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Assisted reproductive techniques (ART) allow infertile couples to conceive. Use of hormones to obtain a controlled ovarian stimulation and an adequate growth of the endometrium preparatory for embryo implantation are not riskless. Among others, thrombotic events can occur during the ovulation induction or pregnancy following ART. As the number of women approaching ART to conceive is steadily increasing, the issue of thrombotic risk in this setting is relevant. Data on the weight of each risk factor and on potential benefit of thromboprophylaxis are largely lacking. In this review, we discuss risk of venous thromboembolism during pregnancy following ART, with a focus on general (i.e.: age, body mass index, thrombophilia, bed rest, transfusions) and ART-specific (i.e., polycystic ovarian syndrome, ovarian hyperstimulation syndrome) risk factors. We also attempt to provide some suggestions to guide clinical practice, based on available data and studies performed outside ART.
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Síndrome de Hiperestimulación Ovárica , Trombosis , Tromboembolia Venosa , Embarazo , Femenino , Humanos , Anticoagulantes , Tromboembolia Venosa/etiología , Técnicas Reproductivas Asistidas/efectos adversos , Inducción de la Ovulación/efectos adversos , Síndrome de Hiperestimulación Ovárica/etiología , Trombosis/etiologíaRESUMEN
BACKGROUND: Thrombotic microangiopathy has been invoked as one of the most important mechanisms of damage in COVID-19 patients. Protease ADAMTS13 is a marker of microangiopathy responsible for controlling von Willebrand multimers size. Von Willebrand factor/ADAMTS13 ratio has been found impaired in COVID-19 patients outside pregnancy. METHODS: We prospectively investigated 90 pregnant women admitted to two tertiary academic hospitals in Italy with a laboratory-confirmed diagnosis of SARS-CoV-2 infection. Demographic, clinical information and routine laboratory data were collected at the hospital admission and until discharge. We investigated whether vonWillebrand /ADAMTS13 axis imbalance is a predictor of adverse outcomes. Logistic regression analysis, which controlled for potential confounders, was performed to evaluate the association between laboratory parameters and clinical outcomes. RESULTS: Most women (55.6%) were parae, with median gestational age at admission of 39 weeks. At hospital admission, 63.3% were asymptomatic for COVID-19 and 24.4% showed more than one sign or symptom of infection. Nulliparae with group O showed Willebrand / ADA MTS-13 ratios significantly lower than non-O, whereas in multiparae this difference was not observed. Logistic regression showed that ratio von Willebrand to ADAMTS13 was significantly and independently associated with preterm delivery (OR 1.9, 95%CI 1.1-3.5). CONCLUSION: This study shows an imbalance of vonWillebrand /ADAMTS13 axis in pregnant women with COVID-19, leading to a significantly higher and independent risk of preterm delivery. Monitoring these biomarkers might support decision making process to manage and follow-up pregnancies in this setting.
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Proteína ADAMTS13/sangre , COVID-19/sangre , Complicaciones del Embarazo/sangre , Nacimiento Prematuro/sangre , Factor de von Willebrand/metabolismo , Centros Médicos Académicos , Adolescente , Adulto , Biomarcadores/sangre , COVID-19/complicaciones , Femenino , Humanos , Italia/epidemiología , Persona de Mediana Edad , Embarazo , SARS-CoV-2 , Centros de Atención Terciaria , Microangiopatías Trombóticas/etiología , Adulto JovenRESUMEN
STUDY QUESTION: What evaluation and care is offered to women after unexplained recurrent pregnancy loss (RPL) or intra-uterine foetal death (IUFD) and what are the reproductive outcomes? SUMMARY ANSWER: Women are assessed for thrombophilia and often treated with low-molecular weight heparin (LMWH) and/or low-dose aspirin (ASA). WHAT IS KNOWN ALREADY: Randomized controlled trials (RCTs) on possible efficacy of heparins and/or aspirin have been inconclusive due to limited power to detect a difference and patient heterogeneity. STUDY DESIGN, SIZE, DURATION: Prospective multicentre cohort study performed in 12 hospitals in three countries between 2012 and 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: All consecutive pregnant women with recurrent PL (≥3 losses or 2 losses in the presence of at least one euploid foetal karyotype) or at least one IUFD. Eligible women may have undergone thrombophilia testing before conception, at the discretion of local providers. The possible assignment of women to treatments (such as LMWH) was not decided a priori but was determined based on the responsible provider's current practice. Aims of