[Risk of thrombosis recurrence among patients with COVID-19- and surgery-associated venous thromboembolism]. / Riesgo de recurrencia de la trombosis en pacientes con tromboembolia venosa asociada a COVID-19 y a cirugía.

Introduction: Recent surgery is a well-known major transient risk factor for venous thromboembolism (VTE) due to the low risk of VTE recurrence after anticoagulation is discontinued. On the other hand, the risk of VTE recurrence among patients with COVID-19-associated VTE is unknown. This study aimed to compare the risk of VTE recurrence between patients with COVID-19- and surgery-associated VTE. Methods: A prospective observational single-center study was performed including consecutive patients diagnosed with VTE in a tertiary hospital from January 2020 to May 2022 and followed up for at least 90 days. Baseline characteristics, clinical presentation, and outcomes were assessed. The incidence of VTE recurrence, bleeding, and death was compared between both groups. Results: A total of 344 patients were included in the study: 111 patients with surgery-associated VTE and 233 patients with COVID-19-associated VTE. Patients with COVID-19-associated VTE were more frequently men (65.7% vs 48.6%, p = 0.003). VTE recurrence was 3% among COVID-19 patients and 5.4% among surgical patients, with no significant differences (p = 0.364). The incidence rate of recurrent VTE was 1.25 per 1000 person-months in COVID-19 patients and 2.29 person-months in surgical patients, without significant differences (p = 0.29). In the multivariate analysis, COVID-19 was associated with higher mortality (HR 2.34; 95% CI 1.19-4.58), but not with a higher risk of recurrence (HR 0.52; 95% CI 0.17-1.61). No differences were found in recurrence in the multivariate competing risk analysis (SHR 0.82; 95% CI 0.40 - 2.05). Conclusions: In patients with COVID-19 and surgery-associated VTE, the risk of recurrence was low, with no differences between both groups.

Riesgo de recurrencia de la trombosis en pacientes con tromboembolia venosa asociada a COVID-19 y a cirugía / Risk of thrombosis recurrence among patients with COVID-19- and surgery-associated venous thromboembolism

Introducción La cirugía reciente es un factor de riesgo transitorio mayor y conocido de tromboembolia venosa (TEV) debido al bajo riesgo de recurrencia de la TEV una vez suspendida la anticoagulación. Por otro lado, se desconoce el riesgo de recurrencia de la TEV en los pacientes con TEV asociada a COVID-19. El objetivo de este estudio consistió en comparar el riesgo de recurrencia de la TEV entre pacientes con TEV asociada a COVID-19 y a cirugía. Método Se realizó un estudio prospectivo, observacional y unicéntrico en el que participaron pacientes consecutivos diagnosticados de TEV en un hospital terciario entre enero de 2020 y mayo de 2022 y que fueron objeto de seguimiento durante un mínimo de 90 días. Se evaluaron las características iniciales, el cuadro clínico y los resultados clínicos. Se compararon las incidencias de recurrencia de la TEV, hemorragias y muertes entre ambos grupos. Resultado En el estudio se incluyó a un total de 344 pacientes: 111 con TEV asociada a cirugía y 233 con TEV asociada a COVID-19. Entre los pacientes con TEV asociada a COVID-19 hubo una mayor frecuencia de varones (65,7 vs. 48,6%, p = 0,003). La recurrencia de la TEV fue de 3% en los pacientes con COVID-19 y de 5,4% en los pacientes quirúrgicos, sin diferencias significativas (p = 0,364). La tasa de incidencia de TEV recurrente fue de 1,25 y 2,29 por 1.000 personas-meses en los pacientes con COVID-19 y quirúrgicos, respectivamente, sin diferencias significativas (p = 0,29). En el análisis multifactorial, la COVID-19 se asoció a una mayor mortalidad (HR = 2,34; IC 95%, 1,19-4,58), pero no a un mayor riesgo de recurrencia (HR = 0,52; IC 95%, 0,17-1,61). En el análisis multifactorial de riesgos competitivos no se observaron diferencias en cuanto a recurrencias (SHR = 0,82; IC 95%, 0,40-2,05). Conclusiones El riesgo de recurrencia fue bajo en los pacientes con TEV asociada a COVID-19 y a cirugía, sin diferencias entre ambos grupos (AU)

