Presence Of Thrombocytopenia Research Articles

Features of chronic heart failure on the background of thrombocytopenia in persons infected with the human immunodeficiency virus

The general context of the study is to review the characteristics of the course of chronic heart failure (CHF) in persons infected with the human immunodeficiency virus (HIV) as a part of a single-stage screening clinical trial.Aim: To determine the features of the CHF course in HIV-infected patients, depending on the presence of thrombocytopenia (TP).Material and Methods. In a multidisciplinary hospital, 240 patients with HIV infection were examined for four years, where a cohort of patients with CHF (160 people) was identified, further divided into groups of patients with TP (107 people) and without TP (53 people). Patients underwent the same amount of research, including echocardiography, non-invasive arteriography, and a detailed laboratory examination.Results. TP in patients with CHF and HIV infection is more common in smokers and people with alcohol dependence and is associated with hemodynamic disorders in the form of higher systolic and diastolic blood pressure, left atrium increase. With TP, the values of NT-proBNP in blood plasma are higher, and in the blood serum – tissue inhibitor of metalloproteinases-1, urea, bilirubin, while the concentration of sodium and potassium ions in the blood serum is lower. Anemia and leukopenia were more common in the group of patients with thrombocytopenia. Patients with TP are more adherent to taking protease inhibitors and non-steroidal anti-inflammatory drugs.Conclusion. The frequency of CHF detection in patients with HIV infection against the background of TP is almost 2 times higher and is more often accompanied by dilatation of the left atrium, higher blood pressure, an increase in TIMP-1 and a decrease in the concentration of potassium ions in the blood serum. The concentration of NT-proBNP in blood plasma has a close inverse correlation with the number of platelets in patients with CHF and TP, and the presence of severe TP ≤ 30 × 109 cells/l increases the chances of developing CHF with low left ventricular ejection fraction by 10.8 times. Smoking, possible alcohol dependence and adherence to taking protease inhibitors and NSAIDs are significant factors associated with the development of thrombocytopenia in HIV-infected patients with CHF.

Fibrinogen contribution to clot strength in patients with sepsis and hematologic malignancies and thrombocytopenia—a prospective, single-center, analytical, cross-sectional study

BackgroundPatients with hematological malignancies (HM) frequently present thrombocytopenia and higher risk of bleeding. Although transfusion is associated with higher risk of adverse events and poor outcomes, prophylactic transfusion of platelets is a common practice to prevent hemorrhagic complications. Thromboelastometry has been considered a better predictor for bleeding than isolated platelet counts in different settings. In early stages of sepsis, hypercoagulability may occur due to higher fibrinogen levels. ObjectivesTo evaluate the behavior of coagulation in patients with HM who develop sepsis and to verify whether a higher concentration of fibrinogen is associated with a proportional increase in maximum clot firmness (MCF) even in the presence of severe thrombocytopenia. MethodsWe performed a unicentric analytical cross-sectional study with 60 adult patients with HM and severe thrombocytopenia, of whom 30 had sepsis (sepsis group) and 30 had no infections (control group). Coagulation conventional tests and specific coagulation tests, including thromboelastometry, were performed. The main outcome evaluated was MCF. ResultsHigher levels of fibrinogen and MCF were found in sepsis group. Both fibrinogen and platelets contributed to MCF. The relative contribution of fibrin was significantly higher (60.5 ± 12.8% vs 43.6 ± 9.7%; P < .001) and that of platelets was significantly lower (39.5 ± 12.8% vs 56.4 ± 9.7%; P < .001) in the sepsis group compared with the control group. ConclusionPatients with sepsis and HM presented higher concentrations of fibrinogen than uninfected patients, resulting in greater MCF amplitudes even in the presence of thrombocytopenia.

General Anesthesia for Cesarean Delivery for Thrombocytopenia in Hypertensive Disorders of Pregnancy: Findings From the Obstetric Airway Management Registry

(Anesth Analg. 2023;136:992–998) In Africa, maternal morality following cesarean delivery is 50× more likely compared to morality rates in high-income countries, and spinal anesthesia (SA) is the preferred anesthetic method during cesarean delivery. For parturient patients with hypertensive disorders (ie, preeclampsia, eclampsia, or gestational hypertension), there is an increased risk for adverse outcomes, including spinal epidural hematoma following SA, so thrombocytopenia should be excluded before neuraxial blockade. An accurate platelet count is necessary before SA in emergent situations of fetal distress, which can be complicated when laboratory services are unavailable or off-site. The primary aim of this study was to determine which patients received general anesthesia (GA) when the presence of thrombocytopenia was known versus suspected. The secondary aim was perioperative platelet counts of patients with suspected thrombocytopenia to determine how often GA may have been avoided in favor of SA if platelet count was known.

