COVID 19 and febrile neutropenia: Case report and systematic review.

OBJECTIVES: In pandemic conditions, patients with febrile neutropenia are also at risk of COVID-19. Aim of this systematic review is to evaluate COVID-19 cases presented with febrile neutropenia and provide information regarding incidence, clinical course and prognosis. METHODS: We systematically searched on COVID-19 and febrile neutropenia cases in PubMed, SCOPUS and Web of Science. RESULTS: A total of 19 febrile neutropenic patients were analyzed. A male predominance was noted. Eleven cases had hematological malignancies. Fourteen of the cases were previously received chemotherapy. Five patients had severe neutropenia: 3 had hematologic cancer and none died. 17 (89.5%) cases have pulmonary involvement and seven of them had severe disease with acute respiratory distress syndrome (ARDS). Three cases with ARDS were died. 12 of them received G-CSF for treatment. Five cases were developed respiratory failure after G-CSF use. Overall mortality was 15.8%, while death was not observed in patients without malignancy and solid organ tumors, the mortality rate was 27% in cases with hematological malignancies. CONCLUSION: In ongoing pandemic, febrile neutropenic patients should be precisely evaluated for COVID-19 disease. It should be remembered that there may not be typical signs and symptoms and laboratory findings of COVID-19 disease because of the immunosuppression.

Matrix Metalloproteinases 2 and 9 Polymorphism in Patients With Myeloproliferative Diseases: A STROBE-Compliant Observational Study.

Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction-restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment.

Bone-like mineral nucleating peptide nanofibers induce differentiation of human mesenchymal stem cells into mature osteoblasts.

A bone implant should integrate to the tissue through a bone-like mineralized interface, which requires increased osteoblast activity at the implant-tissue boundary. Modification of the implant surface with synthetic bioinstructive cues facilitates on-site differentiation of progenitor stem cells to functional mature osteoblasts and results in subsequent mineralization. Inspired by the bioactive domains of the bone extracellular matrix proteins and the mussel adhesive proteins, we synthesized peptide nanofibers to promote bone-like mineralization on the implant surface. Nanofibers functionalized with osteoinductive collagen I derived Asp-Gly-Glu-Ala (DGEA) peptide sequence provide an advantage in initial adhesion, spreading, and early commitment to osteogenic differentiation for mesenchymal stem cells (hMSCs). In this study, we demonstrated that this early osteogenic commitment, however, does not necessarily guarantee a priority for maturation into functional osteoblasts. Similar to natural biological cascades, early commitment should be further supported with additional signals to provide a long-term effect on differentiation. Here, we showed that peptide nanofibers functionalized with Glu-Glu-Glu (EEE) sequence enhanced mineralization abilities due to osteoinductive properties for late-stage differentiation of hMSCs. Mussel-inspired functionalization not only enables robust immobilization on metal surfaces, but also improves bone-like mineralization under physiologically simulated conditions. The multifunctional osteoinductive peptide nanofiber biointerfaces presented here facilitate osseointegration for long-term clinical stability.

Thrombopoietin and mean platelet volume in patients with ischemic stroke.

OBJECTIVE: The aim of this study was to evaluate mean platelet volume (MPV), thrombopoietin (TPO), and platelet levels in patients with ischemic stroke and compare this with healthy controls. METHODS: We prospectively studied 50 patients with ischemic stroke and compared them with 37 control participants who have evaluated in internal medicine polyclinic and had no history of cerebrovascular events. All patients were within 24 hours after stroke; MPV and TPO were measured on admission. RESULTS: Both TPO and MPV values were significantly higher in patients with stroke (P = .00; P = .001). CONCLUSION: Increased TPO levels may increase both platelet count and platelet size, resulting in more hemostatic tendency, which may contribute to the progression of ischemic stroke.

Human Immunodeficiency Virus (HIV)-Negative and Human Herpes Virus-8 (HHV-8)-Positive Primary Effusion Lymphoma: A Case Report and Review of the Literature.

