Management of Iliac and Femoral Thrombosis. Adam Lackey UCH Surgery Grand Rounds November 13, 2006

Transcription

1 Management of Iliac and Femoral Thrombosis Adam Lackey UCH Surgery Grand Rounds November 13, 2006

2 Overview Definitions/Anatomy Pathogenesis Prevalence Diagnosis Treatment/Prevention

3 Definitions/Anatomy Deep venous system composed of Femoral, Profunda Femoris, Popliteal, Tibial Peroneal veins. Superficial system composed of Greater Saphenous, pudendal, Smaller and Accessory Saphenous veins. Deep Venous Thrombosis is an disease consisting of thrombosis of any of the deeper system. -1

4 Definitions/Anatomy

5 Pathenogenesis Virchow s famous triad, first advanced in 1856 still applies: -2

6 Prevalence Depends on particular cohort of patient Predisposition (hypercoagulability) Previous clots (endothelial injury, stasis from from abnormality) Type of surgery (hypercoagulability, stasis) Diagnosis (hypercoagulabiliy)

7 Prevalence -3

8 Prevalence In one prospective case study of 212 patients with symptomatic VTE disease in 2003, 11% had thrombus restricted to the femoral territory, 67% had thrombus extending into the iliac veins. A surprising 22% had thrombus noted in the IVC at the time of diagnosis. There was no correlation between extent of DVT and rate of PE (50% for femoral, 51% for iliac, 42% for IVC involvement). -12

9 Diagnosis There is a dangerous form of venous thrombosis, uncommon enough to make it s study difficult, yet so often fatal as to make it s recognition a matter of importance.in it s early stages, it usually recognizable and probably curable -8

10 Diagnosis/Clinical The diagnosis of DVT requires, to use an overused phrase, a high index of suspicion. -1 Clinical symptoms are noted in only 40% of patients with DVT

11 Diagnosis/Clinical Sometimes.it s just that easy

12 Diagnosis/Clinical Phlegmasia alba dolens: swollen leg, pitting edema, pain, blanching Phlegmasia cerulea dolens: massively swollen leg, edema, pain, bluish discoloration Homans sign: Dorsiflexion of foot causes pain behind the calf. Potentially causes embolism. Postthrombotic syndrome: affects % of patients with a history of DVT; characterized by pain on standing, dependent edema, induration of tissues, pruritus, ulcers.

13 Diagnosis/Clinical Well s Criteria: recent meta-analysis showed across 15 studies showed an overall negative predictive value of 96%.-6 D-dimer is usually used to bolster the Well s criteria, unfortunately, this is frequently elevated in post-surgical patients.

14 Diagnosis/Imaging Duplex ultrasound: evaluates compressability of venous system. Doppler flows can show absence of flow around a clot prospective study showed, using a focused exam, surgeons can detect DVT with 90% specificity, 99.6% sensitivity, 99.3% accuracy. -7

15 Diagnosis/Imaging Overall, ultrasound seems to have a sensitivity of 89% (95% CI 85-92), specificity of 94% (95% CI 90-98), PPV of 94% (95% CI 90-97). -11

16 Treatment/Prevention The easiest way to treat iliofemoral thrombosis is to prevent it review showed of 1907 high risk patients, only 75.2% received any DVT prophylaxis. On 50.3% received Grade A recommended prophylaxis. -9

17 Treatment/Prevention Treatment Compression stockings Pneumatic compression devices Heparin and LMWH IVC filters

18 Treatment/Prevention Graduated Compression Stockings Reduce venous cross section, which Increases venous blood flow Reduces distension of veins, in turn reducing damage to vein wall and exposure to TF Improves coaptation of vein valve cusps Reduces post-thrombotic syndrome

19 Treatment/Prevention Caution should be used: improperly applied stockings can cause pressure sores. Knee high stockings appear to be as effective as thigh-high, with less complications of misuse meta-analysis showed relative risk reduction of 64% (end point: DVT) over 1505 patients simply by applying compression stockings. -10

20 Treatment/Prevention

21 Treatment/Prevention SCDs/IPCs/Venodynes Increase venous outflow from lower ext? Of activation of fibrinolytic system, not confirmed by studies as of yet. Over 5 trials, 613 patients, Odds ratio is 0.43, 95% CI , P<

