Deep Vein Thrombosis

Faculty of Medicine University of Brawijaya

Definitions
Thrombophlebitis: thrombosis of superficial veins of legs Deep vein thrombosis (DVT): deep veins of legs, more serious Embolus: piece of thrombotic material breaks off and travels through the circulatory system

Virchows Triad

Hypercoagulability presence of tissue debris, collagen or fats in the veins Endothelial injury Damage to the vein walls, which can occur during surgery as the physician retracts, twists, folds or manipulates veins Venous flow disturbance (stasis or turbulence) stagnant blood flow through veins

DVT Statistics

Deep vein thrombosis (DVT) occurs in approximately 2 million Americans each year Each year 600,000 of these patients develop pulmonary embolism Each year as many as 200,000 patients die of pulmonary embolism More people die each year from pulmonary embolism than do from breast cancer Pulmonary embolism is the most frequent cause of maternal death associated with childbirth Women are affected by pulmonary embolism more often than men DVT recurs in 5-10% of patients the year after anticoagulant therapy is discontinued DVT recurs in 30% of patients eight years after anticoagulant therapy is discontinued

Risk Tutor, Deep Vein Thrombosis (DVT) and Underwriting 2003

Relative increase in event rates per 10 000 women at 5.1 years of follow-up in the WHI

26% increase in breast cancer (38 vs 30) 41% increase in strokes (29 vs21) 29% increase in heart attacks (37 vs 30) Doubled rates of blood clots in legs and lungs (34 vs 16) 37% less colorectal cancer (10 vs16) 34% fewer hip fractures and 24% less total fractures (10 vs15 and 147 vs191)

Writing Group for WHI. JAMA 2002;288:321-333

Inherited Risk Factors for developing DVT :

Antithrombin

III deficiency Protein C deficiency Protein S deficiency Dysfibrinogenimia Plasminogen disorders

Acquired Risk Factors for developing DVT

Age greater than 40, and increases with age Birth control pills Cancer (although having a clot does not necessarily mean that you have cancer) and chemotherapy Certain congenital heart defects Congestive heart failure (CHF) Chronic respiratory failure Hipercoagulability state Hormone replacement therapy (HRT) (often administered to postmenopausal women) History of obesity Prior DVT Prolonged immobility (e.g air travel) or paralysis Stroke Surgery, including orthopedic, pelvic, and abdominal surgeries (which can trigger the formation of blood clots) Trauma Hipercoagulability factor Varicose veins (varicosities)

Risk Tutor, Deep Vein Thrombosis (DVT) and Underwriting 2003

Superficial vs. Deep Vein Thrombosis

There are three types of veins in the legs: superficial, communicating, and deep. Superficial veins are close to the skin. For example, the bluish veins you see inside your wrist, or the veins that bulge when you exercise Deep veins lie near the bones, surrounded by muscle. Connecting the two side are communicating veins

Proximal DVT vs Distal DVT

proximal DVToccurring between the groin and the kneetends to be more hazardous and painful than distal DVT. That's because of the greater likelihood of significant localized symptoms and the increased risk of developing a pulmonary embolism as a complication. In addition, there's evidence that DVT involving the iliac vein has the highest risk of recurrent episodes, in which new blood clots form.

Anatomy of leg veins

Deep veins of the leg

Two major types of veins, deep and superficial Deep veins, located in the center of the leg near the leg bones, are enclosed by muscle and return approximately 85% of the blood to the heart. As shown in the diagram, the iliac, femoral, popliteal, and tibial (calf) veins are the deep veins in the leg. Superficial veins are near the surface of the skin and have very little muscle support. Superficial veins return approximately 15% of the blood to the heart

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Deep Vein Thrombosis

Blood clots of the deep veins of the legs, called deep vein thrombosis or DVT, can have lethal outcomes. A portion of the leg clot can break off and move up to the lungs. This is known as a pulmonary embolism. A pulmonary embolism can case sudden death.

Risk Tutor, Deep Vein Thrombosis (DVT) and Underwriting 2003

Symptoms of DVT

Pain Sudden swelling in affected leg Enlargement of superficial veins Reddish-blue discoloration Skin that is warm to the touch

Risk Tutor, Deep Vein Thrombosis (DVT) and Underwriting 2003

Homans sign
Passive dorsal flexion (bending of the foot towards the calf) causes pain in the calf muscles. The mechanism is thought to involve placing traction on the posterior tibial vein pain if the patient has a deep vein thrombosis Indicative of established venous thrombosis (inflammation of a vein usually associated with a clot) of the leg. Accurate in only about the cases. Better procedure venography. The test has fallen into disfavour because of the risk of precipitating a pulmonary embolism.

