Independent risk factors for COVID-19-associated coagulopathy.

OBJECTIVE: Past three years since the beginning of the outbreak, we have obtained satisfactory data on COVID-19. However, data on risk factors of COVID-19-associated coagulopathy (CAC) are extremely limited. Prediction of CAC might be a game changer since it is related to poor prognosis. Seeking independent risk factors for CAC was the main aim of the study. PATIENTS AND METHODS: 510 hospitalized COVID-19 patients were retrospectively screened. Forty-eight of them were excluded due to irrelevant D-dimer or ferritin elevation. The remaining patients were stratified into three groups as overt coagulopathy, significant pulmonary microthrombosis, and patients without coagulopathy. The overt coagulopathy group included cases with macrothrombosis or disseminated intravascular coagulation (DIC). The significant pulmonary microthrombosis group covered the cases that had clinical deterioration with simultaneous marked D-dimer elevation. The group of patients without coagulopathy included the asymptomatic patients with normal or elevated D-dimer levels. RESULTS: Overt coagulopathy developed in 3.2% and significant pulmonary microthrombosis in 10.1% of the patients. In the multivariate analysis, not receiving low molecular weight heparin (LMWH) (p=0.002), a level of D-dimer >15,000 U/ml (p=0.013) were associated with overt coagulopathy. In addition, levels of initial LDH >480 IU/L (p=0.022) and initial ferritin >1,000 ng/ml (p=0.036) were associated with significant pulmonary microthrombosis. Not receiving LMWH (p=0.001) was also associated with significant pulmonary microthrombosis, when multivariate analysis was performed by the parameters with a p-value <0.1 in the univariate analysis. Furthermore, all cases with DIC had Gram-negative bacterial sepsis. CONCLUSIONS: Not receiving LMWH, high levels of D-dimer, initial LDH, and initial ferritin are independent risk factors for CAC. DIC does not appear to develop based on COVID-19.

Inflammatory pseudotumor following hematopoietic stem cell transplantation: a new case and review of the literature.

Inflammatory pseudotumor (IPT) is a rare tumor that occurs in various organs and tissues. The clinical picture varies from the more frequent benign lesions to the rare malignant tumors with distant metastases. IPT associated with hematopoietic stem cell transplantation (HSCT) is rarely reported. In this article, we review the reports of IPT after HSCT and describe the first case of bladder IPT. We also review the possible factors involved in the pathogenesis. IPT might be rare but it is a potentially serious complication of HSCT. It should be considered in patients with otherwise unexplained inflammatory symptoms or signs or with any mass lesion in the post-HSCT period. A knowledge of this entity and insistence on a definitive biopsy of mass lesions in the post-HSCT period can avoid unnecessary treatment such as radical surgery, chemotherapy or radiotherapy.

Time-related changes in the incidence, severity, and clinical outcome of hepatic veno-occlusive disease in hematopoietic stem cell transplantation patients during the past 10 years.

Veno-occlusive disease (VOD) of the liver occurs in 10% to 50% of patients after hematopoietic stem cell transplantation (HSCT), ranging from a mild reversible disease to a fulminant course with a mortality rate close to 100%. We retrospectively evaluated the clinical signs, diagnosis, prognosis, therapy, and outcome of 13 hepatic VOD cases which developed after HSCT. A total of 193 consecutive patients (age: 15-62 years; median 33 years) with various hematologic diseases underwent 197 HSCT (allogeneic HSCT, n = 128; autologous HSCT, n = 69). In general, the conditioning regimen consisted of cyclophosphamide combined either with total body irradiation or busulfan. Since 2000, to reduce hepatic complications, all patients received ursodexycolic acid and discontinuation of norethisterone which inhibits ovulation. VOD diagnosed clinically was mainly managed in supportive fashion. Five patients received thrombolytic therapy (t-plasminogen activator [t-PA], n = 3; defibrotide [DF], n = 2). VOD developed in 13 of 197 cases (6.6%). All except one were in the allogeneic group who had received a busulfan-containing conditioning regimen; Ten (77%) were severe. Thirty-three of 197 (17%) cases died before day 100 with VOD as the cause in eight (24%). All of the t-PA administered patients died with significant hemorrhagic complications. DF patients improved completely, even after renal and respiratory failure, despite high total bilirubin levels. Only one patient who received DF became a long-term survivor; the other died with sepsis during the following days. The dramatic improvement with regard to VOD during DF therapy was encouraging.