Acute myocardial infarction in a patient with thrombotic thrombocytopenic purpura: a case report and literature review

Acute myocardial infarction (AMI) induced by thrombotic thrombocytopenic purpura (TTP) has been previously reported, but comorbidity with autoimmune hemolytic anemia is rare. The index patient, a 55-year-old woman, presented with acute ST-elevation myocardial infarction (STEMI). A diagnosis of TTP was established on the presence of thrombocytopenia, microangiopathic hemolytic anemia, acute kidney injury, fever, and neurologic symptoms (ischemic stroke); autoimmune hemolytic anemia was established based on Comboost test. Percutaneous coronary intervention and dual antiplatelet therapy were not initiated due to elevated risk of bleeding. Instead, the patient was treated with glucocorticosteroid and plasmapheresis. Despite the treatment, the patient suffered a watershed acute cerebral infarction, and finally died of gastrointestinal bleeding. This case highlights the challenges in managing STEMI in TTP patients.

Three Years’ Experience of the Infective Endocarditis Team in a University Hospital

Objective: Infective endocarditis is a serious disease with high morbidity and mortality due to serious embolic complications. The follow-up of the patients requires multidisciplinary evaluation. We aimed to share the experience of the infective endocarditis team in our hospital and to guide the work of the teams to be formed in the future. Methods: Our study was planned as descriptive, cross-sectional, and observational. The patients were diagnosed by the modified Duke criteria. The National Infective Endocarditis Consensus Report was considered during the diagnosis, follow-up, and treatment process. Results: Fifty (45.4%) of 110 patients followed by the team were diagnosed with endocarditis. Thirty of the patients (51.8%) were male, the median age was 63.5 (18-87) days, and the median duration of symptoms was 35.7 (1-180) days. 76% of the diagnoses were definite endocarditis, 46% of the cases had an acute course, aortic valve involvement was 38%, and native valve involvement was 60%; the most isolated agent was Stapyhylococcus aureus. Community-acquired infection was 46%. The most common predisposing factors were prosthetic heart valve (38%) and hemodialysis (46%). Fever was observed in 64% of the patients and dyspnea in 58%. The rate of detection of vegetation by transesophageal echocardiography was 68%. Brain, pulmonary embolisms, and spondylodiscitis were the most common complications. The median time for blood culture to become negative was 3 (3-15) days, the operation time for 15 patients was 8 (1-30) days, and the 30-day hospital mortality was 28%. A statistically significant correlation was found between mortality and the presence of previous endocarditis, ejection fraction below 50%, complication development, hospitalization in the intensive care unit, presence of thrombocytopenia, Charlson comorbidity index ≥5, and vegetation size ≥1 cm (p&lt;0.05). We determined that the presence of previous endocarditis increased the risk of mortality 14 times (p=0.025). Conclusion: Mortality and morbidity rates can be reduced by detecting underlying diseases, controlling complications, applying early effective antibiotic and anticoagulant treatment, surgical interventions at the right time, and rapid supportive treatments for sepsis by teams formed with a multidisciplinary approach.

Comparison of Surgical Risk Scores in a European Cohort of Patients with Advanced Chronic Liver Disease.

Patients with advanced chronic liver disease (ACLD) or cirrhosis undergoing surgery have an increased risk of morbidity and mortality in contrast to the general population. This is a retrospective, observational study to evaluate the predictive capacity of surgical risk scores in European patients with ACLD. Cirrhosis was defined by the presence of thrombocytopenia with <150,000/uL and splenomegaly, and AST-to-Platelet Ratio Index >2, a nodular liver edge seen via ultrasound, transient elastography of >15 kPa, and/or signs of portal hypertension. We assessed variables related to 90-day mortality and the discrimination and calibration of current surgical scores (Child-Pugh, MELD-Na, MRS, NSQIP, and VOCAL-Penn). Only patients with ACLD and major surgeries included in VOCAL-Penn were considered (n = 512). The mortality rate at 90 days after surgery was 9.8%. Baseline disparities between the H. Mar and VOCAL-Penn cohorts were identified. Etiology, obesity, and platelet count were not associated with mortality. The VOCAL-Penn showed the best discrimination (C-statistic90D = 0.876) and overall predictive capacity (Brier90D = 0.054), but calibration was not excellent in our cohort. VOCAL-Penn was suboptimal in patients with diabetes (C-statistic30D = 0.770), without signs of portal hypertension (C-statistic30D = 0.555), or with abdominal wall (C-statistic30D = 0.608) or urgent (C-statistic180D = 0.692) surgeries. Our European cohort has shown a mortality rate after surgery similar to those described in American studies. However, some variables included in the VOCAL-Penn score were not associated with mortality, and VOCAL-Penn's discriminative ability decreases in patients with diabetes, without signs of portal hypertension, and with abdominal wall or urgent surgeries. These results should be validated in larger multicenter and prospective studies.

