Occurrence of a Clonal T-Cell Population in a Case of Chronic Myelomonocytic Leukemia

Chronic myelo-monocytic leukemia (CMML) is an aggressive myeloid neoplasm with some features of a myelodysplastic syndrome (MDS) and others of a myeloproliferative neoplasm (MPN). Rarely, patients with CMML have a co-existing lympho-proliferative disorder (LPD). In most cases, the lymphoid neoplasm is diagnosed first, and the CMML is considered to be a secondary therapy-induced form of leukemia. We report herein a unique case of de-novo CMML, with an underlying clonal T-cell population and describe its clinical presentation and laboratory findings. A 70-year old male presented with a 3-month history of cough, dsypnea, abdominal distension, and low-grade fever. Physical and radiological examination revealed hepatosplenomegaly but no lymphadenopathy. Peripheral blood had absolute monocytosis with marrow showing CMML with 10% blasts along with dysplasia in myeloid and erythroid lineages. Flow cytometry indicated possibility of chronic myelo-monocytic leukemia with 13% monocytic cells along with an additional clonal population of gamma/delta T cells (15%) with aberrant immunophenotype. Polymerase chain reaction (PCR) analysis was positive for clonal T-cell rearrangement. A diagnosis of CMML with an underlying clonal T-CLPD was made. The synchronous occurrence of CMML and T-cell neoplasm may be attributed to a genetic mutation common to both. Currently, there are no treatment guidelines for group of patients; hence individualized therapeutic strategies should be implemented to enable symptomatic improvement and provide optimum care.

A Clinical Triad with Fatal Implications: Recrudescent Diffuse Large B-cell Non-Hodgkin Lymphoma Presenting in the Leukemic Phase with an Elevated Serum Lactic Acid Level and Dysregulation of the TP53 Tumor Suppressor Gene – A Case Report and Literature Review

Despite representing 30% to 40% of newly diagnosed cases of adult non-Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL) rarely presents (1) in the leukemic phase (2) with dysregulation of the TP53 tumor suppressor gene and (3) an elevated serum lactic acid level. In this case report and literature review, we highlight this unfortunate triad of poor prognostic features associated with an aggressive and fatal clinical course in a 53-year-old man with recrudescent DLBCL. A leukemic presentation of de novo or relapsed DLBCL is rare and may be related to differential expressions of adhesion molecules on cell surfaces. In addition, TP53 gene mutations are present in approximately 20% to 25% of DLBCL cases and foreshadow worse clinical outcomes. Finally, an elevated serum lactic acid level in DLBCL that is not clearly associated with sepsis syndrome is a poor prognostic factor for survival and manifests as type B lactic acidosis through the Warburg effect.

Factors Involved in the Development of Inhibitory Antibodies in Patients with Hemophilia in Colombia: A Case-Control Study

Background: The appearance of inhibitory antibodies against antihemophilic factors is one of the most serious complications related to hemophilia. Objective: The objective of this study was to identify variables and factors related to the development of inhibitory antibodies in a group of patients undergoing antihemophilic therapy in Colombia. Methods: A case-control study in patients with hemophilia treated in Specialized Healthcare Provider Institutions (IPS-E) in 21 cities of Colombia of any age and with a diagnosis of inhibitory antibodies against factor VIII or IX during 2016. Four controls per case paired by age and type of hemophilia were used. Sociodemographic, clinical, and pharmacological variables were identified and analyzed. Results: Seventeen patients with inhibitory antibodies and 68 controls with hemophilia were identified. The mean age was 28.3 ± 17.8 years. A total of 94.1% had hemophilia A, and 88.2% of the cases and 50.0% of the controls had severe hemophilia; 47.1% of the cases and 54.4% of the controls were receiving prophylaxis with coagulation factors. Multivariate analysis showed that having severe hemophilia (OR:17.0, 95%CI:1.32–219.60) and lack of knowledge of the coagulation factor with which the patient was treated before entering the care program in the IPS-E (OR:8.9, 95%CI:1.82–43.75) were significantly associated with a higher probability of developing inhibitory antibodies. Conclusion and relevance: Coagulation factors associated with the development of inhibitory antibodies were severe hemophilia and lack of knowledge of the type of factor used prior to entering the follow-up cohort.