Deep Vein Thrombosis - Histology

Patient: Over time a thrombus leads to inflammatory changes in the wall of the vein. Wall is markedly thickened. Clot is partially organized and undergoing partial resolution Normal: Walls not thickened, lumens patent, no inflammation

Clinical Prediction

Developed by P. Wells & colleagues Wells

score

Several years hundreds of patients Criteria for predicting the likelihood the patient has thromboembolism
PE (pulmonary embolism) 7 predictors DVT 9 predictors

Add points score probability of PE or DVT

Low Moderate Probability of Disease 2.5% (PE); 3.0% (DVT) 28% (PE); 16% (DVT)

Wells Clinical Probability Score

Clinical Hx/Sign Signs/Sx of DVT Pulse > 100/min
Bedrest > 3 days (except BR)

Criteria
Leg swelling objectively measured
AND

Score 3.0 1.5

Pain with palpation - deep vein region

Immobilization Previous DVT or PE

Hemoptysis Malignancy

OR

1.5 1.5
1.0

Surgery in previous 4 weeks

Must have been objectively diagnosed

Receiving active Rx for Ca

OR

Have received Rx for Ca in previous 6 months

OR

1.0

Receiving palliative Rx for Ca

PE as likely or more likely than alternative DX

No specific criteria use Hx, Px, CXR, EKG etc. to decide

3.0

TOTAL

Wells Clinical Probability Score

Clinical Probability Low Moderate High Score <2 26 >6 LR 0.12 1.9 6.0 Positive Pred Value 3% 28% 55%

Diagnosing DVT
Diagnosing DVT is difficult, and current diagnostic techniques have both advantages and disadvantages The most commonly used diagnostic tests include:

Venography Duplex or Doppler ultrasonography Magnetic resonance imaging (MRI) Cuff-impedence plethysmography

Risk Tutor, Deep Vein Thrombosis (DVT) and Underwriting 2003

Venography

Venography uses a radiographic material injected into a vein on the top of the foot. The material mixes with blood and flows toward the heart. An X-ray of the leg and pelvis will then show the calf and thighs veins and reveal any blockages Although venography is very accurate and can detect blockages in both the thigh and the calf, it is also costly and cannot be repeated often. In addition, the injected material may actually contribute to the creation of thrombi

Risk Tutor, Deep Vein Thrombosis (DVT) and Underwriting 2003

Uses of color duplex scanning

Venous

Diagnosis of deep vein thrombosis above the knee Assessing competence of valves in deep veins Superficial venous reflux: Assessing patient with recurrent varicose veins Identify and locate reflux at saphenopopliteal junction Preoperative mapping of saphenous vein

Color Duplex scanning is both sensitive and specific (90-100% in most series) for detecting proximal deep vein thrombosis. Venous ultrasonography less reliable for diagnosing calf vein thrombosis

Richard Donnelly, David Hinwood, Nick J M London, The ABC of arterial and venous disease 1998

Investigations of venous disease

Color duplex scanning of sapheno-popliteal junction. The calf muscles are manually compressed producing upward flow in the vein (top), which appears as a blue color for flow towards the heart (panel A). Sudden release of the distal compression causes reflux, seen as a red color indicating flow away from the heart (panel B)

Richard Donnelly, David Hinwood, Nick J M London, The ABC of arterial and venous disease 1998

Magnetic resonance imaging (MRI)

Magnetic resonance imaging (MRI) is particularly effective in diagnosing DVT in the pelvis, and as effective as venography in diagnosing DVT in the thigh. This technique is being increasingly used because it is noninvasive and allows simultaneous visualization of both legs. However, an MRI is expensive, not always readily available, and cannot be used if the patient has certain implants, such as a pacemaker. In addition, the patient can experience claustrophobia

Risk Tutor, Deep Vein Thrombosis (DVT) and Underwriting 2003

Investigations of venous disease

Criteria for diagnosis of deep vein thrombosis

Failure of vein to collapse on direct compression Visualisation of thrombus within lumen Absent or abnormal venous pulsation on Doppler scanning

Richard Donnelly, David Hinwood, Nick J M London, The ABC of arterial and venous disease 1998

D-DIMER
Fibrin Degradation Product Highly sensitive, but a nonspecific screening test for DVT Can be elevated in pregnancy, inflammation, advanced age, trauma, post-op period, and cancer D-Dimer is only specific if it is negative

95-99% negative predictive value (ELISA)