Adrenal Abscesses: A Systematic Review of the Literature.

Objective: To summarize the existing knowledge about adrenal gland abscesses, including etiology, clinical presentation, common laboratory and imaging findings, management and overall morbidity and mortality. Design: Systematic literature review. Methods: We performed a search in the PubMed database using search terms: 'abscess and adrenal glands', 'adrenalitis', 'infection and adrenal gland', 'adrenal abscess', 'adrenal infection' and 'infectious adrenalitis'. Articles from 2017 to 2022 were included. We found total of 116 articles, and after applying exclusion criteria, data from 73 articles was included in the final statistical analysis. Results: Of 84 patients included in this review, 68 were male (81%), with a mean age of 55 years (range: 29 to 85 years). Weight loss was the most frequent symptom reported in 58.3% patients, followed by fever in 49%. Mean duration of symptoms was 4.5 months. The most common laboratory findings were low cortisol (51.9%), elevated ACTH (43.2%), hyponatremia (88.2%) and anemia (83.3%). Adrenal cultures were positive in 86.4% cases, with Histoplasma capsulatum (37.3%) being the leading causative agent. Blood cultures were positive in 30% of patients. The majority of the adrenal infections occurred through secondary dissemination from other infectious foci and abscesses were more commonly bilateral (70%). A total of 46.4% of patients developed long-term adrenal insufficiency requiring treatment. Abscess drainage was performed in 7 patients (8.3%) and adrenalectomy was performed in 18 (21.4%) patients. The survival rate was 92.9%. Multivariate analysis showed that the only independent risk factor for mortality was thrombocytopenia (p = 0.048). Conclusion: Our review shows that adrenal abscesses are usually caused by fungal pathogens, and among these, Histoplasma capsulatum is the most common. The adrenal glands are usually involved in a bilateral fashion and become infected through dissemination from other primary sources of infection. Long-term adrenal insufficiency develops in 46% of patients, which is more common than what is observed in non-infectious etiology of adrenal gland disorders. Mortality is about 7%, and the presence of thrombocytopenia is associated with worse prognosis. Further prospective studies are needed to better characterize optimal testing and treatment duration in patients with this relatively rare but challenging disorder.

Re-evaluation of the risk of venous thromboembolism after COVID-19 vaccination using haematological criteria

An elevated risk of venous thromboembolism (VTE) following a first dose of the ChAdOx1 adenovirus-vectored vaccine was found in a national epidemiological study in England using routine discharge diagnosis codes. Separately, the syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) was identified using haematological criteria based on presence of thrombocytopenia, significantly elevated D-dimers and development of anti-PF4 antibodies. To re-evaluate risk estimates using haematological criteria, we obtained the haematology results for hospital admitted patients aged 18–64 years in 43 National Health Service trusts in England who were included in the national epidemiological study. Diagnoses were confirmed and haematological parameters obtained from local records without knowledge of vaccination status. The haematological parameters in patients admitted for a confirmed VTE following ChAdOx1 or BNT162b2 mRNA vaccination were then compared with those in a randomly selected 40% sample of unvaccinated patients with VTE. Overall, 12 (14%) of the 84 vaccinated cases had a diagnosis compatible with VITT, 11 after a first dose of ChAdOx1 and one after a first dose of BNT162b2. Thrombocytopenia (platelet count <150 × 109/L) occurred in 17 vaccinated (20%) and 4 (4%) of 108 unvaccinated patients, with all 6 cases of severe thrombocytopenia (<50 × 109/L) occurring within 42 days of a first dose of ChAdOx1. The attributable risk estimates for a cerebral venous thrombosis (CVT) or other VTE with thrombocytopenia after a first dose of ChAdOx1 vaccine were 2.82 and 9.62 per million doses respectively. However, elevated risks were also found after a first dose of ChAdOx1 for VTE without thrombocytopenia with relative incidences for CVT and other VTE of 2.67 (1.77–3.77) and 1.93 (1.57–2.35) respectively. While we identified a distinct population with features of VITT within 42 days of receiving ChAdOx1 vaccination, confirming current diagnostic criteria, we also found evidence of an increased risk of a VTE without thrombocytopenia after ChAdOx1 vaccine.

