Clinical Efficacy of Conventional Heparin Anticoagulation Combined with Apixaban in the Treatment of Patients with Cerebral Venous Thrombosis and Its Effect on Serum D-Dimer and FIB Expression

Objective. The aim of this study was to explore the clinical efficacy of conventional heparin anticoagulation in combination with apixaban in the treatment of patients with cerebral venous thrombosis (CVT) and its influence on serum D-dimer (D-D) and fibrinogen (FIB). Methods. One hundred and fifty-seven consecutive CVT patients admitted to our hospital from January 1, 2006, to December 31, 2013, were allocated into two groups according to the different treatment methods, of which 95 cases received standard anticoagulation therapy (standard group (SG)) and the remaining 62 cases were given apixaban therapy (research group (RG)). The curative effects and the changes of coagulation function during the treatment, as well as the incidence of adverse reactions, were analyzed in the two groups. The changes of D-D and FIB levels before treatment and at days 1, 4, and 7 posttreatment were detected. Results. In treatment efficacy, RG was superior to SG. No evident difference was observed in the incidence of adverse events or coagulation function between the two groups. At day 1 posttreatment, D-D level was increased largely in both SG and RG, but the increase was much more significant in RG. However, D-D level was decreased gradually with time in both groups, and the reduction was more notable in RG. The FIB level in SG declined gradually with time after treatment and was higher than that in RG at the same time point. In RG, FIB was decreased gradually at day 1 and day 4 posttreatment, and its level at day 7 posttreatment showed no difference compared with that at day 4 posttreatment. Spearman’s analysis identified that the higher the D-D level or the lower the FIB level at day 1 posttreatment was, the better the treatment efficacy was. After seven-day treatment, the lower the level of D-D and FIB was, the better the therapeutic effect was. Logistic analysis indicated that age, time of diagnosis, deep vein thrombosis (DVT), Glasgow Coma Scale (GCS) score, infection, Apixaban, D-D, and FIB all independently affect the treatment effect of patients. Conclusions. The combined use of Apixaban with heparin is high-performing and safe in the treatment of CVT. The changes of D-D and FIB levels during the treatment are strongly linked to the therapeutic effect, which can be used as plausible evaluation indexes for the efficacy of CVT.

MO871HEPARIN INDUCED THROMBOCYTOPENIA AND HEMODIALYSIS - SINGLE CENTRE EXPERINCE

Background and Aims Heparin-induced thrombocytopenia (HIT) is a potentially fatal adverse reaction after administration of unfractionated or fractionated heparin, which underlies the generation of antibodies to the heparin complex and platelet factor 4 (PF4). It occurs in 5% of patients treated with unfractionated heparin and 0.5 - 1.5% fractionated heparin. The aim of the study is to determine the incidence and outcome of hemodialysis patients with HIT over 4-years period. Method This retrospective study analyzed patients who were tested for evidence of positive anti-heparin antibody in the period from 2015 to 2020 in Zvezdara University Medical Center. The diagnosis was confirmed by the 4T clinical scoring system, a positive antiheparin-PF4 ELISA test and a positive platelet aggregation test with heparin. Results During observation period, total of 64 tests were performed, out of which 23 patients were positive. Out of them, 14 patients were on HD, 7 patients (geriatric, surgery and cardiology departments) received therapy due to peripheral thrombosis, AIM or arrhythmia and 2 patients during 2020 due to SARS-CoV-2 bilateral pneumonia. All patients treated at nephrology, started hemodialysis (HD) with unfractionated heparin, while others were treated with LMWH. 4T scoring showed that 64% of patients had a moderate risk of developing HIT, while high risk was assessed in 36% of patients. Thrombotic complications in the form of deep venous thrombosis had 53% of patients and pulmonary thromboembolism had 17,5 % of patients. The greatest decrease in Tr was the most commonly observed between 10th and 14th day (61% of patients) and 39% from 4th to 10th day from start of heparin administration. In addition to heparin withdrawal and treatment with alternative non-heparin anticoagulation (fondaparinoux), 7 patients needed plasma treatment. 11 patients on HD were transferred to peritoneal dialysis (PD), and 3 patients recovered renal function. Overall mortality was 52%, and it was below 30% in hemodialysis patients. Conclusion HIT should be considered in patients at risk. It is necessary to abolish heparin treatment and use alternative method (PD) or alternative anticoagulation. Hemodialysis patients have better prognosis than other comparable patients

Prothrombotic immune thrombocytopenia after COVID-19 vaccine

We report five cases of prothrombotic immune thrombocytopenia after exposure to the ChAdOx1 vaccine (AZD1222, Vaxzevria) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients presented 5 to 11 days after first vaccination. The spectrum of clinical manifestations included cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis (SVT), arterial cerebral thromboembolism, and thrombotic microangiopathy (TMA). All patients had thrombocytopenia and markedly elevated D-Dimer. Autoantibodies against platelet factor 4 (PF4) were detected in all patients although they had never been exposed to heparin. Immunoglobulin from patient sera bound to healthy donor platelets in an AZD1222-dependant manner, suppressed by heparin. Aggregation of healthy donor platelets by patient sera was demonstrated in the presence of buffer or AZD1222 and was also suppressed by heparin. Anticoagulation alone or in combination with eculizumab or intravenous immunoglobulin (IVIG) resolved the pathology in three patients. Two patients had thromboembolic events despite anticoagulation at a time when platelets were increasing after IVIG. In summary, an unexpected autoimmune prothrombotic disorder is described after vaccination with AZD1222. It is characterized by thrombocytopenia and anti-PF4 antibodies binding to platelets in AZD1222-dependent manner. Initial clinical experience suggests a risk of unusual and severe thromboembolic events.

COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A review of the potential mechanisms and proposed management

With over 600 million coronavirus (COVID-19) vaccine doses administered globally, adverse events are constantly monitored. Recently however, reports of thrombosis and thrombocytopenia following vaccination with the ChAdOx1 nCoV-19 vaccine have emerged. This paper aims to review the available literature and guidelines pertaining to vaccine-induced immune thrombotic thrombocytopenia (VITT) and the proposed guidelines, while offering a potential approach that unifies the available evidence. While the risk of VITT remains extremely low and the benefits outweigh the risks, experimental studies are needed to clarify the pathophysiology behind VITT and possibly decrease the risk of thrombosis and other adverse events occurring. However, treatment should not be delayed in suspected cases, and IV immunoglobulin and non-heparin anticoagulation should be initiated.

Cardiopulmonary bypass in a child with severe Factor XII deficiency

Factor XII (FXII) deficiency presents as a prolonged activated partial thromboplastin time (aPTT) but is not associated with clinically significant bleeding. Activated clotting time (ACT) is used routinely to monitor anticoagulation with unfractionated heparin in patients undergoing cardiopulmonary bypass (CPB). The coagulation activator reagents in most ACT tests are dependent on adequate FXII concentrations to initiate contact factor coagulation pathways. We report the case of a 14.7 kg girl undergoing CPB with a pre-admission FXII concentration of <1% and aPTT >200 seconds. The child was transfused with fresh-frozen plasma to replenish FXII, allowing safe ACT monitoring of heparin anticoagulation throughout CPB.

Anticoagulation in COVID-19.

In 2020 declared the COVID-19 pandemic. A new SARS-Cov-2 betacoronavirus transmitted through respiratory secretions of infected people, causing lesions in the pulmonary microvasculature, endothelial activation, massive release of pro-inflammatory substances "cytokine storm", which lead to a procoagulant state and on which it will depend the development of the serious disease. The management of coagulopathy induced by COVID-19 entails stratifying the risk of thrombosis, for which heparins are the treatment of choice, especially in hospitalized patients. Low molecular weight heparin (LMWH) is the first option since its administration implies longer times and less exposure of health personnel. Unfractionated heparin is another alternative but requires laboratory controls and is sometimes not available. Heparin-induced thrombocytopenia (HIT) and bleeding are serious adverse events secondary to the use of heparin anticoagulation.

Comparison between regional citrate anticoagulation and heparin for intermittent hemodialysis in ICU patients: a propensity score-matched cohort study

Background Regional citrate anticoagulation (RCA) is the gold standard of anticoagulation for continuous renal replacement therapy but is rarely used for intermittent hemodialysis (IHD) in ICU. Few studies assessed the safety and efficacy of RCA during IHD in ICU; however, no data are available comparing RCA to heparin anticoagulation, which are commonly used for IHD. The aim of this study was to assess the efficacy and safety of RCA compared to heparin anticoagulation during IHD. Methods This retrospective single-center cohort study included consecutive ICU patients treated with either heparin anticoagulation (unfractionated or low-molecular-weight heparin) or RCA for IHD from July to September in 2015 and 2017. RCA was performed with citrate infusion according to blood flow and calcium infusion by diffusive influx from dialysate. Using a propensity score analysis, as the primary endpoint we assessed whether RCA improved efficacy, quantified with Kt/V from the ionic dialysance, compared to heparin anticoagulation. The secondary endpoint was safety. Exploratory analyses were performed on the changes in efficacy and safety between the implementation period (2015) and at long term (2017). Results In total, 208 IHD sessions were performed in 56 patients and were compared (124 RCA and 84 heparin coagulation). There was no difference in Kt/V between RCA and heparin (0.95 ± 0.38 vs. 0.89 ± 0.32; p = 0.98). A higher number of circuit clotting (12.9% vs. 2.4%; p = 0.02) and premature interruption resulting from acute high transmembrane pressure (21% vs. 7%; p = 0.02) occurred in the RCA sessions compared to the heparin sessions. In the propensity score-matching analysis, RCA was associated with an increased risk of circuit clotting (absolute differences = 0.10, 95% CI [0.03–0.18]; p = 0.008). There was no difference in efficacy and safety between the two time periods (2015 and 2017). Conclusion RCA with calcium infusion by diffusive influx from dialysate for IHD was easy to implement with stable long-term efficacy and safety but did not improve efficacy and could be associated with an increased risk of circuit clotting compared to heparin anticoagulation in non-selected ICU patients. Randomized trials to determine the best anticoagulation for IHD in ICU patients should be conducted in a variety of settings.