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Pathology Outlines - Infarct / pulmonary emboli

Anticoagulation Strategies for Pulmonary Embolism (KEYNOTE)

Fatal cor pulmonale caused by extensive tumor emboli in the small pulmonary arteries without emboli in the major pulmonary arteries or metastases in the pulmonary parenchyma. American Journal of Cardiology 72 2 : , Yearbook of Critical Care Medicine , Use of helical CT is associated with an increased incidence of postoperative pulmonary emboli in cancer patients with no change in the number of fatal pulmonary emboli. Journal of the American College of Surgeons 5 : ; Discussion , Pulmonary micro-tumor emboli resulting in paradoxical emboli: a case report.

Microscopic histologic description. Microscopic histologic images. Small thromboemboli. With recanalization. Left: fat emboli; right: amniotic fluid emboli.

Home About Us Advertise Amazon. Telephone: ; Email: CommentsPathout gmail. In patients with hypotension due to massive PE, 0. Vasopressors may also be given if IV fluids fail to sufficiently increase blood pressure.

Norepinephrine is the most commonly used first-line agent. Epinephrine and dobutamine have inotropic effects, but it is not clear how much these affects the normally thin-walled RV. Anticoagulation is the mainstay of therapy for PE, and rapid reduction of clot burden via thrombolytic therapy or embolectomy is indicated for patients with hypotension that does not resolve after fluid resuscitation, and for selected patients with impaired RV function.

Placement of a removable percutaneous inferior vena cava filter IVCF should be considered for patients with contraindications to anticoagulation or for those with recurrent PE despite anticoagulation. For example, patients who have acute PE, residual clot in the leg, and cannot be anticoagulated, should have a filter placed because they have persistent risk of subsequent DVT. Most patients with PE should be hospitalized for at least 24 to 48 h.

Patients with abnormal vital signs or massive or submassive PE require longer periods of hospitalization. ICU admission should also be considered if patients have:. Patients with incidentally discovered PE or those with very small clot burdens and minimal symptoms may be managed as outpatients if their vital signs are stable, education is undertaken, and if a reasonable plan for outpatient treatment and follow-up is in place. Initial anticoagulation followed by maintenance anticoagulation is indicated for patients with acute pulmonary embolism to prevent clot extension and further embolization as well as new clot formation.

Anticoagulant therapy for acute PE should be started whenever PE is strongly suspected, as long as the risk of bleeding is deemed low. Otherwise, anticoagulation should be started as soon as the diagnosis is made.

The dating of pulmonary emboli

The likelihood of benefit and harm in treatment of emboli in smaller, subsegmental vessels particularly asymptomatic and incidentally discovered emboli is currently unknown, and it is feasible that in certain settings harm may outweigh benefit. Still, treatment is currently recommended. The primary complication of anticoagulation therapy is bleeding, and patients should be closely observed for bleeding during hospitalization.

Factor Xa inhibitors apixaban and rivaroxaban. Intravenous argatroban for patients with heparin -induced thrombocytopenia. Intravenous unfractionated heparin has a short half-life useful when the potential for bleeding is deemed higher than usual and is reversible with protamine.

An initial bolus of unfractionated heparin is given, followed by an infusion of heparin dosed by protocol to achieve an activated PTT 1. Therefore, unfractionated heparin requires ongoing hospitalization to administer. Further, the pharmacokinetics of unfractionated heparin are relatively unpredictable, resulting in frequent periods of over-anticoagulation and under-anticoagulation and necessitating frequent dose adjustments.

Regardless, many clinicians prefer this IV unfractionated heparin regimen, particularly when thrombolytic therapy is given or contemplated or when patients are at risk of bleeding because if bleeding occurs, the short half-life means that anticoagulation is quickly reversed after the infusion is stopped. Subcutaneous low molecular weight heparin has several advantages over unfractionated heparin including.

Weight-based dosing results in a more predictable anticoagulation effect than does weight-based dosing of unfractionated heparin. Lower risk of heparin -induced thrombocytopenia compared with standard, unfractionated heparin. In patients with renal insufficiency, dose reductions are needed see table Some Low Molecular Weight Heparin Options in Thromboembolic Diseaseand subsequent verification of appropriate dosing should be done by checking serum factor Xa levels target: 0.

