DVT PROPHYLAXISDVT PROPHYLAXIS

Dr. Ranjith R Thampi CRRIDepartment of Obstetrics and Gynaecology

Background

It is a common, yet preventable perioperative complication.

Highest risk in critical care and spinal cord injury patients- 60-80%

Post- Ortho Procedures: 40-60%

Post-General Surgery/ Obstetric- 15-40%

Variable for Urologic Cases

Incidence

• Incidence of Thrombophlebitis in Antepartum period is 2/1000 pregnancies; of which, Majority(Superficial) is 1.7/1000 pregnancies and DVT is 3.6/1000 pregnancies

• In Postpartum period, incidence of superficial thrombophlebitis increases by 7 times(12/1000) and that of DVT by 4-5 times(15/1000)

• Thromboembolic complications in pregnancy occur in 2-5/1000 deliveries, where clinical presentation of DVT is found in 0.5-0.7% and PE is found in 0.3%-1.2%.

Sites for DVT

Ileo-femoral veins (80% cases)

Popliteal veins Calf veins(extending

proximally in 30% cases)

Inferior Vena Cava(rarely)

Pathogenesis

• Physiologic changes during pregnancy predispose to DVT with a 6-fold increase from non-pregnant state, due to Virchow’s triad, i.e.,- Venous Stasis- Altered Blood Coagulability- Vascular damage

*InfectionAll concert together in promoting DVT in low flow areas.

Risk Factors

Risk Factors

THE COAGULATION

CASCADE

Coagulation mechanism

INTRINSIC PATHWAY

XIIXIIa

XIXIa

IXIXa

X Xa

PROTHROMBIN THROMBIN

VVa

FIBRINOGEN FIBRIN

VIIIa VIII

EXTRINSIC PATHWAY

XIIXIIa

XIXIa

IXIXa

X Xa

PROTHROMBIN THROMBIN

VVa

FIBRINOGEN FIBRIN

VIIIa VIII

VIIVIIa

Tissue Factor from damaged endothelium

Anticoagulants and Thrombolytics

XIIXIIa

XIXIa

IXIXa

X Xa

PROTHROMBIN THROMBIN

VVa

FIBRINOGEN FIBRIN

VIIIa VIII

VIIVIIa

Tissue Factor from damaged endothelium

Degradation

PlasminPLASMINOGEN

FACT(Researched)

– Type A blood is associated with lower levels of antithrombin III and higher levels of factor VIII than type O blood.

– Women of reproductive age with type A blood are 4 times as likely to develop DVT.

– This association of risk with blood type A does not extend to older men or to women past reproductive age

• Tenderness occurs in 75% confined to the calf muscles or over the course of the deep veins in the thigh.

• Warmth or erythema of skin can be present over the area of thrombosis.

• Clinical signs and symptoms of pulmonary embolism as the primary manifestation occur in 10% of patients with confirmed DVT.

• The pain and tenderness associated with DVT does not usually correlate with the size, location, or extent of the thrombus

Clinical Features

• Many patients are asymptomatic

• Pedal Edema, principally unilateral, is the most specific symptom

• Leg pain (50%, )

• Pain can occur on dorsiflexion of the foot (Homans sign).

Clinical Features

Signs of DVT

• Tenderness• Warmth or erythema of skin Can be present • Clinical signs and symptoms of pulmonary

embolism as the primary manifestation occur in 10% of patients with confirmed DVT

• Moses’ sign- tenderness elicited by squeezing or pressing firmly on sole of foot or calf

Phlegmasia cerulea dolens

Patients may have variable discoloration of the lower extremity.

The most common abnormal hue is reddish purple from venous engorgement and obstruction.

In rare cases, the leg is cyanotic frommassive ileofemoral venousobstruction. This ischemic form of venous occlusion was originally described as phlegmasia cerulea dolens or painful blue inflammation.

The leg is usually markedly edematous, painful, and cyanotic. Petechiae are often present

Differential Diagnosis

• Abcesses

• Baker’s cyst

• Cellulitis

• Musculoskeletal Injury

• Venous stasis

INVESTIGATIONS

• D-dimer

• Contrast Venography

• Duplex ultrasonography

• Impedance plethysmography

• MRI

• Nuclear Medicine Imaging Studies

D-dimer

Recent interest has focussed on the use of D-dimer in the diagnostic approach to Deep Vein Thrombosis

D-dimer has high sensitivity but low specificity

D-Dimer levels remain elevated in DVT for about 7 days.

Venous Thromboembolism suspected

Contrast Venography

For many reasons, including allergic

reactions, contrast-induced Deep Vein Thrombosis noninvasive studies have essentially replaced venography as the initial diagnostic test of choice.

