Thromboelastography-Guided versus Standard-of-Care or On-Demand Platelet Transfusion in Patients with Cirrhosis and Thrombocytopenia Undergoing Procedures: A Randomized Controlled Trial.

PURPOSE: To determine the rate of platelet transfusion in patients with cirrhosis and severe thrombocytopenia (platelet counts <50 × 109/L) undergoing high-risk invasive procedures when prescribed by thromboelastography (TEG) compared with empirical and on-demand transfusion strategies. MATERIALS AND METHODS: This was a single-center, single-blinded, randomized controlled trial. Patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures were randomized into 3 groups: TEG group, transfusions based on TEG parameters; standard of care (SOC) group, 3 units of random donor platelets before procedure; and on-demand group, transfusions based on procedural adverse events/clinician's discretion. The primary outcome was periprocedural platelet transfusion in each arm. RESULTS: Eighty-seven patients were randomized (29 in each group) with no significant differences in demographics/coagulation profile/procedures. The median platelet count was 33 × 109/L (interquartile range, 26-43 × 109/L). Percutaneous liver biopsy was the most common procedure (46, 52.9%). Significantly lower number of patients in the TEG group received platelets (4 cases, 13.8%; 95% CI, 3.9-31.7) compared with SOC group (100%; 95% CI, 88.1-100; P < .001). Four patients in the on-demand group received platelets (13.8%; 95% CI, 3.9-31.7). Minor (World Health Organization [WHO] Grade 2) procedure-related bleeding occurred in 3 (10%; 95% CI, 2.2-27.4) patients in the TEG-guided transfusion group compared with 1 (3.4%; 95% CI, 0.1-17.8) patient each in the SOC and on-demand groups (P = .43), although the study was not powered for comparison of bleeding rates. No bleeding-related mortality was observed in any of the 3 groups. CONCLUSIONS: TEG-prescribed transfusion reduced prophylactic transfusions in patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures.

Auer rods and faggot cells: A review of the history, significance and mimics of two morphological curiosities of enduring relevance.

Myeloid differentiation in blasts is distinguished by the presence of one or more needle-shaped crystalline structures called Auer rods. Auer rods manifest either alone or as faggot cells (containing bundles of Auer rods) in various types of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Their presence largely portends a better prognosis in AML (as markers of maturation/differentiation) and upstages cases of MDS and MDS/MPN. Observation of these rods in residual blasts in treated cases of AML indicates an absence of remission. This article traces their historical discovery and examines their pathogenetic intricacies, as well as our current understanding of their relevance in myeloid neoplasms. Studies evaluating their prognostic impact in AML and MDS are catalogued. We also discuss a variety of other hematological and non-hematological neoplasms where structures potentially mistakable for Auer rods have been described. Even as the diagnostic approach to hematological malignancies has evolved from a morphology + cytochemistry + immunophenotyping-dependent one in the last century to a predominantly molecular genetics-based classification currently, and even as high-throughput sequencing and structural variation detection techniques surpass morphology in detecting clinically-relevant sub-categories of similar-appearing tumours, we review these curious microscopic structures that have withstood the test of time with respect to their diagnostic relevance.

Trisomy 21, transposition of the great arteries and abnormal myelopoiesis.

Down syndrome is a well-recognised genetic condition associated with several comorbidities. Although CHD is common in Down syndrome, transposition of the great arteries is exceptionally rare. We describe a neonate with Down syndrome who presented with transient abnormal myelopoiesis and transposition of the great arteries. Down syndrome may accelerate pulmonary hypertension in transposition of the great arteries and is associated with poor outcomes.

Anemia and its association with glycemia and transaminitis in patients with type 2 diabetes mellitus: A cross-sectional pilot study.

