Thrombotic and microangiopathic effects have been reported in COVID‐19 patients. This study examined the contribution of the hereditary thrombophilia factors Prothrombin (FII) and Factor V Leiden (FVL) genotypes to the severity of COVID‐19 disease and the development of thrombosis. This study investigated FII and FVL alleles in a cohort of 9508 patients (2606 male and 6902 female) with thrombophilia. It was observed that 930 of these patients had been infected by SARS‐CoV‐2 causing COVID‐19. The demographic characteristics of the patients and their COVID‐19 medical history were recorded. Detailed clinical manifestations were analyzed in a group of cases (n = 4092). This subgroup was age and gender‐matched. FII and FVL frequency data of healthy populations without thrombophilia risk were obtained from Bursa Uludag University Medical Genetic Department's Exome Databank. The ratio of males (31.08%; 27.01%) and the mean age (36.85 ± 15.20; 33.89 ± 14.14) were higher among COVID‐19 patients compared to non‐COVID‐19 patients. The prevalence of FVL and computerized tomography (CT) positivity in COVID‐19 patients was statistically significant in the thrombotic subgroup (p < 0.05). FVL prevalence, CT positivity rate, history of thrombosis, and pulmonary thromboembolism complication were found to be higher in deceased COVID‐19 patients (p < 0.05). Disease severity was mainly affected by FVL and not related to genotypes at the Prothrombin mutations. Overall, disease severity and development of thrombosis in COVID‐19 are mainly affected by the variation within the FVL gene. Possible FVL mutation should be investigated in COVID‐19 patients and appropriate treatment should be started earlier in FVL‐positive patients.
BACKGROUND: Zoledronic acid (zoledronate) is the most commonly used bisphosphonate derivative for the prevention of bone related complications in patients with multiple myeloma. Monthly given and yearly given long acting zoledronate are two different forms of zoledronate. Monthly given zoledronate is the novel agent accepted as the standard treatment for the prevention of multiple myeloma bone related complications. Yearly given long acting zoledronate has no data on the use of multiple myeloma bone disease prevention. AIM:Our primary goal is investigating the vertebral fracture protective effects of a long acting zoledronat agent(Aclasta®) in multiple myeloma patients with associated osteoporosis .We choose vertebrae as the target because bones with the most frequent fractures in multiple myeloma are the vertebrae. As a secondary goal ;we planned to evaluate in preventing fracture development in other bones. METHODS:Patients diagnosed with active multiple myeloma in the Sanlıurfa Mehmet Akif Inan Education and Research Hospital Hematology Clinic at year 2017 were evaluated. Patients fulfilled the inclusion criteria(men and women over the age of 18 and newly diagnosed patients with multiple myeloma,who have lomber vertebra( L1-L4 total or L2-L4) or total femur or femur neck measurements of "(-)1 or lower of any of the T-values" by bone mineral densitometry). Five pa tients were identified who fulfilled these criteria. Four of the patients were female and one patient was male,the age range was between 42 and 76 years.All patients received weekly VCD (bortezomib 1.3 mg /m2 cyclophosphamide 500 mg ,dexamethasone 20 mg) intravenously. During the first administration of chemotherapy , long acting zoledronat (Aclasta®),5 mg was administered with a half-hour intravenous infusion . Simultaneously with the first administration of long acting zolendronat(Aclasta®),600 mg elemental calcium and 400 U vitamin D3 were administered daily to the patients. At the first evaluation time point ,sixth month of treatment beginning ,MRI evaluation of the vertebral column was planned to undergo for all five patients.At the same time patients were questioned for complaints consistent with bone fractures before each chemotherapy session and patients with suspected fracture are planned to be evaluated with MRI. RESULTS: All patients were in complete remission at the end of the induction treatment.Two of the patients had autologous stem cell transplants.One patient had a tooth extraction before autologous bone marrow transplantation.Any jaw complications did not develop in this patient.None of the five patients developed myeloma-related bone complications ,neither vertebral nor other bones, at the sixth month of therapy.No adverse effects(electrolyte disorders ,albuminuria,etc.) were observed in patients during the administration and follow up period of the drug. CONCLUSION: It is universaly recommended to apply zoledronate once a month for intravenously at least two years in patients with myeloma. Before every application serum creatinine, serum electrolytes, serum calcium levels and every 3 months albuminuria should be evaluated . Zoledronates have side effects such as fatigue (30%), low blood pressure (11%) and nausea (29%) .Every month we need blood testing to detect electrolyte abnormalities before the therapy and follow up albuminüria as possible side effects of the drug.There is a risk of exposure to side effects every month too.But most important point is ease of application and the cost. Monthly treatment's cost is 1080 USD with it's cheapest generic (U.S market price).When we compare monthly zoledronate with the application of yearly long-acting zoledronate , patients will not have to live all the above-mentioned side effects ,necessity of laboratory evaluation every month, and the cost is only 350 USD with cheapest generic(U.S market price).Long-acting zoledronate is more advantageous considering factors such as cost, ease of administration and frequency of side effects. What is missing here is the large clinical efficacy studies. Our study is first study in the literature and the result are not inconclusive because patient group is very small.But at the same time, we are thinking that long acting zoledronate is a promising agent for preventing bone complications in multiple myeloma patients.So we are planning a phase 3 study to reevaluate our proposal in a larger patient group. Disclosures No relevant conflicts of interest to declare.