APPROACH TO TESTING

DVT Pathway
Patients with Suspected DVT Clinical Probability Assessment

Low

Moderate

High

D-Dimer

D-Dimer

USnd leg

Neg

Positive

Neg

Positive

Normal

Positive

STOP

USnd leg

STOP

USnd leg

Venography

TREAT

Normal

Positive

Normal

Positive

Normal

Positive

STOP

TREAT

USnd Leg
in 1 week

TREAT

STOP

TREAT

Normal

Positive

USnd: ultrasound
STOP TREAT

Treating DVT
Practical

measures for treating

DVT include:
Elevating the affected leg Applying heat to relieve pain and swelling Wearing compression bandages or support hose to reduce swelling and decrease pooling of blood Avoiding long periods of immobility, particularly in the weeks following the episode
Risk Tutor, Deep Vein Thrombosis (DVT) and Underwriting 2003

Medications

Drugs generally used to treat deep vein thrombosis fall into 3 basic categories:
Anticoagulants These drugs do not dissolve clots but weaken their stability and prevent further expansion Thrombolytic agents these drugs actually help to dissolve clots Antiplatelet agents these drugs discourage new clots from forming

Risk Tutor, Deep Vein Thrombosis (DVT) and Underwriting 2003

Anticoagulants
Warfarin: An oral anticoagulant suitable for long-term use, warfarin is typically begun at the same time as unfractionated heparin or lowmolecular-weight heparins but needs more time to take effect 3 to 5 days is about average. Once blood tests have confirmed that warfarin is working adequately, other therapy can usually be stopped

Risk Tutor, Deep Vein Thrombosis (DVT) and Underwriting 2003

Oral Anticoagulants
Common names: coumadin, coumarin, warfarin, dicumarol, Ximelagatran Reduction in synthesis of Vit K dependent factors II, VII, IX, X

Contraindications to anticoagulation therapy:

bleeding disorders history of hemorrhagic stroke metastatic disease involving the central nervous system pregnancy or immediate post-partum state major abdominal or orthopedic surgery within 7 days gastrointestinal bleeding

Monitoring Oral Anticoagulants

Narrow therapeutic index for the drug Variability due to drug interactions, dietary interactions, hepatic function Complications: hemorrhage, urticaria, alopecia, skin necrosis

Heparin
given intravenous available as unfractionated and in LMW(low molecule weight) form Rapid inhibition of serine proteases increases antithrombin ability to neutralize serine proteases LMWH cannot be monitored by the APTT

Heparin Complications
Heparin induced thrombocytopenia Drug-induced immune response Platelet count decrease of 50% in patients Platelets recover when heparin stopped

Thrombolytic Therapy

Administered by intravenous infusion or directly into the clot via catheter, thrombolytic agents like streptokinase and tissue plasminogen activator (TPA) target the fibrin mesh that binds clots together, causing it to disintegrate. Hospitalization is required, and risk of bleeding complications is greater than with heparin or lowmolecular-weight heparins. At present, thrombolytic therapy is reserved for patients with new large clots and those who are at high risk of long-term complications due to a clotting disorder or other predisposing condition

Risk Tutor, Deep Vein Thrombosis (DVT) and Underwriting 2003

PROTOCOL FOR THE TREATMENT OF PROXIMAL DEEP-VEIN THROMBOSIS IN OUTPATIENT SETTINGS WITH SUBCUTANEOUS LOW-MOLECULAR WEIGHT HEPARIN

A. Day One 1. Medications: Start the patient on enoxaparin 1mg/kg SQ BID or dalteparin 120IU/kg SQ BID and warfarin 5mg po QD (starting dose maybe lower in elderly patients or patients with hepatic disease). If the patient is going home arrange for a home care nurse. If the patient or significant other is unable to administer the LMWH at home, an outpatient clinic or a skilled nursing facility should be considered as options.

PROTOCOL FOR THE TREATMENT OF PROXIMAL DEEP-VEIN THROMBOSIS IN OUTPATIENT SETTINGS WITH SUBCUTANEOUS LOW-MOLECULAR WEIGHT HEPARIN

2. Laboratory: aPTT, CBC, platelets, INR 3. Nursing: a. The patient or family member is educated regarding the administration of the LWMH. b. The patient is educated regarding the use of LMWH and warfarin (indications, side effects, drug/food interactions). The education/training is documented. 4. Pharmacy: a. Provide and/or support nursing regarding patient education/training issues. b. If necessary or desired, repackage the LMWH in ready-touse syringes.