22 Treatment/Prevention Heparin Meta analysis of 12 trials with 3352 patients treated with low dose heparin showed overall incidence of above knee DVT was 1.4% vs 6.4% for treated and controls. Dosing was 5000U SC 2 hrs prior to OR and BID/TID until discharge. No significant differences in hemorrhagic complications except wound hematomas (6.3% vs 4.1%) --23

23 Treatment/Prevention From Ting et al, Ref #2. Also consistent with ACCP 7 th Annual Conference on Antithrombic and Thrombolytic Therapy.

24 Treatment/Prevention Special consideration: Trauma Immobile, significant venous injury, hypercoagulable. Unfortunately, also frequently with contraindications to anticoagulation. Without prophylaxis, DVT risk exceeds 50%, PE is a significant cause of death in this population.

25 Treatment/Prevention 2004 prospective, uncontrolled study of 94 patients with multiple trauma had IVCF placed by surgeon. 96.8% had uncomplicated placement of filter No PEs were diagnosed while filters were in place (one diagnosed after filter removed) Authors noted that placement of filters had high efficacy to protect against PE, low complication rate, and further delineation of indications is warranted.

26 Treatment Bedrest vs mobilization Anticoagulation vs no anticoagulation Duration of anticoagulation Heparin vs LMWH Coumadin vs LMWH Thrombectomy Fibrinolytics IVC filter

27 Treatment/Bedrest vs early mobilization Theory: mobilizing patients with DVT increases likelyhood of clots breaking off and causing PE German RCT study with 122 patients Bed rest for 8-10 days vs early mobilization on day 2 SPECT lung imaging on days 2 and % of bed rest group had PE on baseline scan vs 62% early ambulation group 17% of bed rest group had new PE on late scan vs 22% of the early ambulation group P=0.250, no statistical difference. The only clinically evident PE was in the bedrest group. -13

28 Treatment/Bedrest vs early mobilization 2001 RCT study of 129 patients with DVT showed clinically silent PEs in 66 (51.2%), 53% in the immobile group and 44.9% in the ambulating group. Follow up V/Q scan at 4 days showed 6 new perfusion defects in the immobile group vs 10 in the ambulating group, between group difference was 4.4% and not significant (95% confidence interval of %). At 3 month follow up, one patient from each group died of PE. Also noted was no significant difference between rates of free floating thrombus (17% in the ambulating group vs 12% in the bed rest group) -14

29 Treatment/Heparin Only one completely controlled study of heparinization in VTE 1960 article looked at patients with known PE (and therefore DVT of some type) Of 35 patients, 19 received no anticoagulation. Over 1 yr, 5 of these patients died, all from PEs. An additional 5 had recurrent symptomatic PEs. There were no PE related deaths in the treated group, and no recurrent PEs. P= for fatal PEs and p= for all recurrent symptomatic VTE events. The remainder of the study was canceled and redesigned at that point. -20

30 Treatment/Duration of heparinization 1990 RCT of 199 patients randomized to two groups: 5 day course of heparin vs 10 day course of heparin, followed by 3 months of oral coumadin for both groups. -16 No significant difference between rates of symptomatic new VTE (7% in the 10d vs 7.1% in the 5d) Bleeding complications were observed in 12% of the 10d and 9.1% of the 5d groups, not significant.

31 Treatment/Unfractionated Heparin vs LMWH 2000 meta-analysis of 13 studies of heparin vs LMWH (4457pts) showed no significant difference for: -15 Recurrent thromboembolism (p=0.20) Pulmonary embolism (p=0.94) Major bleeding (p=0.08) Minor bleeding (p=0.28) Thrombocytopenia (0.62) There was a significant difference in overall mortality in favor of the LMWH arm (p=0.03)

32 Treatment/Unfractionated Heparin vs LMWH

33 Treatment/Unfractionated Heparin vs LMWH No significant difference were associated with different formulations of LMWH

