Episodes Of Thrombosis Research Articles

The problem of inpatient thrombosis of coronary arteries in patients with COVID-19 on the background of intensive antithrombotic therapy

Myocardial infarction claims million lives on the planet each year. Pharmacotherapy in combination with percutaneous coronary interventions have significantly reduced morbidity and mortality in this cohort. Despite optimal therapy and prophylaxis, there is a group of patients with recurrent, often fatal, coronary thromboses. During the COVID-19 pandemic, some patients developed episodes of thrombosis in blood vessels of various organs, including brain, heart or lungs, even on therapeutic anticoagulation. The patient was admitted to the department of cardiology and reperfusion therapy, with a confirmed diagnosis of COVID-19 resulted in acute ST-segment elevation myocardial infarction. Patient underwent urgent coronary angiography with thromboaspiration and stenting of the infarct-dependent right coronary artery followed by optimal medical treatment with the use of triple antithrombotic therapy. His condition became stable with the resolution of ST-segment elevation on electrocardiogram. A few days later, the condition of the patient deteriorated again with recurrent of chest pain and a new ST segment elevation. Repeated coronary angiography revealed recurrent thrombosis in the right coronary artery. The mechanisms of thrombosis in COVID-19 are not fully understood. Among possible, the direct effect of the virus on tissues, activation of pro-inflammatory system and coagulation system, impaired vasodilation, and decreased fibrinolytic activity are discussed. These mechanisms may lead to vascular thrombosis in different organs, particularly heart, lungs, and brain.

Analysis of 6 pediatric nephrotic syndrome cases with complications of cerebral sinovenous thrombosis and literature review.

Cerebral venous sinus thrombosis (CVST) is a rare but serious complication of nephrotic syndrome (NS) in children. To investigate the clinical characteristics of CVST in children with NS in order to timely diagnose this complication and reduce poor outcome. Collect and analyze clinical data and magnetic resonance venography (MRV) results of children with NS complicated with CVST. Data of 6 patients with NS complicated with CVST were collected. 4 of the patients were steroid-sensitive nephrotic syndrome (SSNS) and 2 were steroid-resistant nephrotic syndrome (SRNS). The occurrence of CVST was observed within a time frame ranging from 12 days to 3 years following the diagnosis of NS. One patient had two episodes of thrombosis in three years, while the other five patients had only one episode of thrombosis. All patients had proteinuria at the time of episode of thrombosis. All patients presented with headache, and three of them had strabismus, seizures, and transient blindness, respectively. Neurological examination was negative. All patients were diagnosed with CVST by MRV within 3-16 days of the onset of headache. Two patients had TRPC6 gene mutation. All patients had resolution of neurological symptoms after anticoagulation treatment. CVST may occur in the early stages of NS. There is currently a lack of specific diagnostic indicators to reliably identify the presence of CVST in patients with NS. Children with NS who have neurological symptoms should be promptly evaluated with imaging studies. Whether TRPC6 gene mutation is also a risk factor for CVST remains to be further studied.

Evaluation of Cangrelor Use After Percutaneous Coronary Intervention in Patients With Mechanical Circulatory Support

To describe cangrelor use in patients on concurrent mechanical circulatory support who underwent postpercutaneous coronary intervention. A single-center, retrospective, cohort study. At a quaternary teaching hospital. Included patients were ≥18 years old, admitted to the intensive care unit, underwent percutaneous coronary intervention with stent placement, initiated on mechanical circulatory support, and received cangrelor in the postpercutaneous coronary intervention period. Retrospectively analyzed cangrelor use in patients on mechanical circulatory support. The primary outcome was the incidence of thrombosis and bleeding events during cangrelor administration. Additional outcomes included initial cangrelor dose, number of cangrelor dose adjustments per patient, survival from mechanical circulatory support, and mortality within 30 days. Overall, 19 patients were included in this study. In total, 14 patients (74%) experienced a bleeding event; however, 93% were classified as a minor bleed. There was 1 major bleeding event. There were no thrombotic events observed during cangrelor administration. The median initial cangrelor dose was 0.5 µg/kg/min. There were 10 patients who underwent dose adjustment, with the majority being dose reductions based on antiplatelet monitoring (VerifyNow assay). Survival from mechanical circulatory support occurred in 17 patients (89%), and 30-day mortality occurred in 8 patients (42%). For patients receiving cangrelor as a bridge to oral P2Y12 inhibitor therapy on mechanical circulatory support, the authors observed a low rate of major bleeding and no episodes of thrombosis. Lower starting doses appear feasible with no observed increased risk of thrombotic complications. Future studies are needed to confirm these observations.

Microneurosurgical treatment of a small perimesencephalic pure pial arterial malformation: an under-recognized etiology of angiographically occult subarachnoid hemorrhage. Illustrative case.

