PREVENTION AND TREATMENT OFDEEP VEIN THROMBOSIS DeShawndre Bridley 6th Year Doctorate of Pharmacy Candidate Florida A&M University
OBJECTIVES Case Presentation Outline DVT Pathophysiology Epidemiology Diagnosis Complications Discuss Pharmacological Management Review Case Study
CASE PRESENTATION M.H. is a 47 y/o, 268lb WF admitted to the ER on 10/22/07 CC: “My calf started to swell last week. Now the pain is so bad that I’m having a hard time walking.” HPI: Noticed swelling of the right calf approximately 4 days ago. She reported to the ED of her local hospital 1 day after the onset of calf pain and swelling. Venous Dopplers were performed and the patient was told that she had a blood clot in her right leg. According to the patient she was given a prescription for an injection and instructed to follow-up with her PCP within the next 1 to 2 days. She failed to have the prescription filled because her pharmacy did not have the drug in stock. Because of increasing pain and discomfort, M.H. was seen by her physician this morning who recommended hospitalization to initialize therapy for her blood clot.
CASE PRESENTATION PMH: Previous DVT at the age of 38; treated with warfarin for 3 months FH: Father died at 42 from MI; mother alive at 71 with breast cancer diagnosed 5 years ago, s/p radiation/chemotherapy; sister alive and well. No family history of venous thromboembolic disease reported.
CASE PRESENTATION SH: Patient lives with her husband and 16 y/o son; works in a department store as a cashier. 24 pack-year smoking history; currently smokes ½ to 1 ppd. (-) EtOH or IVDA Meds: Raloxifene 60mg PO qd Multivitamin 1 tab PO qd Denies the use of herbal products
WHAT IS A DEEP VEIN THROMBOSIS?
DEEP VEIN THROMBOSIS Deep vein thrombosis (DVT) is the development of thrombi in the deep veins of the extremities or pelvis. DVT Deep venous thrombophlebitis
EPIDEMIOLOGY & DEMOGRAPHICS Annual incidence in urban population is 1.6 cases/1000 persons. The risk of recurrent thromboembolism is higher among men than women Annual incidence is 0.1% in white population
ETIOLOGYThe etiology is often multifactorial (prolonged stasis, coagulation abnormalities, vessel wall trauma).The following are risk factors for DVT:• Prolonged immobilization (≥3 days)• Postoperative state• Trauma to pelvis and lower extremities• Birth control pills, high-dose estrogen therapy;
ETIOLOGY Visceral cancer (lung, pancreas, alimentary tract, GU tract) Age >60 yr. History of thromboembolic disease Hematologic disorders (e.g., antithrombin III deficiency, protein C deficiency, protein S deficiency, heparin cofactor II deficiency, sticky platelet syndrome, G20210A prothrombin mutation, lupus anticoagulant, dysfibrinogenemias, anticardiolipi n antibody, hyperhomocysteinemia, concurrent homocystinuria, high levels of factors VIII, XI, and factor V Leiden mutation)
ETIOLOGY Pregnancy and early puerperium Obesity, CHF Surgery requiring >30 min of anesthesia Gynecologic surgery (particularly gynecologic cancer surgery)
ETIOLOGY Recent travel (within 2 wk, lasting >6 hr) Smoking and abdominal obesity Central venous catheter or pacemaker insertion Superficial vein thrombosis, varicose veins
DIAGNOSIS Symptoms: The patient may complain of leg swelling, pain, or warmth. Signs: The patient’s superficial veins may be dilated, and a “palpable cord” may be felt in the affected leg. The patient may experience pain in the back of the knee when the examiner dorsiflexes the foot of the affected leg.
DIAGNOSIS Laboratory Tests Serum Concentrations of D-dimer, a by- product of thrombin generation, usually are elevated. The patient may have an elevated erythrocyte sedimentation rate (ESR) and White Blood Cell (WBC) count.
NONPHARMACOLOGIC THERAPYInitial bed rest for 1-4 days followed by gradual resumption of normal activity Patient education on anticoagulant therapy and associated risks
ACUTE GENERAL PHARMACAOTHERAPY Traditional treatment consists of IV unfractionated heparin for 4 to 7 days followed by warfarin therapy. Low–molecular-weight heparin enoxaparin (Lovenox) is also effective for initial management of DVT and allows outpatient treatment. Recommended dose is 1 mg/kg q12h SC and continued for a minimum of 5 days and until a therapeutic INR (2-3) has been achieved with warfarin
DOSAGES FOR LMWH AND UFH Enoxaparin (Lovenox) 1mg/kg every 12 hours or 1.5mg/kg every 24 hours Dalteparin (Fragmin) 100units/kg every 12 hours or 200units/kg every 24 hours Tinzaparin (Innohep) 175units/kg every 24 hours UFH: Loading dose of 80 to 100units/kg (max. 10,000units) followed by a continuous IV infusion at an initial rate of 17 to 20 units/kg/h (max. 2300 units/h)
ADVANTAGES OF LOW MOLECULAR WEIGHT HEPARIN OVER UNFRACTIONATED HEPARIN More reliable dose-response relation No need for laboratory monitoring with the activated partial thromboplastin time (although can be monitored with anti-Xa activity) No need for dose adjustments Lower incidence of thrombocytopenia No excess bleeding Can be administered by the patient at home Economically advantageous
ACUTE GENERAL PHARMACOTHERAPY Once-daily fondaparinux (Arixtra), a synthetic analog of heparin, is also as effective and safe as twice daily enoxaparin in the initial treatment of patients with symptomatic DVT. Selective inhibitor of factor Xa Dose: 7.5mg SC daily
ACUTE GENERAL PHARMACOTHERAPY Warfarin therapy should be initiated when appropriate (usually within 72 hr of initiation of heparin). Interferes with vitamin K dependent factors (II, VII, IX, X) Interactions: Ethanol, Vitamin E, Cranberry juice Pregnancy category X
ACUTE GENERAL PHARMACOTHERAPY Low–molecular-weight heparin, when used, should be overlapped with warfarin for at least 5 days and until the INR has exceeded 2 for 2 consecutive days.
