Reduced Volume and Faster Infusion Rate of Activated Prothrombin Complex Concentrate: A Phase 3b/4 Trial in Adults with Hemophilia A with Inhibitors.

Background Activated prothrombin complex concentrate (aPCC) is indicated for bleed treatment and prevention in patients with hemophilia with inhibitors. The safety and tolerability of intravenous aPCC at a reduced volume and faster infusion rates were evaluated. Methods This multicenter, open-label trial (NCT02764489) enrolled adults with hemophilia A with inhibitors. In part 1, patients were randomized to receive three infusions of aPCC (85 ± 15 U/kg) at 2 U/kg/min (the approved standard rate at the time of the study), in a regular or 50% reduced volume, and were then crossed over to receive three infusions in the alternative volume. In part 2, patients received three sequential infusions of aPCC in a 50% reduced volume at 4 U/kg/min and then at 10 U/kg/min. Primary outcome measures included the incidence of adverse events (AEs), allergic-type hypersensitivity reactions (AHRs), infusion-site reactions (ISRs), and thromboembolic events. Results Of the 45 patients enrolled, 33 received aPCC in part 1 and 30 in part 2. In part 1, 24.2 and 23.3% of patients with regular and reduced volumes experienced AEs, respectively; 11 AEs in eight patients were treatment related. AHRs and ISRs occurred in four (12.1%) and two (6.1%) patients, respectively. In part 2, 3.3 and 14.3% of patients with infusion rates of 4 and 10 U/kg/min experienced AEs, respectively; only one AE in one patient was treatment related; no AHRs or ISRs were reported. Most AEs were mild/moderate in severity. Overall, no thromboembolic events were reported. Conclusions aPCC was well tolerated at a reduced volume and faster infusion rates, with safety profiles comparable to the approved regimen.

Stability of Hemoglobin Constant Spring Identified by Capillary Electrophoresis.

OBJECTIVE: Hemoglobin Constant Spring (HbCS) is often missed by routine hemoglobin analysis. The aim of this research was to study HbCS stability as identified by capillary electrophoresis (CE) to determine the specimen storage time limit. METHODS: The EDTA blood of 29 HbCS samples were kept at 4°C and analyzed every workday until CE could not detect HbCS or until 7 weeks after blood collection. The genotypes were confirmed by multiplex polymerase chain reaction. RESULTS: The median subject age was 27 years and 10 subjects were male. The HbCS levels were stable during the first 7 days but became undetectable in 5 cases (17.2%) after 1 week. All of them were heterozygous HbCS. Longer detection times were correlated with the higher baseline HbCS levels, with a correlation coefficient of 0.582 (P  ≤ 0.001). CONCLUSION: Routine hemoglobin typing and quantitation should be performed within 1 week after blood collection to detect low HbCS levels, especially in heterozygous HbCS.

Immunogenicity and risks associated with impaired immune responses following SARS-CoV-2 vaccination and booster in hematologic malignancy patients: an updated meta-analysis.

Patients with hematologic malignancies (HM) have demonstrated impaired immune responses following SARS-CoV-2 vaccination. Factors associated with poor immunogenicity remain largely undetermined. A literature search was conducted using PubMed, EMBASE, Cochrane, and medRxiv databases to identify studies that reported humoral or cellular immune responses (CIR) following complete SARS-CoV-2 vaccination. The primary aim was to estimate the seroconversion rate (SR) following complete SARS-CoV-2 vaccination across various subtypes of HM diseases and treatments. The secondary aims were to determine the rates of development of neutralizing antibodies (NAb) and CIR following complete vaccination and SR following booster doses. A total of 170 studies were included for qualitative and quantitative analysis of primary and secondary outcomes. A meta-analysis of 150 studies including 20,922 HM patients revealed a pooled SR following SARS-CoV-2 vaccination of 67.7% (95% confidence interval [CI], 64.8-70.4%; I2 = 94%). Meta-regression analysis showed that patients with lymphoid malignancies, but not myeloid malignancies, had lower seroconversion rates than those with solid cancers (R2 = 0.52, P < 0.0001). Patients receiving chimeric antigen receptor T-cells (CART), B-cell targeted therapies or JAK inhibitors were associated with poor seroconversion (R2 = 0.39, P < 0.0001). The pooled NAb and CIR rates were 52.8% (95% CI; 45.8-59.7%, I2 = 87%) and 66.6% (95% CI, 57.1-74.9%; I2 = 86%), respectively. Approximately 20.9% (95% CI, 11.4-35.1%, I2 = 90%) of HM patients failed to elicit humoral and cellular immunity. Among non-seroconverted patients after primary vaccination, only 40.5% (95% CI, 33.0-48.4%; I2 = 87%) mounted seroconversion after the booster. In conclusion, HM patients, especially those with lymphoid malignancies and/or receiving CART, B-cell targeted therapies, or JAK inhibitors, showed poor SR after SARS-CoV-2 vaccination. A minority of patients attained seroconversion after booster vaccination. Strategies to improve immune response in these severely immunosuppressed patients are needed.

