Clot Waveform Analysis: From Hypercoagulability to Hypocoagulability - A Review.

CONTEXT.­: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are coagulative screening tests used for the diagnosis of several pathologic conditions, such as liver failure, coagulation factor deficiencies, anti-phospholipid antibodies (lupus anticoagulant), and factor VIII inhibitors. A new test was developed several years ago to detect the amount of thrombin generated during plasma clotting, using low tissue factor concentrations and fluorogenic substrates, and it has since been used successfully in conditions ranging from hypocoagulable to hypercoagulable states. However, the test is expensive and difficult to perform in nonspecialized laboratories, and efforts have thus been made to find an economic and easily implementable test suitable for routine use, even in nonspecialist laboratories. OBJECTIVE.­: To evaluate clot waveform analysis (CWA) of PT and aPTT, aiming to show the dynamics of clot formation; that is, the "hidden" features of both tests. CWA can be implemented by using an automated coagulometer with dedicated software. The aim of this review was to evaluate whether CWA is able to detect both hypercoagulative and hypocoagulative states. DATA SOURCES.­: Using MedLine, we searched and retrieved articles relating to CWA. We only considered articles published in English, but with no limits in terms of article type, publication year, or geography. CONCLUSIONS.­: CWA was shown to be a reliable test in patients with both hypercoagulable and hypocoagulable states. It represents a simple and inexpensive global test that can easily provide information on the behavior of the coagulation system. Both the first and second derivatives are computed by using dedicated software implemented with an on-board algorithm in a routine automated coagulometer.

Is anticoagulative therapy in systemic sclerosis to be reconsidered?

Systemic sclerosis is a rare disease with a high mortality rate. It is a multisystem connective tissue disease due to endothelial autoimmune activation along with tissue and vascular fibrosis, inducing vasculopathy, with an angiogenesis wasting. The endothelial damage provokes platelet activation and immune cell adhesion. The detachment of endothelial cells leads to the interaction of platelets and collagen present in the exposed subendothelial layer. This provokes the activation of several coagulative factors, inducing a pro-thrombotic condition by thrombin generation, which converts fibrinogen into fibrin. Moreover, thrombin has other functions, such as the induction of hyperplasia in smooth muscle cells and fibroblasts, thereby favouring fibrosis. An increased risk of venous thromboembolism has been found in systemic sclerosis, whereas pulmonary hypertension may be due to the obstruction of small pulmonary arteries. Pulmonary veno-occlusive disease may also occur. Warfarin showed inconsistent results, while the outcomes of a randomised, placebo-controlled clinical trial on apixaban versus placebo are still awaited. A new anticoagulation strategy based on anti-factor XI drugs is being developed, with the aim of achieving optimal anticoagulation along with a low risk of bleeding. The molecule types under investigation in this category include monoclonal antibodies, small molecules, natural inhibitors, antisense oligonucleotides, and aptamers. Patients with systemic sclerosis may be ideal candidates for clinical trials planned to analyse the efficacy and safety of these molecules.

Do we need more guidance on thrombophilia testing? Challenges and special considerations.

INTRODUCTION: Thrombophilia testing (TT) is a laboratory procedure designed to detect the risk factors involved in the pathogenesis of vascular occlusions. The role of TT is also controversial because it has a limited impact on the choice and duration of antithrombotic treatments. AREAS COVERED: We reviewed, by examining MEDLINE up to October 2023. Accepted and not accepted thrombophilia markers are discussed along with the appropriateness or not of prescribing TT in several conditions such as: provoked and unprovoked venous thromboembolism (VTE), women who are planning a pregnancy whose relatives had VTE or have a hereditary thrombophilia, before assumption of estro-progestins, after multiple pregnant loss, arterial thrombosis, retinal vein occlusion, and splanchnic vein thrombosis. EXPERT OPINION: TT is not essential in the management of VTE, but it may be useful for limiting adverse events in case of thrombophilia. We expose our criticism of items afforded by other guidelines by presenting our opinion based on both the scientific evidence and clinical practice. We also deal with common mistakes in prescribing and interpretations of TT hoping to purpose an educational approach on this topic. Finally, we emphasize the creation of the expert in hemostasis and thrombosis who should be present in every hospital.

