Heparin Therapy Research Articles

ECMO (extra corporeal membrane oxygenation) in major trauma: A 10 year single centre experience

Aim To review the indications, complications and outcomes of extracorporeal membrane oxygenation (ECMO) in major trauma patients.Methods Single centre, retrospective, cohort study.Results Over a ten year period, from 13,420 major trauma patients, 11 were identified from our institutional trauma registry as having received ECMO. These patients were predominantly younger (mean 39 +/- 17 years), male (91%) and severely traumatised (median ISS 50, IQR 34 - 54). Veno-venous (VV) ECMO was used predominantly (n = 7, 64%), to treat hypoxic respiratory failure (mean PaO2/FiO2 ratio 69.7 +/- 38.6), secondary to traumatic lung injury. Veno-arterial (VA) ECMO was used less frequently, primarily to treat massive pulmonary embolism following trauma. Major bleeding complications occurred in four patients, however only one patient died from haemorrhage. Heparin free (2/11), delayed (3/11) or low dose heparin (2/11) therapy was frequently utilised. The median time from injury to ECMO initiation was 1 day (IQR 0.5 – 5.5) and median ECMO duration 9 days (IQR 6.5 – 10.5). ECMO was initiated <72 hours in 6 patients, with survival to discharge 67%, compared to 20% in those initiated >72 hours. Overall survival to discharge was 45%, and was higher with VV ECMO (64%), than other configurations (25%).Conclusion ECMO was rarely used in major trauma, the most common indication being severe hypoxaemic respiratory failure secondary to lung injury. In this severely injured cohort, overall survival was poor but better in VV compared to VA and better if initiated early (<72 hours), compared to late.

Clinical study of anticoagulant therapy in patients with severe coronavirus disease

OBJECTIVE: The prognosis of COVID-19 is related to thrombotic events. This study investigated prognostic risk factors, anticoagulant therapy effects, and potential instruction of treatment or prognostic with D-dimer in patients with severe COVID-19 receiving anticoagulant therapy. MATERIALS AND METHODS: We undertook a retrospective study of 87 severe COVID-19 patients who had prophylactic low-molecular-weight heparin (LMWH) therapy. Patients were divided into two groups according to whether high-flow oxygen therapy was required during hospitalization: Better and poor prognoses. RESULTS: Multivariate logistic regression using risk factors measured before LMWH therapy revealed that older age (P &lt; 0.035) and higher C-reactive protein (CRP) levels (P = 0.002) had a prognostic value. Anticoagulant therapy yielded significant changes in CRP levels (P &lt; 0.001), white blood cell counts (P = 0.001), neutrophil counts (P &lt; 0.001), neutrophil/lymphocyte ratios (P &lt; 0.001), eosinophil counts (P = 0.031), and D-dimer levels (P &lt; 0.001) in the better prognosis group and in D-dimer levels (P = 0.043) only in the poor prognosis group. Prognoses at different D-dimer levels at anticoagulant therapy initiation varied. Among 47 and 40 patients with D-dimer levels ≤4 and &gt;4 μg/ml fibrin equivalent unit (FEU), 33 (70.6%) and 18 (45%) had better prognosis (P = 0.012), respectively. CONCLUSION: Anticoagulant therapy reduced inflammation in patients with better prognosis; conversely, minimal effect was observed in those with poor prognosis. During LMWH therapy patients with D-dimer levels, patients receiving anticoagulant therapy at D-dimer levels ≤4 μg/ml FEU had a better prognosis than those at &gt;4 μg/ml FEU.

Proton pump inhibitors: important information for cardiologists

Thromboembolic disorders occupy an important place in the structure of cardiovascular pathologies. Anticoagulants and antiplatelet agents proved to be the most efficient preventive medications for this group of patients, they enable reduction of the risk for both primary and secondary thromboembolic complications. However, their main shortcoming is the high potential of serious adverse events, basically related to gastrointestinal tract. That’s why, to prevent stress ulcers and bleedings in these patients, administration of antiplatelet agents, thrombolysis and heparin therapy is obligatory combined with the proton pump inhibitors. The authors presented data of evidence‑based medicine regarding one of the proton pump inhibitors, Ezolong, that contains esomeprazole (branded generic of Organosyn company). This combined medication is a modern formulation with the improved properties and more prolonged and predictable effect. Apart from its high protective efficacy, Ezolong is well tolerated, which is explained by the peculiarities of its pharmacodynamics and pharmacokinetics. Based on the complex of its clinical effects and safety profile, it is the drug of choice for patients with cardiovascular diseases. Ezolong is marketed in various formulations. Availability of its injectable formulation allows to achieve a quick intake of the active substance into the body, which is important for the therapy of acute pathologies and in case of impossibility of oral administration of the drug. Capsulated Ezolong provides easy administration, dosing accuracy, high adherence to the therapy of patients receiving outpatient treatment.&#x0D;

Optimal Bridging Strategy Post-Ventricular Assist Device Implantation Remains Unclear.