Pial arterial malformations (PAMs) are rare vascular lesions consisting of dilated tortuous arteries without venous drainage. Current PAM understanding is limited by the lesion's rarity, limited anatomopathological studies, and frequent misclassifications. A 23-year-old male experienced two spontaneous subarachnoid hemorrhages (SAHs) over 6 months with initially unremarkable diagnostic cerebral angiograms. Magnetic resonance imaging (MRI) and angiography after the second SAH revealed a small perimesencephalic ovoid lesion within the left crural cistern, between the left superior and posterior cerebral arteries, appearing to be an exophytic cavernoma, a thrombosed aneurysm, or a hemorrhagic tumor. Microsurgical resection was achieved with a pterional craniotomy and anterior clinoidectomy. The resected lesion was characteristic of a pure PAM arising from superior cerebellar arterial branches. Small pure PAMs can be deceitfully dynamic lesions causing episodes of hemorrhage, complete thrombosis (angiographically occult), recanalization, and rehemorrhage. Small thrombosed vascular malformations or aneurysms should be included in differential diagnoses of angiographically occult SAH. MRI can be diagnostic, but the true angioarchitecture can only be elucidated with microneurosurgery. The only definitive cure is removal. The microneurosurgical strategy should account for worst-case scenarios, provide adequate skull base exposures, and include bypass revascularization options when thrombosed aneurysms are encountered.

Long-term outcome in vaccine-induced immune thrombocytopenia and thrombosis

BackgroundRapid diagnosis and treatment has improved outcome of patients with vaccine-induced immune thrombocytopenia and thrombosis (VITT). However, after the acute episode, many questions on long-term management of VITT remained unanswered. ObjectivesTo analyze, in patients with VITT, the long-term course of anti–platelet factor 4 (PF4) antibodies; clinical outcomes, including risk of recurrent thrombosis and/or thrombocytopenia; and the effects of new vaccinations. Methods71 patients with serologically confirmed VITT in Germany were enrolled into a prospective longitudinal study and followed for a mean of 79 weeks from March 2021 to January 2023. The course of anti-PF4 antibodies was analyzed by consecutive anti-PF4/heparin immunoglobulin G enzyme-linked immunosorbent assay and PF4-enhanced platelet activation assay. ResultsPlatelet-activating anti-PF4 antibodies became undetectable in 62 of 71 patients (87.3%; 95% CI, 77.6%-93.2%). In 6 patients (8.5%), platelet-activating anti-PF4 antibodies persisted for >18 months. Five of 71 patients (7.0%) showed recurrent episodes of thrombocytopenia and/or thrombosis; in 4 of them (80.0%), alternative explanations beside VITT were present. After further COVID-19 vaccination with a messenger RNA vaccine, no reactivation of platelet-activating anti-PF4 antibodies or new thrombosis was observed. No adverse events occurred in our patients subsequently vaccinated against influenza, tick-borne encephalitis, varicella, tetanus, diphtheria, pertussis, and polio. No new thrombosis occurred in the 24 patients (33.8%) who developed symptomatic SARS-CoV-2 infection following recovery from acute VITT. ConclusionOnce the acute episode of VITT has passed, patients appear to be at low risk for recurrent thrombosis and/or thrombocytopenia.