Background:Iron deficiency (ID), with or without anemia, represents a major global health problem afecting more than 2 billions people worldwide. Oral iron treatment always becomes the first choise for the treatment of iron deficiency. An other treatment option is parenteral iron therapy and generally is prefered for patients with oral iron treatment is not effective. But today there is a number of conditions where intravenous iron use is well‐established or increasingly considered as first‐option approach. All these developments in the parenteral iron area show strong probability of increasing use of parenteral iron drugs for anemic patients.Aims:We this case report we aim to share our clinical case in a rare situtionMethods:Case reportResults:Our patient is 36 years old female and she was diagnosed as iron deficiency anemia in an outpatient clinic. She was treated with ferric carboxymaltose. One month later she was reevaluated her for treatment response and her anemia was treated succesfully but her serum ferritin value was measured as 3500 ng/ml. It was found unusual and she was referred to our clinic for evaluation of hiperferritinemia. We evaluated the patient and no pathological findings were found other than skin brown discoloration. We measured patient's serum ferritin level again and ferritin level was high (3000 ng / ml) as one month before. When we investigated ferric carboxymaltose dose, we saw that in contrast to the ferric carboxymaltose recommended maximum 2000 mg dose for adult patients, it was administered to the patient at a total dose of 8000 mg in two months period as weekly 1000 mg dose.The patient underwent cardiac T2 ∗ magnetic resonance imaging (MRI), liver T2 ∗ MRI, brain MRI. The patient MRI showed significant increase iron in the liver and spleen, whereas increased iron accumulation in brain and heart was not detected with MRI.Deferasirox was started at a dose of 20 mg / kg / day. The ferritin level decreased to 1600 ng / mL from 3000 mg/mL level at the second treatment week with iron chelation therapy. Patient's skin color was not changed significantly. We decide to continue until the serum ferritin value decreases below 1000 ng/mL.6 months after deferasirox treatment ferritin levels go down step by step and reached to 700 ng/L level. We repeated liver T2 ∗ MRI and there is significant reduction in liver iron accumulation. And her skin discoloration was decreased.Summary/Conclusion:There is no literature data about overdose of ferric carboxymaltose case. We found only two postmarketing adverse case report of national pharmaceutical agencies. First case is a hypophosphatemic osteomalacia case resulted from 8000 mg ferric carboxymaltose usage in 4 month period. The second case is from in France. Ferric carboxymaltose,18000 mg total cumulative dose in six months is received and presented as movement disorder complication. It was reported that iron chelation therapy partially alleviates gait disturbance and relieves it from the dependency on the bed which emerged in the first period in this case. According to these data, first step in ferric carboxymaltose overdose cases;it should be aimed to prevent the development of neurological complications and bone complications. The best way of to prevent these complications can be done with rapid beginning iron chelation therapy. Our case is the first reported case in our country and third case report in the world.
