TOC | Pulm

Pulmonary Embolism (PE) & Deep Vein Thrombosis (DVT)      Anticoagulation Rx  

REF: Acute Pulmonary Embolism 2008

Deep Vein Thrombosis Diagnosis:

• Clinical signs and symptoms are unreliable for the diagnosis of deep venous thrombosis.
• D-dimer assay for DVT screening test                         See D-Dimer for DVT Screening Algorithm 2006  
• Contrast venography (only 90% sensitivity ) is the gold standard in the diagnosis of DVT.
• Doppler ultrasound imaging of the venous system has become the procedure of choice for the diagnosis of proximal leg DVT.   The sensitivity is about 89% to 100% and the specificity is 97% to 100%.
• Spiral Chest CT scan to evaluate for pulmonary embolism
• Impedance plethysmography (IPG) has a sensitivity of 95% and a specificity of 94% for the diagnosis of acute DVT.  Recent studies suggest that the sensitivity and specificity may not be this high. False-positive IPG studies have been reported when the vasculature of the leg is engorged in patients who are pregnant or who suffer from severe congestive heart failure.
• Pulmonary angiogram to confirm pulmonary embolism if indicated clinically (Gold standard)
• Radioiodine-labeled fibrinogen - the sensitivity above the midthigh diminishes rapidly because of background radiation from the trunk and thus the test is less useful for proximal DVT detection. In addition, for hip surgery, the surgical field overlaps the area of interest on the radiofibrinogen scan.
• When a radioactive tracer such as Tc-labeled albumin is injected into a foot vein, external scintillation detectors can visualize the major veins of the leg. These studies can demonstrate obstruction of the deep veins, indicating deep venous thrombosis. Because the perfusion portion of the lung scan is performed with this same material, nuclear venograms of the leg veins can routinely be done with every perfusion lung scan. These nuclear venograms correlate well with contrast venography of the thigh veins and give additional diagnostic information without adding risk to the routine lung scan.
• Proximal thrombi in the popliteal, femoral, and iliac veins often are associated with pulmonary embolisms. They also obstruct the venous outflow of the leg and interfere with the normal pressure/volume relationships in the venous system.

PULMONARY EMBOLISM

The clinical diagnosis of pulmonary embolism is similarly inaccurate and requires objective verification.

• Three clinical syndromes should alert the physician to this diagnosis.
  1. Submassive embolism may produce pleuritic pain and hemoptysis. Physical exam often reveals rales, and chest radiograph shows a parenchymal infiltrate, pleural effusion, or elevated diaphragm.
  2. Acute cor pulmonale may be caused by obstruction of more than 60% to 75% of the pulmonary circulation. Patients may present with shock or loss of consciousness. Chest radiograph is often normal. EKG may show right bundle branch block or right heart strain but often shows only sinus tachycardia.
  3. Unexplained dyspnea. This may be caused by acute submassive pulmonary embolism or multiple small pulmonary embolisms over a long period of time. EKG and chest radiograph may be normal with an acute pulmonary embolism or show signs of cor pulmonale in the chronic situation, but arterial oxygen tension is usually reduced.
• The ventilation/perfusion lung scan is commonly the first test used to verify the diagnosis.
  A high-probability scan was defined as two or more large or moderate segmental perfusion defects without corresponding ventilation or chest radiograph abnormalities. Using this criterion alone, an 88% accuracy rate was found when scans were followed by pulmonary arteriography. If there was a high clinical suspicion of pulmonary embolism, the accuracy rate rose to 96%. This degree of accuracy is satisfactory for clinical purposes. Unfortunately, only 13% of scans showed high-probability type / mismatch, and only 41% of pulmonary embolism patients had high-probability scans.
  Normal or near-normal scans occurred 14% of the time and rarely were associated with positive pulmonary arteriograms or followup diagnoses of pulmonary embolisms, although more than 50% of these scans were not followed by an arteriogram. The combination of a normal or near-normal scan plus a low clinical index of suspicion for pulmonary embolism correctly ruled out pulmonary embolism in 98% of patients. This combination occurred in only 8% of the patients. Scan readings other than high probability or normal can be considered indeterminate, with frequencies of pulmonary embolism ranging from 16% to 40%.
• Pulmonary arteriogram is the gold standard for the diagnosis of pulmonary embolism, should be done for definitive diagnosis in the majority of cases.
• A normal D-dimer test result is useful in excluding pulmonary embolism in patients with a low pretest probability of pulmonary embolism or a nondiagnostic lung scan. Ann Intern Med. 1998;129:1006-1011