To the Editor: It was with enthusiasm that we read the article by Bates et al. describing bivalirudin utilization in a heterogeneous ventricular assist device (VAD) population.1 We were concerned, however, regarding their argument for the potential of bivalirudin as an initial bridging agent post-device implantation. No patients in their cohort received bivalirudin in this setting without being transitioned from either warfarin or heparin for either suspected or confirmed thrombosis or heparin-induced thrombocytopenia. Furthermore, the median time from VAD insertion to initiation of bivalirudin in their study was 116 days. Although we recognize the potential benefits of direct thrombin inhibitor therapy in the scenarios described within their cohort, the evidence for use of bivalirudin during the immediate postimplantation period as a bridge to oral anticoagulation is not well-elucidated. We have published the largest series to date of bivalirudin bridged patients (35) to oral anticoagulation after VAD placement.2 In our analysis, three different strategies were compared: bivalirudin, heparin, and no bridging immediately after VAD implantation. Our results suggested that bivalirudin was no different compared with heparin or no anticoagulation in terms of both thrombotic complications and bleeding events within 30 days of VAD implantation when controlling for international normalized ratio (INR) goals. In addition, the cost of heparin therapy was more than 40 times less than bivalirudin, although with the generic introduction of bivalirudin since the publication of our research, this number has certainly diminished. Overall, neither the Bates et al. data nor ours is sufficient to appropriately answer the question of which strategy is optimal to utilize post-VAD implantation.1,2 In addition, as the authors suggest, device type may also influence the benefits or weaknesses of various anticoagulant therapies. With the dramatic reduction in the rate of suspected of confirmed pump thrombosis observed in MOMENTUM-3, it is unclear if benefits observed in patients with older generation devices will translate to benefits in patients with the HeartMate 3.3 A large randomized trial, although welcome, is unlikely to be undertaken leaving a gap in the literature, which has yet to be filled for over a decade. Statements, however, on the utility of an approach without conclusive data, such as the use of bivalirudin in the post-implant period, and with some evidence showing that it has no discernable benefit should be made cautiously, if at all.

Management of the Gastrointestinal System Bleeding Caused by Direct-Acting Oral Anticoagulants

Direct-acting oral anticoagulants include dabigatran, which is a thrombin inhibitor, and rivaroxaban, apixaban, and edoxaban, which are anti-Xa agents. These are administered in the secondary prophylaxis and treatment of venous thromboembolism (VTE) and pulmonary embolism (PE), in the prophylaxis of VTE that may develop after major elective orthopedic surgery, in reducing stroke and systemic embolism that may occur in non-valvular atrial fibrillation, whereas its use in acute coronary syndrome is still controversial. Although it is specified that direct-acting oral anticoagulants are as effective as heparin therapy and reduce the risk of bleeding due to all causes, many important studies have also reported that they increase the risk of gastrointestinal system (GIS) bleeding.

Anticoagulation and Transfusion Management During Neonatal and Pediatric Extracorporeal Membrane Oxygenation: A Survey of Medical Directors in the United States.