The Essential Thrombocythemia in 2020: What We Know and Where We Still Have to Dig Deep

The Essential Thrombocythemia is a Chronic Philadelphia-negative Myeloproliferative Neoplasm characterized by a survival curve that is only slightly worse than that of age- and sex-adjusted healthy population. The criteria for diagnosis were reviewed in 2016 by WHO. The incidence varies from 0.2 to 2.5:100 000 people per year, with a prevalence of 38 to 57 cases per 100 000 people. The main characteristics of ET are the marked thrombocytosis and the high frequency of thrombosis. The spectrum of symptoms is quite wide, but fatigue results to be the most frequent. Thrombosis is frequently observed, often occurring before or at the time of diagnosis. The classification of thrombotic risk has undergone several revisions. Recently, the revised-IPSET-t has distinguished 4 risk classes, from very low risk to high risk. Driver mutations seem to influence thrombotic risk and prognosis, while the role of sub-driver mutations still remains uncertain. Antiplatelet therapy is recommended in all patients aged ⩾ 60 years and in those with a positive history of thrombosis or with cardiovascular risk factors, while cytoreductive therapy with hydroxyurea or interferon is reserved for high-risk patients.

Autoimmune Hemolytic Anemia After Relapse of Chronic Myeloid Leukemia: A Case Report

Autoimmune hemolytic anemia is one of the differential diagnoses for anemia in patients with lymphoproliferative neoplasia, such as chronic lymphocytic leukemia, who experience sudden drop in hemoglobin. The association between autoimmune hemolytic anemia and chronic myeloid leukemia on the contrary is unusual. Here we present a patient with a background of chronic myeloid leukemia treated previously with Tyrosine Kinase Inhibitors, then developed autoimmune hemolysis simultaneously with chronic myeloid leukemia relapse. Hemolysis was treated with steroids with good response.

Diffuse Large B-Cell Lymphoma Relapsing in Leukaemic Phase Presenting as Acute Leukaemia

Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of the newly diagnosed adult non-Hodgkin lymphomas, but rarely presents in leukaemic phase. Here in, we report a case of DLBCL presenting in leukaemic phase and masquerading as acute leukaemia. A 28-year-old woman presented to our outpatient department with complaints of fever for 1 week. Her peripheral blood smear showed 5% to 8% blasts. Bone marrow aspirate showed an infiltration by ~30% blasts. Flow cytometry and immunohistochemistry confirmed relapse of DLBCL. Also, patient’s poor response to therapeutic regimen for DLBCL prompted to consider second differential diagnosis of acute leukaemia. This case is a learning case, as it emphasizes the combined role of diagnostic ancillary techniques along with clinical judgments for management. The case also makes us more vigilant towards the pathobiology of DLBCL and dynamics of personalized individual treatment response.

Effects of Serum Albumin Levels on Antithrombin Supplementation Outcomes Among Patients With Sepsis-Associated Coagulopathy: A Retrospective Study

Background:Severe sepsis is commonly associated with mortality among critically ill patients and is known to cause coagulopathy. While antithrombin is an anticoagulant used in this setting, serum albumin levels are known to influence serum antithrombin levels. Therefore, this study aimed to evaluate the outcomes of antithrombin supplementation in patients with sepsis-associated coagulopathy, as well as the relationship between serum albumin levels and the effects of antithrombin supplementation.Methods:This retrospective study evaluated patients who were >18 years of age and had been admitted to either of two intensive care units for sepsis-associated coagulopathy. The groups that did and did not receive antithrombin supplementation were compared for outcomes up to 1 year after admission. Subgroup analyses were performed for patients with serum albumin levels of <2.5 g/dL or ⩾2.5 g/dL.Results:Fifty-one patients received antithrombin supplementation and 163 patients did not. The Cox proportional hazards model revealed that antithrombin supplementation was independently associated with 28-day survival (hazard ratio [HR]: 0.374, P = 0.025) but not with 1 year survival (HR: 0.915, P = 0.752). In addition, among patients with serum albumin levels of <2.5 g/dL, antithrombin supplementation was associated with a significantly lower 28-day mortality rate (9.4% vs 36.8%, P = .009).Conclusion:Antithrombin supplementation may improve short-term survival, but not long-term survival, among patients with sepsis-associated coagulopathy.

Enoxaparin Dosing for Venous Thromboembolism Prophylaxis in Low Body Weight Patients

Background: The appropriate dose of enoxaparin for venous thromboembolism (VTE) prophylaxis in low body weight patients is unknown. Objective: The aim of this study is to evaluate the impact of enoxaparin dosing on major and minor bleeding events in low body weight patients. Methods: This was a retrospective cohort study of patients weighing less than 45 kg receiving subcutaneous (SC) enoxaparin for VTE prevention. The primary objective was to determine whether enoxaparin dose was associated with major and minor bleeding. The secondary objective was to determine the incidence of VTE by enoxaparin dose. Results: There were 173 patients included in the study, of which 37 patients received 2 different courses of enoxaparin during hospitalization, resulting in 210 enoxaparin courses. Among all enoxaparin courses, 16.2% were associated with major bleeding and 5.2% with minor bleeding. There was no difference in the incidence of major bleeding by dose (enoxaparin 30 mg SC daily, 30 mg SC twice daily, or 40 mg SC daily; P = .409). Patients who experienced major bleeding were older (54.9 ± 16.1 years) than patients who did not (48.4 ± 18.4 years) ( P = .043). There was no difference in the incidence of minor bleeding by dosing schedule ( P = .14). No patients experienced a VTE. Conclusion and Relevance: The risk of bleeding was similar by enoxaparin dose but increased with age in low body weight patients. Given the low incidence of VTE in this study, it is reasonable to consider decreasing the prophylactic enoxaparin dose in low body weight patients, especially in the elderly population.