DVT Prevention

• Intermittent pneumatic compression (IPC) or Pneumatic plantar compression
• Supportive or graduated compression stocking (GCS)
• Leg exercise or early ambulation if possible
• Enoxaparin (Lovenox) 30 mg q12h subc (for ortho hip or knee replacement or hip fracture pts)
  Heparin 5,000 u subc. q12h (for medical high risk patients)
• [Ref: J Critical Illness September 1997, Vol.12, No.9 - R.Phillip Dellinger ]

PE & DVT Treatment:

• Enoxaparin (Lovenox) 1 mg/kg q12h or 1.5 mg/day subc
• Heparin IV for 5-7 days, start with 5000 u units bolus, then IV infusion to achieve PTT of 1.5-2x
• Coumadin PO started the first day, keep INR 2-3 for 3-6 months.
• Thrombolytic Rx for PE & DVT
• Vena cava Interruption
• Surgical thrombectomy
  
  Streptokinase, urokinase, and tissue plasminogen activator (tPA) have been extensively studied, although definite indications for their use are controversial.
  For acute proximal deep venous thrombosis, thrombolytic therapy often results in marked improvement in leg pain, swelling, and discomfort. Despite early benefit, it is difficult to prove that thrombolytic therapy provides any long-term benefit or prevention of postphlebitic syndromes.
  Acute iliofemoral vein thrombosis appears to be one indication for the use of thrombolytic therapy, because the outcome after heparin therapy alone is so poor.
  
  Early use of thrombolytic therapy for acute pulmonary embolism accelerates resolution of angiographic and lung scan abnormalities, and pulmonary hypertension rapidly resolves when compared to heparin therapy. After several days and at 1 year of followup, little difference can be found between treatment of pulmonary embolism by heparin or thrombolytic agents. At present, thrombolytic therapy is recommended only for patients without a tendency to bleed who have a massive pulmonary embolus, proven by arteriography, which has caused hemodynamic instability. Streptokinase should be given as a 250,000-IU loading dose, followed by 100,000 IU hourly for 24 hours. Urokinase should be given as a 4400-IU/kg of body weight loading dose, followed by 2200 IU/kg hourly for 12 hours. For tPA, infusion of 100 mg over a 2-hour period is effective for clot lysis. A segmental defect on the pretreatment perfusion lung scan is associated with a greater degree of improvement after thrombolytic therapy. There is no advantage to direct delivery of thrombolytic therapy into the pulmonary circulation. After the infusion of the thrombolytic agent, heparin therapy should be reinstituted as soon as the aPTT is once again within therapeutic range (1.5 to 2.0 × control).
  
  Despite reports of better diffusing capacity of the lung at 1 year and better pulmonary circulatory studies at 7 years followup when compared to heparin treatment alone, thrombolytic therapy is currently not indicated for all patients with pulmonary embolism.
  
  For patients with acute pulmonary embolism and the following indications, vena cava interruption is recommended: anticoagulation is contraindicated; despite adequate anticoagulation, recurrent embolization has occurred; anticoagulation must be prematurely discontinued because of bleeding. A recurrent embolism rate of 5% and a vena caval occlusion rate of 3% to 5% are certainly acceptable for clinical use. At present, the stainless steel Greenfield filter appears to be the wisest choice for vena cava interruption.
  
  Surgical embolectomy with cardiopulmonary bypass is indicated only for those patients with hemodynamic instability in whom thrombolytic therapy has either failed or is contraindicated.

Ref:
ACP Library on Disk 2- (c) 1997 - American College of Physicians     
                                                                 
         

Conclusion: Managing patients for suspected pulmonary embolism on the basis of pretest probability and D-dimer result is safe and decreases the need for diagnostic imaging.

Ann Intern Med. 2001;135:98-107.

ACP CLINICAL GUIDELINES                                See   DX of DVT 2007  | DVT Rx (KP)  | Anticoagulation Rx     

Management of Venous Thromboembolism: A Clinical Practice Guideline
from the American College of Physicians and the American Academy of Family Physicians

Vincenza Snow, MD; etc.