the study were: (i) to evaluate factors associated with pregnancy outcome; (ii) to compare clinical management strategies in women with and without a subsequent successful pregnancy; and (iii) to evaluate characteristics of women who may benefit from antithrombotic therapy. A propensity score matching method was used to balance the differences in baseline characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: A matched sample of 265 pregnant women was analysed, with all undergoing thrombophilia screening; 103 out of 119 (86.6%) with and 98/146 (67.1%) without thrombophilia were prescribed with LMWH and/or ASA. Overall, live-births were recorded in 204 cases (77%), PL or IUFD in 61 (23%) pregnancies. Logistic regression showed a significant interaction between thrombophilia and treatment with LMWH (P = 0.03). Findings from sensitivity analysis showed odds ratio (OR) for pregnancy loss in women with inherited or acquired thrombophilia in absence of any treatment was 2.9 (95% CI, 1.4-6.1); the administration of LMWH (with or without ASA) was associated with higher odds of live-birth (OR, 10.6; 95% CI, 5.0-22.3). Furthermore, in women without thrombophilia, the odds of live-birth was significantly and independently associated with LMWH prophylaxis (alone or in association with ASA) (OR, 3.6; 95% CI, 1.7-7.9). LIMITATIONS, REASONS FOR CAUTION: While the propensity score matching allows us to balance the differences in baseline characteristics, it does not eliminate all confounding. WIDER IMPLICATIONS OF THE FINDINGS: Antithrombotic prophylaxis during pregnancy may be effective in women with otherwise unexplained PL or IUFD, and even more useful in those with thrombophilia. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Italian Ministry of Health (Ricerca Corrente 2018-2020). Dr G.P. has received research grant support from Bristol Myers Squibb/Pfizer Alliance, Janssen, Boston Scientific Corporation, Bayer, and Portola and consultant fees from Amgen and Agile Therapeutics. Dr E.G. has received consultant fees from Italfarmaco and Sanofi. All other authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: NCT02385461.
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Aborto Habitual , Trombofilia , Femenino , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Nacimiento Vivo , Embarazo , Sistema de Registros , Trombofilia/complicaciones , Trombofilia/tratamiento farmacológicoRESUMEN
It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p < 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann-Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13-0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.
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Anticoagulantes/uso terapéutico , Transfusión Sanguínea , COVID-19/terapia , Heparina de Bajo-Peso-Molecular/uso terapéutico , Tromboembolia/prevención & control , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Transfusión Sanguínea/mortalidad , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/mortalidad , Toma de Decisiones Clínicas , Femenino , Heparina de Bajo-Peso-Molecular/efectos adversos , Mortalidad Hospitalaria , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Tromboembolia/sangre , Tromboembolia/diagnóstico , Tromboembolia/mortalidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Automated methodologies allowing for rapid detection of Factor V Leiden and Factor II G20210A variants are desirable, due to a high number of tested patients. Here, we report a preliminary validation of a CE-marked in vitro diagnostic (IVD) certified method for simultaneous detection of Factor V Leiden and Factor II G20210A variants on whole blood samples. The novel method is based on Loop-mediated isothermal AMPlification (LAMP) applied for a duplex detection of Factor V Leiden and Factor II G20210A variants without requiring prior DNA extraction, whereas the routine one is a TaqMan SNP genotyping targeting genomic DNA. We tested routine patients for both variants using novel and current methods and estimated concordance rate. Patients were tested under similar laboratory procedures. One hundred and eight patients referred for the thrombophilia testing in the period between 9th December 2019 to 27th February 2020 represented the study population. We routinely identified for the Factor V Leiden variant 163 wild-type, 17 heterozygotes and no homozygote. Concerning the Factor II G20210A variant, we identified 170 wild-type, nine heterozygotes and one homozygous carrier. Two heterozygotes carried both variants (double heterozygotes). The LAMP method showed a 100% concordance rate, detecting rightly all genotypes. The LAMP for a duplex detection of common thrombophilia variants shows analytic performances as good as those of the standard method.
