Challenges in the Management of Blood Diseases during COVID-19 Pandemic

Chronic lymphocytic leukemia (CLL) caregivers play a central role in disease management—a role that has been heightened during the COVID-19 pandemic given the healthcare system’s reliance on frontline family caregivers and CLL patients’ increased risk of infection and mortality. Using a mixed-method design, we investigated the impact of the pandemic on CLL caregivers (Aim 1) and their perceived resource needs (Aim 2): 575 CLL caregivers responded to an online survey; 12 spousal CLL caregivers were interviewed. Two open-ended survey items were thematically analyzed and compared with interview findings. Aim 1 results showed that two years into the pandemic, CLL caregivers continue to struggle with coping with distress, living in isolation, and losing in-person care opportunities. Caregivers described experiencing increasing caregiving burden, realizing the vaccine may not work or didn’t work for their loved one with CLL, feeling cautiously hopeful about EVUSHELD, and dealing with unsupportive/skeptical individuals. Aim 2 results indicate that CLL caregivers needed reliable, ongoing information about COVID-19 risk, information about and access to vaccination, safety/precautionary measures, and monoclonal infusions. Findings illustrate ongoing challenges facing CLL caregivers and provide an agenda to better support the caregivers of this vulnerable population during the COVID-19 pandemic. Full article

Background: At the dawn of the pandemic, severe forms of COVID-19 were often complicated by thromboembolisms. However, routine laboratory tests cannot be used to predict thromboembolic events. The objective of this study was to investigate the potential value of the thrombin generation test (TGT) in predicting hypercoagulability and thrombotic risk in the aforementioned set of patients. Methods: The study panel comprised 52 patients divided into two groups (26 COVID-19 positive and 26 COVID-19 negative); COVID-19-positive patients were further grouped in “severe” (n = 11) and “non-severe” (n = 15) categories based on clinical criteria. The routine blood tests and TGT of these patients were retrospectively analyzed. Results: All 26 COVID-19-positive patients showed decreased lymphocyte, monocyte and basophil counts and increased lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine transaminase (ALT) compared with control patients. Conversely, we did not observe statistically significant differences between severe and non-severe patients despite anecdotal variations in the distribution patterns. TGT without thrombomodulin (TM) addition showed statistically significant differences in the thrombin peak heights between COVID-19-positive and negative patients. After addition of TM, peak height, Endogenous Thrombin Potential (ETP) and velocity index were increased in all COVID-19-positive patients while the percentage of inhibition of ETP was reduced. These trends correlated with the severity of disease, showing a greater increase in peak height, ETP, velocity index and a drastic reduction in the percentage of ETP inhibition in more severely affected patients. Conclusions: Our data suggest that all COVID-19 patients harbor a hypercoagulable TGT profile and that this is further pronounced in severely affected patients. Full article

SARS-CoV-2 infection produces alterations in blood clotting, especially in severe cases of COVID-19. Abnormal coagulation parameters in patients with COVID-19 are important prognostic factors of disease severity. The objective of this study was to evaluate the predictive value of aPTT, D-dimer, INR and PT in the mortality of patients with COVID-19. A retrospective, single-center, observational study was conducted on COVID-19 patients admitted to the Municipal Emergency Clinical Hospital in Timisoara, Romania, between August and October 2021. Patients were confirmed as COVID-19 positive by reverse transcription-polymerase chain reaction (RT-PCR) assay. After applying the inclusion/exclusion criteria, a total of 82 patients were included in the analysis. Receiver operating characteristic (ROC) curves of D-Dimer, INR, PT and aPTT were generated to assess whether the baseline of each of these biomarkers was accurately predictive for mortality in patients with COVID-19. Mortality among patients enrolled in this study was 20.7%, associated with older age and presence of heart disease. The areas under the ROC curve (AUC-ROC) of D-Dimer, INR, PT, and aPTT were 0.751, 0.724, 0.706 and 0.753. Differences in survival for patients with coagulation biomarker levels above cut-off values compared to patients below these values were statistically significant. All evaluated parameters had significant differences and good performance in predicting mortality of COVID-19 patients, except fibrinogen, which had no significant difference. Moreover, aPTT and D-dimer were the best performing parameters in predicting mortality in patients with SARS-CoV-2 infection. Full article

