DEEP VEIN THROMBOSIS

What Is Deep Vein Thrombosis ?

DEFINITION

Deep vein thrombosis is the formation of a blood clot in one of the deep veins of the body, usually in the leg.

IT IS LIKE ICEBERG DISEASE

 Symptomatic deep vein thrombosis is "tip of the iceberg"

EPIDEMIOLOGY Venous ThromboEmbolism related

deaths 3,00,000/anum

7% diagnosed and treated

34% sudden pulmonary embolism

59% as undected

INCIDENCE An annual incidence of symptomatic Venous

ThromboEmbolism as 117 per 100,000 persons .

Venous ThromboEmbolism in hospitalized patients has increased from 0.8% to 1.3% over a period of 20 years (reported in 2005).

Without prophylaxis the incidence of deep vein thrombosis is about –

14% in gynaecological surgery 22% in neurosurgery 26% in abdominal surgery 45%-60% in patients undergoing hip and

knee surgeries. 

15% to 40% Urologic surgery.

ETIOLOGY

Virchow's triad

 describes

three factors that are thought to contribute to thrombosis

VIRCHOW TRIAD More than 100 years ago, Rudolf Virchow

described a triad of factors of -

VENOUS STASIS prolonged bed rest (4 days or more) A cast on the leg Limb paralysis from stroke spinal cord injury extended travel in a vehicle

HYPERCOAGULABILITY

Surgery and trauma - 40% of all thrombo embolic

disease

Malignancy

increased estrogen

Inherited disorders of coagulation -Deficiencies of

protein-S, protein-C, anti-thrombin III.

Acquired disorders of coagulation- Nephrotic syndrome,

Anti-phospholipid antibodies

ENDOTHELIAL INJURY Trauma Surgery Invasive procedure Iatrogenic causes – central venous catheters Subclavian Internal jugular lines These lines cause of upper extremity DVT.

HYPERCOAGULABLE STATE OF MALIGNANCY Up to 15% of cancer patients presents with

VTE VTE is not equally common in all types of

cancer.

The highest incidence is found in mucin-producing adenocarcinomas, pancreas and gastrointestinal tract, lung cancer, and

ovarian cancer.

Cancer Site Prevalence (% )

Pancreas 28

Lung 27

Stomach 13

Colon 13

Breast premenopausal 1 –2

Breast postmenopausal 3 –8

Prostate 2

Unknown primary tumor 1

PATHOPHYSIOLOGY

Vessel trauma stimulates the clotting cascade.

Platelets aggregate at the site particularly when venous stasis present

Platelets and fibrin form the initial clot

RBC are trapped in the fibrin meshwork

The thrombus propagates in the direction of the blood flow.

Inflammation is triggered, causing tenderness, swelling, and erythema.

Pieces of thrombus may break loose and travel through circulation- emboli.

Fibroblasts eventually invade the thrombus, scarring vein wall and destroying valves. Patency may be restored valve damage is permanent, affecting directional flow.

Thrombophlebitis - a thrombus accompanied by inflammation of the vein (phlebitis).

Phlebothrombosis - refers to a thrombus with minimal inflammation.

Dislodgment and migration of a thrombus are known as thromboembolism. Which is common in phlebothrombosis.

PRESENTATION AND PHYSICAL EXAMINATION Calf pain or tenderness, or both

Swelling with pitting oedema

Increased skin temperature and fever

Superficial venous dilatation

Cyanosis can occur with severe obstruction

Less frequent manifestations of venous thrombosis include

Phlegmasia alba dolens, Phlegmasia cerulea dolens, and Venous gangrene. These are clinical spectrum of the same

disorder.

PHLEGMASIA ALBA DOLENS

Thrombosis in only major deep venous channels sparing collateral veins

Causing painful congestion and oedema of leg, with lymphangitis

Which further increases Oedema

PHLEGMASIA CERULEA DOLENS

Thrombosis extends to collateral veins.

congestions, massive fluid sequestration, edema

40-60% also have capillary involvement irreversible venous gangrene

hydrostatic pressure in arterial and venous capillaries exceeds the oncotic pressure

fluid sequestration in the interstitium

Circulatory shock, and arterial insufficiency which causes gangrene.

 c/f sudden severe pain , swelling, cyanosis

 and edema of the affected limb. There is a high risk of massive

pulmonary embolism, even under anticoagulation.

Foot gangrene may also occur. An underlying malignancy is found in

50% of cases. Usually, it occurs in those afflicted by a life-threatening illness.