UNLABELLED: Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma that presents with serosal effusion in body cavities, without obvious tumor masses. Although PEL occurs in immunocompromised patients that are human immunodeficiency virus (HIV) positive, it also occurs in immunocompetent human herpes virus-8 (HHV-8)-positive patients. Herein we present an immunocompetent, HIV-negative, CD-20-negative, HHV-8-positive patient with pleural effusion that was diagnosed as PEL. The CHOP protocol and talc pleurodesis were administered. HHV-8 plays a causative role in PEL and is important for differentiating PEL from other types of lymphoma. As such, in addition to pleurodesis antiviral treatment should be considered for optimal treatment outcome. CONFLICT OF INTEREST: None declared.

Relationship between some clinical situations, autoantibodies, and pseudothrombocytopenia.

The widespread usage of blood count autoanalyzers has led to a major improvement in cellular hematology because of quick and accurate results found in most instances. However, spurious test results also can be observed like pseudothrombocytopenia (PTCP). In our study, we aimed to evaluate the clinical and laboratory factors associated with PTCP. Forty-six patients with PTCP and 69 healthy volunteers were enrolled in the study. Sex distribution was similar between the groups. Hospitalization, infection, the use of low-molecular-weight heparin and pregnancy increased the incidence of PTCP. Atherosclerosis and some drugs such as warfarin and calcium channel blockers were associated with PTCP, but the coincidence was not statistically significant. Antinuclear antibody positivity was higher in PTCP group (18.8% vs 7.2%; P=0.033) but anticardiolipin positivity rates were similar when compared to controls. Pseudothrombocytopenia was frequently misdiagnosed, which led to inappropiate treatments. Therefore, this situation should be kept in mind.

Elevated serum angiotensin converting enzyme levels as a reflection of bone marrow renin-angiotensin system activation in multiple myeloma.

INTRODUCTION: Angiotensin converting enzyme (ACE) is a circulating enzyme that participates in the body's renin-angiotensin system (RAS) and is localized on the endothelial cell surface in the lung and other vascular beds. It catalyses the conversion of decapeptide angiotensin I to octapeptide angiotensin II. In the present study, we aimed to analyse the possible relationship between the levels of ACE in the context of RAS in multiple myeloma (MM) pathogenesis. MATERIALS AND METHODS: The study was conducted on 25 MM patients (13 males, 12 females; median age 66 years, range 47-88) and 20 healthy controls. The clinical features of MM patients including demographics and laboratory findings were summarized. Serum ACE levels were measured by using commercially available kits. RESULTS: The serum ACE levels of MM patients and controls were 32.60±20.26 and 15.35±6.47 respectively. Serum ACE levels were significantly higher in MM patients compared with control groups (p<0.001). CONCLUSIONS: Being an important component of RAS, circulating ACE might be associated with clonal proliferation of malignant plasma cells in the bone marrow microenvironment. Identification of the pathobiological activity of the local RAS in MM would enlighten the biologic basis and clinical management of haematologic disorders.

Serum thrombopoietin levels in patients with non-alcoholic fatty liver disease.

OBJECTIVE: To observe thrombopoietin (TPO) levels in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: The study was performed between November 2010 and March 2011 at the Department of Internal Medicine, Faculty of Medicine, Fatih University, Ankara, Turkey. A total of 60 consecutive patients with ultrasound proven NAFLD (study group), and 28 healthy volunteers (control study) were included in the study. The patient group was divided into 3 subgroups according to the ultrasonographic images as follows: minimal, intermediate, and marked hepatosteatosis. The TPO levels of the patient subgroups were compared with the healthy controls. All the data were collected prospectively, and recorded in FUHIS data collecting system, which is produced by our data-knowledge team. Quantitative measurements of thrombopoietin level were carried out by using the Human Thrombopoietin Quantikine ELISA Kit (R&D Systems, Minneapolis, Minnesota, USA). RESULTS: Thrombopoietin levels were significantly increased in the patient subgroups compared with the controls. The TPO levels were also higher in the patient subgroup of grade 1-nonalcoholic fatty liver disease (grade 1- NAFLD) compared with the control group. CONCLUSION: The TPO increased in patients with NAFLD possibly as an acute phase reactant to decreased inflammation. In clinical practice, physicians should be alerted to increased TPO levels in patients.

Heparin platelet factor 4 antibody positivity in pseudothrombocytopenia.