Individuals with oncohematological diseases (OHD) may develop an impaired immune response against vaccines due to the characteristics of the disease or to its treatment. Humoral response against SARS-CoV-2 has been described to be suboptimal in these patients, but the quality and efficiency of the cellular immune response has not been yet completely characterized. In this study, we analyzed the early humoral and cellular immune responses in individuals with different OHD after receiving one dose of an authorized vaccine against SARS-CoV-2. Humoral response, determined by antibodies titers and neutralizing capacity, was overall impaired in individuals with OHD, except for the cohort of chronic myeloid leukemia (CML), which showed higher levels of specific IgGs than healthy donors. Conversely, the specific direct cytotoxic cellular immunity response (DCC) against SARS-CoV-2, appeared to be enhanced, especially in individuals with CML and chronic lymphocytic leukemia (CLL). This increased cellular immune response, developed earlier than in healthy donors, showed a modest cytotoxic activity that was compensated by significantly increased numbers, likely due to the disease or its treatment. The analysis of the immune response through subsequent vaccine doses will help establish the real efficacy of COVID-19 vaccines in individuals with OHD. Full article

Although thrombosis in coronavirus disease 2019 (COVID-19) infection has attracted attention, the mechanism underlying its development remains unclear. The relationship between platelet activation and the severity of COVID-19 infection was compared with that involving other infections. Plasma soluble C-type lectin-like receptor 2 (sCLEC-2) levels were measured in 46 patients with COVID-19 infection and in 127 patients with other infections. The plasma sCLEC-2 levels in patients with COVID-19 infection {median (25th, 75th percentile), 489 (355, 668) ng/L} were significantly higher (p < 0.001) in comparison to patients suffering from other pneumonia {276 (183, 459) ng/L}, and the plasma sCLEC-2 levels of COVID-19 patients with severe {641 (406, 781) ng/L} or critical illness {776 (627, 860) ng/L} were significantly higher (p < 0.01, respectively) in comparison to those with mild illness {375 (278, 484) ng/L}. The ratio of the sCLEC-2 levels to platelets in COVID-19 patients with critical illness of infection was significantly higher (p < 0.01, p < 0.001 and p < 0.05, respectively) in comparison to COVID-19 patients with mild, moderate or severe illness. Plasma sCLEC-2 levels were significantly higher in patients with COVID-19 infection than in those with other infections, suggesting that platelet activation is triggered and facilitated by COVID-19 infection. Full article

Introduction: Thrombosis and bleeding are recognized complications of the novel coronavirus infection (COVID-19), with a higher incidence described particularly in the critically ill. Methods: A retrospective review of COVID-19 patients admitted to our intensive care units (ICU) between 1 January 2020 and 31 December 2020 was performed. Primary outcomes included clinically significant thrombotic and bleeding events (according to the ISTH definition) in the ICU. Secondary outcomes included mortality vis-a-vis the type of anticoagulation. Results: The cohort included 144 consecutive COVID-19 patients with a median age of 64 years (IQR 54.5–75). The majority were male (85 (59.0%)) and Caucasian (90 (62.5%)) with a median BMI of 30.5 kg/m² (IQR 25.7–36.1). The median APACHE score at admission to the ICU was 12.5 (IQR 9.5–22). The coagulation parameters at admission were a d-dimer level of 109.2 mg/mL, a platelet count of 217.5 k/mcl, and an INR of 1.4. The anticoagulation strategy at admission included prophylactic anticoagulation for 97 (67.4%) patients and therapeutic anticoagulation for 35 (24.3%) patients, while 12 (8.3%) patients received no anticoagulation. A total of 29 patients (20.1%) suffered from thrombotic or major bleeding complications. These included 17 thrombus events (11.8%)—8 while on prophylactic anticoagulation (7 regular dose and 1 intermediate dose) and 9 while on therapeutic anticoagulation (p-value = 0.02)—and 19 major bleeding events (13.2%) (4 on no anticoagulation, 7 on prophylactic (6 regular dose and 1 intermediate dose), and 8 on therapeutic anticoagulation (p-value = 0.02)). A higher thrombosis risk among patients who received remdesivir (18.8% vs. 5.3% (p-value = 0.01)) and convalescent serum (17.3% vs. 5.8% (p-value = 0.03%)) was noted, but no association with baseline characteristics (age, sex, race, comorbidity), coagulation parameters, or treatments (steroids, mechanical ventilation) could be identified. There were 10 pulmonary embolism cases (6.9%). A total of 99 (68.8%) patients were intubated, and 66 patients (45.8%) died. Mortality was higher, but not statistically significant, in patients with thrombotic or bleeding complications—58.6% vs. 42.6% (p-value = 0.12)—and higher in the bleeding (21.2%) vs. thrombus group (12.1%), p-value = 0.06. It did not significantly differ according to the type of anticoagulation used or the coagulation parameters. Conclusions: This study describes a high incidence of thrombotic and bleeding complications among critically ill COVID-19 patients. The findings of thrombotic events in patients on anticoagulation and major bleeding events in patients on no or prophylactic anticoagulation pose a challenging clinical dilemma in the issue of anticoagulation for COVID-19 patients. The questions raised by this study and previous literature on this subject demonstrate that the role of anticoagulation in COVID-19 patients is worthy of further investigation. Full article