PROTOCOL FOR THE TREATMENT OF PROXIMAL DEEP-VEIN THROMBOSIS IN OUTPATIENT SETTINGS WITH SUBCUTANEOUS LOW-MOLECULAR WEIGHT HEPARIN

5. Non-Drug Therapy: a. Elevation of the affected extremity may be beneficial b. Local heat may improve microcirculation. c. Range-of-motion exercises, i.e., flexion/extension of ankle. 6. Patient Activity: a. Reduced activity as long as pain persists. Increase activity as pain

PROTOCOL FOR THE TREATMENT OF PROXIMAL DEEP-VEIN THROMBOSIS IN OUTPATIENT SETTINGS WITH SUBCUTANEOUS LOW-MOLECULAR WEIGHT HEPARIN

B. Day Two 1. Medications: Continue as per day 1 2. Nursing: Home care nurse will reassess the status of the patients affected limb, any bleeding problems, the patients LMWH administration technique and ongoing compliance. 3. Patient Activity: Same as day 1. C. Day Three 1. Medications: Continue as per day 2 2. Laboratory: Check INR and adjust warfarin dose as necessary to maintain INR between 2 and 3. Patient activity: No restrictions. If pain has increased refer the patient to the primary care provider. D. Day Four 1. Medications: Continue both drugs 2. Laboratory: Check INR. Adjust as necessary.

PROTOCOL FOR THE TREATMENT OF PROXIMAL DEEP-VEIN THROMBOSIS IN OUTPATIENT SETTINGS WITH SUBCUTANEOUS LOW-MOLECULAR WEIGHT HEPARIN

E. Day Five 1. Medications: Continue both drugs 2. Laboratory: Check INR and platelet count. Adjust warfarin dose as necessary. F. Day Six 1. Medications: Discontinue LMWH on the evening of day 5 as long as the INR is between 2 and 3. Continue warfarin. G. Day Seven 1. Medications: Continue warfarin for 3 to 6 months. It may be necessary to continue the LMWH for a total of 7 days until INR is stable. 2. Laboratory: Periodically check INR and adjust if necessary

LMWH DOSING IN DVT TREATMENT

Abstract
The goals of acute treatment for deep vein thrombosis (DVT) and pulmonary embolism are both therapeutic and economic. The traditional treatment approach involves the continuous use of intravenous unfractionated heparin (UFH) with concurrent oral warfarin therapy. A heparin bridge is necessary when initiating oral anticoagulant therapy for an acute venous thromboembolic (VTE) event. UFH therapy does, however, include several safety and cost disadvantages. Low molecular weight heparins (LMWH) have been shown to be safe and effective as outpatient DVT treatment, initial inpatient treatment followed by completion of therapy as an outpatient, or standard inpatient therapy. CME Forum 2002;2:26-38)

Principles of DVT Treatment

Three key principles for DVT treatment have emerged, based on clinical studies in this field. First, a heparin bridge is necessary when initiating oral anticoagulant therapy for an acute DVT event. Second, a 5-day heparin bridge with an oral anticoagulant is equivalent to a 10day heparin bridge, when discussing recurrent VTE disease. Third, a weight-based IV nomogram for heparin is superior to standard care in achieving a therapeutic aPTT within the first 24 hours of initiating heparin therapy.

Weight-Based Nomogram for IV UFH

Initial dose 80 U/kg bolus, then 18 U/kg/hour aPTT <35s (<1.2 x control) 80 U/kg bolus, then increase infusion rate by 4 U/kg/hour aPTT 35-45s (1.2-1.5 x control) 40 U/kg bolus, then increase infusion rate by 2 U/kg/hour aPTT 46-70s (1.5-2.3 x control) No change aPTT 71-90s (2.3-3.0 x control) Decrease infusion rate by 2 U/kg/hour aPTT >90s (>3.0 x control) Hold infusion 1 hour, then decrease infusion rate by 3 U/kg/hour

IV = intravenous; UFH = unfractionated heparin; s = seconds; aPTT = activated partial thromboplastin time.

DVT Treatment Algorithm at the Cleveland Clinic, Florida

Inferior vena cava filter

Inferior vena cava filters are inserted to reduce the rate of pulmonary embolism. The indications for their use include:

anticoagulation. In the United Kingdom most vena cava filters are temporary and removed three weeks after the period during which the risk of embolisation is greatest. No consensus has been reached on whether patients with long term filters should receive long term treatment with anticoagulants or not.

