Deep Vein Thrombosis

DeShawndre Bridley
6th Year Doctorate of Pharmacy Candidate
Florida A&M University
PREVENTION AND TREATMENT OF DEEP VEIN THROMBOSIS

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

ETIOLOGY
The 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, anticardiolipin 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
Diagnostic Tests
Duplex ultrasonography
Venography (aka phlebography)
“Gold Standard” for DVT diagnosis

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.

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 unfractionatedheparin
More reliable dose-response relation
No need for laboratorymonitoring with the activated partial thromboplastin time (althoughcan be monitored with anti-Xa activity)
No need for dose adjustments
Lowerincidence of thrombocytopenia
No excess bleeding
Can be administeredby the patient at home
Economically advantageous

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.

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

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).

Insertion of an inferior vena cava filter to prevent pulmonary embolism is recommended in patients with contraindications to anticoagulation

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 patient's 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.

Approximately 20%-50% of patients with DVT develop postthrombotic syndrome characterized by leg edema, pain, venous ectasia, skin induration, and ulceration.

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
Early mobilization as soon as possible after surgery
Graded compression stocking
Pharmacological Methods
UFH
LMWH
Fondaparinux
Warfarin

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).

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:
Acute Deep 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 presentation
Plan:
Treatment
Day 1-5:
Enoxaparin 122 U (1mg/kg) SC every 12 hours for 5 days
Warfarin 5mg by mouth daily

Case presentation
Plan
Day 6
Discontinue LMWH
Patient is to continue on warfarin therapy for at least one year due to prior DVT

REFERENCES
Anderson F.A. , Jr, Spencer F.A., Risk factors for venous thromboembolism. Circulation (2003) 107 : pp 9-16
White R.H., The epidemiology of venous thromboembolism. Circulation (2003) 107 : pp I4-I8.
Antithrombotic Therapy for Venous Thromboembolic Disease The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest - Volume 126, Issue 3 (September 2004)
Barrit DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. Lancet 1960; 1:1309–1312
Crowther MA, Ginsberg JB, Kearon C, et al. A randomized trial comparing 5-mg and 10-mg warfarin loading doses. Arch Intern Med 1999; 159:46–48
Kernohan RJ, Todd C. Heparin therapy in thromboembolic disease. Lancet 1966; 1:621–623
Harrison L, Johnston M, Massicotte MP, et al. Comparison of 5-mg and 10-mg loading doses in initiation of warfarin therapy. Ann Intern Med 1997; 126:133–136

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Deep Vein Thrombosis

by dbridley on Jul 05, 2009

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