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Catastrophic antiphospholipid syndrome (CAPS) is a rare clinical form of antiphospholipid syndrome (APS) associated with life-threatening complications due to simultaneous thrombosis that may affect small and large vessels. It may be localized to the venous and/or arteries at the same time, and there are not available guidelines based on randomized clinical trials or large series. We here report a clinical case of CAPS with onset after resolution of oligo-symptomatic infection SARS-CoV-2, that had transient improvement with warfarin after recurrent thromboses occurred despite treatment off-label with low doses of low molecular weight heparin. Furthermore, we tried to trace a line by which a multidisciplinary team may set specific timing to have follow-up because of the high morbidity, mortality, and prolonged time of hospitalization.

Catastrophic antiphospholipid syndrome (CAPS) is a rare clinical form of antiphospholipid syndrome (APS) associated with life-threatening complications due to simultaneous thrombosis that may affect small and large vessels. It may be localized to the venous and/or arteries at the same time, and there are not available guidelines based on randomized clinical trials or large series. We here report a clinical case of CAPS with onset after resolution of oligo-symptomatic infection SARS-CoV-2, that had transient improvement with warfarin after recurrent thromboses occurred despite treatment off-label with low doses of low molecular weight heparin. Furthermore, we tried to trace a line by which a multidisciplinary team may set specific timing to have follow-up because of the high morbidity, mortality, and prolonged time of hospitalization. [ABSTRACT FROM AUTHOR]

Since MPL mutation is a rare driver gene mutation found in a small number of essential thrombocythemia (ET) patients, the clinical characteristics of patients with MPL mutations and their association with thrombotic events have not yet been elucidated in Japan. We enrolled 579 Japanese ET patients based on the diagnostic criteria of the WHO classification 2017 and compared clinical characteristics of MPL-mutated patients (n = 22; 3.8%) to JAK2V617F-mutated (n = 299; 51.6%), CALR-mutated (n = 144; 24.9%), and triple-negative (TN) (n = 114; 19.7%) patients. Thrombosis during follow up was observed in 4 out of 22 (18.2%) in the MPL-mutated group, which was the highest among all driver gene mutation groups (JAK2V617F-mutated, 8.7%; CALR-mutated, 3.5%; TN,1.8%). The MPL- and JAK2V617F-mutated groups had worse thrombosis-free survival (TFS) than the CALR-mutated (p = 0.043) and TN groups (p = 0.006). Univariable analysis revealed that a history of thrombosis was a possible risk factor for thrombosis among MPL-mutated patients (hazard ratio: 9.572, p = 0.032). MPL-mutated ET patients should require more intensive management to prevent recurrence of thrombosis. [ABSTRACT FROM AUTHOR]

A 45-year-old female presented with unprovoked recurrent venous thromboembolism (VTE), in unusual sites, and pancytopenia, posing a complex diagnostic challenge. Work-up for inherited thrombophilia, antiphospholipid syndrome (APLS) and paroxysmal nocturnal haemoglobinuria were unremarkable. Investigations revealed autoimmune thyroid disease, and a mixed iron/vitamin B12 deficiency due to pernicious anaemia and resultant atrophic gastritis. Hyperhomocysteinaemia due to vitamin B12 deficiency was identified as a potential contributor to her recurrent VTE. This case highlights the unusual initial presentation of autoimmune polyendocrinopathy syndrome type 3B (APS-3B) with recurrent thromboembolism, and emphasises the importance of considering hyperhomocysteinaemia in unprovoked and atypical VTE cases.