To compare current practices within the United States of anticoagulation management and blood transfusion in neonatal and pediatric extracorporeal membrane oxygenation patients with a 2013 international report. Cross-sectional survey distributed between August and December 2019. Extracorporeal Life Support Organization-registered neonatal and pediatric extracorporeal membrane oxygenation centers in the United States. Extracorporeal membrane oxygenation medical directors. None. Eighty-three medical directors at 108 centers responded. After removing four duplicate responses, 79 surveys were analyzed. Seventy-nine percent (n = 62) report a written extracorporeal membrane oxygenation protocol for both anticoagulation and blood product management. Ninety-four percent (n = 74) report unfractionated heparin as their primary anticoagulant; the remaining use the direct thrombin inhibitor, bivalirudin. Ninety percent (n = 71) report measuring antifactor Xa levels. Most centers report using a combination of assays to monitor heparin therapy, either antifactor Xa and activated partial thromboplastin time (54%) or more commonly antifactor Xa and activated clotting time (68%). Forty-one percent use viscoelastic tests to aid management. Goal monitoring levels and interventions generated by out of range values are variable. Fifty-one percent will replace antithrombin. Platelet transfusion thresholds vary by age and center with ranges from 50,000 to 100,000 cells/µL. Eighty-two percent of respondents are willing to participate in a randomized controlled trial comparing anticoagulation strategies for patients receiving extracorporeal membrane oxygenation. Compared with the 2013 pediatric population, extracorporeal membrane oxygenation center anticoagulation and blood transfusion approaches continue to vary widely. Most report continued use of heparin as their primary anticoagulant and follow a combination of monitoring assays with the majority using the antifactor Xa assay in their practices, a significant shift from prior results. Antithrombin activity levels and viscoelastic tests are followed by a growing number of centers. Platelet transfusion thresholds continue to vary widely. Future research is needed to establish optimal anticoagulation and blood transfusion management.

Decreased Platelet Count Due to Heparin in Covid-19

COVID-19 (coronavirus disease-2019) infection may be a extremely prothrombotic state, ensuing from a dysregulation of the coagulation cascade. Therefore, thromboprophylaxis is powerfully suggested in these patients, with some consultants even advocating for therapeutic dosing to forestall thromboembolic events. Heparin-induced blood disorder (HIT) may be a well-known complication of heparin therapy. during this article, we tend to report a case of HIT in a patient with COVID-19. A 52-year-old male with history of one week of dry cough and loose stools. He had a positive COVID-19 reverse-transcriptase–polymerase chain reaction. On admission, the platelet count and liver function test were within normal limits. Throughout his hospitalization, he developed a right femoral deep venous thrombosis and was started on therapeutic anticoagulations. Due to worsening respiratory failure, he was intubated and mechanically ventilated. Between days eight and nine of hospitalization, platelet count decreased from 294000 to 89000 cells/μL. He had a high pretest likelihood for HIT with a 4T score of 6 and a positive anti-PF4/ heparin antibody. Heparin drip was interrupted and was switched to Argatroban. The serotinin assay eventually came back positive, that confirmed the diagnosis of HIT.

Deep vein thrombosis with bulla formation: an uncommon case report and review of literature

Deep vein thrombosis (DVT) is a common disorder that can lead to severe complications. Many factors can increase the risk of developing this disease. As we know, bulla formation due to DVT is extremely rare. A 45-year-old woman was referred to Shahid Sadoughi Hospital (Yazd, Iran) with pain and swelling of the left lower limb from one day beforehand. One day after admission, a large bulla (13 x 19 cm) appeared on the posterior part of her left leg. She had used the low-dose estrogen type of oral contraceptive pills ten days earlier. Color doppler sonography confirmed the presence of DVT. Heparin therapy was done and the patient was discharged in good condition. Bulla formation due to DVT is a very rare complication. It should be considered in patients of low socioeconomic classes and those using oral contraceptive pills. After the occurrence of DVT, we must rapidly move to avert its complications and prevent pulmonary embolism.

Acute Limb Ischemia in Critically ill COVID-19 Patients: a Case Series and Literature Review

Background: The vascular burden increased by COVID-19 infection and including acute limb ischemia (ALI) quickly emerged as a major medical challenge with devastating consequences such as limb loss, multiorgan dysfunction and death. We report a case series of COVID-19 infection associated with ALI to raise awareness and knowledge towards this life-threatening association. Methods: COVIDS-19 patients with acute limb ischemia (ALI) managed in a Moroccan 14 beds COVID-19 ICU between March 2020 and January 2021, were reviewed. Data collected included demographics, clinical presentation, treatments and outcomes. Results: Over the 10-month period, our ICU cared for 407 hospitalized patients with confirmed COVID-19. A total of 6 COVID-19 patients with ALI were identified. The mean age was 61 years (52 - 70) and 5 were men. The most common preexisting condition was diabetes (50%). The mean CRP level was 219 mg/L. Five patients had thrombus in multiple locations. No concomitant deep vein thrombosis was identified. Four patients presented with signs of acute No arterial ischemia with or without respiratory symptoms and were subsequently diagnosed with COVID-19. The remaining two patients developed ischemia during hospitalization. Mean SOFA score was 5 (2 -9). Respiratory support, corticosteroids and heparin therapies were used in all patients. Intubation and vasopressors were required in four patients. Revascularization was performed in five patients and reintervention was necessary in three cases. Four patients died in the ICU while two were successfully discharged. Conclusion: ALI in COVID-19 patients is a challenging life-threatening vascular emergency that requires appropriate multidisciplinary management (intensivists, anesthesiologists, vascular surgeons and interventionists, radiologists, haematologists…) and further studies focused on anticoagulation. Keywords: Acute Limb ischemia, Coagulopathy, COVID-19, SARS-CoV-2, Thrombosis