Background and Aims: Anemia impairs glucose homeostasis, affects glycemic control, and predisposes to complications in diabetics. It correlates with oxidative stress and increases the risk of developing microvascular and macrovascular complications. However, it is an underrecognized comorbidity in diabetics. This study was conducted to assess the prevalence of anemia in diabetic patients and compare the metabolic profiles of anemic and non-anemic diabetics. Methods: This is a cross-sectional study, conducted among type 2 diabetes (T2DM) patients, at the outpatient clinic. Patients with chronic kidney disease (CKD), known hematological disorders, and chronic inflammatory disorders were excluded. Results: Of the 97 patients, 37 (38.14%) were found to be anemic (hemoglobin (Hb): male <13 g/dl, female <12 g/dl). The mean values of fasting blood sugar (FBS) in low and normal mean corpuscular volume (MCV) patients were 265.9 ± 43.7 mg/dl and 157.2 ± 7.2 mg/dl, respectively (P = 0.0026), and those of postprandial blood sugar (PPBS) were 370.3 ± 58.4 mg/dl and 226.3 ± 10.1 mg/dl, respectively (P = 0.0015). It was found that 6 (22.2%) of 27 patients with raised alanine aminotransferase (ALT) had anemia against 27 (45.8%) of 59 patients with normal ALT (P = 0.03). The mean Hb levels in patients with raised and normal ALT were 13.31 ± 2.3 gm% and 12.2 ± 2.0 gm% (P = 0.03), respectively. Conclusions: Blood sugar may have a direct relationship with MCV in T2DM patients. Hb tends to relate to hepatic enzymes likely due to altered dietary patterns in anemics. Further larger studies on the effect of iron supplementation and dietary habits on glycemic control and hepatic steatosis are warranted.

Topical Diclofenac for Prevention of Capecitabine-Associated Hand-Foot Syndrome: A Double-Blind Randomized Controlled Trial.

PURPOSE: Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the underlying associated inflammation. However, systemic side effects of celecoxib have limited routine prescription. Topical diclofenac inhibits COX-2 locally with minimal risk of systemic adverse events. Therefore, we conducted this study to assess the efficacy of topical diclofenac in the prevention of capecitabine-induced HFS. METHODS: In this single-site phase III randomized double-blind trial, we enrolled patients with breast or GI cancer who were planned to receive capecitabine-based treatment. Participants were randomly assigned in a 1:1 ratio to receive topical diclofenac or placebo gel for 12 weeks or until the development of HFS, whichever occurred earlier. The primary end point was the incidence of grade 2 or 3 HFS (Common Terminology Criteria for Adverse Events version 5), which was compared between the two groups using simple logistic regression. RESULTS: In total, 264 patients were randomly assigned to receive topical diclofenac gel (n = 131) or placebo (n = 133). Grade 2 or 3 HFS was observed in 3.8% of participants in the diclofenac group compared with 15.0% in the placebo group (absolute difference, 11.2%; 95% CI, 4.3 to 18.1; P = .003). Grade 1-3 HFS was lower in the diclofenac group than in the placebo group (6.1% v 18.1%; absolute risk difference, 11.9%; 95% CI, 4.1 to 19.6). Capecitabine dose reductions because of HFS were less frequent in the diclofenac group (3.8%) than in the placebo group (13.5%; absolute risk difference, 9.7%; 95% CI, 3.0 to 16.4). CONCLUSION: Topical diclofenac prevented HFS in patients receiving capecitabine. This trial supports the use of topical diclofenac to prevent capecitabine-associated HFS.

Evaluation of Citrated Plasma After Thawing for Routine Coagulation Testing.

