)

4. muscle paralysis during anesthesia

5. hypovolemy and hyperviskosity

6. vascular compression from outside or in cancer with

outgrowth into vessel

CAUSES OF THROMBOSIS

B : Vasular wall damage

Directly:

1. surgicl procedure

2. injury

3. itroduced catheter

4. port in chemotheraphy (long term cathetrisation- till 50% occurence of

thrombi )

Indirectly:

1. local inflammation

2. general inflammatory diseases

3. administration of hypertonic and low Ph solutions

CAUSES OF THROMBOSIS

C: changes in blood clotting ( Activation of the coagulation system and subsequent hypercoaguability)

Thrombophilic condition is a pathologically enhanced readiness for blood clotting accompanied by an increased risk of thrombosis and embolism due to a congenital or acquired disorder

1. As a result of surgery (it disrupts the balance of the coagulation and fibrinolytic systems)

2. Malígnant tumors (cellular proteases directly activate clotting factors)

3. Inflammatory diseases

4. Primary (congenital vrodené thrombphylia) --APC rezistancencia-mutátions f V (faktor V Leiden (3-7% prevalencia), deficit AT III, proteinu C, proteinu (1%prevalency), -increased concentration of factor VIII, --increased inhibitoruaktivátor of plazminogen (PAI), --mutátion génu for protrombin

5. Acquired thrombophilic conditions °°antifosfolipid syndroma –antifosfolipid antibodies •lupus antikoagulans (LAC) •antikardiolipín antibodies (ACLA) primary, -secundary • systemic diseases of connective tissues, rheumatoid arthritis, systemic lupus erytematodes

°°acquired APC rezistence, malignity, pregnancy, contraception

TROMBOGENTETIC FACTORS (RISK FACRORS)

- age 40-50 and above

- imobilisation

- obesitas

- pregnancy, contraception peroral / estrogén/ and other hormonal effects

- surgery and injury

- malígnant disess

- inflammation of connective tissue, inflammatory bowel disease / infection,

sepsis

- anamnésis of thrombembolism

- varices, chronic venous insuficiency

- acute myocardial infarction, heart failure

- paresis, hemiplegia, paraplegia

- hyperviskosity, dehydratation , shock

- nefrotic syndroma

-hemostasis disorders

DIAGNOSIS

Diagnosis is based on

Clinical examination to which it follows

Duplex ultrasonography (ultrasound of veins)

ANTICOAGULATION THERAPY

More than 80 years have elapsed since purified heparin preparations became available for clinical use. The introduction of the second anticoagulant, dicumarol, followed in 1941, and since then a wide application of these two drugs resulted in all fields of medicine. Surgery, leaning heavily on the work of physiologists and biochemists, was first to utilize anticoagulant prophylaxis and therapy, since it is daily confronted with the phenomenon of clotting, and since it daily produces a postoperative state, which is characterized among other things by a transitory increase in the clotting activity of the blood.

ANTICOAGULANT THERAPY IN SURGERY, GEZA DE TAKATS, M.D. Affiliations ,JAMA. 1950;142(8):527-534. doi:10.1001/jama.1950.02910260001001

ANTICOAGULATION THERAPY

For decades, aspirin and warfarin have been the predominant

antiplatelet and anticoagulant alternatives.

From 1982, low molecular weight heparins are used in practice

and have been successfully introduced

Beginning with the introduction of the antiplatelet agent

clopidogrel in 2002,

Several more potent oral antiplatelet and oral anticoagulant

agents have been approved for use - the newer direct oral anticoagulants (eg, direct thrombin inhibitor dabigatran, factor

Xa inhibitors rivaroxaban, apixaban, edoxaban) .

