A Blood-Based Immune Gene Signature with Prognostic Significance in Localized Prostate Cancer.

Prostate cancer (PCa) is one of the most common male cancers worldwide and one of the deadliest if unsuccessfully treated. Τhe need for reliable, easily accessible immune-related molecular biomarkers that could be combined with clinically defined criteria, including PSA and Gleason score, to accurately predict PCa patients' clinical outcomes is emerging. Herein, we describe for the first time a blood-identified immune-related gene signature comprising eight upregulated multi-functional genes associated with poor prognosis. Next-generation sequencing (NGS) analysis of PCa patients' peripheral blood samples revealed a more than three-fold upregulation of each of the eight genes as compared to samples originating from healthy donors. The construction of gene and protein interaction networks revealed different extents of the functional implications of these genes in the regulation of cell proliferation and immune responses. Analysis of the available data from The Cancer Genome Atlas (TCGA) regarding gene expression and survival of prostate adenocarcinoma (PRAD) and pan-cancer (PANCAN) patients revealed that intra-tumoral upregulation of this eight-gene signature (8-GS) was associated with poor 5-year progression-free intervals in PCa patients, even in those with high Gleason scores, and also with an unfavorable prognosis for cancer patients irrespective of the cancer type and even in the early stages. These observations suggest that further investigation of the 8-GS prospectively in randomized clinical trials, in which clinical benefit in terms of evaluating time to disease progression can be assessed, is warranted.

Anemia in Celiac Disease: Multiple Aspects of the Same Coin.

Extraintestinal manifestations of celiac disease (CD) are an integral part of the disease's clinical profile and, frequently, appear as the presenting feature. Given that anemia in CD may be multifactorial, increased awareness is needed on the part of treating physicians, and especially hematologists, to screen for CD. In this study, we highlight anemia as the presenting feature of CD which has remained undiagnosed for several years. In patients with a positive antibody testing or high suspicion of CD, endoscopy with a biopsy of the small intestine is performed, as it is considered the "gold standard" for diagnosing CD. Since most of the manifestations of CD are preventable or treatable with a gluten-free diet, an early diagnosis is vital for the prevention of serious and potentially lethal complications.

Combined monitoring of IgG and IgA anti-Spike and anti-Receptor binding domain long term responses following BNT162b2 mRNA vaccination in Greek healthcare workers.

Studies on the humoral response to homologous BNT162b2 mRNA-vaccination focus mainly on IgG antibody dynamics, while long-term IgA kinetics are understudied. Herein, kinetics of IgG and IgA levels against trimeric-Spike (S) and Receptor-Binding-Domain (RBD) were evaluated by in-house ELISAs in 146 two-dose vaccinated Greek healthcare workers (HCWs) in a 9-month period at six time points (up to 270 days after the first dose). The effect of a homologous booster third dose was also studied and evaluated. The peak of immune response was observed 21 days after the second dose; 100% seroconversion rate for anti-S and anti-RBD IgG, and 99.7% and 96.3% respectively for IgA. IgG antibody levels displayed higher increase compared to IgA. Declining but persistent anti-SARS-CoV-2 antibody levels were detected 9 months after vaccination; IgG and IgA anti-S levels approached those after the first dose, while a more rapid reduction rate for anti-RBD antibodies led to significantly lower levels for both classes, supporting the need for a booster dose. Indeed, a homologous booster third dose resulted in enhanced levels of anti-S of both classes, whereas anti-RBD didn't exceed the peak levels after the second dose. Previous SARS-CoV-2 infection, flu vaccination, BMI<35 and the occurrence of an adverse event upon vaccination, were associated with higher IgG antibody levels over time, which however were negatively affected by age increase and the presence of chronic diseases. Overall, after concurrently using the S and RBD target-antigens in in-house ELISAs, we report in addition to IgG, long-term persistence of IgA antibodies. Regarding antibody levels, homologous mRNA vaccination gives rise to an effective anti-viral protection up to 9 months negatively correlated to age. Considering that COVID-19 is still a matter of public concern, booster vaccine doses remain critical to vulnerable individuals.

Pregnancy and thrombosis risk for women without a history of thrombotic events: a retrospective study of the real risks.