FREQUENCY OF THROMBOCYTOPENIA IN CONFIRMED CASES OF MALARIA IN CHILDREN

Objective: To determine the frequency of thrombocytopenia in confirmed cases of malaria in children&#x0D; Methods: This cross sectional study was conducted in Pediatric Department of Mayo Hospital Lahore from January to June 2018. A total of 80 Children between two years- 12 years of age, of both the genders with confirmed malaria were included by non-probability consecutive sampling. A blood sample was taken within 48 hours of admission and their complete blood count was reviewed for the presence of thrombocytopenia after malaria was confirmed on positive peripheral smear. Thrombocytopenia was defined as platelet count of less than 150,000/µl of blood. All collected data was entered and analyzed in SPSS version 22. Data was stratified for age and gender to address effect modifiers. Presence of thrombocytopenia was presented as frequencies and percentages.&#x0D; Results: Out of total 80 patients with positive malarial parasite (MP) slide, 65 cases (81.25%)were of Plasmodium Vivax,12(15%) were of Plasmodium Falciparum while 3 cases (3.75%) were of Mixed infection. 44 patients( 55%)were having low platelet count (less than 150,000/µl) while 36 patients(45%) had no thrombocytopenia. Out of 44 patients with thrombocytopenia, 16 patients (20%) had mild thrombocytopenia, 21 patients (26.3%) had moderate thrombocytopenia while 7 patients (8.8%) had severe thrombocytopenia. There was no significant association of thrombocytopenia with age, gender or duration of malaria. &#x0D; Conclusions: Frequency of thrombocytopenia in confirmed cases of malaria in children is 55% hence; presence of thrombocytopenia in febrile patients can raise the possibility of malaria leading to early diagnosis and management.

Prevention of Venous Thromboembolism in Medical Patients with Thrombocytopenia or with Platelet Dysfunction: The Last 10 Years.

Current guideline recommendations for primary prophylaxis of venous thromboembolism (VTE) are based on randomized clinical trials that usually exclude subjects at a potentially high risk of bleeding complications. For this reason, no specific guideline is available for thromboprophylaxis in hospitalized patients with thrombocytopenia and/or platelet dysfunction. However, except in patients with absolute contraindications to anticoagulant drugs, antithrombotic prophylaxis should always be considered, for example, in hospitalized cancer patients with thrombocytopenia, especially in those with multiple VTE risk factors. Low platelet number, platelet dysfunction, and clotting abnormalities are also very common in patients with liver cirrhosis, but these patients have a high incidence of portal venous thrombosis, implying that cirrhotic coagulopathy does not fully protect against thrombosis. These patients may benefit from antithrombotic prophylaxis during hospitalization. Patients hospitalized for COVID-19 need prophylaxis, but frequently experience thrombocytopenia or coagulopathy. In patients with antiphospholipid antibodies, a high thrombotic risk is usually present, even in the presence of thrombocytopenia. VTE prophylaxis in high-risk conditions is thus suggested in these patients. At variance with severe thrombocytopenia (< 50,000/mm3), mild/moderate thrombocytopenia (≥ 50,000/mm3) should not interfere with VTE prevention decisions. In patients with severe thrombocytopenia, pharmacological prophylaxis should be considered on an individual basis. Aspirin is not as effective as heparins in lowering the risk of VTE. Studies in patients with ischemic stroke demonstrated that thromboprophylaxis with heparins is safe in these patients also during antiplatelet treatment. The use of direct oral anticoagulants in the prophylaxis of VTE in internal medicine patients has been recently evaluated, but no specific recommendation exists for patients with thrombocytopenia. The need for VTE prophylaxis in patients on chronic treatment with antiplatelet agents should be evaluated after assessing the individual risk of bleeding complications. Finally, the selection of patients who require post-discharge pharmacological prophylaxis remains debated. New molecules currently under development (such as the inhibitors of factor XI) may contribute to improve the risk/benefit ratio of VTE primary prevention in this setting of patients.

