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THROMBOSIS

Karmel L. Tambunan, Lugyanti Sukrisman

Div of Hematology-Medical Oncology

Dept of Internal Medicine

Faculty of Medicine, Univ of Indonesia

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Overview of Hemostasis

Vascular Injury

Platelet adhesion& aggregation

Vasoconstriction Blood coagulation

HEMOSTASIS

Exposed subendothelium

Exposed tissue factor

thrombin

PF3

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The primary haemostatic system:haemostasis and platelet plug formation

Vascularinjury

Formation ofplatelet plug

exposed sub endothelial tissue

trombosit

endothelial cells

sub endothelial tissue

Platelet aggregationPlatelet aggregation

Adhesion

Activation

Aggregation

White clot

Primary haemostasis

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The haemostatic system:secondary haemostasis and clot formation

ThrombinProthrombin

FibrinExtrinsic pathway

Intrinsic pathway

Factor Xa

Fibrin threads

Coagulation cascadeleads to clot formation

Clot growth

Fibrinogen

Activation of the coagulation cascade leads to generation of thrombin and, in turn, fibrin

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What is thrombosis ?

Thrombosis is the formation or presence of a blood clot inside a blood vessel or cavity of the heart

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Thrombosis

1. Arterial thrombosis (white thrombus)

2. Venous thrombosis (red thrombus)

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Thrombosis

Mortality : Cause of death (>60%) in the western country

(Turpie G.L., 1996) About 2 million individual die each year from

an arterial or venous thrombosis or of the consequence thereof (Bick R.L., 1997)

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Thrombosis

Morbidity : Paralysis (non fatal thrombotic state) Cardiac disability (repeated coronary event) Fetal loss syndrome (placenta vascular

thrombosis) Loss of vision (retinal vascular thrombosis) Loss of hearing (?) Stasis ulcers and others manifestations of

postphlebitic syndrome (recurrent DVT)

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Incidence of thrombosis in United States of AmericaDisease US incidence Total in US /year Definable

/100.000 cases reason

Deep Vein Thrombosis 159/100.000 398.000 80%

Pulmonary Embolus 139/100.000 347.000 80 % Fatal Pulmonary Emb. 94/100.000 235.000 80 % Myocardial Infarction 600/100.000 1.500.000 67 % Fatal MI 300/100.000 750.000 67 % Cerebrovascular thromb. 600/100.000 1.500.000 30 % Fatal Cereb. Trhromb. 396/100.000 990.000 30 % Total serious thromb. In US 1498/100.000 3.742.000 50 % Total deaths from above thrmb. 790/100.000 1.990.000 50 %

Bick RL, Clin Appl Throm Hemos 3, Suppl 1, 1997

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CV thrombosis1,000,000

Other causes400,000

COPD90,000

Cancer500,000

Pulmonary disease/flu80,000

Trauma/accident90,000

Leading causing Mortality in the USA

Semin Thromb 21,Sup 1, 2000

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Thrombosis in Indonesia

Epidemiology data: not available Mortality The first cause of death 20.5%, (11.8 % cerebrovascular, 8.7 % coronary

heart disease) (Ministry of Health 1997)

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Causes of Thrombosis

Clinical conditions Arterial

Clinical conditions Venous

Blood protein/platelet defects

Atherosclerosis

Cigarette smoking

Hypertension

Diabetes mellitus

Low-density

lipoprotein cholesterol

Hypertriglyceridemia

Positive family history

Left ventricular failure

Oral contraceptives

Estrogens

Lipoprotein(a)

Polycythemia

Hyperviscosity syndrome

Leukostasis syndromes

General surgery

Orthopaedic surgery

Arthroscopy

Trauma

Malignancy

Immobility

Sepsis

Congestive heart failure

Nephrotic syndrome

Obesity

Varicose veins

Postphlebitic syndrome

Oral contraceptives

estrogens

Antiphospholipid syndrome

Activated protein C

resistance (Fac. V Leiden)

Sticky platelet syndrome

Protein S defects

Protein C defects

Antithrombin defects

Heparin cofactor II defects

Plasminogen defects

Tissue plasminogen

activator defects

Plasminogen activator inhibitor defects

Factor XII defects

Dysfibrinogenemia

Homocystinemia

Arterial thrombosis

1. Stroke non haemorrhagic/ TIA

2. Myocardial infarction/unstable angina

3. Acut abdomen (mesenterial thrombosis )

4. Fetal loss syndrome/ recurrent miscarriage

5. Loss of vision6. Loss of hearing7. Gangrene

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10 % symptomatic (DVT/PE) 90 % asymptomatic Could be life-threatening

asymptomatic

Symptom(+)