Low molecular weight heparins are partially reversible with protamine. Low Molecular Weight Heparin. Treatment Dose. Prophylactic Dose. N ote : Although low molecular weight heparins can be given by continuous IV infusion, this form of administration is rarely necessary or indicated.

Low molecular weight heparins usually are given by sc injection in the abdominal area while the patient is supine. Thrombocytopenia including heparin-induced thrombocytopenia with the potential for thromboembolism. Bleeding caused by over-heparinization with unfractionated heparin can be treated with a maximum of 50 mg of protamine per units unfractionated heparin infused over 15 to 30 min. Over-heparinization with a low molecular weight heparin can be treated with protamine 1 mg in 20 mL normal saline infused over 10 to 20 min, although the precise dose is undefined because protamine only partially neutralizes low molecular weight heparin inactivation of factor Xa.

Fondaparinux is a newer factor Xa antagonist. It has also been shown to prevent recurrences in patients with superficial venous thrombosis. Outcomes appear to be similar to those of unfractionated heparin. Advantages include once or twice daily fixed-dose administration, no need for monitoring of the degree of anticoagulation, and lower risk of thrombocytopenia. The other newer factor Xa inhibitors, apixabanrivaroxabanand edoxabanhave the advantages of oral fixed dosing, the ability to be used as maintenance anticoagulants with no need for laboratory monitoring of the anticoagulant effect.

They also cause few adverse interactions with other drugs, although azole antifungal therapy and older HIV therapies protease inhibitors will increase oral factor Xa inhibitor drug levels, and certain anticonvulsants and rifampin will decrease oral factor Xa inhibitor drug levels.

Although rivaroxaban and apixaban do not require overlap with a parenteral anticoagulant when used as initial therapy, edoxaban requires use of a parenteral anticoagulant for 5 to 10 days. Dose reductions are indicated for patients with renal insufficiency.

Apixaban can be used in patients with renal insufficiency and recent data suggest use is safe in patients undergoing hemodialysis. Anticoagulation reversal of the oral Xa inhibitors rivaroxabanapixabanedoxaban is possible with andexanet, although this drug is not widely available at this time. Also, the half-lives of the newer factor Xa inhibitors are much shorter than the half-life for warfarin.

If bleeding develops that requires reversal, use of 4-factor prothrombin complex concentrate can be considered, and hematology consultation is recommended. The safety and efficacy of these drugs in patients with PE complicated by severe cardiopulmonary decompensation have not yet been studied, and parenteral drugs should be used for anticoagulation in these patients until there is significant improvement in cardiopulmonary function.

The direct thrombin inhibitor dabigatran has also proven effective for treatment of acute DVT and PE. Idarucizumab has proven effective at reversing dabigatran. Finally, in patients with suspected or proven heparin -induced thrombocytopeniaintravenous argatroban or subcutaneous fondaparinux can be used for anticoagulation. Use of the newer oral anticoagulants is currently being studied in patients with heparin -induced thrombocytopenia, but these drugs appear safe after platelet recovery.

Maintenance anticoagulation is indicated to reduce the risk of clot extension or embolization and to reduce the risk of new clot formation. Drug choices for maintenance anticoagulation include. Oral factor Xa inhibitors apixabanrivaroxabanedoxaban. Warfarin is an effective long-term oral anticoagulant option that has been used for decades, but it is very inconvenient for a number of reasons. In most patients, warfarin is started on the same day as heparin or fondaparinux therapy used for initial anticoagulation.

Heparin or fondaparinux therapy should be overlapped with warfarin therapy for a minimum of 5 days and until the INR has been within the therapeutic range 2. The major disadvantages of warfarin are the need for periodic INR monitoring, with frequent dose adjustments, and drug interactions.