Therapeutic plasmapheresis in patients with severe hyperthyroidism in whom antithyroid drugs are contraindicated.

Four patients with Graves' disease in whom antithyroid drugs could not be used were treated by plasmapheresis preoperatively. On admission all patients had severe hyperthyroidism. All patients were treated by beta blockers, cholestyramine and inorganic iodine before plasmapheresis. Plasmapheresis course consisted of three sessions. Removed plasma was replaced by a synthetic colloid solution and human albumin other than fresh-frozen plasma. Plasmapheresis led to decreases in serum T3 concentrations >78-40% and free T4 concentrations >69%. Near-total thyroidectomy could be performed in all patients. Although screening coagulation tests were within normal limits, patients 1 and 4 experienced more blood loss than usual during the operative procedure. Plasmapheresis could be used as an alternative therapeutic option in the preoperative management of severe hyperthyroid patients with contraindications to antithyroid drugs. However, this is an invasive procedure and patients should be followed carefully for prolonged clinic/subclinic coagulopathy due to plasma exchange.

Role of pretransplant interferon-alpha(IFN) treatment in the outcome of stem cell transplantation (SCT) from related donors in chronic myelogenous leukemia (CML): results from three Turkish transplant centers.

Since transplantation cannot be performed immediately after the diagnosis of chronic myelogenous leukemia (CML), interferon treatment is usually required. This study aims to analyze the effects of interferon-alpha (IFN) treatment on allogeneic stem cell transplantation (SCT) outcome. A total of 106 patients aged 16-47 years and transplanted from HLA-identical sibling donors for CML in chronic phase (CP) were evaluated. In all, 48 had received IFN-alpha for a median duration of 5 months (1-18 months) until a median of 1 month prior to transplantation. Of the patients, 50 have received bone marrow transplant (BMT) whereas 56 have received peripheral blood stem cells (PBSCT) between 1991 and 1999 in three major transplant centers in Turkey. Patient characteristics in both groups were similar. More hematological responders were present in the IFN(+) patients (P=0.0001). No difference was found in engraftment kinetics. The incidences of acute or chronic graft-versus-host disease (GVHD), relapse and graft failure were similar in all patients regardless of stem cell source. Overall survival (OS) and disease-free survival (DFS) at 2 years were similar for both IFN(+) or (-) patients following SCT. With multivariate analysis, pretransplant IFN-alpha use, stem cell source, transplant year and CD34+ cell content were not found to be risk factors for OS. In conclusion, prior IFN exposure did not impair BMT or PBSCT outcome.

The frequency of tuberculosis in adult allogeneic stem cell transplant recipients in Turkey.

In general, tuberculosis (Tb) is rarely seen in allogeneic stem cell transplant (alloSCT) recipients, but this observation has been challenged in developing countries such as Turkey, where Tb infection is more prevalent than in Europe and the US. In this retrospective study, we report on the incidence of Tb infections in 351 alloSCT recipients at 4 bone marrow transplantation units in Turkey over the last 10 years. The frequency of Tb in alloSCT recipients after allografting (5 of 351) was far greater than that in the general population (35.4 per 100,000). Of the 351 patients who underwent alloSCT, 77 who received isoniazid (INH) chemoprophylaxis for 6 months did not develop posttransplantation Tb. However, 5 of the remaining 274 patients who received no chemoprophylaxis developed Tb a median of 12 months (range, 10-47 months) after allografting. Antituberculosis therapy resulted in complete recovery in all cases. In 2 additional patients who were found to have active pulmonary Tb at the time of transplantation, alloSCT was delayed until the infections were treated. Infections of mycobacteria other than Mycobacterium tuberculosis were not observed. The number of patients who received and tolerated INH may not be sufficient for firm conclusions, but the data suggest that, in countries where Tb is prevalent, pre- and posttransplantation follow-up for Tb and the use of INH prophylaxis should be considered.