Current Advance in Thrombopoietin Receptor Agonists in the Management of Thrombocytopenia Associated With Chronic Liver Disease: Focus on Avatrombopag

Chronic liver disease (CLD) is a condition that progresses over time toward advanced disease state which is known as liver cirrhosis. Liver cirrhosis leads to dangerous health problems among people living across the world. One such problem that observed in about 75% of cirrhotic patients is thrombocytopenia; which in turn associated with poor prognosis and recovery from CLD. Beyond these, thrombocytopenia in cirrhotic patients led to impairment of coagulation cascade and significantly influenced the utilization of effective mechanism in the management of CLD. By nature, treatment of CLD involves invasive diagnostic and treatment procedures; therefore, in the presence of thrombocytopenia implementing these methods put the lives of patients in a critical health problem due to increased risk of bleeding and mortality. Because of these reasons, prophylactic transfusion of platelets is considered to be one of the most effective options that reduce the risk of bleeding in patients with CLD that required to undergo an invasive procedure. Although platelet transfusion presented with significant advantages in facilitating the invasive procedure in patients with CLD, refractoriness with repeated use and various problems associated with its transfusion limit the continuous utilization of this important option. With these challenges and current advance in the knowledge of thrombopoiesis, the development of relatively safe and alternative drugs that enhance the production of platelets by interacting with thrombopoietin receptor agonists provides a promising option to platelet transfusion. The discovery and approval of romiplostim and eltrombopag in August 2008 and November 2008, respectively, for the treatment of chronic immune thrombocytopenia paved a way and followed by the Food and Drug Administration (FDA) approval of 2 potentially advantageous drugs, lusutrombopag, and avatrombopag, in 2018 for the treatment of thrombocytopenia in patients with CLD that required to undergo elective surgery. Therefore, this review aims to assess pathogenesis of thrombocytopenia and its challenges in the management of liver-related issues and, more importantly, gives emphasis to address the potential use of avatrombopag in the treatment of thrombocytopenia underlying CLD, its pharmacokinetics and pharmacodynamics, as well as its toxicological profiles by presenting the most commonly reported adverse events in various trials.

Routine Preoperative Coagulation Tests in Children Undergoing Elective Surgery or Invasive Procedures: Are They Still Necessary?

Introduction: Preoperative coagulation screening tests in pediatric patients was once routine clinical practice globally and still used as standard practice in some countries before surgical procedures to assess of perioperative bleeding risk. Objective: The study aimed to evaluate unselected routine preoperative coagulation testing in children undergoing elective or invasive surgery to predict abnormal perioperative bleeding. The study also aimed to provide a rational approach of determining bleeding and family history of coagulation disorders as a predictive risk for bleeding. Methods: This retrospective study conducted between 2014 and 2015 (1 year) on normal healthy children aged under 15 years admitted to the hospitals for elective mild to intermediate surgery or invasive procedures. We reviewed and collected the details of the clinical history, previous surgery, trauma, family history, detail of anti-thrombotic medication and coagulation tests performed (prothrombin time (PT), the activated partial prothrombin time (APTT), and international normalized ratio (INR)) at the time of admission. Results: Among 2078 cases, 1940 cases had normal coagulation tests (93.4%), 77 cases had abnormal coagulation results (3.7%), and 61 patients underwent surgery without preoperative coagulation screening (2.9%). In 15 of 77 patients, coagulation tests were normal on repeat testing. A total of 52 were confirmed to have abnormal screening testing. Among these 52 cases, 45 had normal factors assay; where seven patients had abnormal factors assay. Postoperative bleeding occurred only in three cases (0.14%), two cases due to surgical procedures with normal preoperative testing and one due to hemophilia A which was detected postoperatively as no preoperative testing was performed. Conclusions: Routine coagulation screening before surgery or invasive procedures to predict perioperative bleeding in unselected patients is not recommended. Our study emphasizes that selective preoperative testing is more appropriate. Selective criteria for consideration of the latter includes physical examination, type of surgery, family and bleeding history, and concomitant use of antiplatelet and anti-thrombotic therapy.