Introduction Recent surgery is a well-known major transient risk factor for venous thromboembolism (VTE) due to the low risk of VTE recurrence after anticoagulation is discontinued. On the other hand, the risk of VTE recurrence among patients with COVID-19-associated VTE is unknown. This study aimed to compare the risk of VTE recurrence between patients with COVID-19- and surgery-associated VTE. Methods A prospective observational single-center study was performed including consecutive patients diagnosed with VTE in a tertiary hospital from January 2020 to May 2022 and followed up for at least 90 days. Baseline characteristics, clinical presentation, and outcomes were assessed. The incidence of VTE recurrence, bleeding, and death was compared between both groups. Result A total of 344 patients were included in the study: 111 patients with surgery-associated VTE and 233 patients with COVID-19-associated VTE. Patients with COVID-19-associated VTE were more frequently men (65.7% vs 48.6%, p = 0.003). VTE recurrence was 3% among COVID-19 patients and 5.4% among surgical patients, with no significant differences (p = 0.364). The incidence rate of recurrent VTE was 1.25 per 1000 person-months in COVID-19 patients and 2.29 person-months in surgical patients, without significant differences (p = 0.29). In the multivariate analysis, COVID-19 was associated with higher mortality (HR 2.34; 95% CI 1.19-4.58), but not with a higher risk of recurrence (HR 0.52; 95% CI 0.17-1.61). No differences were found in recurrence in the multivariate competing risk analysis (SHR 0.82; 95% CI 0.40 – 2.05). Conclusions In patients with COVID-19 and surgery-associated VTE, the risk of recurrence was low, with no differences between both groups (AU)

Risk of thrombosis recurrence among patients with COVID-19 and surgery-associated venous thromboembolism.

INTRODUCTION: Recent surgery is a well-known major transient risk factor for venous thromboembolism (VTE) due to the low risk of VTE recurrence after anticoagulation is discontinued. On the other hand, the risk of VTE recurrence among patients with COVID-19-associated VTE is unknown. This study aimed to compare the risk of VTE recurrence between patients with COVID-19- and surgery-associated VTE. METHODS: A prospective observational single-center study was performed including consecutive patients diagnosed with VTE in a tertiary hospital from January 2020 to May 2022 and followed up for at least 90 days. Baseline characteristics, clinical presentation, and outcomes were assessed. The incidence of VTE recurrence, bleeding, and death was compared between both groups. RESULTS: A total of 344 patients were included in the study: 111 patients with surgery-associated VTE and 233 patients with COVID-19-associated VTE. Patients with COVID-19-associated VTE were more frequently men (65.7% vs 48.6%, p =  0.003). VTE recurrence was 3% among COVID-19 patients and 5.4% among surgical patients, with no significant differences (p =  0.364). The incidence rate of recurrent VTE was 1.25 per 1000 person-months in COVID-19 patients and 2.29 person-months in surgical patients, without significant differences (p =  0.29). In the multivariate analysis, COVID-19 was associated with higher mortality (HR 2.34; 95% CI 1.19-4.58), but not with a higher risk of recurrence (HR 0.52; 95% CI 0.17-1.61). No differences were found in recurrence in the multivariate competing risk analysis (SHR 0.82; 95% CI 0.40-2.05). CONCLUSIONS: In patients with COVID-19 and surgery-associated VTE, the risk of recurrence was low, with no differences between both groups.

