José Ramón González-Porras

Prospective evaluation of a transfusion policy of D+ red blood cells into D− patients

BACKGROUND: Although D− patients should receive red blood cells (RBCs) from D− donors, the scarcity of D− blood components in certain situations makes the transfusion of D+ RBCs unavoidable. Therefore it is recommended that guidelines be developed in order to standardize transfusion policy in these scenarios.

Prognostic impact of severe thrombocytopenia in low-risk myelodysplastic syndrome.

Thrombocytopenia is very common in myelodysplastic syndrome (MDS); however, its clinical impact in low‐risk patients remains controversial.

Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia

Eltrombopag is effective and safe in immune thrombocytopenia (ITP). Some patients may sustain their platelet response when treatment is withdrawn but the frequency of this phenomenon is unknown. We retrospectively evaluated 260 adult primary ITP patients (165 women and 95 men; median age, 62 years) treated with eltrombopag after a median time from diagnosis of 24 months. Among the 201 patients who achieved a complete remission (platelet count >100 × 109/l), eltrombopag was discontinued in 80 patients. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n = 33), platelet count >400 × 109/l (n = 29), patients request (n = 5), elevated aspartate aminotransferase (n = 3), diarrhea (n = 3), thrombosis (n = 3), and other reasons (n = 4). Of the 49 evaluable patients, 26 patients showed sustained response after discontinuing eltrombopag without additional ITP therapy, with a median follow‐up of 9 (range, 6–25) months. These patients were characterized by a median time since ITP diagnosis of 46.5 months, with 4/26 having ITP < 1 year. Eleven patients were male and their median age was 59 years. They received a median of 4 previous treatment lines and 42% were splenectomized. No predictive factors of sustained response after eltrombopag withdrawal were identified. Platelet response following eltrombopag cessation may be sustained in an important percentage of adult primary ITP patients who achieved CR with eltrombopag. However, reliable markers for predicting which patients will have this response are needed. Am. J. Hematol. 90:E40–E43, 2015.

Risk of recurrent venous thrombosis in patients with G20210a mutation in the prothrombin gene or factor V Leiden mutation

The impact of the G20210A prothrombin mutation, factor V Leiden and 677T mutation of methylene tetrahydrofalate reductase (MTHFR) in recurrent deep venous thrombosis (DVT) is not so clear. We have prospectively monitored 259 patients following a first episode of DVT in order to determine which factors influence the development of a recurrent event. Several clinical and biological factors together with the genetic polymorphisms of factor V Leiden, G20210A prothrombin and 677T MTHFR were assessed. During a median follow-up of 786 patient-years, 27 patients (14%) developed one objective episode of recurrent venous thrombosis. The carriers of a double defect, homozygous or double heterozygous for factor V Leiden and G20210A, had an increased risk after a first episode of DVT, while patients who were isolated heterozygous for factor V Leiden or G20210 had a risk of recurrent DVT similar to patients who had neither mutation (annual incidence of 12.1, 3.1, 2.9 and 2.8%). The 677T MTHFR mutation alone or combined with hyperhomocysteinemia was not associated with an increased risk of recurrent events. The development of proximal DVT (P = 0.01) and the presence of a double defect (P = 0.01) were the only two risk factors independently associated with a high recurrence ratio in the multivariate analysis. Thus, the annual incidence of DVT recurrence in patients without any of these two risk factors was only 0.6% (95% confidence interval, 0.2–0.9). We have identified a group of patients with DVT but at very low risk of re-thrombosis in whom an extended secondary thromboprophylaxis should be carefully considered.

Primary aortoduodenal fistula: new case reports and a review of the literature.

A primary aortoduodenal fistula (PADF) is a communication between the lumen of the aorta and that of the gastrointestinal tract at duodenal level. Unlike primary fistulas, there are other so-called secondary ones, such as the complication of a previously implanted aortic prosthesis; these are far more frequent. Since their first description some 100 years ago, more than 200 PADFs have been reported. The location between the aorta and duodenum, mainly in its third portion, caused by the evolutionary complication of an aortic aneurysm is the most common situation. Although less frequent, communications also occur between other parts of the digestive tract (esophagus, jejunum, ileum, and colon). These are caused by other reasons (infection, tumor, radiation therapy, foreign bodies, etc.). Apart from their rarity, the interest in PADFs lies in the diagnostic and therapeutic difficulties involved in their handling, which clearly affect their prognosis. In the present work, we carried out a literature search on Medline using different key words (primary, aortoenteric, aortoduodenal, aortoesophagic, aorto-enteric, aorto-duodenal, aorto-oesophageal, and a combination of these with fistula) between January 2004 and December 2006. This allowed 34 new cases to be added, which together with those from previous reviews make a total of 366 primary aortoenteric fistulas, of which 267 (72.9%) are PADFs. In this paper, we report two new cases and comment on the historical evolution of this pathology.

Better prognosis for patients with del(7q) than for patients with monosomy 7 in myelodysplastic syndrome.

Abnormalities involving chromosome 7 are frequent in myelodysplastic syndrome (MDS) and suggest a poor prognosis.