Duplex ultrasonography

Sensitivity of duplex ultrasonography for proximal vein Deep Vein Thrombosis is 97% but only 73% for calf vein Deep Vein Thrombosis.

Impedance Plethysmography

Plethysmography is derived from the Greek word meaning "to increase."

This procedure is based on recording changes in blood volume of an extremity, which are directly related to venous outflow.

MRI

• MRI is the diagnostic test of choice for suspected iliac vein or inferior vena caval thrombosis.

• In suspected calf vein thrombosis, MRI is more sensitive than any other noninvasive study.

Nuclear ImagingNuclear medicine studies with I125-labeled fibrinogen are

not recommended now. Radioactive isotope incorporates into a growing thrombus, this test can distinguish new clot from an old clot

Management: All Patients

• Avoid dehydration unless there is a specific clinical reason.

• Encourage early mobilisation.• Aspirin or antiplatelet agents should not be considered

adequate prophylaxis.• Consider temporary IVC filters for patients at a very high

risk of VTE (eg active malignancy or previous VTE event) if there are contra-indications to pharmacological and mechanical prophylaxis. These are devices which can be inserted into the inferior vena cava to prevent the development of a pulmonary embolus.

Choice of prophylaxis:Mechanical

Several methods are available:•Graduated compression stockings are effective in decreasing the risk of DVT, either alone or in combination with pharmacological prophylaxis in high-risk patients. Thigh-length graduated compression/anti-embolism stockings can be used unless contra-indicated (eg in patients with established peripheral arterial disease or diabetic neuropathy). They should be used routinely for surgical inpatients. If thigh-length stockings are not appropriate (for reasons of fit or compliance) knee-length stockings may be used instead.•Stocking compression profile should be equivalent to the Sigel profile (a pressure profile for elastic stockings) and approximately: 18 mm Hg at the ankle 14 mm Hg at the mid-calf 8 mm Hg at the upper thigh•Staff trained in the use of compression stockings should show the patient how to wear them correctly, monitor their use and provide assistance when needed.•Patients should be encouraged to wear stockings from admission until they return to their normal level of mobility.•Intermittent pneumatic compression or foot impulse devices may be used instead of, or as well as, graduated compression stockings while patients are in hospital.

Choice of prophylaxis:Pharmacological

Choice depends on co-morbidities (e.g renal failure), a patient's wishes and local policies. Options include:

Anticoagulants, Both oral and parenteral.Oral- WarfarinParenteral: UFH LMWH Pentasaccharide(Fondaparinux)

Two new agents, dabigatran and rivaroxaban, have recently been licensed for use in orthopaedic thromboprophylaxis.

-Patients with high risk and those having orthopaedic surgery should be offered LMWH. Fondaparinux is an effective and safe alternative.

-Consideration should be given to the risks and benefits of stopping pre-existing anticoagulation or antiplatelet therapy before surgery.

-Pharmacological prophylaxis may need to be stopped if regional anaesthesia is employed to minimise the risk of haematoma (the timing depending on the type of anticoagulant and the type of procedure)

Oral Anticoagulant- Warfarin

Dose- starts from 5 mg PO daily. Acts by inhibiting Vit. K reductase enzyme, thereby

depleting Vit. K-dependent clotting factors II, VII, IX and X.

Good oral absorption but requires 4-5 days to achieve full anticoagulant effect

Combine with parenteral till INR reaches atleast 2.0 Monitor INR twice weekly for first 2 weeks, then

weekly for 2 weeks, then less frequently.

Recommended INR?

Recommended INR for various indications are as follows-

Prophylaxis of DVT 2 - 2.5Treatment of DVT 2 - 3Recurrent VTE, MI, prosthetic heart valve

disease 3 - 3.5

Parenteral- UFH

Derived from porcine intestinal mucosa Promotes Anti-Thrombin mechanism and

inactivates Thrombin and Factor Xa DVT Prophylaxis dose

5,000 U SC Q8-12H aPTT monitoring not neededTherapeutic Dosingi/v Bolus (80U/Kg) + i/v continuous infusion (18U/Kg/hr)

Safe in patients with Renal Dysfunction

Parenteral- LMWHENOXAPARIN, TINZAPARIN, DALTEPARIN

Produced by chemical or enzymatic cleavage of UFH Inactivates factor Xa to a greater extent than Thrombin. Minimally prolongs the aPTT Factor Xa monitoring is required in Renal dysfunction,

Obesity and Pregnancy DVT Prophylaxis dose

Enoxaparin 40 mg SC once daily for 8-12days Drug of choice in pregnant women requiring longterm

anticoagulation for thrombosis and in those with mechanical heart valves

Parenteral- LMWH

• ENOXAPARIN1 mg/Kg SC Q12H

• TINZAPARIN175 IU/Kg SC daily

• DALTEPARIN200 IU/Kg SC daily

Drug of choice in cancer patients and in those with failed oral anticoagulation.