Pulmonary embolism with contraindication to anticoagulation, and Recurrent pulmonary embolism despite adequate

Greenfield Vena Cava Filter

The Greenfield Filter is permanently implanted in the vena cava where it prevents pulmonary embolism by capturing blood clots (emboli) before they can be transported to the lung. When an embolus enters the cone-shaped Greenfield Filter, it is directed toward the center of the filter and trapped. The Greenfield Filter is designed to allow adequate blood flow around the captured clot. Over time, a natural process called clot lysis will dissolve the trapped embolus.

Implant the Greenfield Vena Cava Filter

specially designed system to place the filter. This system is introduced through either a vein in the groin or the neck and then guided to the vena cava. When releases the filter from the introducer system, the hooks at the base of the legs attach securely to the wall of the vena cava permanently implanting the filter.

Greenfield Filter cannot become clogged

In rare instances, the filter may trap an embolus large enough to obstruct the flow of blood through it. However, the Greenfield Filter is designed to provide blood flow even when almost entirely filled with clot. The continuous flow of blood helps the body's natural process of clot lysis dissolve the trapped clot. Leg swelling may indicate that an embolus has obstructed blood flow through the filter.

Management of the acute event of DVT

The standard approach to management is an initial course of heparin followed by secondary prophylaxis with warfarin. LMWH --> high bioavailability which means they can be administered subcutaneously once or twice daily, at a dose based on body weight. treatment with LMW heparin and warfarin simultaneously on day one. The heparin will have full anticoagulant activity within a few hours but the warfarin takes several days to achieve therapeutic effect. The heparin will have full anticoagulant activity within a few hours but the warfarin takes several days to achieve therapeutic effect. It is recommended that LMWH is continued for at least five days and should only be stopped when the warfarin has reached a therapeutic level for a period of at least 24 hours. Thrombolitic --> high risk of bleeding, just for massive limb threatening thrombosis (rapidly restore vessel patency)

Diagnosis
Venography remains the gold standard in the detection of DVT, but it is invasive, time consuming, and requires considerable operator experience to interpret adequately. The current standard of care is ultrasound; The sensitivity and specificity of Doppler ultrasound in detecting DVT in the lower extremities is greater than 95 percent.

Treatment
Anticoagulation

Limitations

of Anticoagulation

Therapy Catheter-Directed Thrombolysis

Anticoagulation
To

prevent thrombus propagation, decrease the risk of recurrent DVT, and prevent pulmonary emboli.

Limitations of Anticoagulation Therapy

Contrary to popular belief, heparin and warfarin therapy ---> do not actively dissolve thrombus. Veins have a limited capacity to break down clot naturally, and in patients with symptomatic DVT, anticoagulation alone cannot remove the offending thrombus, reduce limb swelling, or alleviate pain. Spontaneous thrombolysis of DVT after anticoagulation therapy will occur in fewer than 10 percent of patients, and 40 percent of patients will continue to propagate thrombus despite therapeutic levels of heparin. The usual consequence is transformation of the clot into fibrous web-like bands within the vein, valvular damage, and/or permanent vein occlusion, and development of symptoms of post-thrombotic syndrome.

Catheter-Directed Thrombolysis

an emerging treatment alternative for selected patients with extensive, symptomatic DVT. The procedure, which is performed in a hospital catheterization suite, is designed to rapidly remove the clot, restore flow within the vein, and potentially preserve valve function to minimize the risk of post-thrombotic syndrome. The interventional radiologist inserts a catheter into the popliteal or other leg vein and threads it into the vein containing the clot. The catheter tip is placed into the clot and urokinase is infused directly to the thrombus. The fresher the clot, the faster it dissolves usually in 1 to 2 days. Any narrowing in the vein that might lead to future clot formation can be identified by venography and treated with balloon angioplasty or stent placement. Clinical resolution of pain and swelling and restoration of blood flow in the vein is greater than 85 percent using the technique.8-10

Indications for catheter-directed thrombolysis

Indications for catheter-directed thrombolysis include patients with acute iliofemoral DVT, multi-level DVT (e.g., calf, popliteal, and femoral vein), or massive DVT (phlegmasia cerulea dolens). Optimal candidates are otherwise active, healthy patients with spontaneous DVT who seek therapy within 7 to 10 days from the onset of symptoms. DVT that is several weeks old typically does not dissolve easily with catheter-directed techniques since the soft clot has transformed into firm scar tissue. The most frequent minor complication of catheter-directed thrombolysis is hematoma at the site of catheter placement, which occurs in 5 percent of cases. The risk of a major lifethreatening complication (major bleed or pulmonary embolus) is less than 0.1 percent and routine placement of inferior vena cava filters during catheterdirected thrombolysis is not generally recommended.

Thank You Good Luck