Emphysematous pyelonephritis: An assessment of prognostic factors and the role of early pigtail drainage

Abstract Introduction: The management of emphysematous pyelonephritis (EPN), a necrotizing renal infection, has shifted from more invasive to less invasive approach in due course of time with decrease or reduction in mortality rate. Aim: To analyze the clinical spectrum, prognostic factors, different management strategies, and the outcome of the patients of EPN with the role of early pigtail drainage. Materials and Methods: The study was carried out at a tertiary care hospital from January 2016 to December 2021 and included patients who were diagnosed with EPN. The data on the demographic profile, clinical features, biochemical parameters, imaging studies, management, and outcome of patients of EPN were recorded. Results: A total of 51 patients of EPN were studied and were divided into two groups, responders (40 patients) and nonresponders (11 patients), based on their clinical progression and outcome. Among responders and nonresponders, a significant difference was seen in terms of age, presentation of altered consciousness and shock, average hemoglobin, average serum creatinine, and presence of thrombocytopenia. Out of total 51 patients, 13 (25.49%) showed a response with antibiotics only, DJ stenting was done in five (9.8%) patients, and pigtail catheterization in 33(64.7%) patients. There was a significant difference seen in the response with early pigtail drainage. Nephrectomy was needed in eight (15.68%) patients, and the mortality rate was 9.8%, with the death of five patients. Conclusion: Advanced age, lower hemoglobin levels, thrombocytopenia, raised serum creatinine levels, altered mental status, and presence of shock can be used as a score for poor prognosis. With the use of broad-spectrum antibiotics and early pigtail drainage, a large number of patients with EPN can be managed effectively. Nephrectomy should be reserved for patients who fail to respond to conservative management or those with advanced disease with the presence of multiple risk factors.

Applications of Artificial Intelligence in Thrombocytopenia

Thrombocytopenia is a medical condition where blood platelet count drops very low. This drop in platelet count can be attributed to many causes including medication, sepsis, viral infections, and autoimmunity. Clinically, the presence of thrombocytopenia might be very dangerous and is associated with poor outcomes of patients due to excessive bleeding if not addressed quickly enough. Hence, early detection and evaluation of thrombocytopenia is essential for rapid and appropriate intervention for these patients. Since artificial intelligence is able to combine and evaluate many linear and nonlinear variables simultaneously, it has shown great potential in its application in the early diagnosis, assessing the prognosis and predicting the distribution of patients with thrombocytopenia. In this review, we conducted a search across four databases and identified a total of 13 original articles that looked at the use of many machine learning algorithms in the diagnosis, prognosis, and distribution of various types of thrombocytopenia. We summarized the methods and findings of each article in this review. The included studies showed that artificial intelligence can potentially enhance the clinical approaches used in the diagnosis, prognosis, and treatment of thrombocytopenia.

Peripheral hypothyroidism and TAFRO syndrome: Particularity of management

TAFRO syndrome is defined by the presence of thrombocytopenia, hydrops, fever, fibrosis, renal dysfunction, and organomegaly and can be seen with idiopathic multicentric Castleman disease (iMCD) or as an isolated process without iMCD. The pathophysiology of TAFRO is not well understood, but it is thought to be related to hypercytokinemia. Subclinical hypothyroidism may be a potential factor in the pathogenesis and symptomatology of TAFRO syndrome with elevated vascular endothelial growth factor (VEGF).There are no clear guidelines for the treatment of TAFRO in the absence of a definitive diagnosis of iMCD, resulting in suboptimal management and high morbidity. We report a case of hypothyroidism revealed by TAFRO syndrome.

Mortality predictors in a cohort of patients with COVID-19 admitted to a large tertiary hospital in the city of São Paulo, Brazil: a retrospective study.

There is discrepant information across countries regarding the natural history of patients admitted to hospitals with coronavirus disease (COVID-19), in addition to a lack of data on the scenario in Brazil. To determine the mortality predictors in COVID-19 patients admitted to a tertiary hospital in São Paulo, Brazil. A retrospective analysis of medical records of COVID-19 patients admitted to the Hospital Central da Irmandade da Santa Casa de Misericórdia of São Paulo. Overall, 316 patients with laboratory-confirmed COVID-19 between March 1, 2020, and July 31, 2020, were included. The analysis included the baseline characteristics, clinical progression, and outcomes. The mortality rate of the sample was 51.27%. Age ≥ 60 years was determined as a risk factor after multivariate logistic regression analysis. Patients with an oxygen (O2) saturation ≤ 94% upon admission accounted for 87% of the deaths (P < 0.001). Vasoactive drugs were used in 92% (P < 0.001) of patients who progressed to death, and mechanical ventilation was employed in 88% (P < 0.001) of such patients. However, patients who received corticosteroids concomitantly with mechanical ventilation had a better prognosis than those who did not. The progressive degree of pulmonary involvement observed on chest computed tomography was correlated with a worse prognosis. The presence of thrombocytopenia has been considered as a risk factor for mortality. The main predictors of in-hospital mortality after logistic regression analysis were age, O2 saturation ≤ 94% upon admission, use of vasoactive drugs, and presence of thrombocytopenia.

