Deep Vein Thrombosis 451.1 I80.9

• synonyms: deep vein thrombosis, pulmonary embolism, venous thromboembolic disease (VTD)
• DVT ICD-10:  I80.9 Phlebitis and thrombophlebitis of unspecified site;  See all Phlebitis ICD-10 codes
• ICD-9= 451.1 Phlebitis and thrombophlebitis, of deep vessels of lower extremity
• DVT most commonly occurs 2-6 weeks after after total hip or knee arthroplasty. Pulmonary events on the day of surgery are generally from fat embolism or cardiac events.
• Fatal PE rates of 1% to 3% of untreated patients undergoing joint replacement and asymptomatic PE rates of 10% to 15% have traditionally been sited. More recent reports suggest that the rate of Fatal PE is 0.1% to 0.2%. These rates may be unaffected by thromboprophylaxis. (Simon SR, Ortho Basic Science, 2nd p223)
• Fatal PE rate after primary TKA for patients who did not recieve prophylaxis, but did have short operative times and rapid mobilization = 0.1%, 1.1% for symptomatic DVT. (Warwick D, JBJS 1997;79A:780)
• Coagulation Cascade: Both Intrinsic and Extrinsic pathways lead to the formation of factor X which then leads to the eventual development of Fibrin.
• Intrinsic pathway: monitored by PTT, inhibited by heparin.
• Extrinsic pathway: monitored by PT, inhibited by warfain.
• The left iliofemoral vein passes below the front of the fifth lumbar vertebra and under the right common iliac artery where it can become thickened and stenosed leading to DVT. (Grande LA, Lancet 2009;373:1222)
• Most clinical venous thromboembolism events occur between 2 and 6 weeks after total joint surgery.

Unprotected DVT/PE Frequency Rates (Simon SR, Ortho Basic Science, 2nd p310)

Symptomatic DVT rate: 0.63% for knee arthroplasty and 0.26% for hip arthroplasty. Pulmonary embolism: 0.27% for knee arthroplasty and 0.14% for hip arthroplasty. Using current VTE prophylaxis, approximately 1 in 100 patients undergoing knee arthroplasty and approximately 1 in 200 patients undergoing hip arthroplasty develop symptomatic VTE prior to hospital discharge.  (Januel JM, JAMA 2012;307:294)

1.0% DVT/PE rate within 180-days after fractures distal to the knee.  Increased risks=oral contraception by patients eighteen to fifty years of age (hazard ratio [HR] = 5.23, previous DVT (HR = 6.27), previous PE (HR = 5.45), coagulopathy (HR = 2.47), and peripheral artery disease (HR = 2.34), increasing age, increasing body mass index, cancer, and treatment with nonsteroidal anti-inflammatory drugs have been associated with a increased risk of DVT/PE. (Liv Riisager Wahlsten, J Bone Joint Surg Am, 2015 97(6) 470-7)

DVT / PE Risk Factors

• History of DVT
• Immobilization
• Paralysis
• Obesity
• Malignancy
• Elderly
• Congestive Heart Failure / History of MI
• Pregnancy
• Estrogen use or hormone replacement therapy (Oral Contraceptives)
• Varicose Veins
• Smoking
• Virchow's Triad: venous stasis, hypercoagulability, intimal injury
• General Anesthesia (lower risk with epidural anesthesis)
• Blood transfusion
• Antithrombin III deficiency
• Protein C deficiency
• Protein S deficiency
• Factor V Leiden mutation.
• Myeloproliferative disease
• Activiated protein C reistance
• Bed rest / immobility > 5 days
• Fracture (pelvic, hip, femur, tibia)
• History of stroke
• Inflammatory bowel disease
• Multitrauma
• Major surgery

DVT Clincal Evaluation

• Pain and swelling in affected extremity, palpable cord. Tenderness, redness of discoloration of skin.
• Homan's sign = calf pain with forced ankle dorsiflexion.
• Physical exam specificity and sensitivity are <50%. ((Simon SR, Ortho Basic Science, 2nd p314)
• DVT is often asymptomatic

DVT Xray

• Venography: gold standard, invasive exposes patient to radiation.
• Duplex Ultrasound: non-invasive, technician and radiologist dependent.
• Doppler Ultrasound:
• Fibrinogen I 125 labeling and impedance plethysmography have low specificity and sensitivity and are generally no longer used.

