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

The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed.

/pdf/acute-exacerbations-of-idiopathic-pulmonary-fibrosis-4v5lmmsvxz.pdf

Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Perioperative monitoring of blood coagulation is critical to better understand causes of hemorrhage, to guide hemostatic therapies, and to predict the risk of bleeding during the consecutive anesthetic or surgical procedures. Point-of-care (POC) coagulation monitoring devices assessing the viscoelastic properties of whole blood, i.e., thrombelastography, rotation thrombelastometry, and Sonoclot analysis, may overcome several limitations of routine coagulation tests in the perioperative setting. The advantage of these techniques is that they have the potential to measure the clotting process, starting with fibrin formation and continue through to clot retraction and fibrinolysis at the bedside, with minimal delays. Furthermore, the coagulation status of patients is assessed in whole blood, allowing the plasmatic coagulation system to interact with platelets and red cells, and thereby providing useful additional information on platelet function. Viscoelastic POC coagulation devices are increasingly being used in clinical practice, especially in the management of patients undergoing cardiac and liver surgery. Furthermore, they provide useful information in a large variety of clinical scenarios, e.g., massive hemorrhage, assessment of hypo- and hypercoagulable states, guiding pro- and anticoagulant therapies, and in diagnosing of a surgical bleeding. A surgical etiology of bleeding has to be considered when viscoelastic test results are normal. In summary, viscoelastic POC coagulation devices may help identify the cause of bleeding and guide pro- and anticoagulant therapies. To ensure optimal accuracy and performance, standardized procedures for blood sampling and handling, strict quality controls and trained personnel are required.

/pdf/coagulation-monitoring-current-techniques-and-clinical-use-59whjtf24i.pdf

Coagulation monitoring: current techniques and clinical use of viscoelastic point-of-care coagulation devices

High-resolution melting of DNA is a simple solution for genotyping, mutation scanning and sequence matching. The melting profile of a PCR product depends on its GC content, length, sequence and heterozygosity and is best monitored with saturating dyes that fluoresce in the presence of double-stranded DNA. Genotyping of most variants is possible by the melting temperature of the PCR products, while all variants can be genotyped with unlabeled probes. Mutation scanning and sequence matching depend on sequence differences that result in heteroduplexes that change the shape of the melting curve. High-resolution DNA melting has several advantages over other genotyping and scanning methods, including an inexpensive closed tube format that is homogenous, accurate and rapid. Owing to its simplicity and speed, the method is a good fit for personalized medicine as a rapid, inexpensive method to predict therapeutic response.

/pdf/high-resolution-dna-melting-analysis-for-simple-and-15dm5ilm6n.pdf

High-resolution DNA melting analysis for simple and efficient molecular diagnostics

Background The optimal duration of oral anticoagulation in patients with idiopathic venous thromboembolism is uncertain. Testing of d-dimer levels may play a role in the assessment of the need for prolonged anticoagulation. Methods We performed d-dimer testing 1 month after the discontinuation of anticoagulation in patients with a first unprovoked proximal deep-vein thrombosis or pulmonary embolism who had received a vitamin K antagonist for at least 3 months. Patients with a normal d-dimer level did not resume anticoagulation, whereas those with an abnormal d-dimer level were randomly assigned either to resume or to discontinue treatment. The study outcome was the composite of recurrent venous thromboembolism and major bleeding during an average follow-up of 1.4 years. Results The d-dimer assay was abnormal in 223 of 608 patients (36.7%). A total of 18 events occurred among the 120 patients who stopped anticoagulation (15.0%), as compared with 3 events among the 103 patients who resumed anticoagulation (2.9%), for an adjusted hazard ratio of 4.26 (95% confidence interval [CI], 1.23 to 14.6; P = 0.02). Thromboembolism recurred in 24 of 385 patients with a normal d-dimer level (6.2%). Among patients who stopped anticoagulation, the adjusted hazard ratio for recurrent thromboembolism among those with an abnormal d-dimer level, as compared with those with a normal d-dimer level, was 2.27 (95% CI, 1.15 to 4.46; P = 0.02). Conclusions Patients with an abnormal d-dimer level 1 month after the discontinuation of anticoagulation have a significant incidence of recurrent venous thromboembolism, which is reduced by the resumption of anticoagulation. The optimal course of anticoagulation in patients with a normal d-dimer level has not been clearly established. (ClinicalTrials.gov number, NCT00264277.)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa054444

d-Dimer Testing to Determine the Duration of Anticoagulation Therapy

COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia?

Dengue virus–induced hemorrhage in a nonhuman primate model

A hypercoagulable state follows orthotopic liver transplantation.

○ Objective.-To review the current understanding of the pathophysiology of antithrombin deficiency and its role in congenital thrombophilia. Recommendations for diagnostic testing of antithrombin function and concentration, derived from the medical literature and consensus opinions of recognized experts in the field, are included. These recommendations specify whom, how, and when to test. Data Sources.-Review of the published medical literature. Data Extraction and Synthesis.-A summary of the medical literature and proposed testing recommendations were prepared and presented at the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia. After discussion at the conference, consensus recommendations presented in this article were accepted after a two-thirds majority vote by the participants. Conclusions.-Antithrombin deficiency is an infrequent genetic abnormality that may be a significant contributing cause of thrombophilia. Antithrombin deficiency also may be observed in conjunction with other genetic or acquired risk factors. Assay of antithrombin plasma levels is appropriate in the laboratory evaluation of individuals with thrombophilia, preferably using a functional, amidolytic antithrombin assay. The diagnosis of antithrombin deficiency should be established only after other acquired causes of antithrombin deficiency, such as liver disease, consumptive coagulopathy, or heparin therapy, are excluded. A low antithrombin level should be confirmed with a subsequent assay on a fresh specimen, and family studies may be helpful to establish the diagnosis. Antigenic antithrombin assays may be of benefit in subclassification of the type of antithrombin deficiency and to confirm the decreased antithrombin level in patients with type I deficiency.

Antithrombin deficiency: issues in laboratory diagnosis.

Orthotopic liver transplantation may be associated during the postoperative period with hepatic artery thrombosis, a catastrophic occurrence generally necessitating emergency retransplantation. To assess the contribution of the coagulation mechanism to this complication, the levels of procoagulant and anticoagulant proteins were followed in 41 liver transplant patients during the first 10 postoperative days. The mean activities of all procoagulant factors reach normal values on day 1 except for factors V and VII, which achieve normal activity by day 3. Supernormal levels of factor VIII activity and antigen are noted (peak values on day 5 of 334% +/- 113% and 481% +/- 260%, respectively). The anticoagulant proteins show delayed recovery, with deficient antithrombin III levels seen in 81% of patients on day 3 and 57% on day 5. Similarly, proteins C and S are subnormal in 24% and 21%, respectively on day 3, and 20% and 10%, respectively, on day 5. During this period, elevated levels of thrombin/antithrombin complexes are encountered, reflecting in vivo activation of the coagulation mechanism. Activated thrombin is, therefore, being generated at a time when a decrease in the major regulatory anticoagulant proteins exists. These data suggest an imbalance between the hemostatic and thrombotic mechanisms and indicate a sustained prothrombotic state that may contribute to the risk for hepatic artery thrombosis. Using a regimen of low-dose heparin and fresh frozen plasma infusion, no thromboses have been seen in 65 consecutive liver transplants.

Alexander Duncan

Papers

COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia?

Dengue virus–induced hemorrhage in a nonhuman primate model

A hypercoagulable state follows orthotopic liver transplantation.

Antithrombin deficiency: issues in laboratory diagnosis.

A Hypercoagulable State Follows Orthoptic Liver Transplantation