Venous Thromboembolic Diseases: Epidemiological, Clinical, Para clinical, Therapeutic and Evolutionary Aspects: Retrospective Study over a Period of 7.5 Years about 112 Cases collected in the Internal Medicine and Cardiology Department of Lnth

Introduction: venous thromboembolism (VTE) is a real public health problem in the world due to its frequency and severity since the mortality from an untreated thromboembolic episode is around 30%. Because of its chronic and disabling complications (post-thrombotic disease and chronic thromboembolic pulmonary hypertension), it is responsible for a deterioration in the quality of life of patients. Objective: The aim of this work was to contribute to the study of the epidemiological , clinical, Para clinical, therapeutic and evolutive aspects of venous thromboembolism disease in the internal medicine and cardiology department of the Amirou Boubacar Diallo National Hospital. Patients and Methods: It's a prospective study from July 1st, 2019 to June 30th, 2020 and retrospective from January 1st, 2013 to June 30th, 2019 (7 years and 6 months) about 112 patients with whom the diagnostic of deep venous thrombosis (DVT ) and / or pulmonary embolism (PE) had been done. Results: In our study, the prevalence of venous thromboembolism has been estimated at 3.9% of hospitalized patients with cardiovascular diseases. There was a female predominance (sex ratio 1.38). The average age of patients was 52 years. Teabed-rest prolonged was the frequent risk factor (66%). The clinical symptomatology was dominated by oedema of the lower limb (83.3%) and pain in limb palpation (82.1%) in case of DVT, the dyspnea (23.02%) and thoracic pain (11.6%) in case of PE. The attack of the left lower limb prevailed (45.5%). The sinus tachycardia (25.9%) was the predominant electrical sign at the ECG. Through the Doppler of the lower limbs, the popliteal and femoral veins were the most involved with 22.3% and 17.8% respectively. According to the chest angio-CT, the left pulmonary artery was obstructed in 100% of case. The treatment was essentially made of low molecular weight heparins (90.1%) replaced quickly by vitamin k antagonist (began the first day of the heparin therapy) and / or of unfractionated heparin (9%). The most common complication was PE due to DVT and the overall mortality was 12.5%. Conclusion: VTE is pathology in young adults and elderly characterized by the formation of a clot in a vein responsible for the obstruction of the latter causing local inflammatory signs and / or its pulmonary migration which could be fatal. The prevention and treatment of VTE are based on anticoagulants.

Variability of Activated Clotting Time by Site of Sample Draw During Percutaneous Coronary Intervention: A Prospective Single-Center Study

The activated clotting time (ACT) assay is used to monitor and titrate anticoagulation therapy with unfractionated heparin during percutaneous coronary intervention (PCI). Observations at our institution suggested a considerable difference between ACT values drawn from varying arterial sites, prompting the current study. Patients undergoing PCI with unfractionated heparin therapy were prospectively enrolled. Simultaneous arterial blood samples were drawn from the access sheath and the coronary guide catheter. Differences between Hemochron ACT values were determined, and potential interactions with clinical variables were analyzed. Immediately postprocedure, the simultaneous mean guide and sheath ACTs were 327 ± 62 seconds and 257 ± 44 seconds, respectively, with a mean difference of 70 ± 60 seconds (P < .001). Nearly all (90%) ACT values obtained via the guide catheter were higher than the concurrent ACT drawn from the sheath. Logistic regression analysis demonstrated that lower weight-adjusted heparin doses and absence of diabetes were associated with a greater difference between the ACT values. We conclude that the ACT value is substantially greater when assessed via the guide catheter versus the access sheath. Although the biological mechanisms require further study, this difference should be considered when managing anticoagulation during PCI and when reporting ACT as part of research protocols.