397: DEGREE OF THROMBOCYTOPENIA IN HOSPITALIZED COVID-19 PATIENTS WITH EBV AND CMV COINFECTION

Introduction: Thrombocytopenia (TCP) can be caused by Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and Coronavirus Disease 2019 (COVID-19). This study aimed to evaluate the degree of TCP in COVID-19 patients with co-infection with EBV and/or CMV. Methods: Retrospective study of adult patients admitted to our hospital with COVID-19 infection from March 2020 to February 2022 was conducted. Patients were divided into two groups. Group 1 (G1) had viral co-infection with EBV and/or CMV and group (G2) did not. These groups were analyzed based on the degree of TCP. Thrombocytopenia was classified into mild (100–150x103/uL), moderate (50–99x103/uL), and severe (< 50x103/uL). Primary outcomes were mortality, need for ventilation (NFV), and length of stay (LOS). Descriptive statistics, crosstabulation, Chi-square, and Mann-Whitney tests were used. Results: Of 994 patients, 445 with a median age of 57 [45-68] years were tested for viral co-infection. 262 (58.9%) were male and 327 (73.5%) survived. There was a statistically significant association between co-infection and TCP, X2(3)= 22.335, p= <.001. Of 218 patients in G1, 98 (45.0%) had normal platelet count (NPC), 44 (20.2%) had mild TCP, 47 (21.6%) had moderate, and 29 (13.3%) had severe. Of 227 patients in G2, 132 (58.1%) had NPC, 59 (26.0%) had mild TCP, 26 (11.5%) had moderate, and 10 (4.4%) had severe. There was a statistically significant association between co-infection and mortality, X2(1)= 36.682, p= <.001. In G1, 86 (39.4%) died and 132 (60.6%) survived. In G2, 32 (14.1%) died and 195 (85.9%) survived. There was a significant difference in LOS between the groups, [U= 16935.50, p= <.001]. G1 had a median LOS of 12 [6-19] days and G2 had a median of 7 [4-11] days. There was no statistically significant association between co-infection and NFV, X2(1)= .033, p= .856. In G1, 34 (15.6%) patients were mechanically ventilated and 184 (84.4%) were not. In G2, 34 (15.0%) were ventilated and 193 (85.0%) were not. Conclusions: COVID-19 and viral co-infection with EBV and/or CMV is associated with the presence of thrombocytopenia, mortality, and longer LOS in hospitalized patients. The presence of co-infection is associated with moderate and severe TCP.

Diagnostic and prognostic role of platelets in patients with sepsis and septic shock

Studies investigating the prognostic role of platelets commonly include critically ill patients, whereas data regarding the prognostic impact of platelet count in patients admitted with sepsis and septic shock is limited. Therefore, the study investigates the prognostic role of platelet count in patients with sepsis and septic shock. Consecutive patients with sepsis and septic shock from 2019 to 2021 were included monocentrically. Blood samples were retrieved from the day of disease onset (day 1), days 2, 3, 5, 7 and 10. Firstly, the diagnostic value of platelet count was tested for septic shock compared to sepsis. Secondly, the prognostic value of platelet count was tested for 30-day all-cause mortality. Statistical analyses included univariable t-test, Spearman’s correlation, C-statistics, Kaplan–Meier analyses, as well as multivariable mixed analysis of variance (ANOVA), Cox proportional regression analyses and propensity score matching. A total of 358 patients with sepsis and septic shock were included with a median platelet count of 176 × 106/ml. The presence of thrombocytopenia (i.e. <150 × 106/ml) was associated with increased risk of 30-day mortality (HR = 1.409; 95% CI 1.057–1.878; p = .019), which was still demonstrated after propensity score matching. During the course of sepsis, a nadir was observed on sepsis day 5 with a decrease in the mean platelet count by 21.5%. Especially serum lactate, mean arterial pressure and the presence of malignancies were found to predict platelet decline during the course of sepsis/septic shock. The presence of platelet decline >25% was associated with an increased risk of 30-day all-cause mortality (HR = 1.484; 95% CI 1.045–2.109; p = .028). Following platelet decline, recovery was observed from day 5 to day 10 (mean increase 7.5%). However, platelet recovery was not found to be associated with 30-day all-cause mortality (HR = 1.072; 95% CI 0.567–2.026; p = .832). In conclusion, both thrombocytopenia and platelet decline during the course of sepsis were associated with an increased risk of 30-day all-mortality in patients admitted with sepsis or septic shock.