CLINICAL EXAMINATION

Palpate distal pulses and evaluate capillary refill to assess limb perfusion.

Move and palpate all joints to detect acute arthritis or other joint pathology.

Neurologic evaluation may detect nerve root irritation; sensory, motor, and reflex deficits should be noted

Homans sign: pain in the posterior calf or knee with forced dorsiflexion of the foot.

Moses sign Gentle squeezing of the lower part of the

calf from side to side. Neuhofs sign Thickening and deep tenderness elicited

while palpating deep in calf muscles. Lintons sign After applying torniquet at

saphenofemoral junction patient made to walk , then limb is elevated in supine posation prominent superficial veins will be observed.

Search for stigmata of PE such as tachycardia (common) tachypnea chest findings (rare),

exam for signs suggestive of underlying predisposing factors.

WELLS CLINICAL PREDICTION GUIDE

It pre-test probability score

Helps in early risk stratification and appropriate use of laboratory tests and imaging modalities.

wells criteria is an additional tool to diagnosis rather than being a stand-alone test.

Variable Wells

Active cancer (rx within last 6 months or palliative) 1

Calf swelling >3 cm compared to other calf 1

Collateral superficial veins (non-varicose) 1

Pitting edema 1

Swelling of entire leg 1

Localized pain along distribution of deep venous system 1

Paralysis, paresis, or recent cast immobilization of lower extremities 1

Recently bedridden > 3 days, or major surgery requiring regional or general anesthetic in past 12 weeks 1

Previously documented DVT 1

Alternative diagnosis at least as likely deep vein thrombosis -2

Interpretation

High probability: ≥ 3 (Prevalence of DVT - 53%)

Moderate probability: 1-2 (Prevalence of DVT - 17%)

Low probability: ≤ 0 (Prevalence of DVT - 5%)

Adapted from Anand SS, et al. JAMA. 1998; 279 [14];1094

LIMITATIONS OF WELLS SCORE

It useful in secondary and tertiary care centers, has not been properly validated for use in primary care centers patients with the suspicion of DVT.

The performance of Wells score was decreased when evaluating elderly patients or those with a prior DVT or having those having other comorbidities, which might be equivalent to what is found in a primary care setting.

DIAGNOSTIC STUDIES

Clinical examination alone is able to confirm only 20-30% of cases of DVT

Blood Tests The D-dimer

Imaging Studies

D-DIMER It specific degradation product of cross-linked

fibrin.

Because concurrent production and breakdown of clot characterize thrombosis, patients with thromboembolic disease have elevated levels of D-dimer.

Three major approaches for measuring D-dimer

ELISA latex agglutination blood agglutination test

DURING FIBRINOLYSIS OF FIBRIN, PLASMIN CLEAVES FACTOR XIIIA–CROSS-LINKED FIBRIN INTO AN ARRAY OF INTERMEDIATE FORMS. THE D-DIMER AND E FRAGMENTS ARE THE RESULT OF TERMINAL FIBRIN DEGRADATION

Various kits have a 93-95% sensitivity and about

50% specificity in the diagnosis of thrombotic disease.

False-positive D-dimers occur in patients with

recent (within 10 days) surgery or trauma, recent myocardial infarction or stroke, acute infection, disseminated intravascular coagulation, pregnancy or recent delivery, active collagen vascular disease, or metastatic

cancer

It should be noted that since D-dimer assays present a low specificity for DVT, the value of this test should be limited to ruling out rather than confirming the diagnosis of a DVT.

ALGORITHM FOR DIAGNOSTIC IMAGING

IMAGING STUDIES Invasive venography, radiolabeled fibrinogen noninvasive ultrasound, plethysmography, MRI techniques

VENOGRAM:POPLITEAL VEIN THROMBOSIS

Venography

VENOGRAPHY It detects thrombi in both calf and thigh It can conclude and exclude the diagnosis of

DVT when other objective testings are not conclusive.

Advantages It is useful if the patient has a high clinical

probability of thrombosis and a negative ultrasound.

It is also valuable in symptomatic patients with a history of prior thrombosis in whom the ultrasound is non-diagnostic.

DISADVANTAGE

It can primary cause of DVT in 3% of patients who undergo this diagnostic procedure.

An invasive and expensive.

Although Venography was once considered the gold standard for diagnosis of DVT, today it is more commonly used in research environments and less frequently utilized in clinical practice.

Nuclear Medicine Studies

NUCLEAR MEDICINE STUDIES

Because the radioactive isotope incorporates into a growing thrombus, this test can distinguish new clot from an old clot.