BACKGROUND: During pregnancy and puerperium women are at high VTE risk. Current guidelines recommend dynamic VTE-risk assessment during pregnancy. Based on related RCOG-guidelines we constructed a digital VTE-risk assessment tool: PATrisks ( www.PATrisks.com ). Using this tool, we retrospectively evaluated the thrombotic risk in 742 women from our previous work, women who received thromboprophylaxis based on clinical experience for A) pregnancy complications, B) IVF treatment and C) prothrombotic tendency, in order to investigate whether that practice was justified according to the PATrisks scoring system for VTE prevention. METHODS: Women with pregnancy complications [Group-A: 445], women who had undergone IVF [Group-B:132] and women with a prothrombotic tendency (thrombophilia, family history of VTE, other) [Group-C:165] were assessed using the PATrisks scoring system for thrombotic risk. The women were assigned into one of the following risk categories: low (score ≤ 2), intermediate (score = 3) and high (score ≥ 4). Further analysis per risk factor type (pre-existing or obstetric) and for various combinations of them, was also performed. We evaluated thrombotic risk early in pregnancy, and in the peripartum period. RESULTS: The mean risk score antepartum was higher for women in Group B (3.3 in comparison with 1.9 and 2.0 in Group A and Group C respectively). Moreover, the risk score increased significantly postpartum for all Groups. The chi-square test also proved that there was a higher percentage of women at high or intermediate risk in group B compared to C before birth (55.3% vs.26.1% respectively, p < 0.0001, OR: 3.5, 95% CI: 2.2 - 5.7) and similarly after birth (85.6% vs. 56.4%, OR: 4.6, 95%CI: 2.6-8.2, p < 0.0001). In total 12 (1.6%) out of 742 women experienced thrombotic events, whether pre- or post-partum. CONCLUSIONS: LMWHs are widely prescribed during pregnancy for a number of indications, even when a proven scientific basis for such a practice is lacking. However, a considerable percentage of women were already at VTE-risk according to PATrisks and might have derived an additional benefit from LMWH in the form of VTE prevention. The rational use of these drugs should be optimized by establishing and implementing routine risk assessment for all pregnant women and by providing the necessary education to healthcare professionals.

Characterizing Kinetics and Avidity of SARS-CoV-2 Antibody Responses in COVID-19 Greek Patients.

In-depth understanding of the immune response provoked by SARS-CoV-2 infection is necessary, as there is a great risk of reinfection and a difficulty in achieving herd immunity due to a decline in both antibody concentration and avidity. Avidity testing, however, could overcome variability in the immune response associated with sex or clinical symptoms, and thus differentiate between recent and past infections. In this context, here, we analyzed SARS-CoV-2 antibody kinetics and avidity in Greek hospitalized (26%) and non-hospitalized (74%) COVID-19 patients (N = 71) in the course of up to 15 months after their infection to improve the accuracy of the serological diagnosis in dating the onset of the infection. The results showed that IgG-S1 levels decline significantly at four months (p = 0.0239) in both groups of patients and are higher in hospitalized ones (up to 2.1-fold, p < 0.001). Additionally, hospitalized patients' titers drop greatly and are equalized to non-hospitalized ones only at a time-point of twelve to fifteen months. Antibody levels of women in total remain more stable months after infection, compared to men. Furthermore, we examined the differential maturation of IgG avidity after SARS-CoV-2 infection, showing an incomplete maturation of avidity that results in a plateau at four months after infection. We also defined 38.2% avidity (sensitivity: 58.9%, specificity: 90.91%) as an appropriate "cut-off" that could be used to determine the stage of infection before avidity reaches a plateau.

Panagglutination on the indirect antiglobulin test... this is the challenge!

Panagglutination on the indirect antiglobulin test is one of the most challenging dilemmas of pretransfusion testing. It occurs when patient sera react with all red blood cells tested, that is, with both screening and identification panel cells. Two main questions must be answered. The first is to determine whether panagglutination results from the presence of autoantibody and/or alloantibody (single alloantibody or multiple alloantibodies or antibody to high-incidence antigen). The second problem is to detect the possible concomitant presence of clinically significant alloantibodies masked by panagglutination. The purpose of this mini-review is to describe the situations that can cause panagglutination and to develop algorithms which can resolve the problem. The two main points in the evaluation of panagglutination involve the assessment of the intensity of reactivity with the reagent red cells used and whether the autocontrol is positive or not. It is imperative to understand the laboratory results and the techniques available that guide the investigative process.

