Deep Vein Thrombosis and Treatments BY LAW JIA JUIN (with reliable references)

This article was written by me based on a patient name JL who is a taxi driver

Deep vein thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh).  DVT may be asymptomatic or cause pain and swelling in an extremity. Diagnosis is by history, physical examination, and duplex ultrasonography, with D-dimer or other testing as necessary. Treatment is with anticoagulants.


Warfarin is the main oral anticoagulant but with delayed onset of action. It is used as a treatment and prevention of venous thromboembolism¹. Warfarin antagonizes the effect of vitamin K. Reduced vitamin K is necessary as a cofactor for the carboxylation of clotting precursors to vitamin K-dependent coagulation factors and the synthesis of protein C and S². Thus, it reduces the further formation of blood clots and prevents them from developing on the valves. Warfarin’s full antithrombotic effect is delayed for approximately 5 to 7 days because of its long half-lives of the clotting factors². International Normalised Ratio (INR) readings of the patient are required to be supervised as it determines the dosage of warfarin to be administered².

      
Enoxaparin is a low-molecular-weight-heparin¹. Enoxaparin is used instead of unfractionated heparin (UFH) in treatment of DVT because its side effects are not as severe as UFH². It also has longer half-lives, dose-independent clearance and bioavailability is improved via subcutaneous administration. Activated partial thromboplastin time (aPTT) and laboratory tests are not needed as it has predictable anticoagulant response². Enoxaparin’s anticoagulant action is fast. Both enoxaparin and warfarin prevents growth and occurrence of blood clots².

         
Warfarin and enoxaparin is usually used together in the treatment of DVT because warfarin therapy initially will cause lesser concentration of natural anticoagulants¹. This will lead to abnormal increase in propensity towards blood clotting and this condition is called as hypercoagulable state¹. It is because before the clotting factors are reduced, the action of anticoagulant is already decreasing¹ due to the lessened amount. Thus, when there is less anticoagulant, blood will tend to clot. Therefore, enoxaparin is used as a fast-acting anticoagulant as to compensate the lessened concentration of natural anticoagulants¹. Enoxaparin therapy can be stopped once the INR is greater than 2 and stable for two consecutive days².                                                                                         

            
Warfarin and enoxaparin is used as first line drug in managing deep vein thrombosis³. JL should be screen for any contraindications to anticoagulation therapy and risk factors for major bleeding before initiating the therapy as warfarin is a long term oral anticoagulant drug¹. Warfarin should only be offered when a systematic patient monitoring system is accessible¹. For JL, 7.5 - 10mg of warfarin could be a good start if a PT or INR can be obtained daily¹. Decreasing or maintaining the dose of warfarin depends on INR result¹. Due to its narrow therapeutic index, frequent dose of warfarin adjustments and careful patient monitoring is required¹. The duration of therapy for warfarin is based on JL’s risk of venous thromboembolism recurrence and major bleeding¹. The duration therapy of warfarin is shown in Table 1⁴.When taking warfarin, medications contain aspirin should be avoided as well as alcohol⁵. JL may experience changes in the INR due to fluctuating intake of dietary vitamin K¹.

            
Enoxaparin must not be administered intramuscularly or intravenously¹. Enoxaparin is used as bridge therapy until the warfarin has reached its therapeutic level⁶. 1.5 mg/kg which means for JL is 105 mg once daily of enoxaparin which given subcutaneously should be given for at least 5 days, at most 14 days which serve as superior protection against venous thromboembolism². Discontinue using of enoxaparin after 5 days if INR > 2.0¹. No routine laboratory monitoring is required for enoxaparin as enoxaparin will achieve predictable anticoagulant response¹. If JL is allergic to heparin or pork products, he should not take enoxaparin⁴. Besides, enoxaparin syringes should be kept at room temperature⁵ .Aspirin should be avoided during enoxaparin treatment as it will increase risk of bleeding⁵.

Table 1: Duration of therapy of oral anticoagulant, warfarin

          
INR which was developed to incorporate with the International Sensitivity Index help standardize the difference in sensitivity in individual thromboplastin reagent. INR is recommended for monitoring oral anticoagulant therapy. INR is not a laboratory test but a mathematical calculation that corrects for the variability in PT results caused by variable sensitivities (ISI) of the thromboplastin used.
INR= ISI

           
PT evaluates the generation of thrombin and the formation of fibrin via the extrinsic and common pathway. Conversely, the APTT measures the time required to generate thrombin and fibrin polymers via intrinsic and common pathway. INR is used instead of PT or APTT is because INR monitoring combines testing accuracy. INR is essentially a corrected PT that adjusts for the several dozen assays used worldwide⁷.

            
           
 In short, JL should follow the correct prescription. Besides, he should avoid any injuries when he carries out daily activities.  JL should also move his lower limbs when he is on duty. Lastly, JL should keep himself hydrated with drinking water everyday to retain his blood viscosity.

Reference:

1. Stuart T. Haines and Edith A. Nutescu Venous Thrombolism. In: Marie A. Chrisholm – Burns, Barbara G. Wells, Terry L. Schwinghammer, Patrick M. Malone, Jill M. Kolesar, John C. Rotschafer, et al, editors. Pharmacotherapy Principles and Practice. 6th ed.  McGraw-Hill; 2008. p. 141-153.

2. Terry L. Schwinghammer. Venous Thrombolism. IN: Barbara G. Wells, Joseph T. DiPiro, Terry L. Schwinghammer & Cecily V. DiPiro, editors. Pharmacotherapy Handbook. 7th ed. McGraw-Hill; 2009. p. 169-174.

3. http://www.ncbi.nlm.nih.gov/pubmed/18568442 Narin C, Reyhanoglu H, Tülek B, Onoglu R, Ege E, Sarigül A, Yeniterzi M, Durmaz I.

Department of Cardiovascular Surgery, Selcuk University, Meram Medical School, Beysehir Yolu, Meram, 42080, Konya, Turkey.

4. http://www.acadmed.org.my/index.cfm?&menuid=67

Clinical Practice Guidelines July 2003 MOH/P/PAK/74.03(GU)

5. http://www.outcomes-umassmed.org/dvt/add_info/dvtguide.cfm

Adapted from the October 1996 BPHC Pharmacy and Therapeutic Committee Review of low-molecular-weight heparins by Amy Santoro, PharmD.

6.http://www.aafp.org/online/etc/medialib/aafp_org/documents/clinical/clin_recs/dvtmanagementguideline.Par.0001.File.dat/DVTMgmt-Guideline-AnnIntMed.pdfManagement of Venous Thromboembolism: A Clinical Practice Guideline from the American College of Physicians and the American Academy of Family Physicians 

Vincenza Snow, MD; Amir Qaseem, MD, PhD, MHA; Patricia Barry, MD, MPH; E. Rodney Hornbake, MD; Jonathan E. Rodnick, MD; Timothy Tobolic, MD; Belinda Ireland, MD, MS; Jodi B. Segal, MD; Eric B. Bass, MD, MPH; Kevin B. Weiss, MD, MPH; Lee Green, MD, MPH; Douglas K. Owens, MD, MS; and the Joint American College of Physicians/American Academy of Family Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism*

Ann Intern Med. 2007;146:204-210.

7. Mary Louise Turgeon. Chapter 23 Principles of Hemostasis and Thrombosis. IN: Pamela Lappies, Kevin Dietz, ed. Clinical Hematology Theory and Procedures. 4th ed. United States of America: Lippincott Williams & Wilkins; 2005. p.355-356.