Manejo del déficit de hierro en distintas situaciones clínicas y papel del hierro intravenoso: recomendaciones del Grupo Español de Eritropatología de la SEHH / Management of iron deficiency in various clinical conditions and the role of intravenous iron: recommendations of the Spanish Erythropathology Group of the Spanish Society of Haematology and Haemotherapy

El déficit de hierro a consecuencia de pérdidas de sangre, trastornos de absorción y/o carencias dietéticas origina anemia ferropénica, cuyo tratamiento persigue eliminar la causa subyacente y restaurar la hemoglobina y los depósitos de hierro. Habitualmente, los dos últimos objetivos pueden conseguirse mediante ferroterapia oral. El hierro de administración intravenosa (FEIV) debe limitarse a los sujetos refractarios o intolerantes a los preparados orales, o que requieran una repleción rápida. Su utilización indiscriminada podría incrementar la morbimortalidad por sobrecarga iatrogénica. Este hecho, unido a la creciente popularidad del FEIV y a la carencia de guías de referencia en nuestro idioma, condujo al Grupo Español de Eritropatología de la Sociedad Española de Hematología y Hemoterapia a elaborar este trabajo, que recoge las principales recomendaciones acerca del uso óptimo del FEIV en los déficits de hierro y pretende constituir una guía de referencia de buenas prácticas para el manejo clínico de estas situaciones

Iron deficiency due to blood loss, absorption disorders and dietary deficiencies causes iron-deficiency anaemia, whose treatment seeks to eliminate the underlying cause and restore haemoglobin and iron deposits. Typically, the latter 2 of these objectives can be achieved through oral iron therapy. Intravenous iron administration (IIA) should be limited to those patients refractory or intolerant to oral preparations or who require rapid repletion. The indiscriminate use of IIA can increase morbidity and mortality due to iatrogenic overload. This fact, coupled with the growing popularity of IIA and the lack of reference guidelines in Spanish, led the Spanish Erythropathology Group of the Spanish Society of Haematology and Haemotherapy to develop this study, which presents the main recommendations on the optimal use of IIA in iron deficiency and attempts to constitute reference guidelines on good practices for the clinical management of these conditions

Management of iron deficiency in various clinical conditions and the role of intravenous iron: Recommendations of the Spanish Erythropathology Group of the Spanish Society of Haematology and Haemotherapy. / Manejo del déficit de hierro en distintas situaciones clínicas y papel del hierro intravenoso: recomendaciones del Grupo Español de Eritropatología de la SEHH.

Iron deficiency due to blood loss, absorption disorders and dietary deficiencies causes iron-deficiency anaemia, whose treatment seeks to eliminate the underlying cause and restore haemoglobin and iron deposits. Typically, the latter 2 of these objectives can be achieved through oral iron therapy. Intravenous iron administration (IIA) should be limited to those patients refractory or intolerant to oral preparations or who require rapid repletion. The indiscriminate use of IIA can increase morbidity and mortality due to iatrogenic overload. This fact, coupled with the growing popularity of IIA and the lack of reference guidelines in Spanish, led the Spanish Erythropathology Group of the Spanish Society of Haematology and Haemotherapy to develop this study, which presents the main recommendations on the optimal use of IIA in iron deficiency and attempts to constitute reference guidelines on good practices for the clinical management of these conditions.

Atypical IgM multiple myeloma with deletion of c-MAF.

IgM multiple myeloma (MM) is a rare subtype of myeloma that shares clinical and pathological features with Waldenström's macroglobulinaemia. These are two separate entities that differ both in therapy and prognosis. We report a 57-year-old male, who presented with anaemia, hypercalcaemia, acute renal failure and several vertebral fractures that clinically suggested a multiple myeloma. Further investigations revealed a serum monoclonal component of IgM lambda type and a bone marrow infiltrated by small, lymphoplasmocytic cells. IgM MM was finally diagnosed by means of both inmunophenotypic and immunohistochemistry techniques, stressing the importance of inmunophenotypic evaluation when clinical and morphological features are discordant. Fluorescence in situ hybridization (FISH) studies disclosed a particular combination of deletion 13q14, t(11;14) and monoallelic deletion C-MAF without t(14;16). The clinical evolution after a Bortezomib-containing polychemotherapy and autologous stem cell transplantation (ASCT) conditioned with busulphan and melphalan is also presented. This very uncommon case highlights the impact of immunophenotyping on the differential diagnosis between IgM MM and WM, to choose the best treatment and establish an appropriate outcome.