Kinetics of Nucleocapsid, Spike and Neutralizing Antibodies, and Viral Load in Patients with Severe COVID-19 Treated with Convalescent Plasma.

COVID-19 is an ongoing pandemic with high morbidity and mortality. Despite meticulous research, only dexamethasone has shown consistent mortality reduction. Convalescent plasma (CP) infusion might also develop into a safe and effective treatment modality on the basis of recent studies and meta-analyses; however, little is known regarding the kinetics of antibodies in CP recipients. To evaluate the kinetics, we followed 31 CP recipients longitudinally enrolled at a median of 3 days post symptom onset for changes in binding and neutralizing antibody titers and viral loads. Antibodies against the complete trimeric Spike protein and the receptor-binding domain (Spike-RBD), as well as against the complete Nucleocapsid protein and the RNA binding domain (N-RBD) were determined at baseline and weekly following CP infusion. Neutralizing antibody (pseudotype NAb) titers were determined at the same time points. Viral loads were determined semi-quantitatively by SARS-CoV-2 PCR. Patients with low humoral responses at entry showed a robust increase of antibodies to all SARS-CoV-2 proteins and Nab, reaching peak levels within 2 weeks. The rapid increase in binding and neutralizing antibodies was paralleled by a concomitant clearance of the virus within the same timeframe. Patients with high humoral responses at entry demonstrated low or no further increases; however, virus clearance followed the same trajectory as in patients with low antibody response at baseline. Together, the sequential immunological and virological analysis of this well-defined cohort of patients early in infection shows the presence of high levels of binding and neutralizing antibodies and potent clearance of the virus.

SARS-CoV-2 antibody kinetics eight months from COVID-19 onset: Persistence of spike antibodies but loss of neutralizing antibodies in 24% of convalescent plasma donors.

Elucidating the characteristics of human immune response against SARS-CoV-2 is of high priority and relevant for determining vaccine strategies. We report the results of a follow-up evaluation of anti-SARS-CoV-2 antibodies in 148 convalescent plasma donors who participated in a phase 2 study at a median of 8.3 months (range 6.8-10.5 months) post first symptom onset. Monitoring responses over time, we found contraction of antibody responses for all four antigens tested, with Spike antibodies showing higher persistence than Nucleocapsid antibodies. A piecewise linear random-effects multivariate regression analysis showed a bi-phasic antibody decay with a more pronounced decrease during the first 6 months post symptoms onset by analysis of two intervals. Interestingly, antibodies to Spike showed better longevity whereas their neutralization ability contracted faster. As a result, neutralizing antibodies were detected in only 76% of patients at the last time point. In a multivariate analysis, older age and hospitalization were independently associated with higher Spike, Spike-RBD, Nucleocapsid, N-RBD antibodies and neutralizing antibody levels. Results on persistence and neutralizing ability of anti-SARS-CoV-2 antibodies, especially against Spike and Spike-RBD, should be considered in the design of future vaccination strategies.

A Phase II Study on the Use of Convalescent Plasma for the Treatment of Severe COVID-19- A Propensity Score-Matched Control Analysis.

COVID-19 is a global pandemic associated with increased morbidity and mortality. Convalescent plasma (CP) infusion is a strategy of potential therapeutic benefit. We conducted a multicenter phase II study to evaluate the efficacy and safety of CP in patients with COVID-19, grade 4 or higher. To evaluate the efficacy of CP, a matched propensity score analysis was used comparing the intervention (n = 59) to a control group (n = 59). Sixty patients received CP within a median time of 7 days from symptom onset. During a median follow-up of 28.5 days, 56/60 patients fully recovered and 1 patient remained in the ICU. The death rate in the CP group was 3.4% vs. 13.6% in the control group. By multivariate analysis, CP recipients demonstrated a significantly reduced risk of death [HR: 0.04 (95% CI: 0.004-0.36), p: 0.005], significantly better overall survival by Kaplan-Meir analysis (p < 0.001), and increased probability of extubation [OR: 30.3 (95% CI: 2.64-348.9), p: 0.006]. Higher levels of antibodies in the CP were independently associated with significantly reduced risk of death. CP infusion was safe with only one grade 3 adverse event (AE), which easily resolved. CP used early may be a safe and effective treatment for patients with severe COVID-19 (trial number NCT04408209).

