DEEP VENOUS THROMBOSIS A PRACTICAL APPROACH TO IMPROVING CLINICAL OUTCOMES

Transcription

1 DEEP VENOUS THROMBOSIS A PRACTICAL APPROACH TO IMPROVING CLINICAL OUTCOMES Jose M. Borromeo M.D. Vascular Surgeon Iowa Heart Center

2 Disclosures: AstraZeneca Pharmaceuticals Cook CVRx LeMaitre Vascular, Inc. Medtronic NIH Employer-Iowa Heart Center/Mercy-Des Moines

3 Outline Epidemiology Anatomy & Physiology Pathophysiology Risk Factors Natural History of DVT Complications of DVT Diagnosis Treatment Options Guidelines and treatment algorithms Endovascular and Surgical adjuncts to treatment Recommendations

4 Epidemiology and Clinical Significance Annually 900,000 cases of VTE in the US 275,000 new cases annually in the US It is estimated that 684,000 cases of DVT and 434,000 PE with 543,000 fatalities from VTE in the EU 1% incidence with 0.36% mortality in all hospitalized patients

5 ANATOMY The venous anatomy is highly variable compared to the arterial system Components 1. Superficial Veins 2. Deep Veins 3. Perforating Veins

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10 PHYSIOLOGY 60-70% of blood volume is found in the venous system 80% of this is found in vessels <200 microns in diameter Skeletal muscle related veins are responsive to catecholamines Pressures in the lower extremity venous system are largely determined by gravity and venous system integrity

11 PHYSIOLOGY Venous pressures are increased in the lower extremities Venous flow is pulsatile Valvular closure and integrity are important in blood transport cranially Calf muscle pump creates venous flow Most of the blood flows via the deep system Blood flows from the superficial to the deep veins

12 PATHOPHYSIOLOGY Abnormal functioning of the lower extremity veins results in venous insufficiency Venous insufficiency results from injury to vein walls and valves Tissue changes are a result of prolonged venous hypertension and stasis Inflammation, cellular and molecular modulators result in delayed vascular and cutaneous changes

13 PATHOPHYSIOLOGY OF DVT Virchow s Triad (1850) Stasis Vessel Wall Injury Hypercoagulability Stewart (1974) Thrombosis and inflammation Inflammatory mediators up-regulate procoagulant factors and inhibit fibrinolysis ( Selectins)

14 Pathophysiology of DVT Disturbance in the normal balance of hemostasis and thrombolysis Initial thrombus is composed of RBC and fibrin Subsequent increase in pro-inflammatory factors leading to fibrinolysis and vessel wall fibrosis Clinical effects due to venous obstruction and valvular reflux

15 Complications of DVT Early: Acute Pulmonary Embolism Late: Recurrent Venous thromboembolism (VTE) Post-thrombotic syndrome (PTS)

16 Thrombotic risk factors and Hypercoagulability Congenital Hypercoagulability Factor V Leiden Prothrombin G20210A Protein C Deficiency Protein S Deficiency Antithrombin Factor XI excess Acquired Hypercoagulability Advanced age Antiphospholipid antibodies Malignancy Situational Hypercoagulability Surgery Trauma Pregnancy Oral contraceptives Hormone therapy Adapted from Shalhub S, Meissner M, Therapy in Vascular and Endovascular Surgery, 5 th ed. P. 877.

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18 Natural History of DVT Proximal extension is variable Recanalization as a normal process of healing as early as 6-12 weeks of an acute event Greater recanalization is seen in patients who present with transient risk factors Prolonged recanalization is proportional to the degree of thrombus burden Greater recurrence of DVT inpatients with diminished recanalization

19 Natural History of DVT Calf veins are the most common site of origin, although 40% arise from the proximal veins In-hospital mortality rate is 5-12% 3 and 5 year mortality rates are 30 and 39% If untreated, 30-50% will develop PE, 10% of which are fatal Incidence of recurrent VTE with treatment is <5%

20 Natural History of DVT 20% of all first time VTE are associated with underlying malignancy 1 in 200 of patients with cancer will develop VTE Most recurrent VTE occurs after anticoagulants have been discontinued ( highest 6 t0 12 after the index event) Cumulative recurrence rates as high as 23%

21 Risk of recurrence is related to the underlying thrombotic risk factors Unprovoked DVT carries a threefold risk of recurrence compared to those with transient risk factors Calf vein DVT have a 23% risk of proximal extension