Patients with thrombotic antiphospholipid syndrome (APS) require long-term anticoagulation due to the high-thrombotic recurrence risk. Vitamin K antagonists (VKA) have been traditionally considered the standard of care in thrombotic APS. Nevertheless, the risk of recurrence persists with VKA. There are publications considering different intensities of anticoagulation with VKA; however, the standard-intensity anticoagulation (international normalized ratio between 2.0 and 3.0) is the most recommended. Furthermore, there is no consensus on the role of antiplatelet treatment in thrombotic APS. Nonvitamin K antagonist oral anticoagulants (NOACs) have emerged as an alternative to VKA for many indications. There are, however, discrepancies regarding the management with NOACs in thrombotic APS. In this review, we update the different clinical trials with NOACs in venous, arterial, and microvascular thrombosis and suggest how these patients should be managed in agreement with the expert panels. Although scarce data are published regarding the current role of NOACs in thrombotic APS, the clinical trials failed to demonstrate noninferiority of NOACs compared with VKA, especially in patients with triple antiphospholipid antibodies positivity and/or arterial thrombosis. Single or double antiphospholipid positivity should be analyzed on a case-by-case basis. In addition, we focus on different areas of uncertainty that still remain in thrombotic APS and NOACs. To summarize, emerging clinical trials are needed to provide robust data on the management of thrombotic APS. [ABSTRACT FROM AUTHOR]

The current study involving 318 essential thrombocythemia (ET) patients with prior thrombosis was designed to identify risk factors that were predictive of recurrent thrombosis. The whole cohort was randomly split into derivation and validation cohorts. The random forest method, support vector machine with built-in recursive feature elimination model, and logistic multivariable analysis were performed in the derivation cohort, and cardiovascular risk factor (CVF) and RBC distribution width with standard deviation (RDW-SD) were finally selected as independent predictors. Subsequently we devise a 3-tiered model (low risk: 0 points; intermediate risk: 1-1.5 points; and high risk: 2.5 points) and it showed good discrimination in all cohorts. Moreover, the model was significantly correlated with rethrombosis-free survival (rTFS) (p = 0.0007 in the derivation cohort; p = 0.0019 in the validation cohort). In the whole cohort, cytoreductive therapy was more effective than antiplatelet agents alone for 10-year rTFS (p = 0.0336). No significant difference in 10-year rTFS was observed among interferon (IFN), hydroxyurea (HU), and IFN + HU therapy (p = 0.444). The present study helps identify individuals who need close monitoring and provides valuable risk signals for recurrence in ET patients with prior thrombosis. Highlights: Reliable biomarkers to accurately predict recurrence in essential thrombocythemia patients who have a previous thrombosis have been lacking thus far, and the prognostic significance remains to be carefully defined. Based on machine learning algorithm, we confirmed that CVF and RDW-SD ≥ 47 fL were independent predictors of recurrence, and both were associated with reduced rTFS. Cytoreductive agents still play a fundamental role on treating thrombosis in high-risk ET patients. [ABSTRACT FROM AUTHOR]

Limited evidence exists to guide the management of recurrent thrombosis occurring despite therapeutic anticoagulation in patients with thrombotic antiphospholipid syndrome (APS). In this case series, fondaparinux, with or without an antiplatelet agent, provided an effective and safe option in three patients with thrombotic APS, all two triple and one single positive for antiphospholipid antibodies, who had recurrent venous and/or arterial thromboembolism. Rituximab was also used in all patients. Recurrent events occurred despite therapeutic anticoagulation, including at high-intensity, with warfarin and subsequent low-molecular-weight heparin. There were no major bleeding events. Adjunctive therapies used for thrombosis included catheter-directed thrombolysis and rituximab. [ABSTRACT FROM AUTHOR]

A 72-year-old female patient with mixed rheumatic mitral valve disease and persistent atrial fibrillation underwent mitral valve replacement and suffered from a combined thrombosis of the bioprosthetic valve and the left atrium as soon as 2 days post operation. The patient immediately underwent repeated valve replacement and left atrial thrombectomy. Yet, four days later the patient died due to the recurrent prosthetic valve and left atrial thrombosis which both resulted in an extremely low cardiac output. In this patient's case, the thrombosis was notable for the resistance to anticoagulant therapy as well as for aggressive neutrophil infiltration and release of neutrophil extracellular traps (NETs) within the clot, as demonstrated by immunostaining. The reasons behind these phenomena remained unclear, as no signs of sepsis or contamination of the BHV were documented, although the patient was diagnosed with inherited thrombophilia that could impede the fibrinolysis. The described case highlights the hazard of immunothrombosis upon valve replacement and elucidates its mechanisms in this surgical setting. [ABSTRACT FROM AUTHOR]