#3179 PREDICTORS OF VASCULAR ACCESS THROMBOSIS IN MAINTENANCE HEMODIALYSIS PATIENTS – QA, KT/V AND CONVECTIVE VOLUME

Abstract Background and Aims Vascular access (VA) is vital for hemodialysis (HD) treatments and should allow to achieve the recommended dose of dialysis. Thrombosis is the primary cause of VA failure in grafts (AVG) and fistulas (AVF) and should be avoided as it can lead to significant patient morbidity and mortality. However, despite its importance, predictors of VA thrombosis are not completely established. Even if large randomized controlled trials are lacking to clearly identify the ideal surveillance strategies and benefits of surveillance, evidence suggests that when combined with preemptive interventions, prospective monitoring and surveillance and early detection of dysfunctional VA may reduce the thrombosis rate and improve its long-term patency. Several monitoring and surveillance techniques of VA can be used, from unexplained drop in dialysis adequacy (Kt/V and convective volume) to the noninvasive estimation of VA blood flow (Qa). The aim of this study was to assess whether these parameters can predict VA thrombosis. Method We retrospectively evaluated all episodes of VA thrombosis admitted in our Vascular Access Centre (VAC) between July 2019 and December 2022. Patient's demographics, VA characteristics and data from dialysis sessions were collected. Descriptive statistics were calculated and expressed as mean (standard deviation) or median (IQR) or count (%), as adequate. Values were compared using Mann-Whitney for independent samples and Pearson chi-squared test with 95% confidence intervals (CI). The predictors of VA thrombosis studied were Qa, Kt/V and convective volume (CV), in the case of the patients on hemodiafiltration. Qa was measured using the thermodilution method called blood temperature monitoring (BTM®), and Kt/V and CV with Online Clearance Monitoring (OCM®). In this study, we evaluated the ratio between the last measured value of Qa prior to the thrombosis episode and the average of the previous three months (Qa trend), and the ratio between the last measured value of Kt/V and CV before the thrombosis episode and the average of the previous month (Kt/V trend and CV trend, respectively) as predictors of VA thrombosis Results From July 2019 and December 2022, we treated, in our VAC, 386 VA thrombosis episodes in 226 patients. In our study population, mean age was 71.1 (± 13.2) years, 64% were male, 31% had diabetes. The dialysis vintage was 51 (69) months and the VA vintage was 42 (62) months. 70.2% of the VA thrombosis were on AVF. Prior to thrombosis the median of Qa obtained by BTM was 650 (495) mL/min, the median of kt/v was 1.43 (0.62) and the median of CV was 22.4 (6.3). The average of the previous values for Qa, Kt/V and CV were 658 (353) ml/min, 1.53 (0.35) and 23.5 (3.9) L. The median (IQR) of Qa trend, Kt/V trend and CV trend were -8,5 (33,3) %, -6,0 (28,2) % and -2,5 (17,0)%. We found no statistical significance for Qa trend and CV trend between AVF and AVG as predictors of VA thrombosis, but the reduction in Kt/V values was significantly more pronounced in AVF (-6.8%; Q1 -30.1% to Q3 0.7%) than in AVG (-3.8%; Q1 -18.0% to Q3 + 5.0%) (p = 0.007) as predictor of thrombosis. In 68.9% of VA thrombosis, we noticed a reduction in Kt/V value before the episode (73.8% in AVF and 57.5% in AVG, p = 0.002). We found no statistically significance in the reduction of Qa and CV values between AVF and AVG thrombosis episodes. Conclusion Our study showed that Kt/V trend was a better predictor of VA thrombosis than Qa trend and CV trend, especially in AVF.

Integral assays of hemostasis in hospitalized patients with COVID-19 on admission and during heparin thromboprophylaxis.

Blood coagulation abnormalities play a major role in COVID-19 pathophysiology. However, the specific details of hypercoagulation and anticoagulation treatment require investigation. The aim of this study was to investigate the status of the coagulation system by means of integral and local clotting assays in COVID-19 patients on admission to the hospital and in hospitalized COVID-19 patients receiving heparin thromboprophylaxis. Thrombodynamics (TD), thromboelastography (TEG), and standard clotting assays were performed in 153 COVID-19 patients observed in a hospital setting. All patients receiving treatment, except extracorporeal membrane oxygenation (ECMO) patients (n = 108), were administered therapeutic doses of low molecular weight heparin (LMWH) depending on body weight. The ECMO patients (n = 15) were administered unfractionated heparin (UFH). On admission, the patients (n = 30) had extreme hypercoagulation by all integral assays: TD showed hypercoagulation in ~75% of patients, while TEG showed hypercoagulation in ~50% of patients. The patients receiving treatment showed a significant heparin response based on TD; 77% of measurements were in the hypocoagulation range, 15% were normal, and 8% remained in hypercoagulation. TEG showed less of a response to heparin: 24% of measurements were in the hypocoagulation range, 59% were normal and 17% remained in hypercoagulation. While hypocoagulation is likely due to heparin treatment, remaining in significant hypercoagulation may indicate insufficient anticoagulation for some patients, which is in agreement with our clinical findings. There were 3 study patients with registered thrombosis episodes, and all were outside the target range for TD parameters typical for effective thromboprophylaxis (1 patient was in weak hypocoagulation, atypical for the LMWH dose used, and 2 patients remained in the hypercoagulation range despite therapeutic LMWH doses). Patients with COVID-19 have severe hypercoagulation, which persists in some patients receiving anticoagulation treatment, while significant hypocoagulation is observed in others. The data suggest critical issues of hemostasis balance in these patients and indicate the potential importance of integral assays in its control.

Antithrombotic and hemostatic stewardship: Evaluation of romiplostim for treatment of thrombocytopenia at a large academic medical center.