Pseudothrombocytopenia (PTCP) is a laboratory event of platelet clustering related to drugs used for anticoagulation. This condition is engendered by autoantibodies against platelets in usually EDTA-anticoagulated blood. Pseudothrombocytopenia has no clinical significance but when evaluated as true thrombocytopenia, this misconception may lead to unnecessary diagnostic procedures. Heparin-induced thrombocytopenia with thrombosis (HITT) is a complication of heparin treatment caused by heparin platelet factor 4 (HPF-4) antibodies, leading to platelet activation and hypercoagulability. In our study, 48 patients with PTCP and 36 healthy volunteers were included. Heparin platelet factor 4 antibody positivity was detected in 12 patients from PTCP group; nobody from control group had. Citrated serum samples and peripheral blood smears showed normal platelet count. Of the 4 patients using heparin derivative, 1 (2.1%) had antibody positivity but without any bleeding symptoms. In conclusion, HPF-4 antibody positivity might be a risk factor for PTCP. Clinicians should be aware of this kind of condition.

Serum thrombin activatable fibrinolysis inhibitor levels in patients with newly diagnosed multiple myeloma.

Multiple myeloma has been associated with the development of thromboembolic events. Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme, which potently inhibits fibrinolysis. The purpose of the present study was to assess the TAFI levels in patients with newly diagnosed multiple myeloma. Twenty-seven newly diagnosed multiple myeloma patients (16 women and 11 men) and 27 age-matched healthy individuals (14 women and 13 men) were included in the study. Serum TAFI levels were significantly increased in patients with multiple myeloma (46 ± 13. 3 vs. 36. 6 ± 9.7 µg/ml) compared with healthy individuals. Serum TAFI levels were negatively correlated with serum albumin (CC: -0.453, P < 0.05) and hemoglobin levels (CC: -0.392, P < 0.05) and positively correlated with the ß-2 microglobulin levels (CC: 0.524, P < 0.05). In this study, we observed significantly elevated TAFI levels in patients with multiple myeloma and higher serum TAFI levels were suggested to be associated with higher disease stage. With these results, a possible role of elevated TAFI levels in thromboembolic manifestations in the course of multiple myeloma can be suggested.

The significance of serum transferrin receptor levels in the diagnosis of the coexistence of anemia of chronic disease and iron deficiency anemia.

OBJECTIVE: Iron deficiency anemia is the most common cause of microcytic anemia throughout the world. Ferritin levels are good indicators of iron stores; however, levels may increase irrespective of iron stores in cases of chronic disease. Therefore, it is difficult to diagnose iron deficiency anemia coexisting with anemia of chronic disease. MATERIALS AND METHODS: To determine the level of transferrin receptor in subjects, 30 patients with iron deficiency anemia, 30 patients with anemia of chronic disease and 30 patients with both diseases were included in the study. RESULTS: Mean serum transferrin receptor levels were 5.99±2.98 mg/L in the iron deficiency anemia group, 1.90±1.15 mg/L in the anemia of chronic disease group and 3.07±0.90 mg/L in the combination group. Comparing groups with each other revealed significant differences (p<0.05). CONCLUSION: It is concluded that the assessment of serum transferrin receptor levels is a useful method for the diagnosis of iron deficiency anemia in patients.

Treatment of adverse perinatal outcome in inherited thrombophilias: a clinical study.