SARS-CoV-2 and finding of vein thrombosis: can IMPROVE and IMPROVEDD scores predict COVID-19 outcomes?

Diffuse thrombosis represents one of the most predominant causes of death by COVID-19 and SARS-CoV-2 infection seems to increase the risk of developing venous thromboembolic diseases (VTE). Aim of this study is to analyze the relationship between validated predictive scores for VTE such as IMPROVE and IMPROVEDD and: (1) Intensification of Care (IoC, admission to Pulmonology Department or Intensive Care Unit) (2) in-hospital mortality rate 3) 30-days mortality rate. We retrospectively evaluated 51 adult patients with laboratory diagnosis of SARS-CoV-2 infection and calculated IMPROVE and IMPROVEDD scores. All patients underwent venous color-Doppler ultrasound of the lower limbs to assess the presence of superficial vein thrombosis (SVT) and/or deep vein thrombosis (DVT). Patients with normal values of D-dimer did not receive heparin therapy (LMWH); patients with ≥ 4 ULN values of D-dimer or with a diagnosis of DVT were treated with therapeutic LMWH dosage, while the remaining patients were treated with prophylactic LMWH dosages. We found strong relations between IMPROVE score and the need for IoC and with the in-hospital mortality rate and between the IMPROVEDD score and the need for IoC. We defined that an IMPROVE score greater than 4 points was significantly associated to in-hospital mortality rate (p = 0.05), while an IMPROVEDD score greater than 3 points was associated with the need for IoC (p = 0.04). Multivariate logistic analysis showed how IMPROVE score was significantly associated to in-hospital and 30-days mortality rates. IMPROVE score can be considered an independent predictor of in-hospital and 30-days mortality.

Early thromboembolic complications after total cavopulmonary connection/Fontan operation in children: A five year single centre review

BackgroundPatients following total cavopulmonary connection (TCPC)/Fontan surgery are at a higher risk of developing systemic and non-systemic thromboembolic complications (TEC). Despite their potential for being serious and life threatening, very few studies have investigated TEC profile in the early postoperative period in children. ObjectivesTo study the incidence, symptom profile, possible risk factors, and outcomes in the early postoperative period for up to 12 months following the TCPC/Fontan surgery. MethodsWe conducted a retrospective case note review of all children undergoing TCPC/Fontan procedure during a five year period (2014–2018) at our hospital. Electronic case notes and outpatient clinic letters of all identified children were reviewed till 12 months after the date of their TCPC/Fontan surgery. ResultsFour out of 96 children (4.2%) developed TEC over the study period - three of them within 2 weeks of surgery. Symptoms ranged from hemiparesis, low cardiac output, and limb pain with swelling. No risk factors could be identified which significantly increase the hazard risk for the development of TEC. There was no significant difference in the incidence of TEC between children initiated on standard or targeted heparin therapy postoperatively in the cardiac ICU. ConclusionTEC are not uncommon and can present with serious or life threatening symptoms. Due to lack of robust pediatric evidence, there is an urgent need for coordinated, multi-center long term longitudinal follow up research for determining best clinical practice for prevention, surveillance, diagnosis, and treatment of this potentially life threatening complication.

Neonatal acute limb ischemia

Abstract Acute limb ischemia is a rare disorder in the perinatal period. The etiology and management of acute limb ischemia is not well described. We report 4 cases of acute limb ischemia in the neonatal period. Observations We present the cases of four premature neonates aged between 6 and 15 days. The mothers of one of the neonates had a history of gestational diabetes. Three neonates were born by eutocic vaginal delivery and one, by cesarean section. Reasons for hospitalization of the neonates included infections (3 cases), hyaline membrane disease (2 cases) and congenital malaria (1 case).The neonates presented with cyanosis localized in the fingers (1 case), cyanosis on the fingers extending to the forearm (2 cases) and cyanosis localized in the toe (1 case). All patients had a peripheral intravenous catheter implanted in the affected limb. In three cases, there was an infectious syndrome and in one case, hemostasis was impaired. Doppler ultrasound of the blood vessels in the affected limb revealed arterial thrombosis in 2cases. Management involved antibiotics, heparin therapy and fasciotomy. During hospitalization, 1 patient had spontaneous distal phalanx amputation, 1 required surgery for forearm segmental gangrene and 2 died. Conclusion Neonatal acute limb ischemia is rare but can be fatal due to functional and vital repercussions. Treatment outcomes depend on early diagnosis, etiology and treatment.