Assessment of Factor V Gene G1691A Mutation (Factor V Leiden) among Chronic Hepatitis C Patients with Thrombocytopenia

Background: Factor V plays a crucial role in the coagulation process. Factor V Leiden (FVL) is considered a mutant form of factor V, which may contribute to blood vessel thrombosis. Also, Hepatitis C Virus (HCV) infection may exert some coagulation changes leading to Portal Vein Thrombosis (PVT). Thrombocytopenia in patients with chronic HCV infection constitutes a major challenge. Objective: This study aimed to investigate the incidence of FVL (factor V gene G1691A mutation) and its influence on coagulation among HCV chronically infected patients suffering from thrombocytopenia. Besides, it was designed to demonstrate the association of chronic HCV infection with coagulation disturbances in such patients. Methods: This study was conducted on blood samples of a total of 54 subjects (33 HCV chronically infected patients and 21 healthy controls). HCV chronically infected patients with thrombocytopenia (Platelet Count [PLC] below 150 thousand/microliter) were selected. Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPPT) were previously determined as coagulation parameters. Protein C and protein S antigens were determined by ELISA as coagulation-regulating (anticoagulants) parameters. All samples were investigated for the presence of FVL by real-time PCR. Results: PLC, PT, and protein C antigen showed highly significant differences (p &lt; 0.001) between controls (group 1) and HCV chronically infected patients (group 2). Likewise, a highly significant change (p = 0.006) was achieved for the protein S antigen. A non-significant change was detected for the incidence of FVL with a heterozygous pattern between controls (group 1) and HCV chronically infected patients (group 2). Additionally, non-significant changes were detected for all of the investigated coagulation and coagulation-regulating (anticoagulants) parameters between control subjects with negative FVL (subgroup 1) and others with positive FVL (subgroup 2). Similarly, non-significant changes for such parameters were recoded for HCV chronically infected patients with negative FVL (subgroup 3) and others with positive FVL (subgroup 4). Conclusion: Chronic HCV infection in the presence of thrombocytopenia is associated with coagulation disturbances. The incidence of FVL with its heterozygous pattern is unaffected by chronic HCV infection, and no association is shown with worsening of coagulation in chronic hepatitis C patients suffering from thrombocytopenia.

A Phase I Open Label Study of Fostamatinib, a SYK Inhibitor, in Patients with Lower-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia

INTRODUCTION: Ineffective hematopoiesis in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) have been associated to upregulated innate immune and inflammatory signals. Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that is highly expressed in hematopoietic cells and mediates signaling through Toll-like receptors and pattern recognition receptors leading to activation of the ERK, AKT, NF-kB and p38 signaling cascades. Given prior data suggesting that inhibition of these signals might be associated with improved hematopoiesis in MDS we hypothesized SYK inhibition might have therapeutic efficacy in lower-risk MDS and CMML. METHODS: To study this we designed an open label phase I clinical trial of fostamatinib, a SYK inhibitor, for patients with lower-risk MDS or CMML (defined as those with a score <3.5 by the revised International Prognostic Scoring System [IPSS-R]) and no response to prior erythroid stimulating agents or hypomethylating agents (HMAs). Patients with MDS with del(5q) must have received prior therapy with lenalidomide and those with MDS with ring sideroblasts must have received luspatercept. Patients had to be transfusion dependent, defined as prior RBC or platelet transfusions within the past 28 days, or have hemoglobin <10g/dL or platelets <75x109/L. Patients with profound neutropenia (ANC <0.5x109/L) where excluded. The study includes an intra-patient dose escalation design by which patients start therapy at a dose of fostamatinib of 100mg po bid on days 1-28 of a 28-day cycle. If no response to therapy, by IWG 2006 response criteria, is observed after 8 weeks of therapy dose will be escalated to 150mg po bid on days 1-28 of a 28-day cycle and then, in the absence of response after an additional 8 weeks of therapy, to 200mg po bid on days 1-28 of a 28 day cycle. Patients achieving no response after the second dose escalation will be discontinued from study (Figure 1a). The primary endpoint of the study is to assess the safety and tolerability of fostamatinib. Secondary objectives included overall response rates, transfusion independence and survival outcomes. The study includes futility and safety stopping rules. This study is registered at clinicaltrials.gov (NCT05030675). RESULTS: To date, a total of 5 patients have been treated on study as of July 2022 including 3 patients with MDS and ring sideroblasts. Patient characteristics are detailed in Figure 1b. Median age is 71 years (range 59-82). Median number of prior therapies was 5 (range 4-6) including one patient with a prior allogeneic stem-cell transplant. Four (80%) patients had received prior therapy with HMA. Two patients were transfusion dependent of RBC at the time of enrollment with one patient who was eligible based on the presence of thrombocytopenia. At the current data cut off, three patients developed treatment emergent adverse events the main including grade 1-2 diarrhea or constipation. One patient developed COVID-19 infection during the course of therapy and had mild symptomatology. Fostamatinib was not discontinued in this patient. No episodes of expected on-target uncontrolled hypertension or transaminitis have been observed so far. To date, only 4 patients have completed at least 2 cycles of therapy (8 weeks) and are eligible for response, and only 2 patients have dose escalated beyond 100mg po bid: 1 currently at the 150mg po bid dose level, and 1 at the maximum dose of 200mg po bid. With a median follow up of only 2.7 months (95% CI 0-5.6), no responses have been observed. All 5 patients remain on study: 3 (60%) at the 100mg po bid dose, 1 (20%) at 150mg po bid and 1 (20%) at 200mg po bid. CONCLUSIONS: Preliminary data suggests that treatment with fostamatinib at doses of up to 200mg po bid can be safely administered in patients with lower-risk MDS who have failed available therapies. Enrollment is ongoing to determine the potential efficacy of doses of up to 200mg bid. Additional correlative studies to determine predictors of response are underway. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prevalence, risk factors, severity and outcome of neonatal thrombocytopenia.