DVT Differential Diagnosis

• Baker Cyst
• Cellulitis
• Gasctrocnemius Contusion
• Lymphedema
• Gasctocnemius Tear

DVT Prophylaxis

• All patients should be taught to actively dorsiflex and plantar flex the ankle and toes in sets of 20 every half hour while awake. Patients should be out of bed and ambulating ASAP. All patients should be out of bed and sitting in a chair for several hours at a time to encourage deep breathing and avoid recombency. Avoid prolonged immobility.
•  Risk of major bleeding is 0.3% for control, 0.4% for aspirin, 1.3% for warfarin, 1.8% for LMWH, and 2.6% for unfractionated heparin. (Salvati EA, Pelligrini VD Jr, Sharrock NE, et al: Recent advances in venous thromboembolic prophylaxis during and after total hip replacement. J Bone Joint Surg Am 2000;82:252-270.)
• No prophylactic agent has been associated with a significantly different risk for fatal PE. (Freedman KB, JBJS 2000;82A:929)
• DVT Prophylaxis recommendations: Patients without significant risk factors for DVT should be given aspirin, Ted hose and ICD's post-operatively and discharged on aspiring for 6weeks. Patients with risk factors (previous DVT/PE, postoperative ileus) should be begin with SQ LMWH (Enoxaparin 40mg SQ QD and then switched to oral warfin for 8weeks.
• Chronic Anticoaguation for cardiac indications: Enoxaparin 40mg SQ QD while in hospital resume Xarelto, pradaxa, eliquis POD#2.
• Prophylaxis options: Coumadin, LMWH, Aspirin
• Elevated DVT Risk Patients: hypercoagulable states(polycythemia, spinal cord injury, multitrauma), previous history of cancer, previous documented PE, genetic predisposition
• Elevated risk of Major Bleeding: history of bleeding disorder, recent GI bleed, recent hemorrhagic strock, known coagulation factor deficiency
• Patients with known bleeding disorders such as hemophilia (Factor VIII deficiency) and active liver disease generally treated with a pneumatic compression device alone to minimize risk for excessive bleeding and wound complications.
• Patients with known contraindications to anticoagulation should be considered for vena cava filter
• Recommedation 3.3.2: Elevated PE risk, standard major bleeding risk
  -LMWH starting 12-24 hrs postop (or after epidural catheter removal) for 7-12 days
  -Synthetic pentasaccharides starting 12-24 hrs postop (or after epidural catheter removal) for 7-12 days
  -Warfarin starting either night before or night after surgery for 2-6 weeks. INR goal<2.0
• Recommendation 3.3.3: Standard PE risk, elevated major bleeding risk
  -Examples=thrombocytopenia, bone marrow suppression, known hemophilia or other coagulation defects, recent radiation, chemotherapy
  -Consider hematology consultation. Correct clotting defect is possible using clotting factor, platelet or frozen plasma transfusion
  -Aspirin 325mg BID starting the day of surgery for 6 weeks
  -Warfarin starting either night before or night after surgery for 2-6 weeks. INR goal<2.0
• Recommendation 3.3.4: Elevated PE risk, elevated major bleeding risk
  -Aspirin 325mg BID starting the day of surgery for 6 weeks
  -Warfarin starting either night before or night after surgery for 2-6 weeks. INR goal<2.0

Home DVT prophylaxis / SCD Options

• JO Global VENAPRO
• ActiveCare Safe DVT prevention
• Thermotek VComp iPC DVT therapy device
• Covidien Kendall SCD 
• ArjoHuntleigh DVTCare at home
• Abrexis DVTmax-3000

DVT Classification / Treatment

• Treatment is indicated for all DVTs proximal to the knee. Treament for DVT below the knee is controversial. Distal clots have a 20% chance of propagation and should be followed with serial ultrasound (every 7-10 days for 3-4 weeks) if not treated.
• IV heparin or low-molecular-weight heparin followed by conversion to long-term warfarin (usually 3 months). INR goal = 2-3.
• Consider direct intraclot lacing of the thrombus with alteplase (maximum daily dose, 50 mg per leg per day; maximum of four treatments) and full systemic anticoagulation. (Chang R, Radiology 2008;246:619).
• Preoperative diagnosis of DVT in a patient with lower extremity/pelvic DVT: vena cava filter

PE Clinical Evaluation

• Dyspnea, pleuritic chest pain, tachypnea (90%), tachycardia (60%), rales, pyrexia hemoptysis, sweating, feeling of apprehension, hypotension.

PE Xray

• EKG: right-bundle branch block, right axis deviation, ST depression, T wave inversion in lead III. EKG changes occur in 25%, usually with large embolization.
• CXR: generally normal, may show hyperlucency, or enlarged hilar artery. Non-specific findings = pleural effusion, etatlectasis, elevated hemidiaphragm.
• ABG: Findings are nonspecific. PO2 < 60mmHg is highly suggestive of repiratory distress. Normal PO2 does not exclude PE.
• V/Q scan: most commonly used. Indeterminate scans must be followed with spiral CT/pulmonary angiography or duplex ultrasound.
• Pulmonary angiogram: Gold standard, invasion
• Spiral CT: 70% sensitivity, 88% specificity.

PE Classification / Treatment

• Continous IV heparin for 7-10 days, monitored by PTT(maintain between 60 and 80 sec). Convert to 3 months of oral warfarin (maintain INR at 3.0).
• Alternative treatment: LMWH
• Bleeding, expanding hematoma with anticoagulation.  Placement of a vena cava filter, halt anticoagulation, blood transfusion if required, consider exploration of hematoma/nerve palsy. 