Risk factors associated with adverse pregnancy outcomes in patients with new-onset systemic lupus erythematosus during pregnancy.

To investigate the risk factors for Adverse pregnancy outcome (APOs) in patients with new-onset SLE during pregnancy. Eighty-five patients with new-onset SLE during pregnancy were analyzed retrospectively. Univariate and multivariate logistic regression were used to identify risk factors for different APOs (pregnancy loss, preterm birth, fetal growth restriction, and eclampsia/preeclampsia). A two-sided p-value below 0.05 was considered significant, and two-sided 95% confidence intervals (CIs) are reported. Multivariate analysis indicated that renal involvement (aOR: 7.356; 95%CI:1.516,35.692) and greater SLE disease activity index (SLEDAI) grade (aOR:5.947;95%CI: 1.586,22.294) increased the risk for composite APO, and that use of heparin therapy (aOR: 0.081; 95%CI: 0.012, 0.532) was a protective factor. Advanced gestational age at disease onset (aOR: 0.879; 95%CI: 0.819,0.943) and high serum albumin level (aOR: 0.908,95%CI: 0.831,0.992) protected against pregnancy loss. Renal involvement increased the risk for preterm birth (aOR: 2.272; 95%CI: 1.030,7.222) and fetal growth restriction (aOR: 9.070; 95%CI: 1.131,72.743). Hypertension (aOR: 19.185; 95%CI: 3.921,93.868), renal involvement (aOR: 8.380, 95%CI: 1.944,74.376) increased the risk for eclampsia/preeclampsia. New onset SLE during pregnancy increased the risk for multiple APOs. Timely management of the risk factors identified here may help to improve pregnancy outcomes in these patients.

Venous thromboembolic complications in patients with intracerebral hemorrhage

To evaluate the effectiveness and safety of various heparin therapy regimens for venous thromboembolic complications in patients with acute cerebral circulatory disorders of the hemorrhagic type. In a prospective single-center study, treatment results of 62 patients with hypertensive brain hematoma were analyzed. All patients were divided into two comparable groups: the group of «very early» prophylactic heparin therapy or the first 48 hours from the moment of the disease (n=35) and the group of «early» prophylactic heparin therapy, or later than 48 hours from the moment of the intracerebral hematoma development (n=27). The end points of the study were: venous thrombosis, pulmonary embolism (fatal and non-fatal), recurrent intracerebral hemorrhage, other clinically significant hemorrhagic complications, and intrahospital mortality. In the group of «very early» and «early» prophylactic heparin therapy, the results were as follows: venous thrombosis 22.9% vs. 29.6% (p=0.36), total rate of PE 2.9% vs. 11.1% (p=0.03), nonfatal PE 0% vs. 7.4% (p=0.007), fatal PE 2.9% vs. 3.7% (p=0.76), recurrent intracerebral hemorrhage and other hemorrhagic complications 0% in both groups, intrahospital mortality was 54.3% versus 48.1% (p=0.54). The earliest administration of direct anticoagulants in prophylactic doses in patients with hemorrhagic stroke leads to the decrease in the frequency of venous thrombosis and thromboembolic complications, without being accompanied by the development of repeated intracranial and other hemorrhagic events.

Practicability of Bivalirudin plus Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis.

A variety of antithrombotic drugs are used during percutaneous coronary interventions (PCIs). We aimed to investigate the practicability of the use of bivalirudin and GPIs in patients receiving PCI. We searched 7 of 629 relevant records from PubMed, the Cochrane Library, EMBASE, and Web of Science for randomised controlled trials. There were no significant differences in the rates of major adverse cardiac events (MACE) between bivalirudin plus GPI and heparin (all P > .05). Bivalirudin plus planned GPI was similar to bivalirudin monotherapy in terms of the risk of MACE (risk ratio [RR] = 1.07; 95% confidence interval [CI] = .91 − 1.27; P = .55). Bivalirudin plus provisional GPI was associated with lower bleeding risk (RR = .57; 95% CI = .47 − .69; P < .01) compared to using heparin plus GPI. Compared to bivalirudin alone, bivalirudin plus planned GPI evidently increased bleeding risk (RR = 2.20; 95% CI = 1.73 − 2.79; P < .01). Patients receiving bivalirudin or heparin therapy had semblable efficacy endpoints, but those receiving bivalirudin had a significantly lower bleeding risk. For high-risk bleeding patients, bivalirudin plus provisional GPI can have a better antithrombotic effect than heparin, without increasing the bleeding risk.