22 Pulmonary Embolism (PE) Most serious early complication of acute DVT Can occur in up to 50-80% of symptomatic DVT patients Can occur in 7-17% of patients presenting with acute upper extremity DVT Can occur in up to 10% of patients with calf vein DVT ( risk less than 2% for fatal PE)

23 Risk of recurrence of VTE VTE provoked by surgery, 3% at 5 years VTE provoked by transient nonsurgical risk factor, 15% at 5 years Unprovoked VTE not related to cancer, 30% recurrence at 5 years VTE associated with cancer, 15% annual risk of recurrence Distal DVT, ½ risk than after a proximal DVT Second unprovoked DVT/PE, 50% higher

24 Post-thombotic syndrome(pts) Long-term sequelae of LE VTE 29-79% of patients present with some degree of PTS 7-23% have severe manifestations 4-6% develop ulceration Patients who present with recurrent VTE have 6-fold increased incidence of PTS Result from venous hypertension- proximal obstruction and distal reflux

25 Post-Thrombotic Syndrome(PTS)

26 Diagnosis and Clinical Presentation of Acute DVT Calf pain Calf swelling Calf and leg tenderness Prominent superficial veins Pain with foot dorsiflexion (Homan s sign) *Up to 70% of patients with Sx consistent with DVT will not have it, and up to 50% of patients with DVT may lack any specific signs and symptoms

27 Diagnosis and Clinical presentation Variable, ranging from asymptomatic to massive swelling/pitting edema Diagnosis based on clinical probability complemented by objective testing Advanced venous compromise: phlegmasia alba dolens, phlegmasia cerulea dolens

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29 Differential Diagosis Muscle strain, tear, or twisting injury to the leg 40 percent Leg swelling in a paralyzed limb 9 percent Lymphangitis or lymph obstruction 7 percent Venous insufficiency (reflux) 7 percent Baker's cyst 5 percent Cellulitis 3 percent Knee abnormality 2 percent Unknown 26 percent Hull R, Hirsh J, Circulation, :622.

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31 Diagnosis Signs and symptoms are nonspecific and of varying specificities Requires confirmatory testing that is resource intensive Duplex ultrasound as the primary diagnostic modality D-Dimer is useful but specificity depends highly on the clinical probability of disease Best strategy incorporates clinical, D-dimer and selective ultrasound evaluation

32 Diagnostic Testing Duplex ultrasound D-Dimer CT venography MR Venography Contrast Venography Impedance plethysmography Isotope Scintigraphy

33 Diagnosis: Compression Ultrasound

34 D-Dimer Products of degradation of cross-linked fibrin by plasmin Reflect the presence of intravascular fibrin, sensitive for thromboembolism Low sensitivity (35%): Elevations seen in DIC, malignancy, post-op states, infection, trauma and pre-eclampsia and with high bilirubin levels Most useful in patients with low pre-test probability of disease and negative result

35 Lohr J and Griffith NM, Rutherford s Vascular Surgery, 7 th ed. p.764

36 Lohr J and Griffith NM. Rutherford s Vascular Surgery, 7 th ed. p. 768.

37 Treatment Extremity elevation- short term Immediate anticoagulation Early Mobilization Compression therapy Limited use of IVC Filter Selective thrombolysis and catheter based interventions

38 Anticoagulation Unfractionated Heparin (UFH) Low Molecular weight heparins (LMWH) Fondaparinux Vitamin K antagonists Direct thrombin inhibitors ( IV Lepirudin, Bivalrudin) Apixaban Rivaroxaban Edoxaban Dabigatran Thrombolysis

39 ACCP Guidelines: Antithrombotic Therapy for VTE Disease (Chest Feb 2012, updated Nov 2015) Shorter duration of initial therapy Role of time-limited and Extended Therapy Recommendations for VTE and malignancy Updates with NOACs Limited role for IVC filters Recommendations for systemic lysis Recommendations for catheter based therapy

40 Duration of therapy is patient specific Careful risk factor assessment Strong need to evaluate individual patient risks of anticoagulant therapy (HAS BLED) Extended therapy for unprovoked VTE Extended therapy for cancer patients Recommendations for VKA and LMWH and NOACs ( increasing role of new agents)