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Factor V/genética , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , Protrombina/genética , Trombofilia , Adulto , Coagulación Sanguínea/genética , Pruebas de Coagulación Sanguínea/métodos , Femenino , Técnicas de Genotipaje/métodos , Humanos , Italia/epidemiología , Masculino , Mutación , Polimorfismo de Nucleótido Simple , Reproducibilidad de los Resultados , Trombofilia/diagnóstico , Trombofilia/epidemiología , Trombofilia/genéticaRESUMEN
Knowledge of the distribution of risk factors for superficial thrombosis (SVT) in low-risk population is fundamental to improve the prevention of the disease in each individual and high-risk settings of patients. Exact frequency data for the low-risk population are scarce, but could be useful for optimal use of prophylactic strategies against venous thrombosis. Blood donors represent a low-risk population, because are healthier than the general population. The objective of this study was to assess the prevalence of vein thrombosis, particularly SVT, and associated risk factors in a low-risk population such as blood donors. In this multicentre cross-sectional study, donors from six Italian blood banks responded to a self-administered questionnaire. The enrolment lasted from 1st June 2017 to 30th July 2018. History of vein thrombosis was referred by 89 (0.76%) individuals, (49 men) with an age-dependent effect. The prevalence reached 2.9% in women and 0.8% in men aged ≥ 49 years, with a significant difference only for women. After controlling for potential confounders, a significant and independent association was found between a history of vein thrombosis and age (OR: 1.03, 95%CI 1.01-1.05), varicose veins (OR: 15.8, 95%CI 7.7-32.6), plaster cast/bed rest (OR: 2.3, 95% CI 1.0-5.3) and transfusion (OR: 5.1, 95% CI 1.3-19.5). This study shows that low-risk individuals share the same risk factors for SVT as patients in secondary care. It also suggests that transfusion confers an increased risk of SVT in healthy population.
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Donantes de Sangre , Trombosis de la Vena/epidemiología , Adulto , Bancos de Sangre , Estudios Transversales , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Factores de RiesgoRESUMEN
BACKGROUND: May-Hegglin anomaly is an autosomal dominant inherited condition, characterized by thrombocytopenia, giant platelets and Dohle-like bodies. Incidence is unknown and affected individuals can show from mild to moderate-severe haemorrhagic symptoms. The cyst of cavum veli interpositi (a virtual space filled with fluid within the third ventricle) is rarely reported in the foetal period. Furthermore, it is unclear whether isolated cavum veli interpositi cysts are a normal variant or developmental malformations. The simultaneous presence of these two anomalies was never described. CASE PRESENTATION: We describe a very rare case of a twin monochorionic pregnancy in a woman with the May-Hegglin anomaly, whose foetuses carried cavum veli interpositi cysts. Since childhood, our patient had shown macro-thrombocytopenia, deafness and bleeding (epistaxis and menorrhagia), but she was misdiagnosed until the age of 30 years when our Centre identified a de novo allelic variant in the gene MYH9 coding for the non-muscle myosin heavy chain IIa. Our patient bled neither during the pregnancy, nor in the peripartum period. Children are now eight-months-old and have never bled, although both inherited the MYH9 variant and have thrombocytopenia with giant platelets. Furthermore, none of them developed psychomotor disorders. CONCLUSIONS: To the best of our knowledge, this is the sixth case of twin pregnancy in a woman carrying May-Hegglin anomaly and the first one with cavum veli interpositi cysts in the neonates. We speculate that MYH9 could have, at least in part, played a role in the development of both conditions, as this gene has a pleiotropic effect.