• The dose and frequency is controlled by aPTT measurement which is kept at 50-80 sec or 1.5-2.5 times the patient’s pretreatment value. If this test is not available whole blood clotting time should be measured and kept at 2 times the normal value.

• After a constant maintenance infusion of 18 U/kg is initiated, the aPTT is checked 6 hours after the bolus and adjusted accordingly. .

• The aPTT is repeated every 6 hours until 2 successive aPTTs are therapeutic. Thereafter, the aPTT is monitored every 24 hours as well as the hematocrit and platelet count.

Parenteral- FONDAPARINUX

• Synthetic pentasaccharide structurally similar to Heparin

• Selective Factor Xa Inhibitor

• Monitoring of factor Xa levels similar to LMWH (renal dysfunction)

• Dosing FONDAPARINUX 7.5 mg SC daily

VIIa

Xa

IXa

XIa

XIIa

Selective Indirect Factor Xa inhibition Tissue

factor

AntithrombinFondaparinux

Fibrinogen Fibrin clot

Factor II(prothrombin)

×

Indications of warfarin

1. Prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism.

2. Prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement.

3. To reduced the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.

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)

Heparin Side Effects

• Bleeding• Osteoporosis

(inhibits osteoblasts, activates osteoclasts)– > 3 mths, > 20,000 units qd

• Thrombocytopenia• Type I HIT• Type II HIT (3-5%)

• Skins lesions- urticaria, papules, necrosis• Hypoaldosteronism, hyperkalemia

Heparin Contraindications

• Bleeding disorders, HIT.• Severe hypertension, threatened abortion,

piles• SABE, large malignancies, Tuberculosis’• Ocular and neurosurgery, LP• Chronic alcoholics, cirrhosis, renal failure

BUT…What if treatment with anti-BUT…What if treatment with anti-coagulant is contraindicated???coagulant is contraindicated???

IVC filter.

These pulmonary emboli removed at autopsy look like casts of the

deep veins of the leg where they

originated.

Pre-pregnancy counselling and a management plan should be offered to all women who are at high risk of VTE. All pregnant women should have their risk factors assessed and documented.

This assessment should be repeated if there is a hospital admission for any reason or if complications develop. Thrombophilia should be excluded in women with a previous non oestrogen-related VTE which has been provoked by a minor risk factor.

Prophylaxis should begin as soon as possible in pregnancy.

LMWH is the prophylaxis of choice, being safer and equally effective as UFH.

Any woman with three or more persistent or recurrent risk factors identified should be considered for antenatal prophylaxis.

LMWH should not be given routinely to women who have had one previous VTE event providing this is non oestrogen-related and they have no other risk factors but they should be monitored closely.

VTE & Pregnancy

VTE & Pregnancy

Women should be offered prophylaxis antenatally if: They have a history of recurrent DVTAn unprovoked, oestrogen-related or pregnancy-related VTEA previous VTE and a first-degree relative with a history of DVT or proven diagnosis of thrombophiliaWomen with asymptomatic inherited or acquired thrombophilia should be monitored closely antenatally but should be referred to a local expert if: They have antithrombin deficiencyThe have more than one thrombophilic defect (including homozygosity for factor V Leiden)They have additional risk factors

Women given LMWH should not have any more LMWH injections if they have vaginal bleeding or go into labour.

Mobilisation should be encouraged during and after labourFluid intake should be encouragedWomen with two or more risk-persisting risk factors should be considered for LMWH for 7 days postnatally.Women with three or more such factors should be given graduated compression stockings as well as LMWHWomen with BMI>40kg/m2 should be considered for LMWH prophylaxis for 7 days postnatally

The decision to initiate LMWH at the time of discharge for women who have had emergency or elective LSCS and duration of treatment will depend on what risk factors are present (age, weight, co-morbidities, family history of thrombophilia)

After delivery

After delivery

Women who have had a VTE before the current pregnancy should be considered for LMWH for six weeks postnatally. If they are receiving LMWH before pregnancy, preventive doses of LMWH should be given until 6 weeks postpartum. A postnatal risk assessment should then be made. Patients on long-term warfarin can recommence this when the risk of haemorrhage is lowBreast-feeding is no contra-indication to either warfarin or LMWH

Repeated risk assessments for VTE should be carried out if women develop intercurrent problems, or they require surgery or readmission for any reason in the puerperium

For women with additional risk factors lasting >7 days postpartum – eg: wound infection, prolonged admission - thromboprophylaxis should be continued for up to six weeks or until the risk factors have resolved