Rasha A Al-Khafaji,1,2 Louise Schierbeck1 1Cardiology Department, Nordsjælland (North Zealand) University Hospital, Hillerød, Denmark; 2Endocrinology and Nephrology Department, Nordsjælland (North Zealand) University Hospital, Hillerød, DenmarkCorrespondence: Rasha A Al-Khafaji; Louise Schierbeck Tel +45 31 32 11 89; +45 48 29 52 15Email rasha.alkhafaji2@gmail.com; louise.schierbeck@gmail.comAbstract: Modern diagnostic strategies of venous thromboembolism (VTE) have been developed. In this review, the diagnostic algorithms for deep-vein thrombosis (DVT) and their parameters are discussed individually in the context of reporting a case of DVT in a 43-year-old Caucasian female with a moderate pretest probability stratified by Wells’ score and a negative high quality D-dimer test. The patient was on treatment with Xarelto (rivaroxaban), 20 mg PO daily at the time of presentation. The diagnosis was verified through a complete lower limb ultrasound (US). This case highlights the diagnostic challenges and pitfalls of the current algorithms, especially those seen in a subgroup of patients such as patients with cancer, pregnancy, recurrent VTE or are on anticoagulation therapy at the time of presentation. The diagnosis of DVT is less plausible in a patient who is on anticoagulation therapy, but physicians should be aware of such a possibility. Physicians should also know in advance the numerous clinically relevant limitations of D-dimer testing before interpreting the results. Unifying the current diagnostic strategies, modifying the current Wells’ score and using the protocol of a whole-leg compression US instead of the limited US protocol are among the several cautious suggestions that have been proposed based on this review to possibly decrease the incidence of missed DVT.Keywords: compression ultrasound, recurrent thrombosis, rivaroxaban, Wells’ score

Coagulation dysfunction is a serious issue in patients with Coronavirus disease-19 (COVID-19). With regard to recently published studies, a high number of patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19 developed life threatening thrombotic complications despite anticoagulation. We report a case of young woman with the type-II heparin-binding site (HBS) antithrombin (AT) deficiency (Budapest 3-homozygous), who developed acute deep vein thrombosis on two occasions due to COVID-19 infection in the course of stable anticoagulation with vitamin K antagonist. The first thrombotic event was observed during mild COVID-19 infection, while the second thrombotic event she developed 2 months after she was negative for severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). Our case highlights the complexity of the treatment in this particular type of thrombophilia and the need for precaution even in mild forms of viral infection. In the treatment of acute thrombosis, AT-deficient patients may benefit from the use of AT concentrate along with low-molecular weight heparin (LMWH), while in cases of type II-HBS, AT supplementation is mandatory. [ABSTRACT FROM AUTHOR]

Venous thromboembolism is not a rare complication in children with cancer. Despite the advantages of the treatment of venous thromboembolism there is still a probability of venous thromboembolism recurrence. In adult patients with cancer venous thromboembolism recurrence an influence on the lower survival rate. In children with cancer venous thromboembolism recurrence is a rare complication, but it can significantly reduce the quality of life. Risk factors of venous thromboembolism recurrence in children with cancer are not properly investigated.

