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 Venous Thromboembolic Disease

Anthony J. Comerota , M.D., H. Edward Garrett, Jr., M.D., Richard Welling, M.D.

Includes:

  • Deep Venous Thrombosis
  • Deep Venous Thrombosis Prophylaxis
  • Pulmonary Emboli
  • Caval Interruption
  • Subclavian/Axillary Thrombosis
  • Venous Thrombectomy/Thrombolytic Therapy
  • Anticoagulation
  • Additional Important/Non-Core Cirriculum Topics:
  • Acute Caval Thrombosis Syndrome
  • Pulmonary Embolectomy (open & catheter based)
  • Renal Vein Thrombosis
  • Budd- Chiari Syndrome

I. Etiology, Risk Factors, Epidemiology and Pathophysiology

1. To understand that Rudolf Virchow , the Father of cellular pathology, wrote the classic triad of stasis, hypercoagulable state and vein wall damage leading to venous thrombosis.

2. To understand that all three elements can be involved in patients undergoing elective operations, causing postop DVT remote from the operative wound.

3. To understand that risk factors are quantitative and that increasing the number of risk factors increases the likelihood of venous thromboembolic complications.

4. To understand that not all risk factors are created equal. Malignancy, older age, obesity, long bone fractures, joint replacement, pelvic operations and a previous history of DVT/PE carry more weight (and higher risk) than other considerations.

5. To be familiar with the known hypercoagulable states, and to understand the relative frequency, mechanism of action and treatment of each. (These include: anticardiolipin/antiphospholipid antibodies, lupus anticoagulant, protein C and protein S deficiency, antithrombin III deficiency, hyperfibrinogenemia , plasminogen deficiency, factor V Leiden mutation (activated protein C resistance), heparin induced thrombocytopenia, Coumadin ( warfarin ) induced skin necrosis.

6. To realize that pulmonary embolism is the most common preventable cause of death in hospitalized patients.

7. To understand that many patients, and perhaps a majority, receive inadequate DVT prophylaxis.

8. To understand the alterations of coagulation which occur during pregnancy.

II. Spectrum of Venous Thrombosis

1. To understand that asymptomatic DVT can be dangerous (80% of fatal pulmonary emboli occur in patients who do not carry the diagnosis of acute DVT).

2. To understand that 20-30% of isolated calf DVT will extend if untreated.

3. To understand that the superficial femoral vein is actually the main deep vein of the thigh.

4. To appreciate that as an increasing number of segments are involved with venous thrombosis , the clinical picture of acute DVT is increasingly severe and the more problematic the post- thrombotic sequelae .

5. To understand that phlegmasia alba and phlegmasia cerulea dolens refer to the clinical findings resulting from iliofemoral DVT, not that the underlying etiology is different.

6. To appreciate that venous gangrene is not equivalent to phlegmasia cerulea dolens .

7. To appreciate the difference that extensive greater saphenous thrombosis is best treated by ligation and stripping whereas, extensive greater saphenous thrombophlebitis is best treated by ligation of the saphenofemoral junction, warm soaks, compression and nonsteroidal anti-inflammatory agents.

8. To appreciate that short segment distal superficial disease is best treated symptomatically.

III. Diagnosis

Goals:

1. To understand that the absence of clinical findings does not exclude deep venous thrombosis.

2. To appreciate that if the thigh is swollen, the common femoral vein and/or iliac veins, or the superficial femoral and profunda must be involved with the thrombotic process, assuming acute DVT is the etiology of swelling.

3. To understand that physiologic tests, including a venous doppler , impedance plethysmography (IPG), phleborheography (PRG), air plethysmography (APG), or any maximal outflow technique cannot detect nonocclusive venous thrombosis.

4. To appreciate that physiologic tests are inadequate for use as screening tests and inadequate as endpoint testing for efficacy of DVT prophylaxis.