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Quistes/diagnóstico por imagen , Pérdida Auditiva Sensorineural/genética , Complicaciones del Embarazo/genética , Tercer Ventrículo/anomalías , Trombocitopenia/congénito , Adulto , Quistes/embriología , Quistes/genética , Femenino , Pérdida Auditiva Sensorineural/diagnóstico , Humanos , Recién Nacido , Embarazo , Complicaciones del Embarazo/diagnóstico , Resultado del Embarazo , Embarazo Gemelar , Trombocitopenia/diagnóstico , Trombocitopenia/genética , Ultrasonografía PrenatalRESUMEN
The number of hip fractures in anticoagulated patients is predicted to increase, due to people living longer. However, evidence regarding urgent perioperative management of elderly patients with hip fracture who take oral anticoagulants (vitamin K antagonists or direct oral anticoagulants) is scarce. In this article, the authors present a narrative review of the evidence to date supporting the urgent management of hip fracture in anticoagulated elderly patients. They discuss the complexity of managing the high risk of procedure-related bleeding and, at the same time, the high risk of thromboembolism. The role of a bridging procedure and the best strategy of anticoagulation reversal are also reviewed. Further studies are required to improve the evidence in urgent surgery, especially in frail elderly patients.
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Anticoagulantes/uso terapéutico , Fracturas de Cadera/complicaciones , Tromboembolia Venosa/prevención & control , Vitamina K/antagonistas & inhibidores , Administración Oral , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/diagnóstico , Hemorragia/terapia , Humanos , Medición de Riesgo , Factores de Riesgo , Tromboembolia Venosa/complicacionesRESUMEN
Severe ADAMTS13 deficiency (activity < 10%) is pathognomonic of thrombotic thrombocytopenic purpura. ADAMTS13 testing is time-consuming and unavailable in many hospitals. Recently, a seven-variables score named PLASMIC score, has been developed to stratify acute patients, based on their risk of having a severe ADAMTS13 deficiency. We present the application of this score in a cohort of patients referred to our Center. From 2012 to 2017, 42 patients with suspected thrombotic microangiopathies from 6 Centers were referred to Hemostasis and Thrombosis Center of "Casa Sollievo della Sofferenza" Hospital/Research Institute for ADAMTS13 testing. For all patients, relevant medical and laboratory information were collected. To obtain the statistical measure of the discriminatory power of PLASMIC scoring system, the Area Under the Curve Receiver Operating Characteristic (AUC ROC) was calculated. We were able to calculate the PLASMIC score in 27 out of 42 patients; we found a good discrimination performance of the score with a resulting AUC value of 0.86 (95% CI 0.71-1.0; p = 0.015). All patients but one with a high risk PLASMIC score (6-7) showed a severe deficiency. Among patients belonging to the intermediate risk (PLASMIC score 5) group, 2 showed normal ADAMTS13 activity and 2 levels below 10%. In none of the patients in the low risk group (PLASMIC score 0-4), a severe ADAMTS13 deficiency was found. Present results confirm and extend previous data regarding the predictive value of the PLASMIC score. Indeed, it shows a good diagnostic performance and can be useful for decision makers to properly and promptly define the better therapeutic approach.
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Proteína ADAMTS13/deficiencia , Medición de Riesgo/métodos , Microangiopatías Trombóticas/diagnóstico , Anciano , Humanos , Italia , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Púrpura Trombocitopénica Trombótica/diagnóstico , Curva ROC , Índice de Severidad de la EnfermedadRESUMEN
Congenital fibrinogen disorders can be quantitative (afibrinogenemia, hypofibrinogenemia) or functional (dysfibrinognemia). To date, several genetic variants have been identified in individuals with fibrinogen disorders. The complexity of the fibrinogen molecules, formed by three non-identical chains and with a trinodal organization, renders the identification of molecular causes and of clinical and biochemical phenotypes very challenging. However, the acknowledgement of the type of molecular defect is crucial for a safer therapy, which is going to improve the clinical management of these patients. In this review, some aspects concerning molecular and clinical findings available on congenital fibrinogen disorders will be discussed.