34 Treatment/Heparin Time to theraputic range appears to play an important role in heparization review showed in 523 subjects, patients who achieved therapeutic aptt in < 24hrs had lower rates of recurrent venous thromboembolism up to 100 days out from the initial event(p=0.002).-27

35 Treatment/Heparin

36 Treatment/Coumadin After initial anticoagulation, patients are usually transitioned to Coumadin. The American College of Chest Physicians recommends: -17 INR Low ( ) and high ( ) intensity therapy not recommended (1A) 3 months of therapy for patients with first VTE and reversible risk factor 6-12 months of therapy for patients with first VTE and no known cause (1A), possible need for lifelong anticoagulation (2A) 12 months of anticoagulation for patient with known hypercoagulable state (1A), possible need for lifelong anticoagulation. Indefinite therapy for patients with two or more VTE events (1A)

37 Treatment/Coumadin Special case: cancer patients ACCP recommends 3-6 months of LMWH (1A) followed by possible indefinite therapy (or until cancer resolves) (1C) 2003 RCT study of 672 patients with cancer and a symptomatic, proximal DVT -18 LMWH for 5-7d followed by coumadin or LMWH only for 3 months. Over the 6 month study period, an increased rate of VTE was noted in the coumadin group (p=0.002). No significant differences in bleeding (p=0.27) or death (p=0.53) were noted.

38 Treatment/Coumadin

39 Treatment/Coumadin Coumadin has a long half-life (mean of 40 hrs) and is metabolized by the Cyp-450 pathway. Can be very difficult to manage and requires monitoring of INR levels. Recent prospective study showed that most patients can be started on a standard dose of 5mg with INR checks at 4 and 6 days. 21% and 52% therapeutic on days 4 and 6, with only 3% and 17% super-therapeutic at days 4 and

40 Treatment/Lysis and stenting Up to 95% of patients with iliofemoral DVT have deficient muscle pump function and valvular competency at 5yrs. Mechanical thrombectomy alone in one 2002 prospective, non-random study showed only 26% significant thrombus resolution. This number was significantly increased to 62% when catheter directed lytic therapy was used as well. (p=0.006 over 15 limbs in the MT group, 20 limbs in the lysis+mt group) -25

41 Treatment/Lysis and stenting 2001 prospective, non-random study of 51 patients showed significantly improved patency with catheter directed lysis and stenting over conventional therapy with heparin. -26 Limited application in post-surgical patients due to bleeding risk. -23

42 Treatment/IVC Filters Placing a barrier in the IVC to prevent PE is attributed to Trousseau in The first IVC filters became available in 1960s. A 1998 RCT of 400 patients with DVT that were high risk for PE studied IVC filters in addition to anticoagulation. -26 Risk of PE was significantly reduced in the patients with a filter, but the incidence of recurrent DVT was increased.

43 Treatment/IVC filters *no significant difference in bleeding (p=0.41) or death (p=0.65)

44 Treatment/IVC filters

45 Treatment/IVC Filters Other relative indications include free floating thrombus, obesity, DVT with PHTN, prophylaxis for some general surgery/ortho/bariatric populations.

46 Treatment/Summary th ACCP Conference on Antithrombotic and THrombolytic Therapy Treat while awaiting objective confirmation of diagnosis (1C) At least 5 day course of heparin or LMWH (1A) LMWH should be given if patients are eligible to continue treatment at home (1C) Initiate coumadin concurrently with IV/SC anticoagulation and continue with INR 2-3. (1A)

47 Treatment/Summary IV thrombolytic treatment (catheter directed or not) is not recommended (1A) unless px is at risk for limb gangrene (1C) Venous thrombectomy is not recommended (1C) except in cases of limb gangrene (2C) IVCF is not recommended (1A) except in patients meeting criteria (2C) Ambulation as tolerated is recommended (2B) LMWH and Coumadin duration as previously discussed

48 Treatment/Summary Elastic compression stocking recommended for 2 years after DVT (1A) Intermittent pneumatic compression recommended (2B) and compression stockings (2C) recommended for PTS. A: RCT with strong consistent results, B: inconsistent results from RCT, C+: observational studies with very strong effects, C: observational studies. 1: benefits greater than risks, 2: benefits not greater than risks.