OBJECTIVE: We aim to find the time in which a thawed citrate plasma sample that was preserved can be analyzed for routine coagulation testing without losing precision. METHODS: Whole blood samples from 30 healthy volunteers were collected in 3.2% sodium citrate vacutainer and centrifuged to separate platelet-poor plasma. Each sample was then aliquoted, one aliquot was used immediately for prothrombin time (PT)-international normalized ratio (INR) and activated partial thromboplastin time (APTT), four were stored at -20°C, and four were stored at -80°C for 24 hours. After 24 hours, the aliquots were taken out and thawed at 37°C in water bath and analyzed after 15, 30, 60, and 120 minutes. STATISTICAL ANALYSIS: Data were presented as mean with standard deviation (SD). Repeated measures ANOVA with Tukey post-hoc test was performed for multiple comparisons. All analysis was done using GraphPAD Prism 8.0 software (GraphPad Software, San Diego, California, USA).  Results: In the case of PT and INR, no statistically significant difference was found between the mean values after thawing for 120 minutes when compared with the mean baseline value. However, the APTT showed a statistically significant difference (p = 0.0232) after 30 minutes of thawing when the sample was stored at -20°C. Furthermore, a statistically significance difference (p = 0.0001) was found after 60 minutes of thawing when the samples were stored at -80°C. CONCLUSION: Plasma samples for the PT and INR may be accepted for assessment up to 120 minutes, when stored at -20°C and -80°C for 24 hours. In the case of APTT, the plasma sample can be used for assessment up to 30 minutes after thawing when stored at -20°C and up to 60 minutes when stored at -80°C.

Cold agglutinin disease in childhood: a case series with review of literature.

Cold agglutinins are autoantibodies that target RBC antigens at temperatures below average core body temperature. They produce RBC agglutination and cold agglutinin disease (CAD), a rare form of autoimmune haemolytic anaemia. Due to it's under recognition, there is a delay between the start of symptoms and the diagnosis. With an emphasis on the laboratory approach, we provide the clinical and analytical findings from five cases of childhood CAD.

A Combination of Inflammatory and Hematological Markers is Strongly Associated with the Risk of Death in Both Mild and Severe Initial Disease in Unvaccinated Individuals with COVID-19 Infection.

Background: Inflammatory and hematological markers are used extensively for early prognostication and monitoring in COVID-19.We aimed to determine whether routinely prescribed laboratory markers can predict adverse outcome at presentation in COVID-19. Methods: This retrospective observational study was performed on 401 samples collected between July to December 2020 from COVID-19 positive subjects, admitted at All India Institute of Medical Sciences, Delhi, India. Clinical details and laboratory investigations within 3 days of COVID-19 positivity were obtained. Clinical outcomes were noted from patient medical records, till discharge or death. Laboratory parameters, with individually defined cut-offs, were used, either singly or in combination to distinguish survival and death for those having severe and non-severe disease at initial presentation. Findings: Total Leukocyte count, Absolute neutrophil count, Neutrophil to Lymphocyte ratio, C-Reactive Protein (CRP), Interleukin-6 (IL-6), Lactate Dehydrogenase, Ferritin and Lymphocyte to CRP ratio (LCR) were significantly altered at presentation in severe COVID-19 as compared to non-severe cases; and, also in those who died due to COVID-19 compared to those who survived. A combination of four markers, CRP (≥3.9mg/dL); IL-6 (≥45.37pg/ml); Ferritin (≥373ng/mL); 1/LCR ≥0.405 was found to strongly predict mortality in cases with non-severe presentation as also in severe cases. Conclusion and Interpretation: The combination of routinely used markers, CRP, IL-6, Ferritin and 1/LCR can be used to predict adverse outcomes, even in those presenting with mild to moderate disease. This would identify subset of patients who would benefit from closer monitoring than usual for non-severe disease.

["Nessuno vuole vedermi": è una battaglia persa contro una malattia tropicale trascurata?] / "Nobody wants to see me": is this a lost battle against a Neglected Tropical Disease?