Detectable serum IgM monoclonal gammopathy in non-hepatitis-associated mixed cryoglobulinemic glomerulonephritis: A case report and literature review.

Cryoglobulinemia is the presence of circulating cryoglobulin which can cause systemic vasculitis and glomerulonephritis. Monoclonal gammopathy of renal significance is strongly associated with type I cryoglobulinemia, but the role of detectable serum monoclonal gammopathy in mixed (type II) cryoglobulinemia is not clearly established. We report a case of a 71-year-old woman who presented with skin rash, leg edema, and azotemia. Investigations showed a positive result for rheumatoid factor, low complement C4 level, positive result for serum cryoglobulin, and positive M-spike on serum protein electrophoresis and IgM kappa monoclonal gammopathy on serum immunofixation. Kidney biopsy revealed membranoproliferative glomerulonephritis, polytypic IgM-dominant deposits in an immunofluorescence study, and microtubular substructures in an electron microscopic study. After an extensive workup, no evidence of myeloma or lymphoma was found. A diagnosis of monoclonal gammopathy of renal significance-associated mixed cryoglobulinemic glomerulonephritis was made. Due to the detectable IgM kappa monoclonal gammopathy in the patient's serum, clonal-directed therapy was administered. The patient had been in clinical remission after treatment with clone-directed therapy with cyclophosphamide and steroids. The literature review for cases of type II cryoglobulinemic glomerulonephritis that have detectable serum monoclonal gammopathy are summarized in this study.

Safe and effective treatment of venous Thromboembolism associated with Cancer: focus on direct Oral Anticoagulants in Asian patients.

Cancer-associated thrombosis (CAT) poses a significant disease burden and the incidence in Asian populations is increasing. Anticoagulation is the cornerstone of treatment, but can be challenging due to the high bleeding risk in some cancers and the high risk of recurrent venous thromboembolism (VTE) in patients with malignancies. Direct oral anticoagulants (DOACs) are well established as first-choice treatments for VTE in non-cancer patients, offering a more convenient and less invasive treatment option than low-molecular-weight heparin (LMWH). Asian patients have exhibited comparable efficacy and safety outcomes with other races in trials of DOACs for VTE in the general population. Although no specific data are available in Asian patients with CAT, results from randomized controlled trials of apixaban, edoxaban, or rivaroxaban versus the LMWH, dalteparin, indicate that DOACs are a reasonable alternative to LMWH for anticoagulation in Asian patients with CAT. This is further supported by analyses of real-world data in Asian populations demonstrating the efficacy and safety of DOACs in Asian patients with CAT. Apixaban, edoxaban, or rivaroxaban are recommended in the most recently updated international guidelines as first-line therapy for CAT in patients without gastrointestinal or genitourinary cancers and at low risk of bleeding. An increased risk of major gastrointestinal bleeding was evident with edoxaban or rivaroxaban, but not apixaban, versus dalteparin in the clinical trials, suggesting that apixaban could be a safe alternative to LMWH in patients with gastrointestinal malignancies. Determining the optimal anticoagulant therapy for patients with CAT requires careful consideration of bleeding risk, tumor type, renal function, drug-drug interactions, financial costs, and patients' needs and preferences.