Acute pulmonary embolism (PE) is a form of venous thromboembolism (VTE) that is common and sometimes fatal. The clinical presentation of. Acta Med Leg Soc (Liege). ; The dating of pulmonary emboli. Knight B. PMID: ; [Indexed for MEDLINE]. MeSH terms. Cause of Death. Pulmonary embolism dating - Want to meet eligible single woman who share your zest for life? Indeed, for those who've tried and failed to find the right man.

Physicians prescribing warfarin should be wary of drug interactions; in a patient taking warfarinvirtually any new drug should be checked. Bleeding can be reversed with vitamin K 2. Vitamin K may cause flushing, local pain, and, rarely, anaphylaxis.

Warfarin -induced necrosis, a devastating complication of warfarin therapy, can occur in patients with heparin-induced thrombocytopenia if warfarin is started before platelet recovery.

Based on these considerations and the development of more convenient oral anticoagulants, it is likely that warfarin use will decline substantially over the coming years. In a patient taking warfarinvirtually any new drug should be checked for potential interactions. The oral factor Xa inhibitor anticoagulants apixaban and rivaroxaban can be used for both initial and maintenance anticoagulation therapy see table Oral Anticoagulants.

These drugs are more convenient than warfarin due to their fixed dosing and lack of need for laboratory monitoring, as well as having fewer drug interactions. In clinical trials, rivaroxaban 1, 2apixaban 3and edoxaban 4 were as effective in non-inferiority analyses as warfarin in preventing recurrent DVT and PE.

A meta-analysis of large phase III randomized controlled trials found that rates of major bleeding, including intracranial hemorrhage, were significantly lower with oral factor Xa inhibitor anticoagulants than with warfarin 5. Edoxaban requires that a preceding 5 to 10 days of initial heparin or low molecular weight heparin be given.

The direct thrombin inhibitor dabigatran can also be used for maintenance anticoagulation therapy. As with edoxaban5 to 10 days of treatment with unfractionated heparin or low molecular weight heparin is needed before dabigatran can be initiated.

Clinically relevant bleeding was lower with dabigatran than with warfarin. The use of dabigatran as maintenance therapy has the same advantages and disadvantages as the use of the factor Xa inhibitors.

The need for initial heparin treatment before edoxaban or dabigatran is given is a reflection of the way the clinical trials were conducted. Factor Xa inhibitors. Factor IIa thrombin inhibitor.

Lung - nontumor - Infarct / pulmonary emboli. Page views in 6, Page views in to date: 5, Table of Contents. Publisher: Oxford University Press Print Publication Date: Feb Pulmonary embolism is usually a consequence of deep vein thrombosis. Fatal cor pulmonale caused by extensive tumor emboli in the small pulmonary arteries without emboli in the major pulmonary arteries or metastases in the.

Subcutaneous low molecular weight heparin is primarily used for high-risk cancer patients or patients with recurrent PE despite other anticoagulants. Aspirin has been studied for long-term maintenance therapy. It appears more effective than placebo but less effective than all other available anticoagulants. Duration of maintenance anticoagulation for PE is dependent on a variety of factors eg, risk factors for PE, bleeding risk and can range from 3 mo to lifelong therapy.

Clearly transient risk factors eg, immobilization, recent surgery, trauma require only 3 mo of treatment. Patients with unprovoked PE, those with more durable risk factors for PE eg, cancer, thrombophilic disorderand those with recurrent PE might benefit from lifelong anticoagulation provided the bleeding risk is low or moderate.

In many patients, degree of risk is less clear eg, with a minor precipitating factor such as a 4 hour flight ; for them, rather than stopping rivaroxaban or apixaban at 6 months, dosage can be decreased.

Low risk for bleeding is defined as no bleeding risk factors, moderate risk for bleeding is defined as one risk factor, and high risk for bleeding is defined as two or more risk factors. As described above, after 6 months of treatment with rivaroxaban or apixabandosage decreases can be considered.

N Engl J Med 26 , N Engl J Med 14 , N Engl J Med 9 , N Engl J Med 15 : , Blood 12 : , J Clin Oncol 36 20 , N Engl J Med , Epub Mar Clot elimination by means of embolectomy or dissolution with IV or catheter-based thrombolytic therapy should be considered for acute PE associated with hypotension that does not resolve after fluid resuscitation massive PE.