Abnormal D-dimer concentration measured during anticoagulation therapy (AT) or within one month of discontinuation, is associated with residual pulmonary obstruction (RPO) and risk of recurrent venous thromboembolism (VTE) after a first episode of pulmonary embolism (PE). We hypothesized that a significant decrease in D-dimer concentration within the first month of AT in patients with a first episode of PE may predict complete recanalization and a lower risk of recurrent VTE. One hundred and fifty patients with PE received anticoagulation therapy for three or six months when control computed tomography angiography (CTA) was performed. D-dimer levels were measured at admission and at 1-, 3- and/or 6-month follow-ups after the initial event. Clinical, echocardiographic, CTA and analytical data were collected. Predictive factors of RPO and predictive ability of D-dimer concentration at 1- and 6-month follow-ups were evaluated. Of the 150 eligible patients, 33 (22%) had RPO in control CTA. Idiopathic PE, a delay of >7 days between symptom onset and diagnosis, and clinical PE severity determined by a s-PESI score ≥ 1 were associated with RPO. D-dimer concentration within a month of AT was significantly higher (823 [558–1259] vs 436 [243–934] ng/ml; p = 0.019) in patients with RPO; decrease (445 [35–1899] vs 912 [476–2858] ng/ml; p = 0.047) and decrease percentage (31.4% vs 76.6%; p < 0.005) in D-dimer concentrations were significantly lower. ROC analysis showed that decrease percentage in D-dimer concentration identified patients with complete recanalization (AUC 0.715, [95% CI, 0.611–0.819], p < 0.005). Decreases of >70% in initial D-dimer at 1-month (OR, 0.56, [95% CI, 0.45–0.70] p = 0.037) and 6-month follow-ups (OR, 0.31 [CI 95%, 0.15–0.66], p = 0.03) were associated with a lower risk of recurrent PE. A significant decrease in D-dimer concentration within the first month of AT is associated with complete recanalization and could predict a lower risk of recurrent thrombosis after a first episode of PE. • Providing evidence on complete resolution after a first pulmonary embolism. • We identify three independent risk factors of residual pulmonary obstruction (RPO). • Absence of RPO can be predicted within the first month of anticoagulation therapy. • Significant decrease in D-dimer concentration is associated with complete recanalization. • Could predict a lower risk of recurrent thrombosis. [ABSTRACT FROM AUTHOR]

Thrombotic antiphospholipid syndrome (APS) is characterised by venous, arterial and/or small vessel thrombosis in the context of persistently positive antiphospholipid antibodies (aPL). The diagnosis and management of thrombotic APS continues to prove challenging for clinicians. We provide a practical guide to the diagnosis of APS including who to test for aPL and which tests to do. We also consider clinical practice points on the management of venous, arterial and small vessel thrombosis, in the context of first and recurrent thrombotic events. Non-criteria manifestations of APS are reviewed. An approach to recurrent thrombosis and anticoagulant-refractory APS is discussed, with options including increasing the anticoagulation intensity of vitamin K antagonists, switching to low-molecular-weight-heparin, the use of fondaparinux and/or the addition of antiplatelet treatment. Adjunctive options such as vitamin D, hydroxychloroquine and statins are also addressed. • Approaches to diagnosis and management of thrombotic APS considered in recent guidelines are summarised. • Clinical practice points are suggested. • Recurrent thrombotic events while on anticoagulation are reviewed. [ABSTRACT FROM AUTHOR]

Introduction: Fibrinolysis is one of the methods extending the use of vascular access in patients with tunneled venous catheters thrombosis. The aim of this study was to assess one-year maintenance of tunneled catheters patency after first effective thrombolysis with urokinase and identify its predictors. Methods: Retrospective analysis included 85 patients (age 69 ± 13 years) with permanent venous catheter thrombosis treated with urokinase at one center in the period 2010–2016. Urokinase was used (depending on weight) at a dose of 10,000 or 20,000 IU in an 8 h infusion to each catheter line. Assessment of one-year efficacy of fibrinolysis included the time between fibrinolysis and following thrombosis of the same catheter in patients that have previously obtained at least partial blood flow. The analysis included medication, comorbidities, catheter patency time and INR value during first thrombosis episode. Results: There were 62.4% patients with type-2 diabetes and 11.8% with neoplasm. The thrombolysis procedure was effective in 73 patients (85.9%). An analysis of the one-year efficacy of thrombolysis procedure included 73 patients. Among them, 23 experienced next episode of catheter-related thrombosis within a year postprocedure. Diabetes increased the risk for recurrent thrombosis [HR =3.19 (1.09-9.41); p = .03]. Conclusions: Patients with diabetes are at higher risk of recurrent catheter-related thrombosis and therefore may require more aggressive anticoagulation therapy for its prevention.

