American journal of blood research最新文献

There are new targets identified by experimental and animal research for treatment of SARS-COV-2 (Severe acute respiratory syndrome-Corona Virus-2) infection. Out of many clinical trials registered, there are ongoing human studies highlighting Sofosbuvir's possible role in the treatment of Covid-19 (Coronavirus Disease 2019). Here we present a case of acute leukemia on directly acting antiviral therapy (DAAs) for HCV infection mitigating SARS-COV-2 infection in a patient undergoing chemotherapy. The child was undergoing chemotherapy, along with directly acting antiviral for acute hepatitis C infection. He initially had features of hypoxia and radiological evidence of covid-19. He had an uneventful course and tested negative ten days after onset of illness. With ongoing trials on Sofosbuvir in covid 19 treatment, our finding, albeit coincidental, points to the possible role even in immune-compromised children.

Both elderly acute myeloid leukemia (AML) patients and those with baseline infections, when treated with intensive chemotherapy, are associated with high induction mortality. We report 24 patients (16-newly-diagnosed, 8-relapsed/refractory) with AML deemed unfit for intensive chemotherapy (by virtue of age >60 years, ECOG-PS 3-4, or those with non-resolving infections at baseline), treated with azacytidine-venetoclax combination as induction chemotherapy. Median follow-up of the study group was 8 months. The overall complete remission (CR)+CR with incomplete count recovery (CRi) rate was 58.3%. 1-year progression-free survival and overall survival of the whole cohort was 44.4% and 55.8%, respectively. On subgroup analysis, newly-diagnosed AML (p=0.05), intermediate-risk cytogenetics (p=0.007), and HMA-naïve (p=0.05) patients had a significantly better outcome. AML patients with baseline infections (versus without infections) treated with azacytidine-venetoclax induction, have lesser induction mortality (compared with historic intensive chemotherapy) with equivalent response rates. A detailed analysis amongst cohorts with different venetoclax durations revealed that, shorter duration (<21 days) venetoclax (versus 21-28 days duration) in induction therapy leads to similar response rates and similar severity of myelosuppression, however, with early count recovery and lesser duration of intravenous antibiotics.

Introduction: In acute myeloid leukemia (AML), a heterogeneous group of leukemias, there are various factors to determine prognosis. Among these prognostic factors, cytogenetic results are increasing in importance day by day. FLT3 mutations are among the most common molecular abnormalities in AML, patients with recurrent or refractory (R/R) AML with this mutation have a low response rate to salvage therapy. Gilteritinib has activity against FLT3, ALK and AXL. This article shall present two cases, for which Gilteritinib was used, a new FLT3 inhibitor, and the results of the treatment. Case 1: A 52-year-old female patient presented to the emergency clinic with weakness and fever. In initial biochemical analysis, leukocyte was 104000/mm³. Peripheral smear contained diffuse myeloid blastoid cells, peripheral blood flow cytometry also supported the AML M0-1 phenotype. The bone marrow biopsy aspiration performed on the 14^th day of induction "3+7" treatment, contained diffuse blastic infiltrate and supported refractory disease. In addition to the FLAG-IDA salvage regimen, 120 mg/day Gilteritinib was also started. Bone marrow aspiration performed on the 28^th day of salvage therapy was compatible with remission. Case 2: 53 years old male patient with also no comorbidity other than known hypertension. In the initial biochemical analysis of the patient, leukocyte was 156000/mm³, platelet 58000/mm³ and hemoglobin 7.6 g/dl. Peripheral blood flow cytometry supported the AML M5 phenotype, whose peripheral smear showed diffuse monoblastoid cells. On the 14^th day of the patient's 3+7 induction treatment, the control bone marrow aspiration showed diffuse blast infiltration and was considered refractory, FLAG-IDA salvage therapy with again 120 mg/day Gilteritinib per oral were started. On the 28^th day, control bone marrow aspiration was evaluated as remission.