COVID-19, as a disease involving the endothelium of multiple organs, is characterized by high mortality rates among hospitalized patients. Patients with hematological malignancies are particularly at risk of an unfavorable course of COVID-19. The endothelial activation and stress index (EASIX) score has been used as a simple predictor of overall survival (OS) in specific groups of hematological cancer patients. EASIX, as a biomarker of endothelial dysfunction, might play a prognostic role in patients with COVID-19. Here, we performed a comprehensive retrospective analysis of the EASIX score in 523 hospitalized COVID-19 patients with or without coexisting hematological cancer. Hematological cancer COVID-19 patients had higher EASIX scores compared to the overall population with COVID-19. In hematological patients, EASIX was a strong predictor of the occurrence of sepsis during COVID-19. Our findings demonstrated EASIX as a strong predictor of intensive care unit admission, in-hospital mortality, the occurrence of acute renal failure and the need for hemodialysis, both in hematological and non-hematological COVID-19 patients. Patients with a high EASIX score on COVID-19 diagnosis had significantly inferior OS compared to patients with low EASIX. We showed for the first time that EASIX might serve as a simple, universal prognostic tool of OS in both hematological and non-hematological COVID-19 patients. Full article

Object: Although many Japanese patients infected with coronavirus disease 2019 (COVID-19) only experience mild symptoms, in some cases a patient’s condition deteriorates, resulting in a poor outcome. This study examines the behavior of biomarkers in patients with mild to severe COVID-19. Methods: The disease severity of 152 COVID-19 patients was classified into mild, moderate I, moderate II, and severe, and the behavior of laboratory biomarkers was examined across these four disease stages. Results: The median age and male/female ratio increased with severity. The mortality rate was 12.5% in both moderate II and severe stages. Underlying diseases, which were not observed in 45% of mild stage patients, increased with severity. An ROC analysis showed that C-reactive protein (CRP), ferritin, procalcitonin (PCT), hemoglobin (Hb) A1c, albumin, and lactate dehydrogenase (LDH) levels were significantly useful for the differential diagnosis of mild/moderate I stage and moderate II/severe stage. In the severe stage, Hb levels, coagulation time, total protein, and albumin were significantly different on the day of worsening from those observed on the day of admission. The frequency of hemostatic biomarker abnormalities was high in the severe disease stage. Conclusion: The evaluation of severity is valuable, as the mortality rate was high in the moderate II and severe stages. The levels of CRP, ferritin, PCT, albumin, and LDH were useful markers of severity, and hemostatic abnormalities were frequently observed in patients in the severe disease stage. Full article