Riassunto. Le malattie tropicali trascurate (NTD) sono una serie di malattie che prosperano nelle comunità povere di risorse, in particolare nei climi tropicali. I fattori sociali, ambientali ed economici contribuiscono alla loro persistenza. La filariosi linfatica (LF), classificata come NTD in tutto il mondo, è una malattia parassitaria causata da vermi microscopici noti come microfilarie. I vermi adulti dimorano solo nel sistema linfatico degli esseri umani. Le zanzare trasferiscono la LF da persona a persona. Gonfiore di braccia, gambe e seno (linfedema) o dello scroto (idrocele) sono alcuni dei sintomi più gravi e dolorosi. La LF ha una grave influenza sia sulla salute mentale e sociale sia su quella fisica, e porta le persone a convivere con una deformazione, una debilitazione e uno stigma legati alla condizione di malattia. Di seguito descriviamo un caso clinico di un uomo con LF, alienato e umiliato dalla sua malattia. L'OMS ha avviato un'iniziativa globale per debellare la LF. Oltre alla somministrazione di trattamenti regolari, è stata posta uguale enfasi sull'apprendimento di come lavare e alzare gli arti colpiti, per aiutare a ridurre la gravità clinica e la progressione del disturbo.

Filariasis in an alcoholic male-coincidental or causal association?

Lymphatic filariasis is a parasitic disease transmitted by mosquitoes that carry minute, thread-like worms. There are usually no signs or symptoms to be seen in patients with this disease for the most part. Some people, however, develop a condition called elephantiasis, which is marked by severe swelling in the arms, legs, breasts, or genitals. We here descibe an interesting case of a 40-year-old alcoholic brought to the emergency department with an alleged history of injury and incidentally found to have microfilariasis after a thorough blood smear screening. This case illustrates the need for smear evaluation in diagnosing microfilariasis and also begs whether these patients may be more susceptible to parasitic infections due to their impaired immune system.

Acquired Bernard-Soulier syndrome and hypodysfibrinogenaemia because of multiple myeloma.

We describe a case of a patient with multiple myeloma with initial presentation simulating a bleeding disorder. Detailed coagulation work-up showed hypodysfibrinogenaemia along with a platelet function defect consistent with acquired Bernard-Soulier syndrome (BSS). Multiple plasma exchanges led to significant improvement in his bleeding symptoms. To the best of our knowledge, this is the first described case of simultaneous presentation of hypodysfibrinogenaemia and BSS secondary to multiple myeloma.

Assessment of Stability of Prothrombin Time, International Normalized Ratio, and Activated Partial Thromboplastin Time Under Different Storage Conditions in Human Plasma.

Background In this study, we aimed to determine the effects of storage time and temperature on commonly performed coagulation tests such as prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT) in human plasma. Methodology Whole blood samples from 100 patients were collected in a 3.2% sodium citrate vacutainer. The blood was centrifuged within two hours of collection at 2,000 g for 10 minutes, and the platelet-poor plasma (PPP) obtained was analyzed for PT, INR, and APTT tests at zero hours (baseline) and repeated at 12 hours, 24 hours, and 36 hours on a fully automated coagulation analyzer at various storage conditions (room temperature, refrigerator, and freezer). The results were categorized into two groups: group 1 comprised results with normal coagulation profile and group 2 comprised results with abnormal coagulation profile. The percentage change of the results from baseline (zero hours) for PT, INR, and APTT tests was also studied. A percentage change of more than ±10% from baseline was considered as a clinically significant change. Results In this study, a total of 95 PPP samples were evaluated. The median age of all patients was 44 years (range: 19-65 years). The male-to-female ratio was 0.9:1. The baseline PT, INR, and APTT values were 12.1 seconds, 1.06, and 26.5 seconds, respectively, in group 1, whereas the baseline PT, INR, and APTT values were 19.1 seconds, 1.80, and 36.0 seconds, respectively, in group 2. In the freezer, the samples were stable for PT, INR, and APTT tests at 12 hours, 24 hours, and 36 hours showing a change of <10% from baseline at all three time-points. In the refrigerator, the samples were stable for PT and INR tests for up to 24 hours showing a change of <10% from baseline. In comparison, the samples for the APTT test were not stable at 12 hours, 24 hours, and 36 hours showing a change of 12.1%, 15.5%, and 17.9%, respectively, from the baseline (zero hours). Finally, at room temperature, the samples deteriorated at 12 hours for all coagulation parameters (PT, INR, and APTT). Conclusions The patient plasma samples for PT, INR, and APTT tests could be safely stored for up to 36 hours in the freezer. In the refrigerator, samples for PT and INR tests could be safely stored for up to 24 hours while the samples for APTT deteriorated at 12 hours. All patient samples for PT, INR, and APTT tests deteriorated at 12 hours at room temperature.