Fatal pulmonary emboli

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Venous stasis Parietal lesion Coagulation anomaly

Age > 60 yrs +

obesity + +

pregnancy + +

Immobilization or paralysis +

Orthopaedic surgery + + +

Trauma of lower limbs + + +

Cardiac insufficiency +

Myocardial infarction (acute phase)

+ +

Stroke + +

Cancer + +

General surgery + + +

Inherited or acquired haemostasis deficiencies

+

Venous insufficiency or varicosis

+ +

Previous history of DVT + + +

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Primary risk factors for VTEPrimary risk factors for VTE

Major surgeryMajor surgery Acute MIAcute MI Major traumaMajor trauma Paralytic strokeParalytic stroke CancerCancer Spinal cord injurySpinal cord injury Pelvic fracturePelvic fracture

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Secondary risk factors for VTE

Haematological Haematological disordersdisorders

Central venous Central venous cathethercathether

Varicose veinsVaricose veins PregnancyPregnancy Oestrogen treatmentOestrogen treatment HospitalizationHospitalization

Congestive heart Congestive heart failure failure

Previous VTEPrevious VTE ImmobilizationImmobilization ObesityObesity Chronic Chronic

respiratory failurerespiratory failure Increasing ageIncreasing age

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DVT risk

Low risk Minor surgery Age <40 No other risk factors Moderate risk

Major surgery Age >40

No other risk factors High risk Major surgery Age >40 MI Additional risk factors

Highest risk

Major surgery

Age >40

History of VTE

Hip fracture

THR or TKR

CVA

Spinal cord injury

Trauma

Malignancy

Congenital hypercoagulability

Chest 1998;114:531S-60S

VTE, venous thromboembolism; THR, total hip replacement; TKR, total knee replacement; MI, myocardial infarction; CVA, cerebrovascular accident

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Pathogenesis : Triad Virchow

1. Vascular lesion/disruption

2. Blood component (coagulation imbalance)

3. Venous stasis

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VTE: A strong relationship between DVT and PE

Almost 50% of patients with proximal DVT of the leg have asymptomatic PE1

DVT (mainly asymptomatic) is found in around 80% of patients with PE2

1. Pesavento R, et al. Minerva Cardioangiologica. 1997;45:369–3752. Girard P, et al. Chest. 1999;116:903–908

Embolus

Migration

Thrombus

DIAGNOSIS OF VTE: CLINICAL FINDINGS

DVT: Non specific Pain, tenderness, unilateral leg swelling,

superficial venous dilatation PE:

Dyspnea, pleuritic pain, cough, hemoptysis

Clinical prediction score for DVT/PE Laboratory test: D-dimer

Hypoxemia, hypocapnia (PE)

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DIAGNOSIS OF VTE: RADIOIMAGING

DVT: Venography/phlebography (gold standard) Compression ultrasonography (CUS) Venous Doppler/duplex scanning

PE: CXR: cardiomegaly, pleural effusion, atelectasis,

elevated hemidiaphragm Pulmonary angiography (gold standard) Ventilation-perfusion lung scintigraphy Spiral CT

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PRINCIPLES THERAPY OF THROMBOSIS BASED ON PATHOGENESIS

PATHOGENESIS THERAPY

RISK FACTORS PREVENTION

- PLATELET ADHESION

-PLATELET AGGREGATION

-BLOOD COAGULATION ANTICOAGULANT

-THROMBOSIS THROMBOLYTIC

ANTIPLATELET

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CURRENTLY AVAILABLEANTITHROMBOTIC DRUGS

ANTIPLATELET AGENTS ANTICOAGULANTS

ORAL PARENTERAL ORAL PARENTERAL

AspirinDypiridamolTiclopidinClopidogrel

GPIIb/IIIaantagonists

CoumarinHeparinLMWHHirudinArgatroban

melagatran

THROMBOLYTICAGENTS

-PARENTERAL-STREPTOKINASE-UROKINASE-tPA

Fondaparinux

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Complications ofDeep Vein Thrombosis

• Permanent vascular damage to lower limb

• Post thrombotic venous insufficiency

• Postphlebitic syndrome

• Pulmonary embolism (PE)

• Pulmonary hypertension

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POST THROMBO-PHLEBITIC SYNDROME

VTE PROPHYLAXIS

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Thank you

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