5. To appreciate that ascending phlebography is the traditional gold standard for diagnosis of DVT, which is being replaced by venous duplex imaging.

6. To understand that the primary diagnostic criterion for DVT with ascending phlebography is visualized thrombus. Nonfilling of a deep vein is a secondary criterion.

7. To appreciate that with ascending phlebography artifacts are due to flow voids from nonopacified blood draining from tributaries, external compression, and laminar flow.

8. To know the appropriate indications for evaluation for a hypercoagulable state.

9. To appreciate that in patients with DVT/PE, blood samples drawn for a hypercoagulable evaluation should be obtained before anticoagulation is initiated.

10. To appreciate that a common finding of a patient with lupus anticoagulant (a misnomer) is prolongation of the PTT on a routine screening blood test.

11. To appreciate that the function of activated factor C is to reduce the activity of factor Va and VIIIa .

12. To appreciate that protein C is vitamin K dependent, has a short half-life, and plasma levels are rapidly reduced by warfarin compounds.

13. To appreciate that antithrombin III is also known as heparin cofactor and is lowered by therapeutic levels of heparin.

14. To appreciate that antithrombin IIIa is significantly increased (approximately 750x) with low dose subcutaneous heparin, which is the basis for low dose heparin prophylaxis.

15. To understand that if DVT is suspected in the pregnant woman and the noninvasive test results are equivocal, ascending phlebography should be performed.

IV. Treatment

Goals:

1. To understand the multiple actions of heparin, the reasons for heparin resistance and the complications of heparin.

2. To understand that platelet counts must be monitored during heparin therapy regardless of the dose or route of administration.

3. To appreciate that the PTT value does not correlate with bleeding complications in patients receiving therapeutic anticoagulation who do not have identifiable comorbidities .

4. To appreciate that early inadequate anticoagulation (sub-therapeutic PTT) increases the risk of recurrent venous thrombosis 15x .

5. To appreciate that warfarin compounds can be started immediately after the heparin is therapeutic.

6. To appreciate that continuous IV heparin is associated with a better therapeutic outcome and fewer bleeding complications than bolus IV or high dose subcutaneous injection.

7. To appreciate that heparin induced thrombocytopenia (HIT) occurs in 4-6% of patients given unfractionated heparin, and is not dose related.

8. To understand that there are two types of HIT, immediate onset and delayed onset (5-10 days), with platelet counts falling to 40% of baseline or less, or absolute platelet counts < 150,000.

9. To understand that HIT is a result of an IgG-Ab to the platelet membrane causing platelet aggregation.

10. To understand that thrombocytopenia in the presence of heparin induced antibodies is associated with an extremely high risk of thrombotic complications, whereas a patient who is antibody positive but does not drop their platelet count does not have an increased risk of thrombotic complications.

11. Once HIT is diagnosed (or suspected), all heparin must be avoided.

12. To understand that HIT occurs significantly less in patients receiving low molecular weight heparin compared to unfractionated heparin.

13. To appreciate that warfarin compounds can produce skin necrosis when given to patients who have a heterozygote protein C deficiency.

14. To understand that in patients with warfarin induced skin necrosis, warfarin compounds cause protein C to drop thereby increasing activity of factors Va and VIIIa , thereby causing increased coagulation.

15. To appreciate that at least six months of oral anticoagulation is required for first time proximal DVT to adequately avoid recurrences.

16. To understand that low molecular weight heparin, given in weight adjusted dose subcutaneously once daily, is at least as effective and possibly more effective as IV unfractionated heparin for acute DVT.

17. To appreciate that the action of low molecular weight heparin is reduction of factor Xa activity, and it does not affect the PTT.

18. To understand the mechanism of action and the relative merits/risks of fibrinolytic therapy for acute deep venous thrombosis.

19. To appreciate that systemic fibrinbolytic therapy for iliofemoral DVT is likely to fail, and that catheter-directed intra-thrombus thrombolysis is preferred.