Use of eltrombopag after romiplostim in primary immune thrombocytopenia

The thrombopoietin receptor agonists (THPO‐RAs), romiplostim and eltrombopag, are effective and safe in immune thrombocytopenia (ITP). However, the value of their sequential use when no response is achieved or when adverse events occur with one THPO‐RA has not been clearly established. Here we retrospectively evaluated 51 primary ITP adult patients treated with romiplostim followed by eltrombopag. The median age of our cohort was 49 (range, 18–83) years. There were 32 women and 19 men. The median duration of romiplostim use before switching to eltrombopag was 12 (interquartile range 5–21) months. The reasons for switching were: lack of efficacy (n = 25), patient preference (n = 16), platelet‐count fluctuation (n = 6) and side‐effects (n = 4). The response rate to eltrombopag was 80% (41/51), including 67% (n = 35) complete responses. After a median follow‐up of 14 months, 31 patients maintained their response. Efficacy was maintained after switching in all patients in the patient preference, platelet‐count fluctuation and side‐effect groups. 33% of patients experienced one or more adverse events during treatment with eltrombopag. We consider the use of eltrombopag after romiplostim for treating ITP to be effective and safe. Response to eltrombopag was related to the cause of romiplostim discontinuation.

AB0 blood group and risk of venous or arterial thrombosis in carriers of factor V Leiden or prothrombin G20210A polymorphisms

Several studies have shown an effect of AB0 blood group on hemostasis. Findings of this study indicate that non-00 group increases the risk and severity of venous thrombosis in carriers of prothrombotic polysmorphisms. See related perspective article on page 649. Background Routine analyses for thrombophilia include determination of the presence of factor V Leiden and prothrombin 20210A polymorphisms. However, the usefulness of these determinations is controversial and the clinical benefit remains questioned because of the moderate risk of associated thrombosis in carriers. In the search for clusters of thrombotic risk factors to estimate individual risk better, we studied the effect of AB0 blood group, a highly prevalent factor with mild prothrombotic features, on the risk and severity of venous and arterial thromboses in carriers of these polymorphisms. Design and Methods We genotyped the AB0 blood group in 981 carriers of factor V Leiden or prothrombin 20210A polymorphisms. In order to avoid the over-representation of a particular genotype and to suppress confounding factors, we included only non-related heterozygous carriers without additional genetic risk factors. We studied 609 patients with venous thromboembolism (287 with factor V Leiden, and 322 with prothrombin 20210A), 174 patients with myocardial infarction (78 with factor V Leiden, and 96 with prothrombin 20210A), and 198 controls (96 with factor V Leiden, and 102 with prothrombin 20210A). Results Non-OO blood group did not increase the risk of myocardial infarction in carriers of factor V Leiden or prothrombin 20210A. However, non-OO blood group contributed significantly to the expression of venous thrombosis associated with both factor V Leiden (OR: 1.76; 95%CI: 1.06–2.91) and prothrombin 20210A (OR: 2.17; 95%CI: 1.33–3.53). Exclusion of A2A2 and A2O from the non-00 blood group (because factor VIII-von Willebrand factor levels are similar in these and the 00 blood group) increased the thrombotic risk. Finally, non-OO blood group was associated with an earlier onset in symptomatic carriers of these polymorphisms. Conclusions Our study suggests that non-OO blood group increases the risk and severity of venous thrombosis in carriers of prothrombotic polymorphisms. Thus, AB0 phenotyping or genotyping analyses may be valuable components in assessing future thrombophilic risk profiles and might have implications for the policy of thrombosis prophylaxis and treatment.

Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis has been suggested as a potential risk factor. However, the impact of tacrolimus (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n=68) or plus MTX (TAC/MTX)±ATG (n=34) for GVHD prophylaxis. No significant differences were observed in the incidence of TA-TMA between patients receiving TAC/SIR vs TAC/MTX±ATG (7.4% vs 8.8%, P=0.8). Only grade III–IV acute GVHD, previous HSCT and serum levels of TAC >25 ng/mL were associated with a greater risk of TA-TMA. Patients developing TA-TMA have significantly poorer survival (P<0.001); however, TA-TMA ceased to be an independent prognostic factor when it was included in a multivariate model. In conclusion, the combination of TAC/SIR does not appear to pose a higher risk of TA-TMA. By contrast, we identified three different risk groups for developing TA-TMA.

Analysis of incidence, risk factors and clinical outcome of thromboembolic and bleeding events in 431 allogeneic hematopoietic stem cell transplantation recipients

Allogeneic hematopoietic stem cell transplantation recipients have an increasing risk of both hemorrhagic and thrombotic complications. However, the competing risks of two of these life-threatening complications in these complex patients have still not been well defined. We retrospectively analyzed data from 431 allogeneic transplantation recipients to identify the incidence, risk factors and mortality due to thrombosis and bleeding. Significant clinical bleeding was more frequent than symptomatic thrombosis. The cumulative incidence of a bleeding episode was 30.2% at 14 years. The cumulative incidence of a venous or arterial thrombosis at 14 years was 11.8% and 4.1%, respectively. The analysis of competing factors for venous thrombosis revealed extensive chronic graft-versus-host disease to be the only independent prognostic risk factor. By contrast, six factors were associated with an increased risk of bleeding; advanced disease, ablative conditioning regimen, umbilical cord blood transplantation, anticoagulation, acute III-IV graft-versus-host disease, and transplant-associated microangiopathy. The development of thrombosis did not significantly affect overall survival (P=0.856). However, significant clinical bleeding was associated with inferior survival (P<0.001). In allogeneic hematopoietic stem cell transplantation, significant clinical bleeding is more common than thrombotic complications and affects survival.