Romiplostim is indicated for immune thrombocytopenia (ITP), though is often used off-label for other indications such as chemotherapy-induced thrombocytopenia (CIT) and thrombocytopenia post hematopoietic stem cell transplantation (HSCT). Although romiplostim is FDA approved at a starting dose of 1 mcg/kg, it is often initiated at 2-4 mcg/kg depending on the severity of thrombocytopenia in clinical practice. Given the limited data, but interest in higher doses of romiplostim for indications other than ITP, we aimed to assess our inpatient romiplostim utilization at NYU Langone Health.This was a single-center, retrospective review of 84 adult patients from January 2019 to July 2021. The top three indications were ITP (51, 60.7%), CIT (13, 15.5%), and HSCT (10, 11.9%). The median initial romiplostim dose was 3.8 mcg/kg (range, 0.9-10.8). 51% of patients achieved a platelet count of ≥50 × 109/L by the end of week 1 of therapy. For patients achieving goal platelets by the end of week 1, the median dose of romiplostim was 2.4 mcg/kg (range, 0.9-10.8). There was 1 episode of thrombosis and 1 episode of stroke.We found that higher than FDA-recommended initial doses should be considered to achieve a platelet response. It appears to be safe to initiate romiplostim as higher doses, and to increase doses by greater increments than 1 mcg/kg in order to achieve a platelet response. Future prospective studies are needed to confirm the safety and efficacy of romiplostim in off-label indications and should evaluate clinical outcomes such as bleeding and need for transfusions.

Distinctive Attributes of Indian Patients With Classical BCR::ABL1 Negative Myeloproliferative Neoplasms: Unified Clinical and Laboratory Data.

We report one of the largest single center data from a mixed referral setting in India describing baseline characteristics and outcomes of patients with classical BCR::ABL1 negative myeloproliferative neoplasms (MPNs). Patients diagnosed from June 2019 to 2022 were included. Workup and treatment was as per current guidelines. Diagnosis comprised polycythemia vera (PV) in 51(49%), ET in 33(31.7%) and prefibrotic primary myelofibrosis (MF) pre fibrotic myelofibrosis (prePMF) and myelofibrosis in 10(9.6%) patients each. Median age at diagnosis was 52 years for PV and ET, 65.5 for MF and 79 years for prePMF. Diagnosis was incidental in 63(56.7%) and after thrombosis in 8(7.2%) patients. Baseline next generation sequencing (NGS) was available for 63(60.5%) patients. Driver mutations in PV: JAK2 in 80.3%; in ET: JAK2 in 41%, CALR in 26%, MPL in 2.9%; in prePMF JAK2 in 70%, CALR in 20%, MPL in 10%, and in MF: JAK2 in 10%, MPL in 30% and CALR in 40%. Seven novel mutations were detected of which 5 were potentially pathogenic on computational analysis. After median follow up of 30 months, 2 patients had disease transformation and none had new episodes of thrombosis. Ten patients died, most commonly with cardiovascular events(n=5,50%). Median overall survival was not reached. Mean OS time was 10.19 years(95%CI, 8.6 to 11.74) and mean time to transformation was 12.2 years(95% CI,11.8 to 12.6). Our data indicates comparatively indolent presentation of MPNs in India with younger age and lower risk of thrombosis. Further follow up will enable correlation with molecular data and guide modification of age based risk stratification models.

Endometriosis is associated with an increased whole-blood thrombogenicity detected by a novel automated microchip flow-chamber system (T-TAS®).

Potential thrombotic and antifibrinolytic influence of endometriosis on haemostasis has been recently reported in the literature, as well as increased cardiovascular morbidity in women suffering from the disease. We performed a pilot study to assess the influence of endometriosis on the thrombus formation process under in vitro flow conditions. This study compared women with confirmed endometriosis (n = 23) surgically and control healthy subjects (n = 10). In both groups, the same exclusion criteria were used: a prior episode of thrombosis diagnosed as acquired or inherited thrombophilia, neoplasm, and an uncertain family history of thrombosis. We evaluated the whole blood thrombogenicity using T-TAS® at a shear rate of 240 s-1 (Total-Thrombus Analysis System, Zacros, Japan). The blood clot formation initiation time (T10) and occlusion time (OT) were significantly shortened in the endometriosis group (p < 0.05). The area under the curve (AUC30) of blood clot time formation values (BCTF) was substantially higher in the patients suffering from a disease (p = 0.03). An increase in AUC (TTAS) values by 100 increases the risk of developing endometriosis by 1.56-fold [adjusted OR = 1.56 (p = 0.01); (95% CI: 1.10-2.18)]. Inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), and the leucocyte, neutrophil, basophil, and neutrophil concentrations) were also substantially higher in the endometriosis group (p < 0.05). The alteration of the T-TAS® and NLR values supports the thesis of a shift of the equilibrium towards thrombosis in women who have endometriosis. This phenomenon links to a state of chronic inflammation. It is detectable using a novel system for the quantitative assessment of the platelet thrombus formation process under flow conditions in vitro.

British Society for Haematology guideline for anticoagulantmanagement of pregnant individuals with mechanical heart valves.

British Society for Haematology guideline for anticoagulantmanagement of pregnant individuals with mechanical heart valves.

Characterization of hemodialysis fistulas experienced abrupt thrombosis and determination of a proper follow-up protocol: A retrospective cohort study and an interventionist's perspective.