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Afibrinogenemia , Fibrinógeno , Afibrinogenemia/genética , Afibrinogenemia/metabolismo , Afibrinogenemia/terapia , Fibrinógeno/genética , Fibrinógeno/metabolismo , HumanosRESUMEN
PURPOSE: In placentae from uneventful pregnancies a direct relationship between expression of tissue factor (TF) and tissue-factor pathway inhibitor type 2 (TFPI2) was found, as well as between TF and vascular endothelial growth factor (VEGF). Furthermore, placentae from gestational vascular complications (GVCs) lack these correlations. Aims of the present study are (1) to evaluate a possible role of low-molecular-weight-heparins (LMWHs) in the modulation of the expression of TF, TFPI, TFPI2 and VEGF in placentae from thrombophilic women and (2) to study the possible role of endothelium in the placental expression of markers involved in haemostasis and angiogenesis. METHODS: Fourteen pregnancies in thrombophilic women and 11 uneventful pregnancies in non-thrombophilic women were studied and placentae collected. From each placenta total RNA was obtained. Expression of TF, TFPI, TFPI2 and VEGF was evaluated. Human Vein Endothelial Cells were incubated with increasing doses of LMWH and expression of TF, TFPI and VEGF was measured. RESULTS: Expression of all the markers analyzed in placentae from treated pregnancies was similar to that observed in placentae from uneventful ones. A significant direct relationship between TF and TFPI2, as well as TF and VEGF, was observed in cases treated with LMWHs and controls. Furthermore, the expression of TF and its inhibitors and VEGF in endothelial cells was modulated by LMWH. CONCLUSION: Present data suggest that LMWH during pregnancy in thrombophilic women restores the relationship between markers of haemostasis and angiogenesis. Furthermore, the endothelium is likely to play an important role in this phenomenon.
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Hemostasis/efectos de los fármacos , Heparina de Bajo-Peso-Molecular/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Placenta/fisiología , Adulto , Células Cultivadas , Femenino , Glicoproteínas/análisis , Humanos , Placenta/química , Embarazo , Tromboplastina/análisis , Factor A de Crecimiento Endotelial Vascular/análisisRESUMEN
BACKGROUND: Elderly populations face an increased risk of anemia, leading to elevated transfusion requirements during surgery, especially major orthopedic procedures. Anemia itself increases the risk of thromboembolic events, thus compounding complications in elderly individuals. Polypharmacy and the prevalent use of oral anticoagulants (OAC), particularly for atrial fibrillation, contribute to bleeding risks in this population. Data available in the literature on the peri-operative management of anemia in patients taking OAC is limited and often heterogeneous. MATERIALS AND METHODS: This narrative case-based review focuses on the peri-operative management of elderly patients on OAC undergoing major orthopedic surgery. PubMed/Medline was used to search for relevant literature. RESULTS: With reference to two cases, we critically evaluate the literature, and focus on risk factors, and preventive and therapeutic strategies as fundamental tools to reduce bleeding and correct anemia as soon as possible in elderly patients undergoing major orthopedic surgery. DISCUSSION: Peri-operative management of these patients, especially those on OAC, requires a balanced approach considering bleeding and thrombotic risks. Intravenous iron therapy and tranexamic acid emerge as valuable strategies in minimizing transfusion requirements and optimizing patients' outcomes.
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BACKGROUND: We describe blood supply and usage from March to December 2020 in two research medical hospitals in the Apulia region of Italy: Research Hospital "Casa Sollievo della Sofferenza" (Centre 1) and University Hospital of Bari (Centre 2). MATERIALS AND METHODS: We performed a retrospective observational study of blood component transfusions in the first eight months of the pandemic: 1st March-31st December 2020. We assessed the number of hospitalised patients who were transfused, the number and type of blood components donated and the number and type of blood components transfused in different care settings. RESULTS: Blood donations were lower in 2020 than in 2019, with a significant reduction in red blood cells (RBC) transfused (-29% in 2020 vs 2019) and fewer transfusions in 2020 in the Internal Medicine departments (-67% and -44% in Centres 1 and 2, respectively) and Intensive Care Units (ICUs) (-53% and -54% in Centres 1 and 2, respectively). The overall number of fatalities was significantly lower in 2020 than in 2019; the proportion of fatalities in men was significantly higher in 2020 than in 2019 (53.9% and 41.5%, respectively; p=0.000). Among COVID-19 patients (n=645), 427 (66.2%) were transfused in Infectious Disease departments and the remaining in ICUs. The fatality rate was 14.3% in COVID patients transfused in Infectious Disease departments and 22.5% in those transfused in ICUs. Kaplan-Meier analysis showed 30- and 60-day mortality was significantly higher in patients transfused in 2020 compared to those transfused in 2019. Fatalities were mostly observed in COVID-19 patients. DISCUSSION: Present data may be helpful in understanding the trend of collection and use of blood supplies during periods of pandemic. The implementation of a Patient Blood Management programme is essential to maintain sufficient blood supplies and to keep track of clinical outcomes that represent the most important goal of transfusion.