Thromboelastography determined dynamics of blood coagulation and its correlation with complications and outcomes in patients with coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes abnormalities in the hemostatic system, collectively known as COVID-associated coagulopathy. The dynamics of clot formation are best discerned by whole-blood viscoelastic tests, such as thromboelastography (TEG). We aimed to assess the various abnormalities seen on TEG and explored the predictors of outcomes in these patients. METHODS: Thromboelastography was performed for 28 patients with COVID-19 using an automated thromboelastogram. The hemostatic condition was categorized as hypercoagulable in 17 (63%), hypocoagulable in 2 (7%), and normal in 8 (30%) based on TEG variables, such as reaction time , time until clot reaches a fixed strength, alpha angle, maximum amplitude, and clotting index. Laboratory parameters and clinical outcomes were compared between hypercoagulable and normal groups. RESULTS: Twenty-seven patients with a median age of 50 years (interquartile range, 40-60 years), male-to-female ratio of 0.9:1, median C-reactive protein of 25.7 (10.9-108.8) mg/L, serum ferritin of 693 (317-1031) µg/L, and albumin 2.9 (2.6-3.3) g/dL were included. The median prothrombin time/international normalized ratio and activated partial thromboplastin time were within normal range in the hypercoagulable and normal groups. The severity of COVID-19 was mild in 6 (22.2%), moderate in 2 (7.4%), and severe in 19 (70.4%) patients. Twenty-eight-day mortality among patients with hypocoagulable and hypercoagulable states was higher than normal coagulation status. (log-rank test, P = .002). CONCLUSIONS: Hypercoagulable state, together with a severe inflammatory state, is common in patients with COVID-19, despite thromboprophylaxis. TEG assesses coagulation status better than conventional coagulation tests. Coagulation abnormalities are associated with poor outcomes.

Medical postgraduate (MD) program in Laboratory Medicine in India: The Past, Present and Future.

A medical postgraduate course in the field of Laboratory Medicine for the Bachelor of Medicine and Bachelor of Surgery (MBBS) degree holders has existed for more than two decades in India, initiated and offered by the All India Institute of Medical Sciences, New Delhi, which was created under the special Act of Parliament of India 1956. This course has recently been included in the draft of National Medical Commission's Post Graduate Regulation 2021 list of medical courses, and the foundation guidelines have been laid for other medical colleges and teaching hospitals across the country to start this course. This article, written purely in academic interest, describes the past, present and future of this postgraduate training program in India with an aim to answer several doubts regarding this unique and holistic course with a view to providing a direction to those who are willing to become a laboratory physician through this post-graduation.

Abnormal Chromatin Clumping in Myeloblasts Mimicking Chronic Lymphocytic Leukaemia: A Diagnostic Pitfall.

Abnormal chromatin clumping (ACC) in cells of myeloid lineage is a distinct morphological entity. It has been described mainly in polymorphs in haematological neoplasms involving myelodysplasia or myeloproliferation. We here describe a rare case of ACC in myeloblasts in an elderly man that mimicked chronic lymphocytic leukaemia. Flow cytometry played a crucial role in characterizing the myeloid lineage of the blasts, thus avoiding a misdiagnosis. To the best of our knowledge, this is the third time such a case has been reported in the literature.

A Prospective Study of Specialized Coagulation Parameters in Admitted COVID-19 Patients and Their Correlation With Acute Respiratory Distress Syndrome and Outcome.

