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.

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.

Patients' adherence to oral anticoagulants therapy: Comparison between vitamin K antagonists and direct oral anticoagulants.

BACKGROUND: Patient's adherence to oral anticoagulant therapy is essential to prevent and treat thrombotic events. METHODS: To assess the patients' adherence Morisky Medication Adherence Scale 8-items was used. The target population included 785 consecutive outpatients, of whom 384 were on Vitamin K Antagonists and 401 on Direct Oral Anticoagulants. Moreover, we evaluate which variable among age, gender, having experienced a thrombotic episode, time in the therapeutic range for patients on Vitamin K Antagonists, being naive and once versus twice daily drug assumption for patients on Direct Oral Anticoagulants, could affect adherence to therapy. RESULTS: Morisky Medication Adherence Scale 8-items score was 8 in both groups. The intentional non-adherence obtained the lowest score while the unintentional non-adherence is the most frequent problem in patients treated with either Vitamin K Antagonists or Direct Oral Anticoagulants. Age > 75 years, male gender, having experienced a thrombotic episode, being naive and assuming Direct Oral Anticoagulants twice a day were significantly associated with a higher risk to forget assuming the oral anticoagulant, to have more difficulty in remembering to take it or to bring it in case of travel or leaving home. A low percentage of time in therapeutic range was associated with a not regularly assumption of the anticoagulants. CONCLUSION: Patients treated with Vitamin K Antagonists or Direct Oral Anticoagulants show a good adherence and persistence to their oral anticoagulant therapy. Several factors have been identified to affect patients' adherence and deserve a careful attention by the doctors at the Anticoagulation Clinic.

Retrospective outcomes analysis of 99 consecutive uniportal awake lung biopsies: a real standard of care?

BACKGROUND: Surgical lung biopsy for interstitial lung disease (ILD) is traditionally performed through video-assisted thoracic surgery (VATS) and general anesthesia (GA). The mortality and morbidity rates associated with this procedure are not negligible, especially in patients with significant risk factors and respiratory impairment. Based on these considerations, our center evaluated a safe non-intubated VATS approach for lung biopsy performed in ILD subjects. METHODS: Ninety-nine patients affected by undetermined ILD were enrolled in a retrospective cohort study. In all instances, lung biopsies were performed using a non-intubated VATS technique, in spontaneously breathing patients, with or without intercostal nerve blockage. The primary end-point was the diagnostic yield, while surgical and global operating room times, post-operative length of stay (pLOS), numeric pain rating scale (NPRS) after surgery and early mortality were considered as secondary outcomes. RESULTS: All the procedures were carried out without conversion to GA. The pathological diagnosis was achieved in 97 patients with a diagnostic yield of 98%. The mean operating room length-of-stay and operating time were 73.7 and 42.5 min, respectively. Mean pLOS was 1.3 days with a low readmissions rate (3%). No mortality in the first 30 days due to acute exacerbation of ILD occurred. Both analgesia methods resulted in optimal feasibility with a mean NPRS score of 1.13. CONCLUSIONS: In undetermined ILD patients, surgical lung biopsy with a non-intubated VATS approach and spontaneous ventilation anesthesia appears to be both a practical and safe technique with an excellent diagnostic yield and high level of patient satisfaction.

Empathy and the Educational Approach to Patients With Atrial Fibrillation Treated With Direct Oral Anticoagulants.

Direct Oral Anticoagulants (DOACs) have shown to be at least effective and safer than anti-vitamin K (VKA) for the prophylaxis of cardioembolism during AF. These drugs do not need laboratory monitoring such as the VKA anticoagulants, but they are at risk of poor adherence and persistence as all drugs taken by mouth. Against this drawback, empathy may have an important role because it is important as a tool to be used for effective interpersonal communication. Patients like to be heard and understand that those who listen to them are immersed in their world. Empathy is part, and is a founding principle, of Narrative Medicine which today is a real discipline with many advantages because it is intrinsically therapeutic for the patient (in telling and being heard). Empathy prevents the disconnection that can intervene between the doctor and the patients. Have we ever wondered if we are sufficiently empathetic? Is it possible to measure our empathy? Yes, across Jefferson's scale. A high score on Jefferson's scale could certainly further improve the quality of the management of anticoagulated patients.

Pulmonary Thrombosis: A Clinical Pathological Entity Distinct from Pulmonary Embolism?