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COVID-19 , Enfermedades Transmisibles , Transfusión Sanguínea , COVID-19/epidemiología , COVID-19/terapia , Transfusión de Eritrocitos , Hospitales Universitarios , Humanos , Masculino , PandemiasRESUMEN
BACKGROUND: Blood transfusion is a relevant issue for elderly and frail patients, as they are often anaemic and have chronic diseases. Transfusion of red blood cells (RBC) can potentially affect morbidity and mortality of elderly patients undergoing major orthopaedic surgery. MATERIALS AND METHODS: We carried out a retrospective analysis of 2,593 patients undergoing major orthopaedic surgery between 2013 and 2017 in a single research institution in the Region of Apulia. The aims of the study were: 1) to describe the characteristics of transfused patients according to a restrictive or liberal strategy of transfusion and haemoglobin (Hb) triggers and targets; 2) to investigate the effect of RBC transfusion on mortality and complications. RESULTS: Older, women and patients with American Society of Anesthesiologists (ASA) score 3-4 were more often transfused. Those with lower admission Hb level had a higher risk of being transfused. Hb triggers were associated with the patients' age. A restrictive transfusion strategy was significantly more frequent in patients undergoing primary knee replacement and in those with higher estimated blood loss. We did not observe any significant difference of complications in patients transfused with a liberal vs restrictive strategy. Logistic regression correcting for potential confounders revealed that sex (males more than females), duration of stay in hospital, hip fracture and Charlson score >4 were good predictors of complications and/or mortality. Mortality was significantly higher in males and in older patients with ASA score 3-4. DISCUSSION: In this large cohort of Italian patients undergoing major orthopaedic surgery males were significantly more exposed than women to complications and in-hospital mortality. Furthermore, those undergoing urgent surgery because of hip fracture had a 3-fold higher chance of complications. Charlson score >4 and ASA 3-4 are good predictors of complications and mortality, respectively.
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Anemia , Procedimientos Ortopédicos , Anciano , Anemia/epidemiología , Anemia/terapia , Transfusión Sanguínea , Transfusión de Eritrocitos/efectos adversos , Femenino , Humanos , Masculino , Procedimientos Ortopédicos/efectos adversos , Estudios RetrospectivosRESUMEN
BACKGROUND: Endothelial dysfunction, coupled with inflammation, induces thrombo-inflammation. In COVID-19, this process is believed to be associated with clinical severity. Von Willebrand factor (VWF), and a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS-13), are strong markers of endothelial dysfunction. We evaluated the impact of the VWF/ADAMTS-13 fraction on COVID-19 severity and prognosis. MATERIALS AND METHODS: A cohort study including 74 COVID-19 patients, with 22 admitted to the intensive care unit (ICU) and 52 to the medical ward (MW), was carried out. We also evaluated, in a group of 54 patients who were prospectively observed, whether variations in VWF/ADAMTS-13 correlated with the degree of severity and routine blood parameters. RESULTS: A VWF:RCo/ADAMTS-13 fraction above 6.5 predicted in-hospital mortality in the entire cohort. At admission, a VWF:RCo/ADAMTS-13 fraction above 5.7 predicted admission to the ICU. Furthermore, the VWF:RCo/ADAMTS-13 fraction directly correlated with C-reactive protein (CRP) (Spearman r: 0.51, p < 0.0001) and D-dimer (Spearman r: 0.26, p = 0.03). In the prospective cohort, dynamic changes in VWF:RCo/ADAMTS-13 and the CRP concentration were directly correlated (Spearman r, p = 0.0014). This relationship was significant in both groups (ICU: p = 0.006; MW: p = 0.02). CONCLUSIONS: The present findings show that in COVID-19, the VWF/ADAMTS-13 fraction predicts in-hospital mortality. The VWF/ADAMTS-13 fraction may be a helpful tool to monitor COVID-19 patients throughout hospitalization.
