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.

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.

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.

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.

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.

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.

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.

Increased erythropoietin levels in reactive thrombocytosis.

Erythropoietin, the major humoral regulator of red cell production, was reported to stimulate various levels of megakaryocytopoiesis. We investigated levels of thrombopoietin (TPO) and erythropoietin (EPO) in patients with reactive thrombocytosis (RT) and clonal thrombocytosis (CT). 17 patients with RT and 18 patients with CT and 15 healthy subjects were enrolled into the study. TPO levels were higher in both patient groups than the controls. EPO levels were significantly higher than these in reactive thrombocytosis and in controls (p < 0.05). We suggest that besides TPO, EPO may play an important role in the pathogenesis of RT.