Management of Coagulopathy in Bleeding Patients.

Early recognition of coagulopathy is necessary for its prompt correction and successful management. Novel approaches, such as point-of-care testing (POC) and administration of coagulation factor concentrates (CFCs), aim to tailor the haemostatic therapy to each patient and thus reduce the risks of over- or under-transfusion. CFCs are an effective alternative to ratio-based transfusion therapies for the correction of different types of coagulopathies. In case of major bleeding or urgent surgery in patients treated with vitamin K antagonist anticoagulants, prothrombin complex concentrate (PCC) can effectively reverse the effects of the anticoagulant drug. Evidence for PCC effectiveness in the treatment of direct oral anticoagulants-associated bleeding is also increasing and PCC is recommended in guidelines as an alternative to specific reversal agents. In trauma-induced coagulopathy, fibrinogen concentrate is the preferred first-line treatment for hypofibrinogenaemia. Goal-directed coagulation management algorithms based on POC results provide guidance on how to adjust the treatment to the needs of the patient. When POC is not available, concentrate-based management can be guided by other parameters, such as blood gas analysis, thus providing an important alternative. Overall, tailored haemostatic therapies offer a more targeted approach to increase the concentration of coagulation factors in bleeding patients than traditional transfusion protocols.

Complications of blood donation reported to haemovigilance systems: analysis of eleven years of international surveillance.

BACKGROUND AND OBJECTIVES: The International Haemovigilance Network collects aggregate data on complications of blood donation from member haemovigilance systems (HVS). We analysed the data collected in 2006-2016 in order to learn from it and consider future improvements. MATERIALS AND METHODS: National HVS entered annual data on donation complications and on annual whole blood and apheresis donations in the 'ISTARE' (International Surveillance of Transfusion Adverse Reactions and Events) online database. We calculated national and aggregate donation complication rates. RESULTS: Twenty-four HVS provided data for 138 country years (CY; median 7 CY, IQR 2-8), covering 155 M donations. The overall complication rate was 6·3/1000 donations and the median country rate 3·2/1000 (IQR 1·1-10·1). Overall and severe complication rates varied considerably between HVS. Vasovagal reactions (VVR) were most commonly reported: 4·6/1000 donations, median country rate 3·1/1000 donations (IQR 0·6-7·7). Rare complications included generalized allergic reaction (0·10/100 000) and major blood vessel injury (category available since 2015; 0·12/100 000). Eighteen HVS reported complications of whole blood donation (WBD) and apheresis separately (89 CY, 101·6 M WBD and 26·3 M apheresis donations). The median country VVR rate was 3·4/1000 WBD (IQR 1·0-9·1) and 1·5/1000 apheresis donations (1·0-4·2). Rates of venepuncture-related complications tended to be higher for apheresis: the median country rate of reported haematomas was 0·39/1000 WBD (IQR 0·31-1·2) vs. 4·2/1000 apheresis donations (0·69-5·6). CONCLUSION: International reporting allows HVS to study rates of blood donation complications and capture information about very rare events. The present variability of reporting and severity assessment hampers comparisons between HVS and requires further work.

Current Practice in FFP Preparation and Use in Greece: A National Survey

Objective: Fresh frozen plasma (FFP) transfusion is widely used in modern clinical settings. Practices regarding its use vary due to lack of guidelines from randomized trials. The aim of this study was to assess both the current practices regarding FFP production, use, and wastage and the implementation of quality control (QC), female donor plasma production policies, and use of pharmaceutical hemostatic agents in Greece. Materials and Methods: The study was conducted during February-April 2018. For the first part of the study, data including FFP transfusion indication, hospital department, diagnosis, FFP units/transfusion episode, ABO compatibility, blood donor's sex, and reasons for discarding were collected. For the second part, questionnaire data were analyzed. Results: According to data from 20 Greek hospitals, 12655 FFP units were transfused to 2700 patients during 5069 transfusion episodes in the studied period of time. Most patients were hospitalized in internal medicine, general surgery, and intensive care unit departments. Each patient received on average 4.69 units (2.5 units/episode). Transfusion requests were in accordance with international guidelines in 63.44% of cases and 99.04% of the units were given to ABO-identical patients. Main reasons for discarding included failure to meet quality requirements (30.06%), female donors (22.17%), and other causes (27.26%). Among 96.9% of all transfusion services across the country, 28.26% perform QC according to the directions of the European Directorate for the Quality of Medicines & Health Care and 68.83% discard plasma from female donors. Pharmaceutic hemostatic agents are used in 37.23% of the hospitals. Conclusion: This is the first national survey regarding FFP production and transfusion in Greece. Staff of internal medicine, general surgery, and ICU departments, where most FFP-transfused patients are hospitalized, should be regularly involved in training on contemporary transfusion guidelines. Upcoming centralization of FFP production and inventory management could help in homogenizing practices regarding FFP use and improve product quality. Strengthening the use of pharmaceutic hemostatic agents could improve patients' management.