Discussion and conclusion: Unlike other FLT 3 inhibitors, Gilteritinib has been shown to be a highly effective agent in R/R AML with FLT3 mutations. Being the first data to be reported from Turkey, we think it would be quite guiding the titular.

Background: Procoagulant profile of 2019-nCoV/SARS-CoV-2 has been well documented over the last year. Perturbance in coagulating factors has also been reported in Covid-19 patients, including increased d-dimers and reports of lupus anticoagulant (LA).

Methods: The current study aimed to identify the incidence of positivity of lupus anticoagulant in Covid-19 patients and analyze the association between LA and D-dimer in predicting thrombosis and mortality in one-hundred and five hospitalized adult (age >14 years) patients and forty-three hospitalized pediatric (age <14 years) patients with a confirmed diagnosis of Covid-19 between June 2020 and September 2020.

Results: Twenty-one (20%) adult patients were tested positive for PTT LA, of which nine (8.6%) turned out to be confirmed positive for LA through StaClot and DRVVT Ratio tests. Six (14%) pediatric patients were positive for PTT LA, and only one (2.3%) had positive StaClot. Median D-dimer at admission was positively correlated with age and CRP among adult patients and was significantly higher in expired cases (P=0.001). No association between any of the coagulation tests and thrombosis or mortality was observed in the pediatric cohort.

Conclusion: We report an increased incidence of LA in Covid-19 patients, yet we didn't find any association between thrombotic events or mortality, probably due to the small sample size.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to its name, it is a multisystemic disease and various symptoms other than hemoglobinuria could be occurred. It could be life threatening especially because of thromboembolic events. In the last decade, a terminal complement inhibition with eculizumab approved with promising results for PNH patients. We conducted this study to evaluate the long term experience of eculizumab therapy from Turkey for the first time. Our cohort included 138 patients with PNH treated with eculizumab between January 2008 and December 2018 at 28 centers in Turkey. Laboratory and clinical findings at the time of diagnosis and after eculizumab therapy were recorded retrospectively. The median age was 39 (range 18-84) years and median granulocyte PNH clone size was 74% (range 3.06-99.84%) at the time of diagnosis. PNH with bone marrow failure syndrome was detected in 49 patients and the rest of 89 patients had classical PNH. Overall 45 patients (32.6%) had a history of any prior thrombotic event before eculizumab therapy and only 2 thrombotic events were reported during the study period. Most common symptoms are fatigue (75.3%), hemoglobinuria (18.1%), abdominal pain (15.2%) and dysphagia (7.9%). Although PNH is commonly related with coombs negativity, we detected coombs positivity in 2.17% of patients. Seven months after the therapy, increased hemoglobin level was seen and remarkably improvement of lactate dehydrogenase level during the treatment was occurred. In addition to previous studies, our real life data support that eculizumab is well tolerated with no serious adverse events and improves the PNH related findings.

Hyperhomocysteinemia is linked to TMA-related clinical symptoms such as apparent thromboembolism, microangiopathic hemolytic anemia (MAHA), and various types of end-organ damage due to microvascular thrombi; this is because high plasma levels of homocysteine impair the vascular endothelium. However, the association between hyperhomocysteinemia and pulmonary involvement is unclear. Here, we describe a 63-year-old male who was hospitalized with respiratory failure and MAHA with MDS-like features in the bone marrow. Plasma homocysteine levels were elevated significantly with 199.4 µmol/L (reference: 6.3-18.9) due to a homozygous (T/T) polymorphism for the 677C>T mutation within the MTHFR gene associated with chronic alcoholism-induced folate deficiency. Pulmonary lesions showed ground-glass opacity and there was pleural effusion. The patient was managed successfully with a combination of folate/mecobalamin supplementation, plasma exchange, and a methylprednisolone pulse, followed by oral prednisolone. Clinical symptoms, lung disease, MAHA, and bone marrow abnormalities improved as plasma homocysteine levels normalized.

