Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening microangiopathy usually characterized by microangiopathic hemolytic anemic, thrombocytopenia, and end-organ ischemia associated with disseminated microvascular platelet-rich thrombi and severe deficiency (activity <10%) of A Disintegrin-like And Metalloprotease with ThromboSpondin Type 1 Motif No. 13 (ADAMTS13). It is a medical emergency, and if left untreated, acute mortality is as high as 90%. This review article is a narrative review based on available literature. In addition, the key discussions of the Kingdom of Saudi Arabia experts and members of “Approaches to aTTP Management” Advisory Board meeting held on October 16, 2020, have been incorporated as expert opinions. It was agreed that treatment should be started based on the presumptive diagnosis and continued until remission or an alternate diagnosis is established. Use of caplacizumab in addition to therapeutic plasma exchange and immunosuppression is recommended in confirmed aTTP episodes.

BACKGROUND: Tumor lysis syndrome (TLS) is a common complication of hematological malignancies and consists of either hyperkalemia, hyperphosphatemia, hyperuricemia, or hypocalcemia. These metabolic derangements may result in clinical tumor lysis syndrome in the form of acute kidney injury (AKI), arrhythmias, seizures, and sudden death. OBJECTIVES: This study was conducted to determine the incidence and outcome of TLS and to identify local risk factors in children with hematological malignancies. PATIENTS AND METHODS: This was a retrospective chart review of children ≤18 years diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia, or non-Hodgkin lymphoma between 2014 and 2018. TLS was diagnosed and stratified according to the risk of developing tumor lysis using the Cairo and Bishop definition and Cairo stratification. RESULTS: Among 180 patients, only 11 patients (6%) developed TLS. Four patients had laboratory TLS (LTLS) (36.3%) and six had CLTS (54.5%). The male-to-female ratio was high (2.4:1 in the TLS group). Hyperphosphatemia and hypocalcemia were the most frequently occurring criteria for LTLS (81.8%). The strongest predictors for TLS were hyperuricemia and hypocalcemia at presentation (P < 0.001) followed by diagnosis of T-cell ALL, preceding AKI splenomegaly, high initial white blood cell, and lactate dehydrogenase, with P < 0.05. AKI secondary to tumor lysis occurred in six patients (54.5%), of which five needed dialysis. One patient had seizures secondary to tumor lysis (9.1%) and no patient died from TLS. CONCLUSION: There is a wide variation in reported incidence of TLS from 6% to 45%, likely due to different TLS definitions applied, diverse cohorts and duration. A universal definition and risk-stratified approach to prevent tumor lysis in patients with hematologic malignancies is needed to help in proper comparison between studies.

CONTEXT: Tyrosine kinase inhibitors (TKIs) are the standard of care therapy for chronic myeloid leukemia (CML). The current disadvantages of lifelong treatment include adverse effects and financial burden. AIMS: This study aimed to evaluate the outcomes of treatment-free remission (TFR) in CML patients. SETTINGS AND DESIGN: A retrospective cohort study was conducted in our oncology center. SUBJECTS AND METHODS: Patients ≥18 years old diagnosed with CML, received TKI and had a TFR trial to achieve TFR, with at least 6 months follow-up, and who received TKIs were included. Patients with a previous hematopoietic stem cell transplantation were excluded. The primary outcome was the proportion of patients with sustainable TFR at 6 months. The secondary outcomes were the proportion of patients with sustainable TFR at 12 months, the rate of regaining a major molecular response (MMR) after relapse, and the cost-saving impact. Descriptive statistics were used for the demographics and outcomes. RESULTS: A total of 250 patients were screened for eligibility, 25 patients were enrolled. The median age was 54 years (interquartile range: 45.5–59), 60% were female. TFR was 92% at 6 months and 72% at 12 months. 100% of the patients regained MMR. The total number of TFR days were 17,024 which resulted in a direct cost saving of SR 7,205,601.9, based on Saudi FDA pricing. CONCLUSIONS: The study indicated that the majority of the CML patients achieved 6 months TFR. This initiative has resulted in a significant cost saving. Future studies should characterize potential candidates for TKI discontinuation.