Background. Coronavirus disease 2019 (COVID-19) has a high mortality in certain group of patients. We analysed the impact of baseline immunosuppression in COVID-19 mortality and the role of severe lymphopenia in immunocompromised subjects. Methods. We analysed all patients admitted with COVID-19 in a tertiary hospital in Madrid between March 1st and April 30th 2020. Epidemiological and clinical data, including severe lymphopenia (<500 lymphocytes/mm³) during admission, were analysed and compared based on their baseline immunosuppression condition. Results. A total of 1594 patients with COVID-19 pneumonia were hospitalised during the study period. 166 (10.4%) were immunosuppressed. Immunocompromised patients were younger (64 vs. 67 years, p = 0.02) but presented higher rates of hypertension, diabetes, heart, neurological, lung, kidney and liver disease (p < 0.05). They showed more severe lymphopenia (53% vs 24.1%, p < 0.001), lower SapO₂/FiO₂ ratios (251 vs 276, p = 0.02) during admission and higher mortality rates (27.1% vs 13.5%, p < 0.001). After adjustment, immunosuppression remained as an independent factor related to mortality (Odds Ratio (OR): 2.24, p < 0.001). In the immunosuppressed group, age (OR = 1.06, p = 0.01), acute respiratory distress syndrome (ARDS) (OR = 12.27, p = 0.017) and severe lymphopenia (OR = 3.48, p = 0.04) were the factors related to high mortality rate. Conclusion. Immunosuppression is an independent mortality risk factor in COVID-19. Severe lymphopenia should be promptly identified in these patients. Full article

Background: Acute cerebral infarction (ACI) includes cardiogenic ACI treated with anticoagulants and atherosclerotic ACI treated with antiplatelet agents. The differential diagnosis between cardiogenic and atherosclerotic ACI is still difficult. Materials and Methods: The plasma sCLEC-2 and D-dimer levels were measured using the STACIA system. Results: The plasma sCLEC-2 level was significantly high in patients with ACI, especially those in patients with atherosclerotic or lacunar ACI, and plasma D-dimer levels were significantly high in patients with cardioembolic ACI. The plasma levels of sCLEC-2 and the sCLEC-2/D-dimer ratios in patients with atherosclerotic or lacunar ACI were significantly higher than those in patients with cardioembolic ACI. The plasma D-dimer levels in patients with atherosclerotic or lacunar ACI were significantly lower than those in patients with cardioembolic ACI. The plasma levels of sCLEC-2 and the sCLEC-2/D-dimer ratios were significantly higher in patients with atherosclerotic or lacunar ACI or acute myocardial infarction in comparison to patients with cardioembolic ACI or those with deep vein thrombosis. Conclusion: Using both the plasma sCLEC-2 and D-dimer levels may be useful for the diagnosis of ACI, and differentiating between atherosclerotic and cardioembolic ACI. Full article

Recently, cases of fortuitous discovery of Chronic Lymphocytic Leukemia (CLL) during hospitalization for Coronavirus disease (COVID-19) have been reported. These patients did not show a monoclonal B cell expansion before COVID-19 but were diagnosed with CLL upon a sudden lymphocytosis that occurred during hospitalization. The (hyper)lymphocytosis during COVID-19 was also described in patients with overt CLL disease. Contextually, lymphocytosis is an unexpected phenomenon since it is an uncommon feature in the COVID-19 patient population, who rather tend to experience lymphopenia. Thus, lymphocytosis that arises during COVID-19 infection is a thought-provoking behavior, strikingly in contrast with that observed in non-CLL individuals. Herein, we speculate about the possible mechanisms involved with the observed phenomenon. Many of the plausible explanations might have an adverse impact on these CLL patients and further clinical and laboratory investigations might be desirable. Full article

The risk of venous thromboembolic (VTE) complications, mainly in the form of pulmonary embolism (PE) and deep vein thrombosis (DVT), in COVID-19 is well known, necessitating the administration of thrombotic prophylaxis in most patients. With a high risk of VTE complications or their presence, full anticoagulation may be associated with hemorrhagic complications. COVID-19 bleeding is rarely reported. Here, we present four cases of patients with muscle bleeding: two in the iliopsoas muscle, which resulted in death despite the embolization of the bleeding vessel, and two in the oblique and straight abdominal muscles, which were treated conservatively. In the reported cases, the severity of the bleeding coincided with the severity of the course of COVID-19. When observing a sudden drop in hemoglobin (Hb) in a patient with COVID-19, one must always remember the possible complications in the form of muscle bleeding, which can be fatal. Full article