Introduction: Transfusion is commonly done in clinical indications and complications arising due to Anemia, shock, blood loss, thrombocytopenia due to any cause, ineffective erythropoiesis. Pregnancy is a physiological condition characterized by Anemia, fluid overload, hypercoagulable state, and antifibrinolytic condition, which can cause various reactions that could be anticipated during a blood transfusion. With an aim to understand the effects of transfusions on hematological parameters in pregnancy. The results of whole blood and component transfusion were studied to understand increments and their effects so that rationalized transfusion decisions during pregnancy can be undertaken, considering the physiological changes in pregnancy on hemodynamics are present.

Methodology: A prospective study with 80 pregnant females undergoing blood transfusion was studied. Their coagulation and hematological profile were correlated to derive a conclusion for the effect of transfusion of blood and its products.

Results: A mean increment of 0.55+0.07 g/dL hemoglobin (Hb) was noted along with a slight increase in RBC count (0.25+0.07 millions/mm³), hematocrit (HCT) (1.9+0.42%), TLC (400+565 cells/mm³). This statistically significant mean increase in hemoglobin, RBC count, and hematocrit was significantly lower than that compared to studies in the west and non-anemic patients. A mean increment of 7.79+1.51 µg/dL (statistically significant) in serum iron was seen. A significant improvement in their coagulation profile was achieved by plasma transfusion (FFP). Clotting time (CT) decreased by a mean value of 196.43+56.69 secs and prothrombin time (PT) by 2.64+0.63 secs (P<0.05). All transfusion reactions in our study were associated with PRBC transfusion, non-hemolytic immunological type, urticarial transfusion reactions (UTR) more common in multiparous women-0.2% in primigravida to 21.7% and 37.5% in 3rd and 4th parity similar to that observed in other studies.

Conclusion: Although different researchers have done numerous studies, the physiological profile of pregnant females in India is markedly different in nutritional profile, ethnicity, environmental factors, and background. The availability of tertiary care medical facilities during ANCs is also known to affect pregnancy outcomes and the presentation of patients at term or in labor. The variety of factors affect the baseline hematological status of pregnant females and, hence, post-transfusion hematological factors. These are therefore markedly different from prior published studies. It is concluded that PRBC transfusion in pregnant women causes a lower increase in mean Hb and HCT values than in the west, and ferritin and serum iron are not reliable indicators of Anemia in transfusion. Due to lower increments in all values except platelets could be the reason for this could be contributed by confo

Background: Immune thrombocytopenia (ITP) is a benign hematological disorder characterized by low platelet counts in peripheral blood and spectrum of various bleeding manifestations. Azathioprine is one of the effective, readily available, and affordable immunosupressants available for ITP management in developing countries. We aimed to study the efficacy and long-term safety profile of our patients with ITP who were treated with azathioprine.

Method: This was a retrospective, single-center study conducted at a tertiary care hospital in Northern India. The patients who had received at least one line of therapy before receiving azathioprine were included in this study. All patients received oral azathioprine at a dose of 1 mg/kg/day (50 mg or 100 mg tablet formulations were used), which was increased up to 2 mg/kg/day depending upon the response and adverse effects.

Result: Sixty-three patients were analyzed. Their median age was 28 years (range 15-68); 29/63 patients (46.03%) were females. The median duration from diagnosis to azathioprine initiation was 539 days (323 days-980.5 days). The patients included in the study had received a median of 3 (range 1-6) prior lines of therapies; 38/63 patients (60.32%) had received ≥3 prior therapies. Six patients (9.5%) had relapsed after splenectomy, and 16 patients (25.4%) had relapsed after receiving rituximab. The mean baseline platelet count was 10000/μL. The median time to response was 95 days (90 days-not reached) and the cumulative overall response rate (complete and partial response) at day 90 was 38.1%. Only one patient achieved complete response with azathioprine in our study. The cumulative rate of relapse at five years was 21.2%. Twenty-six patients stopped azathioprine after achieving some response (CR/PR) with Azathioprine for a median duration of 1067.5 days (range: 236 days-2465 days). They were followed up for a median of 870 days (range: 392 days-1928 days), and twelve of them relapsed. Twenty-six patients (26/63, 41.27%) reported one or more adverse events while on azathioprine. Leucopenia was the most frequent adverse event, followed by anemia and hepatobiliary laboratory abnormalities. Serious adverse events (grade ≥3 CTCAEv4) were noted in three patients (4.7%). One patient succumbed to severe sepsis multiorgan dysfunction while being on treatment.