BACKGROUND: The Sysmex XN-series hematology analyzers provide newer parameters including high fluorescence lymphocyte cell percentage (HFLC%) which correlates with the presence of atypical lymphocytes in peripheral blood. We aimed to analyze the sensitivity and specificity of HFLC% as a diagnostic tool and its association with serological status in diagnosed dengue patients and thereby establish a cutoff of HFLC% based on serology. Besides, we also wish to correlate HFLC% with thrombocytopenia in these patients. MATERIALS AND METHODS: A total of 1500 serum samples were subjected to serological evaluation for dengue. After excluding hematological malignancies and autoimmune disorders, the same day complete blood count parameters including HFLC% and platelet counts were collected retrospectively for 292 serologically positive dengue cases and 76 seronegative controls. RESULTS: Our result shows that in nonstructural 1 antigen-positive cases, a cutoff of >5.2% HFLC can have a sensitivity of 79.5% and specificity of 98.6%. We found a different cut off of HFLC% >3.2% (sensitivity 83.4%, specificity 98.6%) for the cases with only immunoglobulin M positivity and a cut off of HFLC% >2.6% (sensitivity 86.1%, specificity 96%) in the dual positive cases (immunoglobulin M with nonstructural 1 antigen). Besides, high HFLC% also shows a strong correlation with platelet count with a Spearman correlation coefficient of −0.6. CONCLUSIONS: The result of our study shows that a specific cutoff of HFLC% can not only help us to suspect dengue fever but also predict the risk of thrombocytopenia in already diagnosed dengue patients. The sensitivity and specificity of HFLC% varied with the serological status of the patients which depend on the days of fever on presentation.

BACKGROUND: Systemic infections are one of several risk factors leading to the development of inflammation and venous thromboembolism (VTE) formation. This study aimed to assess the risk factors associated with the development of VTE in patients admitted to the intensive care unit (ICU). MATERIALS AND METHODS: A retrospective-matched case − control study of patients with VTE in the period between January 1, 2018, and December 31, 2019. We included all adult patients who stayed more than 2 days in ICU before the development of VTE. RESULTS: Univariate and multivariate analyses uncovered three of six factors to have significant influence in the development of VTE in ICU patients: Carbapenem-resistant Enterobactereaceae (CRE) infections (odds ratio [OR] 2.95, 95% confidence interval (CI) 1.21–7.33, P = 0.010), length of ICU stay (OR 1.02, 95% CI 1.01–1.04, P = 0.011), and the sequential organ failure assessment score (OR 1.10, 95% CI 1.01–1.20, P = 0.031); all were found to be independent risk factors in the development of VTE. CONCLUSION: Our findings suggest that, CRE infection is a strong trigger to the development of VTE in patients admitted to the ICU, and draw the attention of the treating clinicians to prioritize these infections in the management protocols to control infection-driven VTE in ICU patients.

BACKGROUND: In Saudi Arabia (KSA) and the United Arab Emirates (UAE), only limited epidemiological data and treatment guidance exist for acquired thrombotic thrombocytopenic purpura (aTTP), a rare, life-threatening blood disorder. AIMS: Expert insights from KSA and UAE were used to obtain local epidemiological data, to characterize current disease management and unmet needs, and to formulate recommendations for the improvement of the diagnosis and treatment of aTTP. Costs and socioeconomic burden were a secondary focus. METHODS: Hematologists from KSA and UAE with clinical experience in the diagnosis and management of aTTP individually answered questions on the burden and management of aTTP via an online survey. Based on these insights, a draft consensus was discussed and refined jointly by the hematologists in a live session for each country. Payers provided information on the economic burden and cost of aTTP management. RESULTS: The experts estimate the incidence of aTTP to 5–6 (KSA) and 1–2 (UAE) per 1,000,000 person-years and anticipate it increasing. Most of the presenting patients are aTTP-naive. Recurrent disease is rare. Diagnosis of aTTP should involve ADAMTS13 activity testing. Plasma exchange and immunosuppression are the current standard of care. Key unmet needs include a lack of awareness of aTTP, access to rapid testing and novel treatments to improve outcomes. CONCLUSION: The expert consensus to address the unmet needs and improve aTTP outcomes include increasing aTTP awareness and access to ADAMTS13 testing; the development of national guidelines; and, additionally, strategies to improve patients' long-term quality of life.

Cold agglutinin disease (CAD) is a distinct type of acquired immune hemolytic anemia. It can be idiopathic (primary) or secondary to infections, neoplasms and autoimmune diseases. Mycoplasma pneumonia and EBV are the infections commonly associated with secondary CAD. In the current COVID-19 pandemic, there are very few case reports showing an association between CAD and COVID-19.

We describe two male patients with unique mutation of the CD40L gene, unlike the classic presentation of X-linked hyper immunoglobulin M immunodeficiency syndrome (XHIGM syndrome), both were healthy until presenting in their early twenties with a challenging symptomatic transfusion-dependent anemia, investigations confirmed XHIGM syndrome with concurrent chronic parvovirus infection.