Introduction: Cytomegalovirus (CMV) infection remains one of the most important complications after allogeneic hematopoietic stem cell transplantation (AlloHSCT). Preemptive therapy with oral VGC or intravenous ganciclovir has replaced universal prophylaxis. We investigated the effect of oral VGC as preemptive therapy on CMV reactivation or infection in AlloHSCT. Patient & Methods: We retrospectively studied 30 consecutive adult recipients of HLA-identical sibling allogeneic peripheral blood stem cell transplant from June 2011 through June 2014 to analyze the safety and efficacy of preemptive therapy for the treatment of CMV infection. Among 30 patients we studied the results of 13 patients with CMV DNA positivity. All 13 recipients and their donors were seropositive for CMV Ig G status. Their diagnosis of pretransplantation were as 8 acute myeloid leukemia (61 %) and 5 acute lymphocytic leukemia (39 %). Median age was 39 years (range 21-54). There were 9 men and 4 women (Table-1). The patients received no prophylaxis against CMV. Blood/serum samples from all patients were routinely monitored for CMV-DNA using PCR twice weekly. We iniciated pre-emptive therapy for CMV as the viral load was above and equal to 500 copies/ml in two consecutive samples. VGC was given twice daily 900 mg for 2 weeks, and maintened at a dose daily 900 mg until viral load is undetectable. Results: The PCR test was persistently negative in 17 patients (57 %) and positive at least once in 13 (43%)patients. All patients with CMV reactivations were on immunsupressive treatment. CMV infection was cleared in most patients within 2 weeks, but for those with stable or increasing CMV levels, the induction period was continued. Twelve patients were treated with oral VGC on an outpatient basis and they all became CMV negative after the first week of treatment. Only one patient received intravenous ganciclovir and he was also CMV negative after the first week of treatment. While no positivity was identified in any of the patients who received VGC on day 21, clinically unimportant low titer CMV positivity was noted in three of these patients. VGC was continued at same dose and no positivity was detected after 2-3 weeks. We were obligated interrupt VGC in only four patients for serious side effects namely neutropenia and thrombocytopenia. We did not observe CMV-related mortality. Conclusions: We concluded that VGC therapy could be safely used at outpatient clinics, with frequent monitorization to prevent severe myelotoxicity. In conclusion, based on our findings, oral VGC is effective and safe in the pre-emptive treatment of CMV disease following allo-HSCT. Therefore, preemptive strategy by oral VGC appears preferable to the prevention of CMV disease in alloHSCT with its advantage of effectiveness and usage in outpatient clinic condition. Table- 1: Management and outcome of the patient characteristics with CMV-reactivation Patients with CMV reactivation/Total number of patient 13/30 Median age, years (range) 39 (21-54) Gender Male Female 9 4 Diagnosis AML ALL 8 5 CMV serologic status Donor+/Recipient + 13 Preperative regimen Bu-Cy CY-TBI Flu/Amsc(FLAMSA) 8 4 1 GVHD propylaxis CSA+MTX CSA+MTX+MM 12 1 GVHD prior to CMV reactivation Acute chronic without GVHD 7 1 5 Prednisolone treatment at the time of starting VCG Yes No 8 5 IST at the time of starting VGC Yes No 13 0 Median duration of CMV reactivation (day) 44 (8-330) Viral load before antivial treament (copies/ml) 1153 (78-12800) Treatment VGC (900 mg, twice daily for induction) GC (5 mg/kg, twice daily for induction) VGC+GC 9 (70 %) 1 (7 %) 3 (23 %) Total treatment duration (day) 24 (10-51) CMV DNA at the end of the treatment Conversion to negative Persistently positive (low titer < 50 copies/ml) 10 (77 %) 3 (23 %) Serious side effects Interruption of therapy due to neutropenia Interruption of therapy due to thrombocytopenia Reactivation 3 (23 %) 1 (7 %) 2 (15 %) Abbreviations: AML: acute myeloid leukemia, ALL: acute lymphoblastic leukemia, CMV: cytomegalovirus,GVHD: graft-versus host disease, CSA: cylosporine, MTX: methotrexate, MMF: mycophenolate mofetil, PDN:prednizolone, IST: Immunosupressive treatment, VGC: valganciclovir, GC: ganciclovir, Bu: Busulfan, Cy: cylophosphamide, TBI: total body irradiation Disclosures No relevant conflicts of interest to declare.
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