ACUTE GENERAL PHARMACOTHERAPY Exclusions from outpatient treatment of DVT include patients with potential high complication risk (e.g., Hemoglobin <7, platelet count <75,000, guaiac-positive stool, recent CVA or noncutaneous surgery, noncompliance).
ACUTE GENERAL PHARMACOTHERAPY Insertion of an inferior vena cava filter to prevent pulmonary embolism is recommended in patients with contraindications to anticoagulation
ACUTE GENERAL PHARMACOTHERAPY Thrombolytic therapy (streptokinase) can be used in rare cases (unless contraindicated) in patients with extensive iliofemoral venous thrombosis and a low risk of bleeding Not generally used unless there is a massive thrombus or limb salvage is necessary (due to gangrene) Has not been shown to decrease morbidity or mortality in PE
CHRONIC PHARMACOTHERAPY Conventional-intensity warfarin therapy is more effective than low-intensity warfarin therapy for the long term prevention of recurrent DVT. The low-intensity warfarin regimen does not reduce the risk of clinically important bleeding.
CHRONIC PHARMACOTHERAPY The optimal duration of anticoagulant therapy varies with the cause of DVT and the patients risk factors: 1. Therapy for 3-6 mo. is generally satisfactory in patients with reversible risk factors (low-risk group). 2. Anticoagulation for at least 6 mo. is recommended for patients with idiopathic venous thrombosis or medical risk factors for DVT (intermediate-risk group). 3. Indefinite anticoagulation is necessary in patients with DVT associated with active cancer; long-term anticoagulation is also indicated in patients with inherited thrombophilia (e.g., deficiency of protein C or S antibody), antiphospholipid, and those with recurrent episodes of idiopathic DVT (high-risk group).
CHRONIC PHARMACOTHERAPY Measurement of d-dimer after withdrawal of oral anticoagulation may be useful to estimate the risk of recurrence. Patients with a first spontaneous DVT and a d- dimer level <250 μg/mL after withdrawal of oral anticoagulation have a low risk of DVT recurrence.
PEARLS AND CONSIDERATIONS When using heparin, there is a risk of heparin-induced thrombocytopenia (with unfractionated more so than with LMWH). Platelet count should be obtained initially and repeated every 3 days while on heparin.
PEARLS AND CONSIDERATIONS Approximately 20%-50% of patients with DVT develop postthrombotic syndrome characterized by leg edema, pain, venous ectasia, skin induration, and ulceration.
PEARLS AND CONSIDERATIONS Exercise following DVT is reasonable because it improves flexibility of the affected leg and does not increase symptoms in patients with postthrombotic syndrome
PREVENTION IS BETTER THAN TREATMENT Mechanical Methods Earlymobilization as soon as possible after surgery Graded compression stocking Pharmacological Methods UFH LMWH Fondaparinux Warfarin
PEARLS AND CONSIDERATIONS Prophylaxis of DVT is recommended in all patients at risk (e.g., low–molecular- weight heparin [enoxaparin 30 mg SC bid] after major trauma, post surgery of hip and knee; enoxaparin 40 mg SC qd post– abdominal surgery in patients with moderate to high DVT risk; gradient elastic stockings alone or in combination with intermittent pneumatic compression [IPC] boots following neurosurgery).
PEARLS AND CONSIDERATIONS Fondaparinux (Arixtra), a synthetic analog of heparin, can also be used for prevention of DVT after hip fracture surgery, hip replacement, or knee replacement. Initial dose is 2.5 mg SC given 6 to 8 hr postoperatively and continued daily. Its bleeding risk is similar to enoxaparin; however, it is more effective in preventing DVT
CASE PRESENTATION Subjective: Calf pain and swelling Risk Factors: Smoking, SERM use, Previous DVT Objective: (+) Homan’s sign in right calf with no palpable cord Factor V Leiden Mutation – positive Venous compression Ultrasonography- RLE shows non compressibility of the right posterior tibial vein with no color flow. Normal compressibility and flow demonstrated within the right common femoral and iliac veins. LLE shows normal compression of the deep venous system from the level of the common femoral vein to the popliteal vein
CASE PRESENTATION Assessment: AcuteDeep vein thrombosis of the right posterior tibial vein requiring initiation of anticoagulation. Venogram not necessary due to positive ultrasound results
DVTs in and/or around the politeal vein are termed proximal
CASE PRESENTATIONPlan:Treatment Day 1-5: Enoxaparin 122 U (1mg/kg) SC every 12 hours for 5 days Warfarin 5mg by mouth daily
CASE PRESENTATIONPlan Day 6 Discontinue LMWH Patientis to continue on warfarin therapy for at least one year due to prior DVT
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