Nuclear medicine studies done with I125-

labeled fibrinogen .

More commonly used in research.

PLETHYSMOGRAPHY Plethysmography measures change in lower

extremity volume in response to certain stimuli.

IMPEDANCE PLETHYSMOGRAPHY

Principle- Blood volume changes in the leg lead to changes in electrical resistance.

Venous return in the lower extremity is occluded by inflation of a thigh cuff, and then the cuff is released, resulting in a decrease in calf blood volume. Any obstruction of the proximal veins diminishes the volume change, which is detected by measuring changes in electrical resistance (impedance) over the calf.

ULTRASONOGRAPHY color-flow Duplex scanning is the imaging test

of choice for patients with suspected DVT inexpensive, noninvasive, widely available Ultrasound can also distinguish other causes

of leg swelling, such as tumor, popliteal cyst, abscess, aneurysm, or hematoma.     

CLINICAL LIMITATIONS Reader dependent Duplex scans are less likely to detect non-

occluding thrombi. During the second half of pregnancy,

ultrasound becomes less specific, because the gravid uterus compresses the inferior vena cava, thereby changing Doppler flow in the lower extremities.

An inability to distinguish old clots from a newly forming clot

Lack of accuracy in detecting DVT in the pelvis or the small vessels of the calf

Lack of accuracy in detecting DVT in the presence of obesity or significant edema

MAGNETIC RESONANCE IMAGING

It detects leg, pelvis, and pulmonary thrombi and is 97% sensitive and 95% specific for DVT.

It distinguishes a mature from an immature clot.

MRI is safe in all stages of pregnancy. Test may not be appropriate for patients with

pacemakers or other metallic implants, it can be an effective diagnostic option for some patients.

DIFFERENTIAL DIAGNOSISo Cellulitis

Thrombophlebitiso Arthritis

Asymmetric peripheral edema secondary to CHF, liver disease, renal failure, or nephrotic syndrome lymphangitisExtrinsic compression of iliac vein secondary to tumor, hematoma, or abscessHematomaLymphedema

Muscle or soft tissue injuryNeurogenic painPostphlebitic syndrome Ruptured Baker cystStress fractures or other bony lesionsSuperficial thrombophlebitis

MANAGEMENT Using the pretest probability score calculated

from the Wells Clinical Prediction rule, patients are stratified into 3 risk groups—high, moderate, or low.

The results from duplex ultrasound are incorporated as follows:

If the patient is high or moderate risk and the duplex ultrasound study is positive, treat for DVT.

If the duplex study is negative and the patient is low risk, DVT has been ruled out.

• When discordance exists between the pretest probability and the duplex study result, further evaluation is required.

If the patient is high risk but the ultrasound study was negative, the patient still has a significant probability of DVT

a venogram to rule out a calf vein DVT surveillance with repeat clinical evaluation

and ultrasound in 1 week. results of a D-dimer assay to guide

management If the patient is low risk but the ultrasound

study is positive, some authors recommend a second confirmatory study such as a venogram before treating for DVT

EMERGENCY DEPARTMANT CARE

The primary objectives of the treatment of DVT are to -

prevent pulmonary embolism,

reduce morbidity, and

prevent or minimize the risk of developing the postphlebitic syndrome.

GENERAL THERAPEUTIC MEASURES :

Bed rest .

Encourage the patient to perform gentle foot & leg exercises every hour.

Increase fluid intake upto 2 l/day unless contraindicated.

Avoid deep palpation .

SPECIFIC TREATMENT :

Anticoagulation

Thrombolytic therapy for DVT

Surgery for DVT

Filters for DVT

Compression stockings

Initial treatment of DVT is with low-molecular-weight heparin or unfractionated heparin for at least 5 days, followed by warfarin (target INR, 2.0–3.0) for at least 3 months.

ANTICOAGULATION

Heparin prevents extension of the thrombus

It is a heterogeneous mixture of polysaccharide fragments with varying molecular weights but with similar biological activity.

MECHANISM OF ACTION Heparin's anticoagulant effect is related

directly to its activation of antithrombin III.

Antithrombin III, the body's primary anticoagulant, inactivates thrombin and inhibits the activity of activated factor X, factor IX in the coagulation process.