Inter-observer variance with the diagnosis of myelodysplastic syndromes (MDS) following the 2008 WHO classification.

Morphology is the basis of the diagnosis of myelodysplastic syndromes (MDS). The WHO classification offers prognostic information and helps with the treatment decisions. However, morphological changes are subject to potential inter-observer variance. The aim of our study was to explore the reliability of the 2008 WHO classification of MDS, reviewing 100 samples previously diagnosed with MDS using the 2001 WHO criteria. Specimens were collected from 10 hospitals and were evaluated by 10 morphologists, working in five pairs. Each observer evaluated 20 samples, and each sample was analyzed independently by two morphologists. The second observer was blinded to the clinical and laboratory data, except for the peripheral blood (PB) counts. Nineteen cases were considered as unclassified MDS (MDS-U) by the 2001 WHO classification, but only three remained as MDS-U by the 2008 WHO proposal. Discordance was observed in 26 of the 95 samples considered suitable (27 %). Although there were a high number of observers taking part, the rate of discordance was quite similar among the five pairs. The inter-observer concordance was very good regarding refractory anemia with excess blasts type 1 (RAEB-1) (10 of 12 cases, 84 %), RAEB-2 (nine of 10 cases, 90 %), and also good regarding refractory cytopenia with multilineage dysplasia (37 of 50 cases, 74 %). However, the categories with unilineage dysplasia were not reproducible in most of the cases. The rate of concordance with refractory cytopenia with unilineage dysplasia was 40 % (two of five cases) and 25 % with RA with ring sideroblasts (two of eight). Our results show that the 2008 WHO classification gives a more accurate stratification of MDS but also illustrates the difficulty in diagnosing MDS with unilineage dysplasia.

Low molecular weight heparin (enoxaparin) versus oral anticoagulant therapy (acenocoumarol) in the long-term treatment of deep venous thrombosis in the elderly: a randomized trial.

This study aims to establish the relative effectiveness and safety of low molecular weight heparin in elderly patients with venous thrombosis in order to find an alternative to oral anticoagulant therapy with less bleeding complications in the long-term treatment of deep venous thrombosis (DVT). One hundred consecutive elderly patients (>75 years old) with venographically demonstrated proximal DVT were included in a randomized trial. All patients were treated for ten days with adjusted doses of intravenous heparin. Informed consent was obtained and on the eight day, patients were randomly allocated to receive acenocoumarol (INR 2.0-3.0) or subcutaneous enoxaparin (4000 anti-Xa units once a day) for three months. All patients were followed-up clinically and venographically for a one year period. The results were analyzed with Fisher's exact test or chi-square test as appropriate. During the treatment and surveillance period, 6 of the 50 patients (12%) who received acenocoumarol and 8 of the 50 patients (16%) who received enoxaparin had new episodes of venous thromboembolism confirmed by objective testing (p = 0.6; 95% CI for the difference: -19.5 to 11.5). Hemorrhagic complications occurred in six of the 50 patients (12%) who received acenocoumarol and in one (2%) of those on enoxaparin (p = 0.1; 95% CI for the difference: -1.8 to 21.8). Vertebral fractures developed in 2 patients (4%) in the enoxaparin group (p = 0.5; 95% CI for the difference: -11.4 to 3.4). These results show that fixed dose enoxaparin seems to be effective and safe in the long-term treatment of proximal DVT in the elderly. In comparison with oral anticoagulants, the findings are inconclusive due to the wide confidence intervals for differences between outcomes, however they suggest that the former may have less bleeding complications with similar efficacy.

The value of comparative volumetric analysis of urinary and blood erythrocytes to localize the source of hematuria.

