Antithrombotic therapy for venous thromboembolic disease.

2011 Update to The Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines

Iron-chelating therapy and the treatment of thalassemia

Most deep vein thromboses (DVTs) start in the calf, and most probably resolve spontaneously. Thrombi that remain confined to the calf rarely cause leg symptoms or symptomatic pulmonary embolism (PE). The probability that calf DVT will extend to involve the proximal veins and subsequently cause PE increases with the severity of the initiating prothrombotic stimulus. Although acute venous thromboembolism (VTE) usually presents with either leg or pulmonary symptoms, most patients have thrombosis at both sites at the time of diagnosis. Proximal DVTs resolve slowly during treatment with anticoagulants, and thrombi remain detectable in half of the patients after a year. Resolution of DVT is less likely in patients with a large initial thrombus or cancer. About 10% of patients with symptomatic DVTs develop severe post-thrombotic syndrome within 5 years, and recurrent ipsilateral DVT increases this risk. About 10% of PEs are rapidly fatal, and an additional 5% cause death later, despite diagnosis and treatment. About 50% of diagnosed PEs are associated with right ventricular dysfunction, which is associated with a approximately 5-fold greater in-hospital mortality. There is approximately 50% resolution of PE after 1 month of treatment, and perfusion eventually returns to normal in two thirds of patients. About 5% of treated patients with PE develop pulmonary hypertension as a result of poor resolution. After a course of treatment, the risk of recurrent thrombosis is higher (ie, approximately 10% per patient-year) in patients without reversible risk factors, in those with cancer, and in those with prothrombotic biochemical abnormalities such as antiphospholipid antibodies and homozygous factor V Leiden.

Natural History of Venous Thromboembolism

In 1994, the American Society of Anesthesiologists established the Task Force on Blood Component Therapy to develop evidence‐based indications for transfusing red blood cells, platelets, fresh‐frozen plasma, and cryoprecipitate in perioperative and peripartum settings. The guidelines were developed according to an explicit methodology. The principal conclusions of the task force are that red blood cell transfusions should not be dictated by a single hemoglobin \"trigger\" but instead should be based on the patient's risks of developing complications of inadequate oxygenation. Red blood cell transfusion is rarely indicated when the hemoglobin concentration is greater than 10 g/dL and is almost always indicated when it is less than 6 g/dL. The indications for autologous transfusion may be more liberal than for allogeneic (homologous) transfusion. The risks of bleeding in surgical and obstetric patients are determined by the extent and type of surgery, the ability to control bleeding, the actual and anticipated rate of bleeding, and the consequences of uncontrolled bleeding. Prophylactic platelet transfusion is ineffective when thrombocytopenia is due to increased platelet destruction. Surgical and obstetric patients with microvascular bleeding usually require platelet transfusion if the platelet count is less than 50 x 109 /l and rarely require therapy if it is greater than 100 x 10 sup 9 /l. Fresh‐frozen plasma is indicated for urgent reversal of warfarin therapy, correction of known coagulation factor deficiencies for which specific concentrates are unavailable, and correction of microvascular bleeding when prothrombin and partial thromboplastin times are > 1.5 times normal. It is contraindicated for augmentation of plasma volume or albumin concentration. Cryoprecipitate should be considered for patients with von Willebrand's disease unresponsive to desmopressin, bleeding patients with von Willebrand's disease, and bleeding patients with fibrinogen levels below 80–100 mg/dL. The task force recommends careful adherence to proper indications for blood component therapy to reduce the risks of transfusion.

Practice guidelines for blood component therapy: A report by the American Society of Anesthesiologists Task Force on Blood Component Therapy

Current status of pulmonary thromboembolic disease: Pathophysiology, diagnosis, prevention, and treatment

Controlled trial of routine administration of platelet concentrates in cardiopulmonary bypass surgery

A comparative analysis of pulmonary perfusion scans with pulmonary angiograms.

Extension of platelet concentrate storage.

IN 1967 the National Heart and Lung Institute organized a multi-institutional controlled clinical trial to evaluate thrombolytic agents in the treatment of pulmonary embolism.' The results of the first phase of that study (The Urokinase Pulmonary Embolism Trial) showed that 12 hours of urokinase compared to heparin and oral anticoagulants alone increased the resolution rate of pulmonary thromboemboli, especially massive emboli, as judged by arteriography, hemodynamics, and lung scanning, assessed within 24 hours of therapy.2 3 4 Serial lung scanning revealed that these differences in embolus resolution rates decreased when assessed at 14 days.4 A second phase (The Urokinase-Streptokinase Pulmonary Embolism Trial), recently completed and reported in more detail in the Journal of the American Medical Association,5 compares 12 hours of urokinase to 24 hours of urokinase and to 24 hours of streptokinase. One hundred sixty-seven patients who satisfied the clinical criteria for embolism within five days of treatment and the specific angiographic criteria applied by

Toby L. Simon

Papers

Current status of pulmonary thromboembolic disease: Pathophysiology, diagnosis, prevention, and treatment

Controlled trial of routine administration of platelet concentrates in cardiopulmonary bypass surgery

A comparative analysis of pulmonary perfusion scans with pulmonary angiograms.

Extension of platelet concentrate storage.

The Urokinase-Streptokinase Pulmonary Embolism Trial (Phase II) Results