Inherited thrombophilia may cause important complications in pregnancies including maternal death, early and late pregnancy loss, preeclampsia, intrauterine growth restriction and placental abruption. This study was developed to investigate the fetal loss and successful birth rates in hereditary thrombophilic patients treated with low-dose acetylsalicylic acid and low molecular weight heparin to determine the necessity and effectiveness of this treatment. Ninety-three patients with the history of recurrent pregnancy loss or thromboembolism were included in this study. Eighty milligram acetylsalicylic acid treatment was started just after the diagnosis for the patients with hereditary thrombophilia, continued throughout pregnancy and ceased 3 days before the delivery. Low molecular weight heparin (LMWH) was started for the patients with the unsuccessful in-vitro fertilization (IVF) history, just after finishing the egg collection. For the other patients, LMWH was started after the positive result of the pregnancy test. Treatment was started for 67 (72%) of patients. Among the treated 67 patients, 38 had MTHFR C677T gene mutation, 25 had protein S deficiency, 19 had FV Leiden mutation, four had protein C deficiency, two had Prothrombin 20210A gene abnormality, two had antiphospholipid anticore syndrome and two had AT III deficiency. Fifty-seven (85.1%) of 67 patients under treatment had pregnancy. Forty-one (61.2%) of those 57 patients had a live birth, whereas 16 (23.9%) of them had abortus under treatment. In regression analysis, only protein C and S deficiencies were found to be independent risk factors. In conclusion, inherited thrombophilia should always be kept in mind as an etiological factor of recurrent abortus. With treatment, success rates are between 60 and 80%. Severe side effects due to treatment are rare. But randomized, double-blind, placebo-controlled studies are still necessary to evaluate the benefit of heparin and acetylsalicylic acid treatment in women with the history of inherited thrombophilia.

Hemostatic alterations in fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is an important cause of liver failure. Whatever its cause, the liver failure is accompanied by multiple changes in the hemostatic system. The objective of the current report was to study several homeostasis parameters such as protein C, protein S, factor 7, factor 8 levels, platelet counts, prothrombin time and activated partial thromboplastin time, and plasminogen activator inhibitor in patients with fatty liver. A total of 28 consecutive patients with ultrasound proven NAFLD and 33 healthy volunteers were included in the study. Plasma prothrombin time and activated partial thromboplastin time were within normal ranges in both NAFLD and control groups. Plasma factor 7, factor 8, protein S, and protein C levels were decreased in NAFLD patients but the difference was not statistically significant, whereas plasminogen activator inhibitor 1 levels were significantly increased in patients with NAFLD compared to controls. In conclusion, in all types of liver disease, some alterations in hemostatic parameters are awaited. As fatty liver disease is very common in clinical practice, clinicians should be aware of this kind of alterations.

Evaluation of 143 cases of immune thrombocytopenic purpura with regards to clinical course and response to treatment.

OBJECTIVE: Immune thrombocytopenic purpura (ITP) is also known as idiopathic thrombocytopenic purpura. Increased platelet destruction and insufficient platelet production are both responsible for its etiopathogenesis. ITP can be diagnosed after excluding other possible causes of thrombocytopenia. MATERIALS AND METHODS: One hundred forty-three cases of chronic ITP that were monitored in a hematology clinic were retrospectively evaluated. All cases received first line treatment of 1 mg/kg/day prednisolone. Corticosteroid nonresponsive (CN) cases and corticosteroid-dependent (CD) cases underwent splenectomies. RESULTS: The rate of CN/CD cases was found to be 53% (n=76). Sixty-six percent of these cases (n=50) underwent splenectomies. The ratio of non-responsive cases to relapse cases after splenectomy (SN/SR) was 30% (n=15). The total number of cases was 41, including those without splenectomy (n=26) and with SY/SR (n=15). Helicobacter pylori (Hp) eradication, immunosuppressive agents and danazol treatments were administered to patients (n=10, n=14 and n=4, respectively). Currently, 13 patients are being monitored without treatment. Fifteen patients who were non-responsive to Hp eradication treatment, immunosuppressive treatment or danazol treatment are still being monitored without any treatment. CONCLUSION: Optimal treatment is not available for splenectomy-resistant cases of ITP. The response rates for Hp eradication treatment, immunosuppressive treatments and anabolic agents are low. Therefore, larger studies with more patients are required using new agents, such as thrombopoietin (TPO) receptor agonists and anti-CD20 monoclonal antibodies.

A rare extramedullary involvement in myeloma: lung parenchyma and association with unfavorable chromosomal abnormalities.