Navigating anemia and anticoagulation in elderly patients undergoing orthopedic surgery: strategies for preventing complications and implementing treatments.

BACKGROUND: Elderly populations face an increased risk of anemia, leading to elevated transfusion requirements during surgery, especially major orthopedic procedures. Anemia itself increases the risk of thromboembolic events, thus compounding complications in elderly individuals. Polypharmacy and the prevalent use of oral anticoagulants (OAC), particularly for atrial fibrillation, contribute to bleeding risks in this population. Data available in the literature on the peri-operative management of anemia in patients taking OAC is limited and often heterogeneous. MATERIALS AND METHODS: This narrative case-based review focuses on the peri-operative management of elderly patients on OAC undergoing major orthopedic surgery. PubMed/Medline was used to search for relevant literature. RESULTS: With reference to two cases, we critically evaluate the literature, and focus on risk factors, and preventive and therapeutic strategies as fundamental tools to reduce bleeding and correct anemia as soon as possible in elderly patients undergoing major orthopedic surgery. DISCUSSION: Peri-operative management of these patients, especially those on OAC, requires a balanced approach considering bleeding and thrombotic risks. Intravenous iron therapy and tranexamic acid emerge as valuable strategies in minimizing transfusion requirements and optimizing patients' outcomes.

Practical Suggestions for an Optimal Management of Vitamin K Antagonists: Italian Federation of Centers for the Diagnosis of Thrombotic Disorders and the Surveillance of the Antithrombotic Therapies (FCSA) Position Paper.

In the era of direct oral anticoagulants, vitamin K antagonists retain a clinically relevant role in thrombotic disorders. In Italy, approximately 20% of the patients on anticoagulant therapies receives a VKA, in most cases warfarin. The optimal management of this drug is challenging and cannot disregard its intricate and unpredictable pharmacokinetic properties and patient's thrombotic and bleeding risk. Several clinical issues encountered during warfarin treatment are still unanswered and are tentatively addressed by physicians. In this regard, the Italian Federation of Centers for the diagnosis of thrombotic disorders and the Surveillance of the Antithrombotic therapies (FCSA) provides some experience-based good clinical practice's suggestions on the following topics: (1) how to start the anticoagulant treatment with warfarin and warfarin induction regimen; (2) how to manage a subtherapeutic INR value; (3) how to manage a supratherapeutic INR value in asymptomatic patients; and (4) how to manage the association of warfarin with interfering drugs.

Living on Oral Anticoagulants: Duke Anticoagulation Satisfaction Scale Results.

BACKGROUND: Direct oral anticoagulants (DOACs) are widely used in patients with atrial fibrillation and venous thromboembolism. The lack of the need for laboratory monitoring and a better safety than vitamin K antagonists (VKAs) has probably changed the quality of life of patients on these oral anticoagulants. This was a real-life prospective observational cohort study. The aim was to evaluate if a long-term treatment with DOACs could offer a better quality of life than VKAs. Moreover, age, gender, education level, time in therapeutic range for VKAs, taking medication once or twice a day for DOACs, the total daily number of medications and thrombotic and bleeding complications were considered as variables probably associated with the quality of life of these patients. METHODS: Between January and December 2021, the Duke Anticoagulation Satisfaction Scale (DASS) 25-items was administered as an interview to patients on either VKAs or DOACs therapy. During the follow-up period, all of the patients were closely monitored to evaluate possible bleeding and thrombotic events. RESULTS: The analysis included 300 outpatients treated with VKAs and 254 treated with DOACs. In general, the quality of life was better in patients taking DOACs (DASS total score: DOACs = 44.7, 42.9-46.5 vs. VKAs = 51, 49.2-52.8, p < 0.0001) as the daily-life limitations, hassles and burdens and the psychological impact were less important than in patients on VKAs therapy. CONCLUSIONS: VKAs negatively influence the daily-life of the patients in terms of both less satisfaction and time-consuming tasks. DOACs confer a better quality of life even if some concerns emerge from not knowing how their therapy is working.