Thrombosis with thrombocytopenia after the second ChAdOx1 nCoV-19 vaccination: A possible immunological mechanism independent of anti-platelet factor 4 antibody.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a distinctive syndrome characterized by unusual site thrombosis accompanied by thrombocytopenia following adenoviral vector vaccines against severe acute respiratory syndrome coronavirus 2. Platelet-activating anti-platelet factor 4-dependent antibodies (anti-PF4 Abs) have been identified as pathogenic antibodies in almost all patients. OBJECTIVE: We proposed an immunological mechanism of VITT independent of anti-PF4 Abs. METHODS: Case report. RESULTS: A 68-year-old Thai woman developed pulmonary embolism and deep vein thrombosis with thrombocytopenia one week after the second ChAdOx1 nCoV-19 vaccination with undetectable anti-PF4 Abs. The platelet count responded rapidly to intravenous immunoglobulin and steroids. Therefore, the high clinical suspicion is essential for early recognition and prompt management irrespective of anti-PF4 Ab results. CONCLUSIONS: We hypothesize that platelet and endothelial activation following ChAdOx1 nCoV-19 vaccination may lead to generation of pathogenic antibodies which account for VITT independent of anti-PF4 Abs.

Post-treatment anti-Mullerian hormone (AMH) levels predict long-term ovarian dysfunction in women with hematological malignancies.

Fertility is a concern in young female survivors of hematological malignancies. We evaluated post-treatment ovarian function in patients by measuring anti-Müllerian hormone (AMH) and conventional hormone levels to correlate with menstruation and fertility.The prospective cohort study included 29 reproductive-aged women diagnosed with Hodgkin lymphoma (n = 11), non-Hodgkin lymphoma (n = 9) or acute myeloid leukemia (n = 9). Hormone assays were measured after treatment was completed and compared to age-matched healthy controls. Menstrual changes and postmenopausal symptoms were assessed annually.Serum AMH levels were significantly lower compared to controls at 12 months after treatment [1.0 (0.18-1.8) vs. 2.2 (1.8-4.8) ng/mL; P < .001). At 12 months, FSH and LH levels were significantly higher compared to controls. The interruption of menstrual cycles was observed in 80% (22/27) of patients. Normal menstruation returned at a median of 1.5 months after cessation of treatment in 71% of patients, while 29% of patients had persistent amenorrhea. Low AMH levels at 12 months after therapy (<1 ng/mL) correlated more strongly with abnormal menstrual cycles than normal AMH levels (46% vs. 0%, P = .04). Four patients with low AMH consulted an infertility clinic.In summary, low serum AMH at 12 months after chemotherapy was associated with persistent menstrual abnormalities.

ChAdOx1 nCoV-19 vaccine-associated thrombocytopenia: three cases of immune thrombocytopenia after 107 720 doses of ChAdOx1 vaccination in Thailand.

We reported three cases of immune thrombocytopenia (ITP) that developed within 6 weeks after ChAdOx1 nCoV-19 vaccination. Antiplatelet factor 4 antibodies were undetectable in all three cases. Therefore, vaccine-induced immune thrombotic thrombocytopenia was very unlikely. Other potential causes of thrombocytopenia were excluded. Their clinical presentations, severity of thrombocytopenia and outcomes were varied. Only one ITP case, an 80-year-old man, received ITP treatments and achieved complete response after 2 weeks of eltrombopag. An 84-year-old man had spontaneous complete remission, and a 55-year-old woman had partial platelet recovery without ITP treatments. Among 107 720 Thais administered the ChAdOx1 vaccine between 16 March and 10 May 2021, these three ITP cases resulted in an estimated risk of ITP of at least one per 36 000 doses, which was approximately similar to the risk of ITP after measles-mumps-rubella immunization. This raises the concern of an increased risk of ITP after ChAdOx1 vaccination.