20. To appreciate that venous thrombectomy is an effective option for patients with acute iliofemoral DVT.

21. To appreciate that the current operative technique of venous thrombectomy has improved compared to the early procedures.

22. To understand that a complete preop evaluation of the contralateral iliofemoral system and vena cava is important prior to venous thrombectomy .

23. To appreciate that an on-table completion phlebogram and correction of an underlying iliac vein stenosis is crucial to successful venous thrombectomy .

24. To appreciate that vena caval filters do not "treat acute DVT", they prevent large pulmonary emboli from occurring.

25. To appreciate that a Bird's nest filter is indicated for patients with a large vena cava.

26. To know reasons why warfarin should be avoided during pregnancy.

27. To understand that the indications for vena caval filters during pregnancy are the same as the non-pregnant patients, however, the filter should be placed in the supra-renal position.

28. To understand that those pregnant patients requiring heparin prophylaxis increase their heparin requirements during the second and third trimester.

V. Pulmonary Embolism

Goals:

1. To appreciate that pulmonary emboli occur without clinical warning in the majority of the patients.

2. To appreciate that the majority of the deaths from pulmonary emboli occur within 1-2 hours of the embolic event, and that untreated pulmonary embolism is associated with a 30 % mortality.

3. To understand the typical signs/symptoms and the usual chest x-ray, blood gas and EKG findings in patients with large pulmonary emboli.

4. To appreciate the proper use of ventilation perfusion lung scan, and understand the valuable integration of predictive values based upon clinical suspicion of PE. (PIOPED data)

5. To appreciate that thrombolysis of pulmonary emboli results in better cardiopulmonary hemodynamic parameters than standard anticoagulation.

6. To understand the indications for operative pulmonary embolectomy and to appreciate that patients considered for a pulmonary embolectomy should be offered high dose fibrinolytic therapy first (if there are no contraindications).

References

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2. Comerota AJ. Venous Thromboembolism . In: Rutherford R ( ed ) Vascular Surgery fourth edition. Philadelphia, W.B. Saunders Company, 1995.

3. Goldhaber SZ. Thrombolytic Therapy for Pulmonary Embolism. In: Comerota AJ ( ed ) Thrombolytic Therapy for Peripheral Vascular Disease. Philadelphia , JB Lippincott , 1993.

4. Hirsh J, Poller L, Deykin D et al. Optimal therapeutic range for oral anticoagulants. ACCP/NHLBI National Conference on Antithrombotic Therapy. Chest 1989 ;2 ( Suppl ):5S.

5. Hull RD, Raskob GE, Hirsh J et al. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal vein thrombosis. N Engl J Med 1986 ;315:1109 .

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8. Plate G, Einarsson E, Olin P et al. Thrombectomy with temporary arteriovenous fistula in acute iliofemoral venous thrombosis. J Vasc Surg 1984 ;1:867 .

9. Shull KC, Nicolaides AN, Fernandes e Fernandes J et al. Significance of popliteal reflux in relation to ambulatory venous pressure and ulceration. Arch Surg 1979 ;114:1304 .

10. Toglia MR, Weg JG. Current concepts: venous thromboembolism during pregnancy. N Engl J Med 1996 ;335:108 - 114.

11. National Institutes of Health Consensus Development Conference. Prevention of venous thrombosis and pulmonary embolism. JAMA 1986 ;256:744 .

12. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). JAMA 1990 ;263:1753 - 9.

13. Hirsh J. Heparin. N Engl J Med 1991 ;324:1565 - 74.

14. Hyers TM, Hull RD , Weg JG. Antithrombotic therapy for venous thromboembolic disease. Chest 1995 ;108:Suppl:335S - 351S.

15. Warkentin TE, Levine MN , Hirsh J et al. Heparin - induced thrombocytopenia in patients treated with low - molecular - weight heparin or unfractionated heparin. N Engl J Med 1995 ;332:1330 - 5.

Posted June 2010