Abrupt thrombosis is a form of thrombosis that occurs unexpectedly and without being preceded by hemodialysis fistula (AVF) dysfunction during dialysis. We found that AVFs with a history of abrupt thrombosis (abtAVF) appeared to have more episodes of thrombosis and required more frequent interventions than those without such history. Therefore, we sought to characterize the abtAVFs and examined our follow-up protocols to determine which one is optimal. We performed a retrospective cohort study using routinely collected data. The thrombosis rate, AVF loss rate, thrombosis-free primary patency, and secondary patency were calculated. Additionally, the restenosis rates of the AVFs under the follow-up protocol/sub-protocols and the abtAVFs were determined. The thrombosis rate, procedure rate, AVF loss rate, thrombosis-free primary patency, and secondary patency of the abtAVFs were 0.237/pt-yr, 2.702/pt-yr, 0.027/pt-yr, 78.3%, and 96.0%, respectively. The restenosis rate for AVFs in the abtAVF group and the angiographic follow-up sub-protocol were similar. However, the abtAVF group had a significantly higher thrombosis rate and AVF loss rate than AVFs without a history of abrupt thrombosis (n-abtAVF). The lowest thrombosis rate was observed for n-abtAVFs, followed up periodically under the outpatient or angiographic sub-protocols. AVFs with a history of abrupt thrombosis had a high restenosis rate, and periodic angiographic follow-up with a mean interval of 3 months was presumed appropriate. For selected populations, such as salvage-challenging AVFs, periodic outpatient or angiographic follow-up was mandatory to extend their usable lives for hemodialysis.

Thromboembolic events in patients with paroxysmal nocturnal hemoglobinuria (PNH): Real world data of a Greek nationwide multicenter retrospective study.

Thrombosis is the most common and a life-threatening complication in patients with Paroxysmal Nocturnal Hemoglobinuria. One-third of patients with PNH experience at least one thromboembolic event during the course of the disease, with thrombosis being the most common cause of death in these patients. The mechanism of thrombosis in PNH is complex and continues to be of great research interest. Since the introduction of C5 complement inhibitors in the treatment of PNH, the incidence of thromboembolic events has decreased substantially. We retrospectively analyzed data concerning the thrombotic episodes of 41 patients with PNH from 14 different national hematology centers in Greece. Sixteen patients (39%) experienced at least one episode of thrombosis, including, seven (43.8%) at diagnosis, seven (43.8%) during the course of the disease and two (12.5%) patients prior to PNH diagnosis. Nearly half of these individuals (n=7, 43.8%) had multiple episodes of thrombosis during the course of their disease. The most common sites of thrombosis were intra-abdominal veins. Three out of 26 patients developed thrombosis while on eculizumab. In none of the 16 patients, the thrombotic event was fatal. Our findings, despite the small number of patients, confirmed that thrombosis continues to be a significant complication of PNH affecting more than one third of the patients.

Eltrombopag for the Treatment of Poor Graft Function Following Haematopoietic Cell Transplantation: Real-Life Data.

Eltrombopag has an off-label indication for haematopoietic cell transplantation in patients experiencing delayed thrombocyte recovery and/or thrombocytopaenia. To present our centre's experience of using this agent not only for post- haematopoietic cell transplantation thrombocytopaenia but also for poor graft functioning in the post-haematopoietic cell transplantation setting. Retrospective cross-sectional study. Thirty-nine patients who had persistent cytopaenia following haematopoietic cell transplantation and treated with eltrombopag at our centre between October 2011 and December 2021 were retrospectively identified. During this period, 9 (23.1%) and 30 (76.9%) patients who underwent allogeneic transplantations, respectively, received eltrombopag. The female-to-male ratio was 12:27, and the median transplant age was 49 (18-70) years. Eight (20.5%) patients had isolated thrombocytopaenia, 19 (49.4%) had bi-lineage cytopaenia and 12 (30.1%) had pancytopaenia. Patients received a median of 50 mg/day (25-150 mg/day) of eltrombopagfor a median duration of 82 (24-386) days. Nine (23.1%) patients had autologous haematopoietic cell transplantation, and 30 (76.9%) had allogeneic haematopoietic cell transplantation (14 unrelated, 9 sibling and 7 haploidentical). The median donor age was 32 (20-67) years. The median follow-up was 16.4 (1.8-84.3) months. The median pre-treatment platelet count was 11x109/l (1-23), which increased to 41x109/l (6-150). The median platelet count increment was 29.5x109/l (p = 0.001). The pre-treatment median neutrophil count was 1.19x109/l (0.39-5.1), which increased to 2.35 x109/l (0.1-5.33) (p = 0.05), and the pre-treatment median haemoglobin was 8.3 (6.2-14) g/dl, which increased to 10 (6.2-14) g/dl (p = 0.001) with eltrombopag. No eltrombopag-related hepatotoxicity occurred; however, 1 (2.6%) patient failed to continue treatment because of two consecutive episodes of deep venous thrombosis. Six (15.4%) patients were unresponsive to eltrombopag and dependent on blood product transfusions. After a median time of 82 days, 61.5% of the patients discontinued eltrombopag successfully. The results confirmed that eltrombopag could provide a rapid, sustained response in patients with poor graft functioning after haematopoietic cell transplantation. This finding is essential given the high rate of non-relapse mortality caused by poor graft functioning after haematopoietic cell transplantation.