Conclusion: We conclude that azathioprine has a good response rate in chronic ITP patients. It is well-tolerated with minimal and manageable side effects.

Venous thromboembolism (VTE) is a multifactorial disease that results from the interaction of both inherited and acquired risk factors. The complications of these risk factors often lead to significant morbidity and mortality. There are many inherited thrombophilia risk factors, such as factor V Leiden (FVL) and prothrombin gene mutation (PT). The prevalence of these mutations varies among geographical locations and ethnic groups.

Objectives: This is a retrospective analysis of laboratory data aimed to estimate the laboratory-based frequency of FVL and PT mutations and assess the concordance between the coagulation assay and FVL molecular test.

Methods: The study reviewed the frequency of positive blood samples tested by molecular and functional-based techniques. The demographic and laboratory data of patients tested in molecular and coagulation laboratories at the Institute for Thrombophilia were reviewed and analyzed.

Results: A total of 1524 samples were tested for FVL, 1023 for PT, and 1057 for APCR. Results showed that 90 (5.9%) patients were positive for FVL, 30 (2.93%) for PT mutations, and 95 (8.99%) had low APCR, while 38 (3.69%) patients had low APCR with no FVL mutation.

Conclusion: This study reports high positive results among patients tested as part of thrombophilia workup or screening for other clinical conditions associated with the increased risk of thrombosis. The limitation of this study was that it had minimal clinical correlation because the data were collected retrospectively from laboratory records.

T cell large granular lymphocytic (T-LGL) leukemia is a rare type of mature T cell neoplasm. The typical features of T-LGL leukemia include an increased number of large granular lymphocytes in the peripheral blood, cytopenia (most commonly neutropenia), and mild-to-moderate splenomegaly. Up to 28% of patients with T-LGL leukemia have rheumatoid arthritis (RA). This study reports ten atypical cases (seven women and three men, median age 60.5 years) of RA-associated T-LGL leukemia presenting with lymphopenia, severe neutropenia, and marked splenomegaly. The weight of the spleens ranged from 892 to 2100 g (median 1100 g). Bone marrow histology and differential counts of bone marrow aspirates revealed no peculiarities in nine of ten cases. The red pulp of the spleen was expanded and showed moderate to strong infiltration by medium-sized slightly pleomorphic lymphocytes in nine cases and subtle infiltration in one. Although lymphocytic infiltration involved both cords and sinusoids, it was more apparent within the splenic cords. The white pulp was preserved and contained prominent germinal centers in eight patients and was atrophic in two patients. Immunohistochemically, malignant lymphocytes were CD3+, CD43+, and CD4- in all cases and TIA-1+ in nine out of ten. TCRαβ positivity and TCRγδ positivity was observed in six and four cases out of ten, respectively. All ten patients had T cell clonality in the spleen tissue, but in three cases it was absent in both blood and bone marrow. STAT3 mutations in the spleen tissue were detected in three of ten cases. In all eight cases studied, neither isochromosome 7q nor trisomy 8 was detected in the spleen tissue. Cases of RA-associated T-LGL leukemia with low LGL count in the peripheral blood, neutropenia, and marked splenomegaly present a diagnostic challenge and can be misdiagnosed as Felty's syndrome or hepatosplenic T cell lymphoma.