Objective: To find out prevalence, risk factors, severity and outcome of neonatal thrombocytopenia (TCP). Study Design: Prospective Observational study. Setting: Neonatal Intensive Care Unit (NICU) of Children Hospital Complex Multan. Period: January 2020 to January 2021. Material &amp; Methods: A total of 191 neonates admitted to NICU during the study period were enrolled. A special proforma was designed to record all study information while SPSS version 26.0 was utilized for data analysis. Prevalence of TCP was noted among neonates admitted in NICU during the study period. Maternal risk factors, neonatal risk factors, severity of TCP and outcome were recorded. Results: In a total of 191 neonates, 110 (57.6%) were male while overall mean age was recorded to be 2.98+2.46 days. The prevalence of TCP was recorded to be 47.1% (90/191). Pregnancy induced hypertension (p=0.0003), premature rupture of membrane (p=0.0105) and eclampsia (0.0215) were found to have significant association with the presence of TCP. Preterm neonates (p&lt;0.0001), small for gestational age (p&lt;0.0001), sepsis (p&lt;0.0001) and nectrozing enterocolitis (p=0.0014) were found to have significant association with TCP. A total of 13 (6.8%) neonates died, out of which, 5 (38.5%) were having severe TCP. Conclusion: Prevalence of neonatal thrombocytopenia at neonatal intensive care unit was found to be high (47.1%). Pregnancy induced hypertension, premature rupture of membrane and eclampsia were found to have significant association with neonatal thrombocytopenia. Preterm, small for gestational age, sepsis and necrotizing enterocolitis were noted to be significantly associated with neonatal thrombocytopenia. Severe thrombocytopenia was noted to be a significant predictor of poor outcomes.

Prevalence and clinical implication of thrombocytopenia and heparin-induced thrombocytopenia in patients who are critically ill with COVID-19

As the COVID-19 pandemic continues to evolve, different clinical manifestations are better understood and studied. These include various haematologic disorders that have been shown to be associated with increased morbidity and mortality. We studied the prevalence of one unusual manifestation, heparin-induced thrombocytopenia (HIT) and its clinical implications in patients who are severely ill with COVID-19 in a single tertiary centre in Israel. The presence of thrombocytopenia, disseminated intravascular coagulation (DIC) and HIT, and their association with clinical course and outcomes were studied. One-hundred and seven patients with COVID-19 were included. Fifty-seven (53.2%) patients developed thrombocytopenia, which was associated with the worst outcomes (ventilation, DIC and increased mortality). Sixteen (28.0%) patients with thrombocytopenia were positive for HIT, all of which were supported by extracorporeal devices. HIT was independently associated with ventilation days, blood product transfusions, longer hospitalisation and mortality.Platelet abnormalities and HIT are common in patients who are critically ill with COVID-19 and are associated with the worst clinical outcomes. The mechanisms underlying HIT in COVID-19 are yet to be studied; HIT may contribute to the dysregulated immunologic response associated with COVID-19 critical illness and may play a significant part in the coagulopathy seen in these patients. As many patients with COVID-19 require aggressive thromboprophylaxis, further understanding of HIT and the implementation of appropriate protocols are important.