41 ACCP Guidelines: Antithrombotic Therapy for VTE Disease (Chest Feb 2012, updated Nov 2015 Patients with proximal DVT/PE are treated with long-term (3 months) of anticoagulation In absence of cancer, NOACs are suggested over VKA ( and VKA over LMWH) In patients with cancer-associated thrombosis, LMWH is suggested over VKA or NOACs If extended therapy is planned, there is no need to change agent after 3 months

42 ACCP Guidelines: Antithrombotic Therapy for VTE Disease (Chest Feb 2012, updated Nov 2015 In patients with proximal DVT/PE provoked by surgery or by nonsurgical transient risk factor, 3 month treatment is recommended. In patients with distal DVT provoked by surgery, 3 month treatment is recommended Patients with UNPROVOKED DVT ( isolated distal or proximal or PE), treatment for AT LEAST 3 months is recommended

43 ACCP Guidelines: Antithrombotic Therapy for VTE Disease (Chest Feb 2012, updated Nov 2015 In patients with 1 st episode of UNPROVOKED proximal DVT/PE, with low to moderate bleeding risk, EXTENDED THERAPY ( no stop date) is suggested. In patients with high risk of bleeding, 3 month over extended therapy is recommended. Patients with 2 nd UNPROVOKED VTE with low to moderate bleeding risk, EXTENDED Tx. Those with high bleeding risk, 3 month treatment only is recommended.

44 ACCP Guidelines: Antithrombotic Therapy for VTE Disease (Chest Feb 2012, updated Nov 2015 Patients with DVT/PE and cancer, EXTENDED anticoagulation is recommended. ( This is still suggested in high bleeding risk individuals) Patients stopping anticoagulant therapy and without contraindication to ASA, ASA is suggested.

45 ACCP Guidelines: Antithrombotic Therapy for VTE Disease (Chest Feb 2012, updated Nov 2015 Patients with distal (calf vein) DVT without severe symptoms or risk for extension, serial imaging for 2 weeks is suggested over anticoagulation. *Pts with high bleeding risk will benefit from serial imaging *Anticoagulation is suggested if patients have severe symptoms, ongoing risk factors for extension or if extension is demonstrated on serial imaging)

46 ACCP Guidelines: Antithrombotic Therapy for VTE Disease (Chest Feb 2012, updated Nov 2015 In patients with acute proximal DVT, they suggest anticoagulant therapy alone over catheter directed thrombolysis. Patients with acute DVT/PE treated with anticoagulants, they recommend against the use of an IVC filter. *Patients who are most likely to benefit from CDT who attach a high value to preventing PTS and lower value to complexity, cost and risk of bleeding with CDT are likely to choose CDT over anticoagulation alone.

47 ACCP Guidelines: Antithrombotic Therapy for VTE Disease (Chest Feb 2012, updated Nov 2015 Suggest not using compression stockings routinely to prevent PTS. (In patients with acute or chronic symptoms, a trial of compression is justified) In patients with subsegmental PE and no proximal DVT and low risk for recurrent VTE, they suggest clinical surveillance over anticoagulation. (Anticoagulation is suggested in patients with high risk for recurrent VTE)

48 ACCP Guidelines: Antithrombotic Therapy for VTE Disease (Chest Feb 2012, updated Nov 2015 In patients with acute PE associated with hypotension without a high bleeding risk, systemic (rather than CDT) is suggested. In patients with high bleeding risk, or failed systemic lysis with shock likely to cause death, catheter assisted thrombus removal is suggested if resources are available.

49 ACCP Guidelines: Antithrombotic Therapy for VTE Disease (Chest Feb 2012, updated Nov 2015 Patients with recurrent VTE while on VKA or NOAC, they suggest switching to LMWH at least temporarily. For recurrent VTE while on LMWH, they suggest increasing the dose by ¼ to 1/3.

50 ACCP Guidelines: Antithrombotic Therapy for VTE Disease (Chest Feb 2012, updated Nov 2015 VTE patients who are most likely to benefit from CDT Iliofemoral DVT Symptoms less than 14 days Good functional status Life expectancy greater than 1 year Low risk of bleeding Impending venous related gangrene

51 Table 15: Risk factors for bleeding with, and contraindications to use of thrombolytic therapy (both systemically and locally administered Major Contraindications Structural intracranial disease Previous intracranial hemorrhage Ischemic stroke within 3 months Active bleeding Recent brain or spine surgery Recent head trauma with fracture or brain injury Bleeding diathesis Relative indications Systolic BP>180 Diastolic BP>110 Female Recent bleeding Recent surgery Low BMI Recent invasive procedure Ischemic stroke >3 months Race Ongoing anticoagulation Traumatic CPR Pericarditis/Pericardial fluid DM retinopathy Pregnancy Age > 75 CHEST Guidelines, November 2015.