PURPOSE: We evaluate comparative volumetric analysis of blood and urinary red blood cells (RBCs) to identify the source of hematuria. Comparative volumetric analysis is defined as the difference between mean corpuscular erythrocyte volume in peripheral blood (MCVB) diluted in urine supernatant after centrifugation and mean corpuscular volume of urinary erythrocytes (MCVU). The potential of MCVB-MCVU to distinguish the origin of hematuria is compared to MCVU alone. The fundamental hypothesis is that RBCs that can go through the glomerulus will be smaller than those from the collecting system or lower urinary tract, thus having a smaller MCVU and larger difference between MCVB and MCVU. MATERIALS AND METHODS: A prospective detailed urological evaluation was performed on 210 patients with glomerular or nonglomerular hematuria detected by urinary sediment, clinical radiological evaluation, endoscopy, cytology and sometimes bladder or renal biopsy. After evaluation 24 cases with an uncertain source of hematuria were excluded from study. Specialized urinalysis, volumetric analysis and clinical investigation were performed in a blind fashion. MCVU and MCVB-MCVU were registered for every patient. The Technicon H-3 system with angle laser scattering dual system allowed measurement of mean corpuscular volume in a minimal number of RBCs, and resuspension of RBC pellets in the same urinary supinate avoided effects of osmolarity and pH on RBC size and shape. Reproducibility in assessing the index was tested in 50 cases in which comparative volumetric analysis was repeated on 2 consecutive days. Unpaired t test was performed, and a threshold value of MCVB-MCVU with maximum sensitivity and specificity to detect glomerular hematuria was identified. The potential of urinary and comparative volumetric analysis to distinguish the source of hematuria was evaluated and compared by receiver operating characteristics curve analysis. RESULTS: Hematuria was nonglomerular in 53 (28.4%) and glomerular in 133 (71.6%) patients. Mean MCVB-MCVU was significantly different for nonglomerular (0.6 fl.) and glomerular (30.5 fl.) sources (p<0.0001). There was a correlation between repeat independent measures of MCVU and MCVB-MCVU. The highest positive predictive value to detect a glomerular origin is desirable so that unnecessary investigation can be obviated without the risk of missing a nonglomerular source. With a limit of 16 fl. specificity and positive predictive value were 98 and 99%, respectively. Receiver operating characteristics curve analysis to localize the source of hematuria revealed significant differences in favor of comparative volumetric analysis versus urinary volumetric analysis alone. CONCLUSIONS: MCVB-MCVU using the Technicon H-3 system is a useful noninvasive and accurate method to locate the source of hematuria. A value of 16 fl. or greater practically rules out a nonglomerular origin and obviates further urological investigation. We have incorporated this investigation in our diagnostic algorithm for hematuria.

Persistent lymphocytosis of natural killer cells in autoimmune thrombocytopenic purpura (ATP) patients after splenectomy.

We report three patients with primary autoimmune thrombocytopenic purpura (ATP) who developed an absolute lymphocytosis (lymphocyte count > 5 x 10(9)/l) after splenectomy and with a lymphocyte count between 5.4 and 8.9 x 10(9)/l. An immunophenotype study showed that the peripheral blood lymphocytosis was a persistent NK cell expansion (CD2+, CD56+, CD3-), and was characterized by a typical large granular lymphocytes (LGL) morphology. Two of these three ATP patients were refractory to splenectomy.

[The first case of thalassemia intermedia in Spain due to the interaction of 3 alpha genes with beta-thalassemia minor]. / Primer caso de talasemia intermedia descrito en España debido a la interacción de tres genes alpha con beta talasemia minor.

We have identified the case of a 9-months-old girl with heterozygotic thalassemia and triplication of alpha genes of globin (alpha alpha alpha 3.7). Molecular defect of thalassemia was a mutation without sense of 39 codon. Patient's phenotype was an intermediate thalassemia with moderate splenomegaly and marked unbalance on the globin chains. This is the first case of intermediate thalassemia, through this mechanism, described in Spain.

Bleeding in acute promyelocytic leukemia (APL): fibrinolysis or defibrination?

The coagulation abnormalities in 20 cases of acute promyelocytic leukemia (APL) treated at a single institution were reviewed. A remarkably uniform picture of defibrination and increased FDPs with well-preserved levels of other coagulation factors including AT-III was seen. Our data, together with those available in the literature, do not support DIC as the underlying mechanism of bleeding but seem rather to point to increased proteolysis as the cause.