Comparison of endovenous laser ablation and conservative treatment in acute thrombophlebitis of the varicose great saphenous vein: rationale, design and first results of clinical trial

Thrombophlebitis of the superficial lower limb veins is one of the most common complications of chronic vein disease. Nowadays a long-term (at least 45 days) subcutaneous injection of fondaparinux sodium or heparin in combination with elastic compression of the limb is recommended for treatment of superficial vein thrombosis with a moderate risk of thrombus propagation to deep venous system. However, long-term use of anticoagulants is not always possible and sometimes contraindicated. Endovenous laser ablation (EVLA) around thrombus-free junction of great or small saphenous veins without subsequent long-term use of anticoagulants seems to be a promising intervention for treatment of acute thrombophlebitis of varicose superficial veins.The prospective single-center randomized open-label clinical trial was dedicated for comparison the efficacy and safety of three following treatments options for patients with acute thrombosis of the varicose great saphenous vein and location of thrombi in the trunk and/ or its large inflows: EVLA close to saphenous vein junction without anticoagulation, EVLA and 7 days of anticoagulation and noninvasive treatment with anticoagulation for 45 days (subcutaneous injections of the fondaparinux 2,5 mg). Class 2 compression stockings are used in all patients. Adverse outcomes are recorded at 7, 45 and 90 days after randomization. These include the progression of superficial vein thrombosis, recurrent superficial vein thrombosis, thrombosis involvement of the superficial segment of the perforating vein up to the fascia, deep vein thrombosis according to compression ultrasound, and pulmonary embolism with symptoms. Bleedings according to the World Society of Thrombosis and Hemostasis and the Academic Research Consortium classification as well other complications are also recorded. The first 30 patients included in the study have a low incidence of venous thrombosis risk factors and localization of the thrombus relatively far from the saphenofemoral junction. EVLA resulted in persistent cessation of venous blood flow at the intervention site. New episodes of venous thrombosis were noted only in the group of medical treatment — deep vein thrombosis of the contralateral tibia 5 days after stopping of 45-day treatment with fondaparinux and thrombus in the recanalized inflow of the great saphenous vein without involving its trunk at the 21st day after stopping of 45-day injection of fondaparinux. There were no complications in the area of intervention and bleedings.

Safety of discontinuation of anticoagulants after venous thromboembolism: whether D-dimer level should be taken into account?

Due to the continued risk of recurrence after a first episode of proximal deep vein thrombosis (DVT) of the lower extremities and/ or pulmonary embolism (PE) occurring without major transient risk factors, long-term use of anticoagulants is indicated in many cases. One attractive way to individualize the duration of treatment in these cases appears to be the assessment of blood D-dimer concentration. However, according to the prospective studies PROLONG, PROLONG II and REVERSE II, even persistent normalization of blood D-dimer concentration does not guarantee the absence of relapse. The available evidence also does not allow a differentiated approach to the assessment of the role of D-dimer for cases where proximal DVT and/or PE occurs in patients without identifiable risk factors or with minor risk factors. An attempt to clarify some of these uncertainties was made in the prospective APIDULCIS study, which included 732 patients who first had proximal DVT and/or PE, with symptoms occurring in the absence of obvious provoking factors (75.6% of cases) or associated with minor (weak) and transient risk factors (24.4%). The prerequisites included a normal blood D-dimer concentration. Patients were discontinued anticoagulants and blood D-dimer concentration measurements were repeated after 15, 30, and 60 days. If it remained low, the anticoagulant was not resumed (39.1% of cases), and when it first increased, apixaban was administered in a dose of 2.5 mg twice daily. The APIDULCIS study confirmed that anticoagulants cannot be discontinued after 1 year of use after the first unprovoked episode of proximal DVT and/or PE, even with persistent normal blood D-dimer concentration; it was shown that recurrence rate after the first episode of proximal DVT and/or PE, provoked by a minor transient risk factor, is high enough even after at least 1 year of anticoagulant treatment and at stable normal blood D-dimer concentration after their cancellation; comfirmed the effectiveness and safety of a reduced dose of apixaban (2.5 mg 2 times a day) during prolonged treatment of the first episode of proximal DVT and/or PE.