49 Treatment/Summary Hyers et al. Antithrombotic therapy for venous thromboembolic disease. Chest. 1998, 114(

50 References 1. Sabiston s textbook of surgery, 17th edition. 2. S.D. Ting and Francis Seow-Choen. Clinics in Colon and Rectal Surgery. 16(2) Walter Ageno, Alessandro Squizzato, David Garcia, and Davide Imberti. Epidemiology and Risk Factors of Venous Thromboembolism. Seminars in Thrombosis and Hemostasis. 32(7) Homans. Thrombosis of the Deep Veins of the Lower Leg Causing Pulmonary Embolism. NEJM. 211(22) The Value of Clinical Findings and D-Dimer Tests in Diagnosing Deep Vein Thrombosis in Primary Care. Ruud Oudega, Arno W. Hoes, Diane B. Toll, Karel G.M. Moons. Seminars in Thrombosis and Hemostasis. 32(7) Tamariz et al. Usefullness of clinical prediction rules for the diagnosis of venous thromboembolism: a systematic review. American Journal of Medicine (117) A Prospective Study of a Focused, Surgeon-Performed Ultrasound Examination for the Detection of Occult Common Femoral Vein Thrombosis in Critially Ill patients. G.S. Rozycki, K.M. Tchorz, Et Al. Archives of Surgery ) 8. Homans, J. Thrombosis of the Deep Veins of the Lower Leg, Causing Pulmonary Embolism NEJM 211(22) *Stratton, MA; Anderson FA; Bussey HI, et al. Prevention of venous thromboembolism: Adherence to the 1995 American College of Chest Physcians Guidelines for Surgical Patients. Arch Internal Med ( ) 10. O. Agu, G. Hamilton, D. Baker. Graduated Compression Stockings in the Prevention of Venous Thromboembolism. British Journal of Surgery. 1999(86) Gualtiero Palareti, Benilde Cosmi, Cristina Legnani. Diagnosis of Deep Vein Thrombosis. Seminars in Thrombosis and Hemostasis. 32(7) Borst-Krafek et al. Proximal extent of pelvic vein thrombosis and its association with pulmonary embolism Journal of Vascular surgery (3) Schellong et al. Bed rest in Deep Vein Thrombosis and the Incidence of Scintigraphic Pulmonary Embolism Thrombosis and Haemostasis ( )

51 References 14. Aschwanden et al. Acute Deep Vein Thrombosis: early mobilization does not increase the frequency of pulmonary embolism. Thrombosis and Haemostasis (42-46). 15. Dolovick et al. A meta-analysis comparing low-molecular weight heparins with unfractionated heparin in the treatment of venous thromboembolism. Archives of Intternal Medicine ( ) 16. Hull et al. Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis. NEJM (18) Buller et al. Anithrombotic therapy for venous thromboembolic disease: The Seventh ACCP Converence of Antithrombotic and Thrombolytic Disease. Chest 2004, 126( ) 18. Agnes et al. LMWH vs a Coumarin for the prevention of recurrent venous thromboembolism in patients with cancer NEJM (2) Hyers et al. Antithrombotic therapy for venous thromboembolic disease. Chest. 1998, 114( Barritt D.W. and Jordan S.C. Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial Lancet ( ) 21. Harper et al. Warfarin induction at 5mg is safe with a low risk of anticoagulant overdose Internal Medicine Journal (35) management of surgical 23. Clagett and Reisch. Prevention of Venous THromboembolism in General Surgery Patients. Annals of Surgery (2) 24. Vedantham et al. Lower extremity venous thrombolysis with adjunctive mechanical thrombectomy. J. Vasc. And Inerventional Radiology. 2002(13) Abu Rahma et al. Iliofemoral Deep Vein Thrombosis: Conventional therapy vs lysis and percutaneous transluminal angioplasty and stenting. Annals of Surgery. 233(6) G. Patrick Clagett and Joan Reisch. Prevention of Venous Thromboembolism in General Surgical Patients. Annals of Surgery. August Hull et al. Relattion between the time to achieve the lower limit of the aptt therapeutic range and recurrent venous thromboembolism during heparin treatment for deep vein thrombosis Archieves of Internal Medicine ( )