Patients who are hypotensive and require vasopressor therapy are obvious candidates. Systemic thrombolytic therapy with alteplase tissue plasminogen activator [tPA]offers a noninvasive way to rapidly restore pulmonary blood flow but is controversial because long-term benefits do not clearly outweigh the risk of hemorrhage.

Regardless, most experts agree that systemic thrombolytic therapy should be given to patients with hemodynamic compromise, particularly when it is severe.

SIR-RFS Critical Care Webinar (6/22/2016): Pulmonary Embolism - Management Beyond Anticoagulation

Others reserve thrombolytic therapy only for patients with massive high-risk PE. Streptokinase and urokinase generally are no longer used. Except for concurrent intracerebral hemorrhage, thrombolytic therapy is sometimes given to patients with massive PE who have "absolute contraindications" to such therapy if death is otherwise expected.

In patients with relative contraindications, the decision to give systemic thrombolytics depends on individual patient factors.

Streptokinase and urokinase are no longer used for acute PE. In the US, when systemic thrombolytics are given, heparin is usually stopped after the initial loading dose. However, in Europe, heparin is often continued, and there is no clear determination as to which method is preferred.

The bleeding risk should be considered. Bleeding, if it occurs, can be reversed with cryoprecipitate or fresh frozen plasma. Accessible vascular access sites that are bleeding can be compressed. The potential for bleeding after systemic thrombolysis has led to increased implementation of catheter-based thrombolysis, because much lower doses of thrombolytic agents are used.

Histological age determination of venous thrombosis: a neglected forensic task in fatal pulmonary thrombo-embolism. Fineschi V(1), Turillazzi E. The autopsy dis- section, documentation, and ancillary studies pertaining to pulmonary emboli .. dating the initiating thrombosis. Thorough sampling of the. Pulmonary embolism is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for.

It is used to treat massive PE. Indications for the treatment of submassive PE are evolving. Other outcomes and safety of catheter-based therapy compared to systemic thrombolysis are under investigation. The most widely studied technique uses high-frequency, low-power ultrasonography to facilitate delivery of the thrombolytics.

Ultrasonography accelerates the thrombolytic process by disaggregating fibrin strands and increasing permeability of lytic drug into the clot.

Dating pulmonary emboli

Standard dosing has been 20 to 24 mg of tPA over 15 or more hours, but lower doses and shorter durations have recently been shown to be effective with this technique. Other clot extraction techniques involve catheter-directed vortex suction embolectomy, sometimes in combination with extracorporeal bypass. Catheter-directed vortex suction embolectomy differs from systemic thrombolysis and catheter-based PE thrombolytic therapy in that a larger bore catheter is required and blood that is suctioned out must be redirected out back into a vein usually femoral.

Patients with venal caval, right atrial, or right ventricular thrombi-in-transit are the best candidates. The pulmonary arteries are difficult to access with the current devices. Veno-arterial extracorporeal membrane oxygenation ECMO may be used as a rescue procedure in severely ill patients with acute PE, regardless of what other therapies are used.

Other smaller suctioning devices are currently being studied. Surgical embolectomy should be considered if use of thrombolysis is contraindicated; in such cases, catheter-directed vortex embolectomy may also be considered and, depending on local resources and expertise, tried before surgical embolectomy.

Surgical embolectomy appears to increase survival in patients with massive PE but is not widely available. Extracorporeal membrane oxygenation ECMO has been used increasingly in catastrophic acute PE when thrombolysis is contraindicated or failed.

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ECMO may serve as a bridge to surgical embolectomy or catheter-directed therapy, or it may buy time for improvement with anticoagulation alone. Bedbound patients and patients undergoing surgical, especially orthopedic, procedures benefit, and most of these patients can be identified before a thrombus forms see table Risk Assessment for Thrombosis.

Preventive measures include low-dose unfractionated heparinlow molecular weight heparinwarfarinfondaparinuxoral anticoagulants eg, rivaroxabanapixabancompression devices, and elastic compression stockings.

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