Гормональная контрацепция в аспекте влияния на систему гемостаза

Aim: to study the hemostasis indicators in female patients with hyperandrogenism (HA) and menstrual disorders (MDs) during combined oral contraceptive (COC) intake, depending on the presence of undifferentiated connective tissue displasia (UCTD). Patients and Methods: the study results of 28 female patients with HA and MDs were divided into 2 groups: group 1 — 22 patients (mean age 22.1±3.2 years) with UCTD, group 2 — 6 patients (mean age 20.5±1.8 years) without UCTD. The content of hormones in the blood (on the 2nd–3rd day of the menstrual period), the parameters of hemostasis before and after 1 month of COCs intake, and the level of homocysteine were determined in all patients. Results: the analysis revealed an increase in the levels of platelet activation markers, coagulation link and fibrinolysis. During COCs intake, an increase in the fibrinogen content was noted in patients of both groups, which, however, did not exceed the reference values. During the correlation analysis, it was found that in groups 1 and 2, the parameters of the fibrinogen baseline, D-dimer and the corresponding indicators after 1 month of COCs intake had a strong correlation with each other (r=0.845, r=0.864). However, group 1 had higher levels of fibrinogen and fibrin degradation products (D-dimer) (p&lt;0.0001) versus those in group 2. The study on the trend of prothrombin time (PTT) and activated partial thromboplastin time (APTT) during COCs intake in female patients with HA and UCTD revealed an acceleration of indicators (p&lt;0.01) versus those before COCs intake. At the same time, the change in blood clotting markers was not realized by episodes of thrombosis in any of the patients. Conclusion: patients with UCTD had changes that characterized the activation of thrombogenesis. When planning hormonal contraception, it is necessary to single out a group of female patients with HA and signs of UCTD as the most vulnerable in relation to an increased risk of thrombogenic events. KEYWORDS: hyperandrogenism, combined oral contraceptive, thrombosis, connective tissue dysplasia, hyperhomocysteinemia. FOR CITATION: Kudinova E.G. Hormonal contraception in terms of effect on the hemostasis system. Russian Journal of Woman and Child Health. 2023;6(2):130–137 (in Russ.). DOI: 10.32364/2618-8430-2023-6-2-130-137.

Mucocutaneous Response to New Therapeutic Strategies in Behçet’s Disease: A Retrospective Cohort Study

Mucocutaneous lesions are the most frequent symptoms of Behçet’s disease (BD). Recently, new therapies are being used to treat refractory cases, but the effect of these treatments on mucocutaneous manifestations has been scarcely reported. Our objective was to describe the mucocutaneous response to the different therapies used to treat BD in routine clinical practice. We retrospectively reviewed the clinical records of all patients diagnosed with BD seen at our institution between January 2010 and January 2022. Patients with BD without mucocutaneous manifestations were excluded. We included 109 patients diagnosed with BD: 51 males (46.8%) and 58 females (53.2%). The mean age at diagnosis was 31.58 years (standard deviation (SD) 12.110) and the mean time of disease evolution was 14.94 years (SD 11.094). Oral ulcers were the most frequent symptom present in 100% of patients, followed by genital ulcers (GU) in 76.1% of patients. Twenty‐four patients (22%) had severe mucocutaneous symptoms (&gt;12 lesions/year) before treatment. We found that among patients with GU there was a higher prevalence of episodes of posterior uveitis and venous thrombosis (p = 0.011 and p = 0.045, respectively). In our series, we observed a lower complete cutaneous response to colchicine in patients with GU, pathergy or severe mucocutaneous symptoms (p &lt; 0.05). Regarding the choice of a TNF‐α inhibitor, we observed a lower prevalence of complete cutaneous response to adalimumab among patients with GU (53.3% complete response in patients with GU vs. 100% in patients without GU, p = 0.022), whereas no differences were found between clinical characteristics in the response to infliximab.