Warfarin (Coumadin)

• Blocks hepatic enzymes (vitamin K epoxide, possilbly vitamin K reductase) leading to decreased carboxylation of vitamin K-dependent factors II, VII, IX, X.
• Fatal PE rate = 0.15%: 1%-5% risk for bleeding complications. (Brookenthal KR, J Arthroplasty 2001;16:293)
• Requires monitoring with PT (Prothrombin time)
• Contraindicated in patients with PUD, GERD, liver insufficiency, alcoholism, uncontrolled hypertension, pregnancy, patients on NSAIDS or history of bleeding disorders.
• The current recommended dosing protocol maintains INR at 1.8 to 2.5.
• Reversed with vitamin K or fresh frozen plasma.
• 1%-5% local or systemic bleeding incidence.
• Multiple drug reactions: rifampin, trimethoprim, cimetidine, phyentoin, cefamandole and phenobarbital are antagonists to warfarin.
• Increased gastric ulcer bleeding risk if used with NSAIDs

Low-Molecular Weight Heparin (LMWH)

• Enoxaparin (Lovenox), dalteparin
• Prevents binding of antithrombin to thrombin. Selectively tagets Factor Xa
• No monitoring needed.
• Use sparingly in patients with renal impairment (metabolized in the kidney)
• Generally considered to provide least rate of radiographically proven DVT, but does not reduce the rate of fatal PE compared to other methods and has significanlty higher bleeding complications, up to 12%.
• LMWH leads to increase in postsurgical bleeding and wound drainage and subsequent infection.
• Burnett RS, Clohisy JC, Wright RW, McDonald DJ, Shively RA, Givens SA, Barrack RL. Failure of the American College of Chest Physicians-1A protocol for lovenox in clinical outcomes for thromboembolic prophylaxis. J Arthroplasty. 2007 Apr;22(3):317-24.
• Novicoff WM, Brown TE, Cui Q, Mihalko WM, Slone HS, Saleh KJ. Mandated venous thromboembolism prophylaxis: possible adverse outcomes. J Arthroplasty. 2008 Sep;23(6 Suppl 1):15-9. doi: 
• Patel VP, Walsh M, Sehgal B, Preston C, DeWal H, Di Cesare PE. Factors associated with prolonged wound drainage after primary total hip and knee arthroplasty. J Bone Joint Surg Am. 2007 Jan;89(1):33-8.

Aspirin DVT Prophylaxis

• Dose:  Aspirin 81mg PO BID x 6 weeks.
• Consider Acid suppression with PPI for patients taking ASA and NSAID combination.
• Inhibits thromboxane-A2 synthesis by irreversibly inhibiting cyclooxygenase (COX)
  in platelets as well as megakaryocytes.
• Aspirin alone proximal DVT rate = 12-15%, fatal PE rate = 0.2%. (Freedman KB, JBJS 2000;82A:929)
• Fatal pulmonary embolism = 0.13 percent, nonfatal pulmonary embolism = 0.94 percent, DVT = 1.01. (Sarmiento A, JBJS 1999;81A:339)
• Contraindications: hypersensitivity to aspirin, previous DVT, chronic venous stasis, PUD, disorders affecting platelet function
• Dosage: aspirin suppository (600 milligrams) immediately after operation followed by 325 milligrams of aspirin twice a day until discharge. Should always be used with graded elastic stockings (Ted hose) and/or intermittent compression devices (Sarmiento A, JBJS 1999;81A:339)
• Generally continued for 6-8weeks post-operatively
• 0.66% rate of symptomatic DVT following TJA for patients treated with Aspirin.  Aspirin is effective with low complication rate.  (Mistry DA, Surg J 2017;3:e191-e196).

Heparin

• Binds antithrombin III causing a conformational change in its structure exposing its active site (arginine). This increases antithrombin IIIs affinity for clotting factors, namely thrombin and Xa, leading to decreased clot formation.
• Fixed low-dose heparin (5,000 U Q 8 to 12 hours) is ineffective in orthopeadic patients.
• Adjusted-dose heparin (maintain PTT of 31.5 - 36 sec) requires monitoring several times per day and frequent dose adustment with a significant rate of wound hematoma, up to 24%,
• Alternative anticoagulation methods with fewer bleeding complications are generally used.

Fondiparinux

• Direct factor Xa inhibitioin which inhibits fibrin formation
• associated with the highest bleeding complications. (Turpie AG, Lancet 2002;359:1721)
• Fondaparinux 2.5mg SQ QD starting the morning after surgery.
• Contraindicated in renal failure patients.

Intermittent Compression Devices

• Pulmonary Embolism 0.6%, DVT incidence = 4.6% (Hooker JA, JBJS 1999;81A:690)
• No risk of bleedig complications.

Vena Cava Filter

• Indications: recent symptomatic PE, known DVT, significant contraindication to anticoagulation.

References

• Johanson NA, JAAOS 2009;17:184

Rivoroxaban (Xarelto)

• oral, selctive Factor Xa inhibitor
• Approved for DVT prophylaxis for hip and knee replacement surgery
• 10mg PO daily: For 12 days after TKA; for 35 days after THA
• Contraindications: hypersensitivity to Xarelto, active major bleeding, spinal/epidural anestesia, renal impairment(CrCl<30mL/min), hepatic impairment