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53 Table 11: Risk factors for bleeding with anticoagulant therapy and estimated risk of bleeding Risk Factors Age > 65 Age > 75 Previous bleeding Cancer Metastatic Cancer Renal failure Liver failure Thrombocytopenia Prior stroke Diabetes Anemia Antiplatelet therapy Poor anticoagulant control Recent surgery Frequent falls Alcohol abuse NSAID use Comorbidity & reduced functional capacity Categorization of Risk of Bleeding Low Moderate High 0-3 months 1.6% 3.2% 12.8% > 3 months 0.8%/yr 1.6%/yr >6.5%/yr CHEST Guideline, November 2015.

54 Rationale for Catheter Directed Therapy (CDT) Iliofemoral DVT have greater risk of PTS Large thrombus burden is associated with higher degree of obstruction and vessel wall and valvular injury Lysis requires clot penetration and increased surface area for plasminogen activation Plasminogen in circulation is easily inactivated by alpha 2 macroglobulin and antiplasmin Allows for direct thrombus action and decreased dose of agent needed

55 Catheter Directed Therapy National Venous Registry (Mewissen): 83% resulted in complete lysis of thrombus, and 90% patency and complete lysis at 1 year, with 5-10% bleeding risk Improvements in dosage and technique Adjunctive pharmaco-mechanical therapy

56 Pharmaco-mechanical Therapy (PMT) Comerota ( 2000, 2009) : Improved QOL at 16 and 22 months with CDT/PMT for IFDVT Significant decrease in CEAP class at 12 months Low recurrence rate ( 9% at 35 months) Recurrence was related to degree of lysis (5% in those with <50% residual thrombus and 38% with > 50% residual thrombus)

57 Catheter Directed Therapy with PMT

58 Catheter Directed Therapy with PMT

59 Catheter Directed Therapy with PMT

60 Venous Compression :May-Thurners Syndrome Iliofemoral DVT resulting from anatomic compression of the left iliac vein by the overlying right common iliac artery 37-61% risk of edema or DVT

61 Courtesy of Z KRAJCER, MD, and SR ATMAKURI, MD

62 Upper Extremity DVT Accounts for 1-4% of all DVTs in the absence of central venous catheters CVCs increase incidence of DVTs by 2-16% 24% of UE DVTs are spontaneous and related to thoracic outlet compression, often in young healthy individuals PTS can occur in 7-46% of patients and is associated with increased functional disability and decreased QOL

63 Axillo-subclavian DVT (Paget-Schroetter syndrome)

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65 Management of Paget-Schroetters syndrome

66 Management of Paget-Schroetters syndrome

67 IVC Filter Indicated for DVT/PE where there is a contraindication to anticoagulation Relative indications for failure of anticoagulation, or in cases of recurrent VTE in patients with severe cardiopulmonary compromise Trend towards limited/ highly selective use of IVC filters

68 Aburhama A. The Vein Book. Ed. Bergan J. p.426

69 IVC and renal vein thrombosis

70 IVC and Renal vein thrombosis

71 Surgical Thrombectomy Indicated when catheter based techniques and lytic therapy have failed or are contraindicated in the setting of impending venous gangrene and limb loss Adjunctive arterio-venous fistula and fasciotomy as indicated

72 Conclusions Understanding of venous anatomy and physiology is essential for treatment Appropriate clinical diagnosis based on presentation, clinical probability and confirmatory testing Anticoagulation remains the mainstay of therapy

73 CHEST Guidelines: ú 3 month duration of anticoagulation with preference for NOACs over VKA ú Extended ( no stop date) anticoagulation for unprovoked VTE in patients without high risk for bleeding ú LMWH preferred for cancer-related thrombosis ú Need for regular re-assessment of risks of anticoagulation : INDIVIDUALIZED

74 Conclusion Catheter directed therapy has a role in selected individuals with extensive proximal DVT ( iliofemoral and axillo-subclavian DVT) When used selectively, adjunctive therapies have been shown to improve outcomes and QOL

75 Thank You Thank You