Background Acute respiratory distress syndrome (ARDS) is a frequent complication of COVID-19 and is associated with a component of thrombo-inflammation and cytokine storm. COVID-19 also affects the hemostatic system causing multiple coagulation abnormalities that is a cause of concern and needs to be addressed.  Objective We aimed to assess coagulation parameters of COVID-19 patients and identify whether they could be used as potential prognostic biomarkers to predict ARDS and immediate outcomes. Methods This was a prospective study done on 68 patients at four serial time points. Patients between 18-85 years admitted to the hospital as in-patients and ICU with a confirmed diagnosis of COVID-19 by RT-PCR were included. Exclusion criteria included pregnancy, patients below and above the mentioned age, previously known coagulopathy, systemic anticoagulants or anti-platelet therapy or vitamin K antagonists and moribund patients. Patients were divided into three categories based on SOFA score at admission, presence (group 1) or absence (group 2) of ARDS and outcome (dead or alive). Routine and specialized coagulation tests were performed on patients' platelet-poor plasma at the time of study inclusion (day 0), days 3, 7 and at discharge on STAR Max®3 (Diagnostica Stago France) automated coagulation analyzer and included prothrombin time (PT), international normalized ratio (INR) (STA® -NeoPTimal), activated partial thromboplastin time (APTT) (STA® -Cephascreen), fibrinogen (STA® Liquid Fib), D-dimer (STA® LiatestD- Dimer), Protein C (STA Stachrom® Protein C), Protein S (STA® Latest Free Protein S) and Antithrombin (STA® Chrom ATIII). ELISA did testing for tissue plasminogen activator (Asserachrom® tPA) as per the manufacturer's protocol. Results Sixty-eight patients, including 43 (63%) males and 25 (37%) females, with a median age of 48 years (IQR 20-85), were recruited in this study. The incidence of ARDS was 34%, with a mortality of 13%. History of contact with a COVID-19 case was present in 71% (48/68) of the patients. Fever was the most common presenting symptom in 84% (57/68) of the patients. The most common comorbidities were hypertension and diabetes mellitus (DM) in 22% (15/68) and 21% (14/68) of the patients. DM (p=0.07) and chronic obstructive pulmonary disease (COPD) (p=0.03) were significantly associated with ARDS. DM (p=0.02), hypertension (p=0.01), and COPD (p=0.02) were also significantly associated with mortality. APTT was markedly prolonged among non-survivors at day 0 (D0) and D7 (p=0.03, p=0.02). D-Dimer was elevated in 38/68 (56%) patients at D0. D-Dimer levels were significantly higher in non-survivors (p<0.001), in ARDS patients (p=0.001) and patients with higher SOFA scores (p=0.001). ROC curve showed that D-dimer cut-off > 2.13 (AUC of 0.86) and >0.85 (AUC of 0.74) predicts mortality and ARDS, respectively. Among the natural anticoagulants, protein C was significantly associated with a high SOFA score at D0 and D3 (p=0.04).  Conclusion Diabetes mellitus, hypertension and COPD were associated with poor outcomes. D-dimer levels must be monitored in COVID patients due to their association with ARDS and mortality. We observed that the levels of natural anticoagulants fell during the illness, making them prone to coagulopathies; however, none were seen in this study. Elevated tPA levels were also found in our patients; fibrinolytic therapy may benefit COVID-19 patients suffering from ARDS.

Stodtmeister Cells (Polymorphs with Pelger-Huët Anomaly) Showing "Faggots" in Mixed Phenotypic Acute Leukemia (T/Myeloid).

"Faggot" cells, named for the resemblance of multiple Auer rods to a bundle of sticks, are often considered sine qua non for acute promyelocytic leukemia. However, blasts in other acute myeloid leukemias rarely also show faggot cells. This case demonstrates faggot cells in stodtmeister cells in mixed phenotypic acute leukemia. In addition to being uncommon, this case also highlights the importance of immunophenotyping and genetic analysis in avoiding misdiagnosis and inappropriate therapy.