Based on the high incidence of thromboembolic events (TEs) observed in lung adenocarcinomas with ALK translocations and taking into account the biological proximity of ROS1 and ALK , we conducted a retrospective analysis of patients with advanced lung carcinoma carrying rearrangements in ROS1 from 23 centres in Spain and one centre in Portugal. The main objective of the study was to analyse the incidence of TE in this population, looking for predictive risk factors, and its impact on overall survival. A total of 58 patients were included. The incidence of TEs throughout the disease was 46.6% (n = 27) with a median follow-up of 19 months (range: 1–78 months) and a median overall survival of 52 months in the total population and 50 months for the patients presenting TEs, with a hazards ratio of 1.12 (95% confidence interval: 0.47–2.65) p = 0.78. The majority of the events were venous (n = 24; 89%) and occurred in the ambulatory setting (n = 18; 67%). Almost half of the patients (n = 13; 48%) presented the TE in the peri-diagnostic period. The high incidence of thrombosis, especially during the cancer diagnosis process, requires special attention from a clinician. Despite the limitations of such a small descriptive study, its results are in accordance with previously reported data. It would be important to design prospective studies of antithrombotic prophylaxis in this population because of their possible impact in reducing the risk of TEs. • Patients with ROS1 NSCLC have an incidence of thromboembolic events of 46.6%. • Most of the thromboembolic events occurred during the diagnostic process of cancer. • Despite high incidence of thromboembolic events, it had no impact in overall survival. • Low albumin is associated with higher risk of thromboembolic events in this cohort. [ABSTRACT FROM AUTHOR]

Background: Inherited thrombophilia represents a prothrombotic disorder that predisposes to thrombosis. Methods: We present a case of a 67-year-old female with a personal and family history of iterative thrombotic events. She was admitted in the Surgical Clinic at the age of 59, presenting the classical symptoms and signs for left lower limb deep vein thrombosis, confirmed by a venous Duplex Ultrasonography. This was the third episode of a venous thrombosis. Under anticoagulant treatment the evolution was good. The patient was advised to test for inherited thrombophilia mutations. Results: Four years later, she experienced another episode of thrombosis. The patient tested positive for five of the most frequent mutations found in inherited thrombophilia. Conclusions: Patients with recurrent venous thrombosis and positive family history for thrombotic events must be checked for thrombophilic conditions, inherited or acquired. [ABSTRACT FROM AUTHOR]

Introduction: Fibrinolysis is one of the methods extending the use of vascular access in patients with tunneled venous catheters thrombosis. The aim of this study was to assess one-year maintenance of tunneled catheters patency after first effective thrombolysis with urokinase and identify its predictors. Methods: Retrospective analysis included 85 patients (age 69 ± 13 years) with permanent venous catheter thrombosis treated with urokinase at one center in the period 2010-2016. Urokinase was used (depending on weight) at a dose of 10,000 or 20,000 IU in an 8 h infusion to each catheter line. Assessment of one-year efficacy of fibrinolysis included the time between fibrinolysis and following thrombosis of the same catheter in patients that have previously obtained at least partial blood flow. The analysis included medication, comorbidities, catheter patency time and INR value during first thrombosis episode. Results: There were 62.4% patients with type-2 diabetes and 11.8% with neoplasm. The thrombolysis procedure was effective in 73 patients (85.9%). An analysis of the one-year efficacy of thrombolysis procedure included 73 patients. Among them, 23 experienced next episode of catheter-related thrombosis within a year postprocedure. Diabetes increased the risk for recurrent thrombosis [HR =3.19 (1.09-9.41); p = .03]. Conclusions: Patients with diabetes are at higher risk of recurrent catheter-related thrombosis and therefore may require more aggressive anticoagulation therapy for its prevention. [ABSTRACT FROM AUTHOR]