Although pulmonary complications developing secondary to lung infections and involvement in ribs occur frequently in multiple myeloma (MM), involvement of the lung parenchyma is quite rare. In clinical studies, the involvement of lung parenchyma has been found to be associated with unfavorable prognosis. Here, a MM case in whom involvement of lung parenchyma was accompanied by unfavorable prognostic cytogenetic markers is presented. A 62-year-old male presented with complaint of cough, and heterogeneous hypodense mass was detected in thorax computerized tomography. The patient underwent bronchoscopic biopsy. Pathological examination revealed diffuse plasma cell infiltration staining with kappa immunohistochemically. In bone marrow biopsy, plasma cell infiltration was observed. In conventional cytogenetic examination, hypodiploidy was established. In cytogenetic examination carried out with fluorescence in situ hybridization, deletion (13q) was determined. In conclusion, in patients diagnosed with MM and presenting with pulmonary mass lesion, lung involvement associated with plasma cell infiltration should also be considered in the differential diagnosis. As overall survival is low in these cases, more aggressive treatment approaches such as high-dose treatment should be immediately considered.

Evaluation of risk factors for thrombophilia in patients with cerebral venous thrombosis.

OBJECTIVE: The increased risk for thrombosis is known as hypercoagulability or thrombophilia. In our study, we aimed to compare the frequency of the identified defects for thrombophilia in patients with central venous thrombosis and under the age of 50 years, with the findings in the current literature. METHODS: Forty-three patients (16-50 years old) were retrospectively evaluated. Thrombophilia investigation included determinations of protein C, protein S, antithrombin, and activated protein C resistance, factor V Leiden (FVL), prothrombin 20210A (PT 20210) and methylene tetrahydrofolate reductase (MTHFR) C677T mutations, antiphospholipid antibodies (APA), factor VIII levels, and homocysteine levels. RESULTS: We detected a single thrombophilic defect in 67.4%, two defects in 27.9% and three defects in 4.7% of our patients. The most common thrombophilic defect was mutation in the MTHFR gene (41.8%), and this was followed by the FVL mutation (34.9%). CONCLUSION: Since the prevalence of individual thrombophilic defects varies in each population, ethnic group and geographical location, screening for thrombophilic defects in patients presenting with cerebral venous thrombosis should primarily investigate the most frequent thrombophilia risk factors.

Role of flow cytometry in multiple myeloma and the prognostic significance of CD87 (uPAR) expression.

OBJECTIVE: The plasminogen activator system consists of the serine protease urokinase plasminogen activator (uPA), two endogenous inhibitors of PAI-1 (plasminogen activator inhibitor-1) as well as the PAI-2 and uPA receptor (uPAR or CD87). The aim of this study was to determine the significance of flow cytometry and CD87, CD45 and CD56 expressions in the diagnosis, follow-up and prognosis of multiple myeloma (MM). METHODS: Twenty-nine MM patients were included in the study. Bone marrow samples were used for flow cytometry. A panel of CD87, CD45, CD56, CD10, CD19, CD20, CD38, and CD138 was tested by flow cytometry. RESULTS: CD87 was negative in 8 (27.5%) cases, dim positive in 9 (31.1%) and bright positive in 12 (41.4%). CD87 expression was significantly higher in CD45 (-) cases. CONCLUSION: Flow cytometry has a significant role in the diagnosis and prognosis of MM. Further clinical studies including large numbers of patients are needed to determine the prognostic role of CD87 in MM.

Risk factors for thrombophilia in young adults presenting with thrombosis.

The increased risk for thrombosis is known as hypercoagulability or thrombophilia. Here, we investigated risk factors for thrombophilia which were screened in young adult patients presenting with thrombotic events or with recurrent abortions with unknown etiology. A total of 115 patients aged between 16 and 50 years who were found to harbor thrombophilia were retrospectively evaluated. The laboratory investigations performed for the assessment of thrombophilia included protein C, protein S, antithrombin III deficiencies, activated protein C resistance, factor V Leiden (FVL), prothrombin 20210A (PT 20210) and methylenetetrahydrofolate reductase (MTHFR) gene mutations, factor VIII elevation, lupus anticoagulant and antiphospholipid antibodies (APA). In 66% of the cases a single thrombophilic defect was identified while some of the patients had combined thrombophilic defects. The most common thrombophilic defect was mutation in the MTHFR gene, and was followed by FVL mutation, the presence of APA and PT 20210 gene mutation, respectively. The patients were divided into two different age groups, 16-35 and 36-50 years, and arterial thrombosis was more common in the older age group. Our results indicated that some important thrombophilic defects such as gene mutations may appear in young adult patients presenting with thrombotic events.