Antiphospholipid syndrome: diagnosis and management

Antiphospholipid syndrome (APS) is an acquired thrombophilia associated with autoimmunity and is a syndrome that should always be considered when examining patients with thrombosis and pregnancy complications. As per the Sydney criteria, a diagnosis can be established with at least one clinical finding, such as arteriovenous thrombosis and the presence of at least one of the antiphospholipid antibodies (aPL), such as anticardiolipin antibodies (aCL). Moreover, phosphatidylserine-dependent anti-prothrombin antibody and anti-b2GPI-domain 1 antibody are correlated with APS manifestations and enable APS diagnosis. In addition to the inhibition of physiological coagulation inhibitors, such as protein C, the activation of vascular endothelial cells and complement activation by aPL is presumed to be the thrombus mechanism of APS. The mainstay of treatment is anticoagulant therapy with warfarin. For treating APS that has developed by arterial thrombosis, antiplatelet agent alone or in combination with warfarin is considered. In the triple positive aPL (aCL, anti-b2GPI antibodies, and lupus anticoagulant are detected at the same time) cases, sufficient anticoagulant therapy is required. Direct oral anticoagulants are not recommended in cases of triple positive aPL or arterial thrombosis. For patients with catastrophic APS, heparin therapy, plasmapheresis, and steroid pulse therapy are recommended.

Treatment of cancer-associated thrombosis: The evolution of anticoagulant choice and clinical insights into practical management.

Low-molecular-weight heparin (LMWH) therapy is recommended over vitamin K antagonists (VKAs) for the treatment of cancer-associated thrombosis (CAT) and extended therapy is recommended in those with active cancer to prevent recurrent thrombosis. However, the inconvenience of daily subcutaneous injections and the cost of LMWH therapy hinder long-term use. Observational data demonstrate that persistence with LMWH therapy is low in clinical practice and that many patients are switched to oral alternatives - namely VKAs and direct oral anticoagulants (DOACs). Recently, the efficacy and safety of apixaban, edoxaban, and rivaroxaban versus LMWH therapy for the treatment of CAT have been demonstrated in randomized trials. This review provides a critical evaluation of studies with DOACs in this setting and an update on the guidance regarding anticoagulant use for the treatment of CAT. In recognition of the heterogeneity of patients with cancer and the challenges of CAT, patient cases with expert clinical perspectives are presented.

Влияние терапии низкомолекулярными гепаринами на уровень плодовой ДНК при проведении неинвазивного пренатального ДНК-скрининга

Study Objective: To evaluate the effect of low molecular heparin (LMH) therapy on non-invasive prenatal DNA screening (NIPS) for chromosomal pathologies. Study Design: cross-sectional study. Materials and Methods. We have examined two groups of pregnant women: group I included 49 patients with constantly low foetal DNA (twice lower than 4%) selected out of 1,505 women examined at Kulakov National Medical Scientific Centre of Obstetrics, Gynaecology and Perinatal Medicine of the Ministry of Health of Russia during the last 2 years. 17 women were administered LMH and 32 women did not receive it. Group II included 113 pregnant women with a normal foetal DNA fraction (at least 4%), that were selected randomly out of patients who were examined during the same period. 56 pregnant women were administered LMH and 57 were not. Next Generation Sequencing was used as an NIPS method. In order to determine the foetal DNA level, we amplified DNA loci with single nucleotide polymorphisms. Study Results. In group I (low foetal DNA fraction), where no LMH therapy was initiated, median values were 3.5% (3.2–3.8%); if LMH was administered, these values made 3.6% (3.4–3.9), while in group II — 7.7% (6.1–9.5%) and 7.9% (6.0–10.5%), respectively; no significant differences (p = 0.29 and p = 0.7, respectively) were recorded in both cases. Conclusion. Use of LMH does not affect NIPS; therefore, it is not necessary to adjust the LMH therapy in pregnant women prior to NIPS. Keywords: non-invasive prenatal DNA screening, heparin, anticoagulants, low molecular heparins, habitual abortion, pregnancy complications.