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There is paucity of data on the transfusion need and its impact on the overall mortality in patients with COVID-19. We explored mortality in hospitalized patients with COVID-19 who required transfusions. Information on clinical variables and in-hospital mortality were obtained from medical records of 422 patients admitted to medical wards or the Intensive Care Unit (ICU). In-hospital mortality occurred in 147 (34.8%) patients, 94 (63.9%) of whom were admitted to the ICU. The median fatalities age was 77 years (IQR 14). Overall, 100 patients (60 males) received transfusion during hospitalization. The overall mortality was significantly and independently associated with age, ICU admission, Chronic Kidney Disease (CKD), and the number of transfused Red Blood Cell (RBC) units. Specifically, CKD was associated with mortality in patients admitted to medical wards, whereas the number of transfused RBC units predicted mortality in those admitted to the ICU. Transfusion strongly interacted with the admission to ICU (OR: 9.9; 95% CI: 2.5-40.0). In patients with COVID-19, age is one of the strongest risk factors in predicting mortality independently of the disease's severity. CKD confers a higher risk of mortality in patients admitted to medical wards. In those admitted to the ICU, the more RBC units are transfused, the more mortality increases.
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Immune-mediated thrombotic thrombocytopenic purpura is a rare and challenging hematological disease caused by the antibody anti-ADAMTS13. Though the mortality rate has decreased considerably in recent years, fatalities still remain unacceptable. This study aimed at further adding to the existing knowledge of this medical challenge. We enrolled 89 consecutive patients observed in six Italian centers (from 8 August 2013 to 28 May 2021) with a diagnosis of immune-mediated thrombotic thrombocytopenic purpura. Clinical information and blood parameters were collected for all patients. We describe clinical manifestations and laboratory data, possible risk factors and the therapeutic management of first episodes or relapses. A total of 74 first episodes and 19 relapses (median 3 years (interquartile range (IQR): 2-7)) were recorded. Seventy percent of patients enrolled at the first episode showed neurological signs and/or symptoms. All the patients enrolled at the first episode were treated with plasma exchange (median = 12; IQR: 8-19.5) and methylprednisolone (1 mg/kg/day). Rituximab (375 mg/m2 weekly for four weeks) and caplacizumab were given to 15 (20.2%) and 2 patients (2.6%), respectively. We observed an overall mortality of 5.4% in the follow-up (median 60 months; IQR: 36.0-103.5). All fatalities occurred after a diagnostic delay. Present data point to the importance of the early detection of factors mostly associated with poor outcomes. It is likely that use of caplacizumab could improve the prognosis in those patients.
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OBJECTIVE: Knowledge about risk factors for venous thromboembolism (VTE) is still limited. A recently found haplotype within the natural anticoagulant protein annexin A5 (ANXA5) exerts an important modulating effect on gene expression. STUDY DESIGN: Eighty-three nonanticoagulated patients with a documented pregnancy-related VTE and 195 controls were investigated. The presence of the ANXA5 haplotypes was determined. RESULTS: Twenty-seven patients (32.5%) carried the M2 haplotype. Among them, 17 (63.0%) had a history of VTE in puerperium and 10 (37.0%) during pregnancy. The prevalence of the M2 haplotype was different as compared with that recorded among controls (odds ratio, 2.7; 95% confidence interval, 1.5-4.9, P < .001). A logistic regression analysis, correcting for potential confounders (age at which the thrombotic event occurred, factor V Leiden, and factor IIA20210 variants) showed a significant increase (odds ratio, 3.4; 95% confidence interval, 1.7-6.7) of the occurrence of VTE in carriers of the M2 haplotype as compared with noncarriers. CONCLUSION: The M2 haplotype within the ANXA5 gene may represent a new thrombophilic risk factor for pregnancy-related VTE.