Anti-SARS-CoV-2 Antibody Responses in Convalescent Plasma Donors Are Increased in Hospitalized Patients; Subanalyses of a Phase 2 Clinical Study.

We evaluated the antibody responses in 259 potential convalescent plasma donors for Covid-19 patients. Different assays were used: a commercial ELISA detecting antibodies against the recombinant spike protein (S1); a multiplex assay detecting total and specific antibody isotypes against three SARS-CoV-2 antigens (S1, basic nucleocapsid (N) protein and receptor-binding domain (RBD)); and an in-house ELISA detecting antibodies to complete spike, RBD and N in 60 of these donors. Neutralizing antibodies (NAb) were also evaluated in these 60 donors. Analyzed samples were collected at a median time of 62 (14-104) days from the day of first symptoms or positive PCR (for asymptomatic patients). Anti-SARS-CoV-2 antibodies were detected in 88% and 87.8% of donors using the ELISA and the multiplex assay, respectively. The multivariate analysis showed that age ≥50 years (p < 0.001) and need for hospitalization (p < 0.001) correlated with higher antibody titers, while asymptomatic status (p < 0.001) and testing >60 days after symptom onset (p = 0.001) correlated with lower titers. Interestingly, pseudotype virus-neutralizing antibodies (PsNAbs) significantly correlated with spike and with RBD antibodies by ELISA. Sera with high PsNAb also showed a strong ability to neutralize active SARS-CoV-2 virus, with hospitalized patients showing higher titers. Therefore, convalescent plasma donors can be selected based on the presence of high RBD antibody titers.

Platelets transfusion in Greece: Where, when, why? A national survey.

BACKGROUND: Platelet transfusion is among the most useful therapeutic tools in modern clinical settings which mean that ensuring an adequate supply is of paramount importance. AIM: The aim of our study was to record the use and wastage of platelet concentrates (PCs) in Greece, so as to come up with evidence-based interventions. METHODS: The study was conducted during May and June 2015. We evaluated the use of random-donor platelets (RDPs) and single-donor apheresis platelets (SDPs). We analyzed such parameters as hospital department and diagnosis, indication for transfusion, PCs' age at the time of transfusion, and wastage rate. RESULTS: We used data from 21 hospitals across the country. A total of 12,061 RDPs and 1189 SDPs were transfused, with an average of 4.84 (±2.72) and 1.12 (±2.73) units per episode, respectively. Most patients had been admitted to the internal medicine and hematology departments. The transfusions were mostly given prophylactically, usually in cases of acute leukemia, and mostly on the day before expiration. Wastage rate was 16.75% for RPDs and 2.70% for SDPs, primarily because of the expiration of the use-by date. CONCLUSIONS: This is the first national survey regarding platelet transfusion in Greece. Since most patients were admitted in internal medicine and hematology departments, we recommend that the staff of the abovementioned departments should undergo training on contemporary transfusion guidelines. Platelet discard rate could further be lowered through the centralization of inventory management along with the extension of the lifetime of PCs by means of emerging technologies.

Red Blood Cell Transfusions in Greece: Results of a Survey of Red Blood Cell Use in 2013.