Annals of Internal Medicine  6 February 2007 | Volume 146 Issue 3

Venous thromboembolism is a common condition affecting 7.1 persons per 10 000 person-years among community residents. Incidence rates for venous thromboembolism are higher in men and African Americans and increase substantially with age. It is critical to treat deep venous thrombosis at an early stage to avoid development of further complications, such as pulmonary embolism or recurrent deep venous thrombosis. The target audience for this guideline is all clinicians caring for patients who have been given a diagnosis of deep venous thrombosis or pulmonary embolism. The target patient population is patients receiving a diagnosis of pulmonary embolism or lower-extremity deep venous thrombosis.

Recommendations:

1. Low-molecular-weight heparin (LMWH) rather than unfractionated heparin should be used whenever possible for the initial inpatient treatment of deep venous thrombosis (DVT). Either unfractionated heparin or LMWH is appropriate for the initial treatment of pulmonary embolism.
   Consistent evidence demonstrates that LMWH is superior to unfractionated heparin for the initial treatment of DVT, particularly for reducing mortality and reducing the risk for major bleeding during initial therapy. Additional trials are needed to more rigorously examine the efficacy of LMWH for the initial treatment of pulmonary embolism, but systematic reviews of existing trials indicate that LMWH is at least as effective as unfractionated heparin for these patients as well. In addition, trials of unfractionated heparin in pulmonary embolism show that many patients are subtherapeutic or supratherapeutic while receiving unfractionated heparin, whereas LMWH is quickly and consistently therapeutic, an important consideration in the treatment of VTE.

2. Outpatient treatment of DVT, and possibly pulmonary embolism, with LMWH is safe and cost-effective for carefully selected patients and should be considered if the required support services are in place.
   In trials that compared inpatient and outpatient treatment, the rates of recurrent DVT, major bleeding, and death during follow-up differed only slightly. These studies were conducted among highly selected groups of patients and in clinical systems with the required support services in place. Several studies allowed a brief inpatient admission for stabilization of the patients before randomization to the outpatient group. While some studies enrolled patients with concomitant pulmonary embolism, most excluded such patients. Inclusion criteria were strict: Most studies excluded patients with previous VTE, thrombophilic conditions, or significant comorbid illnesses; pregnant patients; and those unlikely to adhere to outpatient therapy. Therefore, this recommendation cannot be generalized (1).

3. Compression stockings should be used routinely to prevent postthrombotic syndrome, beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis.
   The evidence demonstrated a marked reduction in the incidence and severity of postthrombotic syndrome among patients wearing compression stockings, either over-the-counter stockings or custom-fit stockings, if use was initiated within 1 month diagnosis of proximal DVT. Most diagnoses of postthrombotic syndrome occurred early, within the first 2 years after DVT.

4. There is insufficient evidence to make specific recommendations for types of anticoagulation management of VTE in pregnant women.
   During pregnancy, women have a 5-fold increased risk for VTE compared with nonpregnant women. Clinicians should avoid vitamin K antagonists in pregnant women because these drugs cross the placenta and are associated with embryopathy between 6 and 12 weeks' gestation, as well as fetal bleeding (including intracranial hemorrhage) at delivery. Neither LMWH nor unfractionated heparin crosses the placenta, and neither is associated with embryopathy or fetal bleeding.

5. Anticoagulation should be maintained for 3 to 6 months for VTE secondary to transient risk factors and for more than 12 months for recurrent VTE. While the appropriate duration of anticoagulation for idiopathic or recurrent VTE is not definitively known, there is evidence of substantial benefit for extended-duration therapy.
   For VTE secondary to transient risk factors, 3 or 6 months of treatment was associated with similar risks for recurrent VTE. In the single study that exclusively enrolled patients presenting with a second episode of VTE, extended-duration (>12 months or indefinite) anticoagulant therapy was associated with fewer recurrences than was termination after 6 months of therapy. For patients with idiopathic VTE (including those with recurrent VTE), extended-duration therapy decreased the relative risk for recurrence by 64% to 95%. Length of therapy in the trials varied widely, from greater than 3 months to 12 months to up to 4 years. The results for extended-duration therapy reflect follow-up only to 4 years; the risk–benefit ratio is not known for longer durations. Clinicians should weigh the benefits, harms, and patient preferences in deciding on the duration of anticoagulation.

6. LMWH is safe and efficacious for the long-term treatment of VTE in selected patients (and may be preferable for patients with cancer).
   Evidence from high-quality randomized trials supports the use of LMWH as comparable to oral anticoagulation for VTE in selected patients. Low-molecular-weight heparin may be a useful treatment for patients in whom control of the international normalized ratio (INR) is difficult and may be more efficacious than oral anticoagulants in patients with cancer.

2008