MCQ corner

1. Selenocysteine is coded by UGA UAG UAA AUG Ans: A. UGA Explanation Selenocysteine (SeCys/SeC) is the 21st amino acid and is found in thioredoxin reductase, glutathione peroxidase, 5’-deiodinase, and selenoprotein P. It is an exceptional case where a stop codon codes for an amino acid. The other stop codons are UAA and UAG. The ability of the protein synthetic apparatus to identify a selenocysteine-specific UGA codon involves the selenocysteine insertion element, a stem-loop structure in the untranslated region of the mRNA.[1] 2. A child with diarrhea for 2 days came to your out-patient department (OPD). On examination, the signs of dehydration were marked and the child was treated with oral rehydration solution (ORS). Glucose absorption was facilitated by which receptors? SGLT1 SGLT2 GLUT4 Sodium–hydrogen antiporter Ans: A. SGLT1 Explanation Absorption of glucose from the intestinal lumen to intestinal cells is by the cotransport mechanism. It is an active transport system and can transport against the concentration gradient.[2] 3. Skeletal derivative of the second pharyngeal arch is Malleus Incus Stapes Maxilla Ans: C. Stapes Explanation Maxilla, malleus, and incus are derived from the first arch.[3] 4. Blastocyst makes contact with a uterus on <3 days 5–7 days 8–11 days 15–16 days Ans: B. 5–7 days Explanation Contact of the blastocyst with endometrium occurs at the time of implantation. Implantation occurs at around 5-7 days.[4] 5. The father of antiseptic surgery is Louis Pasteur Robert Koch Julius Petri Joseph Lister Ans. D. Joseph Lister Explanation Louis Pasteur – the father of microbiology, Robert Koch – the father of microbiology (with Louis Pasteur), and the father of medical bacteriology, Julius Petri – invented the Petri dish.[5] 6. Following were the findings in a Glucose tolerance test (GTT). Fasting blood glucose <75 mg/dl; all blood samples show low blood glucose; urine glucose – nil. The possible diagnosis is Alimentary glycosuria Diabetes mellitus Hypopituitarism Diabetes insipidus Ans. C. Hypopituitarism Explanation In alimentary glycosuria, there will be a peak in the first sample after glucose load and sugar will appear in urine. In diabetes mellitus, fasting and the next two samples will show higher values than the normal reference range and the sample does not return to baseline at the end of the test. In hypopituitarism, there is hypoglycemia and the patient feels fatigued and stressed. In diabetes insipidus, GTT is mostly unaffected.[6] 7. A 10-year-old boy with a history of atopy presented with seasonal recurrent bilateral conjunctivitis and complained of blurred vision for the past 1 week. On lid eversion, giant papillae were seen. All of the following could be seen by slit-lamp examination except: Vascular pannus and punctate epithelial erosions involving the superior cornea. An oval epithelial ulceration with underlying stromal opacification in the central cornea Limbal follicles Conjunctival symblepharon Ans. D. Conjunctival symblepharon Explanation A conjunctival symblepharon is seen in the case of autoimmune disorders such as Sjogren’s syndrome, sarcoidosis, lichen planus, granulomatosis with polyangiitis, etc.[7] 8. Which of the following breast lesion is a noninvasive malignancy? Tubular carcinoma and mucinous carcinoma Intraductal carcinoma of the comedo type Infiltrating ductal carcinoma and lobular carcinoma Medullary carcinoma, including atypical medullary lesions Ans. B. Intraductal carcinoma of the comedo type Explanation A comedo-type ductal carcinoma in situ (DCIS), also known as comedocarcinoma insitu, is the high-grade subtype of DCIS. It completely fills and dilates the ducts and lobules in terminal duct lobular units with plugs of high-grade tumor cells with central necrosis “comedonecrosis.”[8] 9. In patients who develop a documented episode of deep-vein thrombosis, the most significant long-term sequelae are: Claudication Recurrent foot infections Development of stasis ulcer Pulmonary embolization Ans. C-Development of stasis ulcer Explanation Chronic symptoms may occur after 6 weeks or beyond. Pulmonary embolization is the most common complication but is seen as an acute complication.[9] 10. Identify the test from the diagram. Rothera’s test Benedict’s test Barfoed’s test Seliwanoff’s test Ans. A. Rothera’s testFigure 1: Purple permanganate coloured ring [Ferro-penta cyanine complex] at the junction of two fluidsExplanation Rothera’s test was done to identify the presence of ketone bodies in a urine sample. Benedict’s test will contain a green/yellow/orange/brick red precipitate at the bottom. Barfoed’s test has a red scum at the top of the fluid and a little red precipitate at the bottom. Seliwanoff’s test will have a cherry red color.[10] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Antiphospholipid Syndrome as a Cause of Recurrent Portal Vein Thrombosis in a Man with a Medical History of other Thrombosis

Aim: to present a clinical case of antiphospholipid syndrome (APS) manifested as recurrent portal vein thrombosis in a man with a medical history of other thromboses.Key points. APS is a syndrome that includes venous and/or arterial thrombosis, various forms of obstetric pathology, thrombocytopenia, as well as a variety of neurological, skin, cardiovascular and hematological disorders. The article presents a clinical case of a male patient with several episodes of vascular thrombosis, two of which (thrombophlebitis of the veins of the lower extremities and stroke) developed at the age of 39 years, and recurrent thrombosis of the portal vein since 2018. For several years, the patient had the diagnosis of cirrhosis based on the presence of signs of portal hypertension. However, the patient's liver function remained practically intact all the time. During the current examination, APS was suspected, and the result of a blood test for antibodies against phospholipids was positive.Conclusion. This clinical case of APS reflects the difficulties in diagnosing this disease. It should be remembered that cases of thrombosis at a young age may be due to APS.