OBJECTIVE: Greece is ranked as the second highest consumer of blood components in Europe. For an effective transfusion system and in order to reduce variability of transfusion practice by implementing evidence-based transfusion guidelines it is necessary to study and monitor blood management strategies. Our study was conducted in order to evaluate the use of red blood cell units (RBC-U) in nationwide scale mapping parameters that contribute to their proper management in Greece. MATERIALS AND METHODS: The survey was conducted by the Working Committee of Transfusion Medicine&Apheresis of the Hellenic Society of Hematology from January to December 2013. The collected data included the number, ABO/D blood group, patients' department, and storage age of RBC-U transfused. RESULTS: The number of RBC-U evaluated was 103,702 (17.77%) out of 583,457 RBC-U transfused in Greece in 2013. RBC-U transfused by hospital department (mean percentage) was as follows: Surgery 29.34%, Internal Medicine 29.48%, Oncology/Hematology 14.65%, Thalassemia 8.87%, Intensive Care Unit 6.55%, Nephrology 1.78%, Obstetrics/Gynecology 1.46%, Neonatal&Pediatric 0.31%, Private Hospitals 8.57%. RBC-U distribution according to ABO/D blood group was: A: 39.02%, B: 12.41%, AB: 5.16%, O: 43.41%, D+: 87.99%, D-: 12.01%. The majority of RBC-U (62.46%) was transfused in the first 15 days of storage, 25.24% at 16 to 28 days, and 12.28% at 29-42 days. CONCLUSION: Despite a high intercenter variability in RBC transfusions, surgical and internal medicine patients were the most common groups of patients transfused with an increasing rate for internal medicine patients. The majority of RBC-U were transfused within the first 15 days of storage, which is possibly the consequence of blood supply insufficiency leading to the direct use of fresh blood. Benchmarking transfusion activity may help to decrease the inappropriate use of blood products, reduce the cost of care, and optimize the use of the voluntary donor's gift.

Endothelial Protein C Receptor Gene Variants and Risk of Thrombosis.

Endothelial protein C receptor (EPCR) is a candidate mediator in the pathogenesis of thrombosis, as several data in the literature indicate that polymorphisms such as EPCR 4678G/C and 4600A/G are associated with either protective effect or increased risk of thrombosis, respectively. We investigated the prevalence of these polymorphisms in patients with thrombotic disorders as well as their impact on the risk of thrombosis, the age of first thrombotic episode, and recurrence. The prevalence of the rare EPCR alleles 4600G and 4678C was comparable in patients and controls. However, in a subset analysis, we observed that 4600G allele was more prevalent among patients who developed thrombosis at younger age (<35 years). Moreover, the prevalence of 4678C allele was significantly lower in younger patients compared to older patients. Neither polymorphism seemed to have an impact on recurrence regardless of age. Soluble EPCR levels were elevated in 4600AG patients compared to controls while 4678CC patients presented with lower levels of soluble form of EPCR compared to carriers of at least 1 4678G allele. Our data suggest that either the lack of the protective EPCR 4678C allele or the presence of EPCR 4600G allele may be associated with earlier development of thrombosis.

Update on argatroban for the prophylaxis and treatment of heparin-induced thrombocytopenia type II.

Heparin-induced thrombocytopenia (HIT) is a rare but potentially severe complication of heparin therapy that is strongly associated with venous and arterial thrombosis (HIT and thrombosis syndrome, HITTS), which requires urgent detection and treatment with a nonheparin anticoagulant. Argatroban, a synthetic direct thrombin inhibitor, is indicated for the treatment and prophylaxis of thrombosis in patients with HIT, including those undergoing percutaneous coronary intervention. Argatroban has a relatively short elimination half-life of approximately 45 minutes, which is predominantly performed via hepatic metabolism. It is derived from L-arginine that selectively and reversibly inhibits thrombin, both clot-bound and free, at the catalytic site. Argatroban anticoagulation has been systematically studied in patients with HIT and HITTS and proved to be a safe and effective agent for this indication. The current review presents the pharmacology of argatroban, data regarding monitoring of the agent, and an overview of the results of the major clinical trials assessing argatroban anticoagulation in HIT patients. Additionally, data from recent clinical trials with argatroban use in more special indications such as in percutaneous coronary intervention, liver dysfunction, renal replacement therapy, and intensive care medicine, are reviewed. The approved initial dosage of argatroban for adults with HIT or HITTS is 2 µg/kg/minute for patients with normal hepatic function and 0.5 µg/kg/minute for patients with hepatic dysfunction. There is evidence that a reduced initial dose may also be advisable for patients with heart failure, multiple organ dysfunction, severe anasarca, or after cardiac surgery. Given this information, argatroban can be effectively used in treating HIT with monitoring of activated partial thromboplastin time.