The increase in the number of therapeutic agents and the

population at risk requires that surgeons have an understanding of the risks and benefits of reversing these agents in various

settings

PROPHYLAXIS BY RISK GROUPS

Low-risk patients: Under 40 years of age, simple surgery, no risk factors

Moderate risk patients: about 40 years of age, surgery longer than 30 minutes, cardiac insufficiency

Pacients at high risk: age over 40 years, surgery longer than 30 minutes, risk factors (history of thrombosis, malignant disease, thrombophilia, severe skeletal surgery, cardiac insufficiency

MEDICAMENTOUS PREVENTION OF THE DEVELOPMENT OF POST-

THROMBOTIC SYNDROME

At present we have several methods of VTE prevention, which can be divided into mechanical (physical) and medicamentous.

Focusing on coagulation changes

- Low molecular weight heparins (LMWH)

- minidoses of classical heparin (LDUH)

- Vitamin K antagonists (VKA) (warfarin)

- fondaparin, enoxaparin...

- a group of new peroral anticoagulant agents (eg. rivaroxaban, dabigatran, apixaban, edoxaban)

- antiplatellet agents (aspirin, clopidogrel

- Hirudin

- dextran

ANTICOAGULANTS AND SURGERY

Of the anticoagulants,

Low molecular weight heparin, which has a lower risk of bleeding complications

than heparin, is most commonly used in general surgery and orthopedics today.

Standard unfractionated heparin, can be used in the form of microheparinization. i.e., 5000 units prior to surgery and then once every 12 hours

Preoperative preparation of patients on anticoagulant therapy depends on the

type of drug. Operated patients using coumarin-type anticoagulants may undergo surgery at INR values less than 1.5. If the values are higher, it is advisable

to use 5 mg of vitamin K before surgery to adjust the prothrombin time for 1-2 days.

In case of urgent surgery, 500-1000 ml of plasma is administered before surgery

Urgent surgery in patients receiving heparin is possible after neutralization with

protamin- sulfate. If the operation is not emergent, just wait for 6-8 hours.

MEDICAMENTOUS PREVENTION OF THE DEVELOPMENT

OF POST-THROMBOTIC SYNDROME

Length of LMWH prophylactic administration:

Low-molecular-weight heparins should be administered until the patient is fully mobilized and then discontinued or replaced by oral anticoagulants until complete recovery.

In traumatology and orthopedics in hip and knee joint operations, preventive administration of low molecular weight heparins should be continued for at least 4 weeks after surgery. For bone surgery also 8 weeks.

Oral anticoagulants did not find any significant application in primary VTE prevention.

PERIOPERATIVE MANAGEMENT OF LONG-TERM ANTICOAGULATION

The perioperative management of patients who require long-term anticoagulation requires careful analysis of the risk-benefit ratio, balancing the risk of thromboembolism versus the risk of hemorrhage.

Determining the periprocedural risk of thromboembolism requires an understanding of the condition for which the drug is being prescribed. Quantifying the risk associated with the specific indication for an individual patient is required to appropriately manage anticoagulation in the periprocedural period.

‘Bridge’ anticoagulant therapy is the administration of a shortacting

parenteral anticoagulant during the peri-operative period,

when the patient is not taking chronic oral anticoagulant.

WARFARIN AND SURGERY

- basic pharmacological history information is needed before

surgery

-frequent drug especially in the elderly population, often

permanent life-long treatment-atrial fibrillation (even

paroxysmal), venous thrombosis, pulmonary embolism, valvular defects,

-individual dosage tbl. 3 a 5mg, needs regular.Laboratory

checks (3-4 weeks)

-INR (originally Quick's time) most often 2-2.5-3) (30%) INR above 4-5 = the risk of significant spontaneous bleeding

-surgical disciplines accept max. 1.5 INR

- withdraw usually 7 days, laboratory pre - performance

inspection

-transfer to LMWH - cooperation with internist

CONCLUSION

The importance of prevention, active diagnosis and

adequate treatment of deep venous thrombosis is

enhanced by a proven reduction in morbidity and

mortality to venous thrombembolism.