Since Virchow's autopsy studies in the mid-1800s, it has generally been believed that pulmonary embolism (PE) originated from the embolization of fibrin fragments from a deep venous thrombosis (DVT). However, a DVT is often not found in patients with PE (up to 50% of cases). Could fibrin form in the pulmonary vessels without coming from the periphery? In this review, the authors will try to support the hypothesis that a pulmonary thrombosis (PT) may develop. They will do so through different clinical models related to some pathological conditions such as pneumonia, chronic obstructive pulmonary disease (COPD), and asthma, all of which show a close relationship between local inflammation and activation of blood coagulation, two defensive systems that may lead to fibrin deposition in the lungs, thus recognizing the possibility that PT may be a newly recognized entity. An increased risk for PE has been demonstrated in these conditions. Sickle cell disease and assisted reproductive technologies are other very different conditions in which an increased risk for PE has been found. Gaucher's disease is a rare hereditary condition in which the hemostatic system could have a role in the pathogenesis of pulmonary hypertension, which complicates the course of the disease. In particular, the increased risk for PT, common to all these conditions, deserves attention when a patient presents with sudden dyspnea, an unexpected COPD exacerbation, or severe sudden asthmatic dyspnea. As a consequence, prediction scores for venous thromboembolism could be revised.

The venous thromboembolic risk and the clot wave analysis: a useful relationship?

BACKGROUND: Hospitalized patients with acute medical conditions have higher venous thromboembolism (VTE) risk. A patient with a final Padua Prediction Score (PPS) of ≥4 is considered to be at high risk for VTE. The aim of this study was to investigate on a possible relationship between PPS, the dynamics of the clot formation, i.e. the clot waveform analysis (CWA) of aPTT, fibrinogen and D-Dimer in a large group of medical patients. METHODS: CWA in terms of velocity (first derivative), acceleration (second derivative), density (Delta) of aPTT, fibrinogen, D-Dimer and PPS for VTE were determined in 801 medical patients divided in three groups (without antithrombotic prophylaxis and high PPS, without antithrombotic prophylaxis and low PPS, with antithrombotic prophylaxis and high PPS) and a group of healthy subjects. RESULTS: CWA, fibrinogen and D-Dimer values were higher in the medical patients with high PPS with or without antithrombotic prophylaxis when compared with patients without antithrombotic prophylaxis with low PPS and healthy subjects. The second derivative, fibrinogen and D-Dimer were significantly associated with a high PPS score (≥4): odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.03-2.28; OR = 1.91, 95% CI = 1.3-2.79; OR = 3.16, 95% CI = 2.29-4.36, respectively. Interactions between first derivative and D-Dimer (OR = 2.14, 95% CI = 1.23-3.72) and first derivative and fibrinogen (OR = 1.75, 95% CI = 1.02-2.98) were found. CONCLUSIONS: CWA could give useful information to recognize a hypercoagulable state in patients admitted to a medical ward with high and low PPS. First and second derivative aPTT, D-Dimer and fibrinogen levels could be added to PPS to better assess the global thromboembolic risk of these patients.

Dabigatran overdose: a case report of acute hepatitis. Extracorporeal treatment.

Dabigatran is an oral, direct thrombin inhibitor approved by international regulatory agencies for stroke prevention in patients with paroxysmal or persistent non-rheumatic atrial fibrillation (AF). The benefits of dabigatran are widely described, but its use in the geriatric population is not without risk. Chronic kidney disease is a common comorbidity with AF, and thus frequent checks of renal function in elderly patients are recommended. We report a case of dabigatran intoxication in an elderly man affected by heart failure and worsening renal function, who developed acute hepatitis and coma, which was successfully treated with continuous veno-venous hemodiafiltration. Although extracorporeal therapy has been suggested as a strategy for clearing dabigatran during acute bleeding, this approach may be useful in other dabigatran-related, life-threatening conditions, such as that described in this report.

Plasmapheresis for Preventing Complication of Hypertriglyceridemia: A Case Report and Review of Literature.

Severe hypertriglyceridemia is a common indication for the need of plasma exchange in treatment of hypertriglyceridemic-induced pancreatitis when normal therapies fail to garner a response. Application of plasmapheresis to prevent complication of hypertriglyceridemia is limited because of its cost and availability. We present a case of a 44-year-old man with metabolic syndrome and a medical history of secondary polycythemia in obesity hypoventilation syndrome, whose laboratory tests revealed a triglycerides value of 3965 mg/dL. To prevent the complication of pancreatitis due to hypertriglyceridemia, we performed plasma exchange 3 times when conventional treatments did not sufficiently reduce the high level of triglycerides. A review of the current available literature was therefore conducted to provide an overview of the present data on apheretic treatment for patients with severe hypertriglyceridemia. Several case reports and case series have used plasmapheresis in acute treatment of hypertriglyceridemia pancreatitis related. In our case, the choice of plasmapheresis was applied in prevention of possible complications of hypertriglyceridemia.