Abstract Background Direct oral anticoagulants (DOACs) are widely used for secondary prevention of venous thromboembolism (VTE) but their clinical efficacy and safety are not established in Antiphospholipid Syndrome (APS) patients. There is only one randomized controlled trial published while others are still ongoing. Many non-randomized studies have been published in this field with conflicting opinions. Purpose of review We conducted a systematic review using MEDLINE, EMBASE and Cochrane databases from 2000 until March 2018 regarding APS patients treated with DOACs. We performed a patient-level data meta-analysis to a) estimate the prevalence of recurrent thrombosis in APS patients treated with DOACs in the literature, and b) identify variables associated with recurrent thrombosis. Results We identified 47 studies corresponding to 447 APS patients treated with DOACs. Three commercially available DOACs were analyzed: rivaroxaban (n = 290), dabigatran etexilate (n = 144) and apixaban (n = 13). A total of 73 out of 447 patients (16%) experienced a recurrent thrombosis while on DOACs with a mean duration until thrombosis of 12.5 months. Rates of recurrent thromboses were 16.9% and 15% in APS patients receiving either anti-Xa inhibitors or dabigatran respectively. Triple positivity (positivity for all three antiphospholipid antibodies) was associated with a four-fold increased risk of recurrent thrombosis (56% vs 23%; OR = 4.3 [95%CI; 2.3–7.7], p < 0.0001) as well as a higher number of clinical criteria for APS classification. In patients treated with anti-Xa inhibitors, history of arterial thrombosis was associated with a higher risk of recurrent thrombosis (32% vs 14%; OR = 2.8 [95%CI; 1.4–5.7], p = 0.006). In conclusion, DOACs are not effective in all APS patients and should not be used routinely in these patients. Randomized controlled trials assessing clinical efficacy and safety as primary endpoints are underway. In the meantime, a registry of APS patients on DOACs could be proposed to establish in which APS subgroups DOACs would be a safe alternative to warfarin. Highlights • Direct oral anticoagulants are not effective and safe in all APS patients. • Triple positive patients have a four-fold increased risk of recurrent thrombosis. • Most recurrent thromboses occur within 12 months after DOACs initiation. [ABSTRACT FROM AUTHOR]

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An adequate regimen for prophylaxis of venous thromboembolism (VTE) requires identification of reversible and irreversible risk factors. Recent data confirm that the greatest number of pulmonary emboli (PE) occur in non-surgical patients. VTE also develops in many surgical patients upon hospital discharge. These findings emphasize the need for adequate VTE prophylaxis in inflammatory diseases, acute medical illness, and other conditions, as well as the need to optimize anticoagulant regimens after surgery. Establishing VTE risk factors, identifying acquired or inherited thrombophylias and occult or previously undiagnosed malignancy will help design an adequate anticoagulant regimen as secondary VTE prophylaxis for surgical and other patients. Follow up measures should include D-dimer values, ultrasonographic assessment of residual venous thrombosis and echocardiographic parameters, along with other relevant clinical data to assess the risk of VTE reoccurrence. These procedures will ensure the optimal duration of individually tailored anticoagulant therapy, with special attention to comorbidities and tendency to hemorrhage.

Optimal treatment regimen for patients with antiphospholipid syndrome (APS) remain unclear. Therefore, the authors sought to compare the outcomes of vitamin K antagonists (VKAs) vs. direct oral anticoagulants (DOACs) in patients with APS., Methods: MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials comparing efficacy and safety of VKAs and DOACs inhibitors in patients with APS. Recurrent thrombosis, all-cause mortality, stroke, adverse reactions, and bleeding were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs., Results: The analysis included 625 patients from four randomized controlled trials and one post hoc analysis. Meta-analysis showed statistically non-significant difference between DOACs inhibitors and VKAs in the recurrent thrombosis risk (arterial or venous) [RR 2.77 (95%, CI 0.79, 9.65); P =0.11, I 2 =50%]. Consistent results were revealed among patients with the previous history of arterial thrombosis [RR 2.76 (95% CI 0.93, 8.16); P =0.75, I 2 =0%], venous thrombosis [RR 1.71 (95% CI 0.60, 4.84); P =0.31, I 2 =15%] and patients who were triple antiphospholipid positive [RR 4.12 (95% CI 0.46, 37.10); P =0.21, I 2 =58%]. DOACs inhibitors were significantly associated with increased risk of stroke [RR 8.51 (95% CI 2.35, 3.82); P =0.47, I 2 =0%]., Conclusion: DOACs exhibited increased risk of stroke among patients with APS. In addition, although not significant, the higher RRs among patients on DOACs may indicate higher risk of thrombotic events associated with DOACs., Competing Interests: None to declare., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Copyright of Gefaesschirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)