Fondaparinux for the treatment of acute heparin-induced thrombocytopenia: a single-center experience.

Heparin-induced thrombocytopenia (HIT) is a life-threatening immune response to heparin that is associated with a high risk of thromboembolic complications. The syndrome is caused by antibodies that are reactive against complexes of platelet factor 4/heparin (PF4/H). For patients with HIT, the discontinuation of heparin alone is not sufficient and the diagnosis necessitates the administration of an alternative anticoagulant. Fondaparinux is a synthetic pentasaccharide that binds to antithrombin and potentiates inhibition of factor Xa. Data have shown that fondaparinux is structurally too short to induce an antibody response and could be a useful agent to treat HIT. In our hospital, we retrospectively analyzed the use of fondaparinux in the treatment of 24 patients with acute HIT during unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) administration and compared the results to a similar population of 20 patients who were treated with lepirudin. The treated patients had a complete platelet count recovery, and none experienced a new thromboembolic complication or major bleeding. The development of limb gangrene (2 patients who received lepirudin and 1 who received fondaparinux) likely resulted from a delay in diagnosis and treatment initiation. Our data suggest that fondaparinux may be considered a safe and an effective alternative treatment in HIT complicated with or without thrombosis.

Portal, splenic and mesenteric vein thrombosis in a patient double heterozygous for factor V Leiden and prothrombin G20210A mutation.

We herein report a 56-year-old man who presented with abdominal pain, diarrhea and a 22-kg-weight loss over 4 months. He was on acenocoumarol treatment because of portal, splenic and mesenteric vein thrombosis (PSMVT) 3 months before, with admission international normalized ratio (INR):1.6. Doppler ultrasonography and helical computerized tomographic scan of the abdomen showed complete thrombosis of the extrahepatic portal vein extending into the superior mesenteric vein and splenic vein. The manifestation of thrombosis was in the absence of provocative stimuli or local cause. The patient had a negative history of venous thromboembolism. Thrombophilia workup revealed double heterozygosity for factor V Leiden and prothrombin G20210A mutation. He was immediately started with intravenous unfractionated heparin, followed by oral anticoagulation with target INR 2-3. Five days after a Doppler examination showed significant improvement in the flow within the portal vein, and a computerized tomographic scan of the abdomen 1 month later showed extensive recanalization of the portal venous system. The patient is now 36 months out from the second PSMVT episode and is doing well although maintaining oral lifelong anticoagulation. The case is of particular interest in that PSMVT was the first manifestation of this combined disorder. We conclude that all patients presenting with unexplained PSMVT should be investigated for the presence of a hypercoagulable state. Anticoagulation should be considered in all patients with this diagnosis and should be a lifelong therapy in those with an underlying thrombophilia.

Prolonged administration of erythropoietin increases erythroid response rate in myelodysplastic syndromes: a phase II trial in 281 patients.

Treatment with recombinant human erythropoietin (rHuEpo) improves anaemia in approximately 20% of patients with myelodysplastic syndromes (MDS). We investigated the potential advantage of a prolonged administration of rHuEpo to achieve higher erythroid response rates (RR) in 281 MDS patients: 118 with refractory anaemia (RA), 77 with refractory anaemia and ringed sideroblasts (RARS), 59 with refractory anaemia with excess of blasts and blast count < 10% (RAEB-I), and 27 with RAEB and blast count between 11-20% (RAEB-II). rHuEpo was given subcutaneously at a dose of 150 U/kg thrice weekly, for a minimum of 26 weeks. Response to treatment was evaluated after 12 and 26 weeks of therapy. The overall RR was 45.1%; the RR for RA, RARS, RAEB-I and RAEB-II were 48.3%, 58.4%, 33.8% and 13% respectively. A significant increase in RR was observed at week 26 in RA, RARS and RAEB-I patients, as the response probability increased with treatment duration. The RR was higher in the good cytogenetic prognostic group and serum Epo level of > 150 U/l at baseline predicted for non-response. The median duration of response was 68 weeks and the overall risk of leukaemic transformation was 21.7%. These results suggest that prolonged administration of rHuEpo produces high and long-lasting erythroid RR in MDS patients with low blast counts, particularly in those with pretreatment serum Epo levels of < 150 U/l and good cytogenetic prognosis.