Acquired factor VIII inhibitor and subsequent development of non-Hodgkin's lymphoma: a case report and review of the literature.

Acquired hemophilia A (AHA) is a rare disorder caused by the development of factor VIII autoantibodies. It can induce acute and major hemorrhages in patients with negative personal and family history of bleeding. AHA is frequently associated with hematologic malignancies. This study describes the first case of AHA in a patient who developed a mantle cell lymphoma after a year and half of complete remission. It also provides an example of an initial wrong approach in terms of diagnosis and treatment, as well as of a very long course of the disease. Further, a review of AHA-associated lymphomas from 1974 to 2014 is also presented.Clinical and laboratory staff should be alert to the possibility of such an event when the medical history of patients is enriched with new symptoms or signs. A follow-up of at least 2 years might therefore be required.

Thromboembolic disease in patients with rheumatoid arthritis undergoing joint arthroplasty: Update on prophylaxes.

The risk of venous thromboembolism (VTE) in rheumatoid arthritis (RA) and the higher incidence of RA patients undergoing major orthopedic surgery is well recognized. The objective of the present study is to describe the incidence of VTE and discuss the correct prophylaxis in RA patients undergoing knee or hip replacement. A systematic review of studies on thromboprophylaxis in RA patients undergoing major orthopedic surgery was performed. Detailed information was extracted to calculate the rate of VTE in RA orthopedic patients and analyze the thromboprophylaxis performed and bleeding complications. Eight articles were eligible for full review. No difference in the overall rate of VTE was observed between RA patients and controls. No significant differences were found in RA patients in terms of bleeding complications. The data on the optimal prophylaxis to be used in RA patients were insufficient to recommend any of the several options available. In the absence of dedicated guidelines for the care of RA patients undergoing orthopedic surgery, management must be individualized to obtain favorable patient outcome, weighing up all the factors that might put the patient at risk for higher bleeding and thrombotic events.

Thyroid disorders and hypocoagulability.

This review focuses attention on some practical aspects of the relationship between thyroid disorders and hypocoagulability, as related to an impairment of hemostasis and fibrinolysis. An understanding of this topic in daily clinical practice is important given that the interaction between hemostatic abnormalities and thyroid disorders is still poorly recognized by the medical community. Even if the bleeding tendency is in general mild and may be reversed by restoration of an euthyroid state, severe hemorrhagic events may complicate the course of both hyper- and hypothyroidism, as precipitated by such conditions as thrombocytopenia, acquired von Willebrand syndrome, and acquired hemophilia. The pathogenesis of the hemostatic abnormalities resides in either the direct effect of thyroid hormones or some conditions in an autoimmune mechanism. Physicians and endocrinologists should pay close attention to both clinical hemorrhagic events in their patients as well as to any laboratory abnormalities identified by blood coagulation testing.

High frequency of inadequate test requests for antiphospholipid antibodies in daily clinical practice.

BACKGROUND: We have empirically noted that many physicians routinely request anti-phospholipid antibodies (aPL) without a correct clinical indication. The aim of this study was to evaluate retrospectively whether aPL testing at our Thrombosis Centre was justified. METHODS: Medical records from 520 subjects for aPL screening tests for various clinical conditions were reviewed. The aPL screening tests were: lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL) and anti-ß(2) glycoptotein I (aß(2) GPI). Requests for aPL screening were divided into justified, potentially justified or not adequately justified. RESULTS: aPL testing requests were considered justified in 358 (69%) patients, potentially justified in 66 (12.6%) and not adequately justified in 96 (18.4%). LA was positive in 65 (18%) of justified requests and in only one (1%) of the 96 potentially justified requests. None of the 66 not adequately justified for aPL testing was positive for LA. aß(2) GPI was positive in 63 (17.6%) of the 358 justified, in four (6%) of the 66 potentially justified and in five (5.2%) of the 96 not adequately justified requests; aCL IgG were positive in 59 (16.4%) of the 358 justified and in five (7.5%) and six (6.2%) of the potentially justified and not adequately justified requests, respectively. The presence of the triple aPL positivity was found exclusively in the justified requests. CONCLUSIONS: This study suggests that requests for aPL tests should be addressed more adequately. This work could be an example of how to focus attention on requests for laboratory tests especially on the basis of valid clinical criteria before the analyte is measured.