Heparin: Mechanism of ActionAccelerates antithrombin III activity

Prothrombin ThrombinFactor Xa

Factor Va

Factor X

Factor IXa

Factor VIIIa Ca2+, PL

Ca2+, PL

Antithrombin III

(Heparin)

Side effects • Bleeding• Osteoporosis • Thrombocytopenia• Skins lesions- urticaria, papules, necrosis• Hypoaldosteronism, hyperkalemia

CONTRAINDICATIONS-• Bleeding disorders,• Severe hypertension, threatened abortion, piles, • large malignancies, tuberculosis’• Ocular surgery and neurosurgery,• Chronic alcoholics, cirrhosis, renal failure

DOSE IV bolus dose of 5,000 to 10,000 units followed by an infusion of 1,000 units per

hour. Other method of initiating therapy is to begin

with Loading dose of 50-100 units/kg of heparin

followed by a constant infusion of 15-25 units/kg/hr.

LOW MOLECULAR WEIGHT HEPARIN

Selectively inhibit factor Xa . Superior bioavailability Superior or equivalent safety and efficacy Subcutaneous once- or twice-daily dosing No laboratory monitoring Less phlebotomy (no monitoring/no

intravenous line) Less thrombocytopenia

The optimal regimen for the treatment of DVT is anticoagulation with heparin or an LMWH followed by full anticoagulation with oral warfarin for 3-6 months

Warfarin therapy is overlapped with heparin for 4-5 days until the INR is therapeutically elevated to between 2-3.

WARFARIN Interferes with hepatic synthesis of vitamin K-

dependent coagulation factors

Dose must be individualized and adjusted to maintain INR between 2-3

Oral dose of 2-10 mg/d

caution in active tuberculosis or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis

WARFARIN—MECHANISM OF ACTION

Vitamin K

Warfarin

Synthesis of Dysfunctional Coagulation

Factors

VII

IX

X

II

DRAWBACKS OF WARFARIN THERAPY Delayed onset and offset of action.

Frequent blood test monitoring required: - the dose response is unpredictable, - has a narrow therapeutic range

Reversibility of anticoagulant affect is slow.

Requires labor-intensive follow up, Expert dose management, Frequent patient communication.

THROMBOLYTIC THERAPY FOR DVT

Advantages include Prompt resolution of symptoms, Prevention of pulmonary embolism, Restoration of normal venous circulation, Preservation of venous valvular function, Prevention of postphlebitic syndrome.

DISADVANTAGE

Thrombolytic therapy does not prevent

clot propagation, rethrombosis, or subsequent embolization. Heparin therapy and oral anticoagulant

therapy always must followed after a course of thrombolysis.

Thrombolytic therapy is also not effective once the thrombus is adherent and begins to organize

The hemorrhagic complications of thrombolytic therapy are about 3 times higher, including the small but potentially fatal risk of intra-cerebral hemorrhage.

  At present, therefore, thrombo-lysis should be reserved for exceptional circumstances, such as patients with limb-threatening ischemia caused by phlegmasia cerulea dolens.

SURGERY FOR DVT

Indications when anticoagulant therapy is ineffective unsafe, contraindicated. The major surgical procedures for DVT are

clot removal and partial interruption of the inferior vena cava to prevent pulmonary embolism.

These pulmonary emboli removed at autopsy look like casts of the deep veins of the leg where they originated.

THIS PATIENT UNDERWENT A THROMBECTOMY. THE THROMBUS HAS BEEN LAID OVER THE APPROXIMATE LOCATION IN THE LEG VEINS WHERE IT DEVELOPED.

CATHETER-DIRECTED THROMBOLYSIS

Successful clot lysis in > 85%

Better 1-yr patency,

Long-term symptom resolution.

FIRST-GENERATION PCDT

NEW: SINGLE-SESSION PCDT

PowerPulse Isolated Thrombolysis

FILTERS FOR DVT Indications Contraindication to anticoagulation. Significant bleeding complication of

anticoagulation therapy. Pulmonary embolism with contraindication to

anticoagulation. Recurrent thrombo-embolic complication

despite adequate anticoagulation therapy.

Inferior vena cava filters reduce the rate of pulmonary embolism but have no effect on the other complications of deep vein thrombosis. Thrombolysis should be considered in patients with major proximal vein thrombosis and threatened venous infarction

PROPHYLAXIS

Indicated in who underwent major abdominal trauma or orthopaedic surgery or patient having prolonged immobolization (> 3 days).

Benefits of VTE Prophylaxis Improved patient outcomes Reduced costs

METHODS OF VTE PROPHYLAXIS Mechanical:

Graduated Compression Stockings (GCS)

Intermittent Pneumatic Compression Devices (IPC)

Pharmacologic Low molecular weight Heparin.(5000u sc

8hourly ) It inhibits factor Xa and IIA activity.