Viscoelastometric versus standard coagulation tests to guide periprocedural transfusion in adults with cirrhosis: A meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Due to rebalanced haemostasis in cirrhosis, viscoelastometric testing (VET) is more accurate than standard coagulation tests (SCTs) in preprocedural haemostatic evaluation, resulting in decreased unnecessary transfusion. We aimed to determine the impact of VET-guided strategy on postprocedural bleeding, periprocedural transfusion rates and quantities, transfusion-related adverse events (TRAEs), lengths of stay (LOS) and mortality from randomized controlled trials (RCTs) of cirrhotic patients. METHODS: PubMed and EMBASE were searched for RCTs comparing VET-guided with SCT-guided transfusion in cirrhotic adults undergoing esophagogastroduodenoscopy, liver transplantation or other invasive interventions. Using random-effects models, the pooled risk ratios (RRs) and/or mean differences (MDs) of postprocedural bleeding-free events and the other outcomes were estimated alongside 95% confidence intervals (CIs). RESULTS: Of seven included RCTs (n = 421; 72.2% men; mean age 49.1 years), VET-guided transfusion did not change postprocedural bleeding-free statuses (RR 1.05; 95% CI 0.94-1.17). However, VET-based algorithms decreased the rates of fresh frozen plasma (FFP; RR 0.52; 95% CI 0.35-0.77) and platelet transfusions (RR 0.34; 95% CI 0.16-0.73), the quantities of transfused FFP (MD -1.39 units; 95% CI -2.18 to -0.60), platelets (MD -1.06 units; 95% CI -2.01 to -0.12) and cryoprecipitate (MD -7.13 units; 95% CI -14.20 to -0.07) and the risk of TRAEs (RR 0.42; 95% CI 0.27-0.65). The overall mortality rates and LOS were not significantly different between two groups. CONCLUSION: Compared with conventional SCT-guided, VET-guided strategy decreases periprocedural plasma and platelet transfusions and TRAEs, without increasing haemorrhagic complications, LOS or mortality in cirrhosis.

Thromboembolic and hemorrhagic risks after vaccination against SARS-CoV-2: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Thromboembolic and bleeding events after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are major public concerns leading to vaccine hesitancy. Due to low incidence, an individual randomized controlled trial (RCT) is underpowered to determine whether SARS-CoV-2 vaccines increase the risks of thromboembolism and hemorrhage. METHODS: We performed a literature search using PubMed, EMBASE, Cochrane, medRxiv databases, and reference lists of relevant articles to identify RCTs that reported thromboembolic, hemorrhagic events, and thromboembolism/hemorrhage-related death after SARS-CoV-2 vaccination. The primary aim of this systematic review and meta-analysis was to estimate the pooled thromboembolic risk related to SARS-CoV-2 vaccines compared to placebo. The secondary outcomes included estimating the risks of arterial thromboembolism (ATE), venous thromboembolisms (VTE), hemorrhage, thrombocytopenia, and thromboembolism/hemorrhage-related death. RESULTS: Eight RCTs of 4 vaccine platforms comprised of 195,196 participants were retrieved. SARS-CoV-2 vaccines were not associated with an increased risk of overall thromboembolism (risk ratio [RR], 1.14; 95% CI [confidence interval], 0.61-2.14; I2 = 35%), ATE (RR, 0.97; 95% CI, 0.46-2.06; I2 = 21%), VTE (RR, 1.47; 95% CI, 0.72-2.99; I2 = 0%), hemorrhage (RR, 0.97; 95% CI, 0.35-2.68; I2 = 0), and thromboembolism/hemorrhage-related death (RR, 0.53; 95% CI, 0.16-1.79; I2 = 0). Compared to the baseline estimated risk of these outcomes in participants administered placebos, the risk differences with vaccines were very small and not statistically significant. These findings were consistent in the subgroup analysis across 4 vaccine platforms. CONCLUSION: Vaccines against SARS-CoV-2 are not associated with an increased risk of thromboembolism, hemorrhage, and thromboembolism/hemorrhage-related death.

Prevalence of thrombocytopenia, anti-platelet factor 4 antibodies and D-dimer elevation in Thai people After ChAdOx1 nCoV-19 vaccination.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare distinctive syndrome characterized by unusual site thrombosis accompanied by thrombocytopenia after ChAdOx1 nCoV-19 vaccination. Platelet-activating anti-platelet factor 4-dependent antibodies (anti-PF4 Abs) were detected in most cases of VITT. To date, data from Asian countries are lacking. OBJECTIVES: To determine the prevalence of thrombocytopenia, anti-PF4 Abs, and D-dimer elevation in Thai people administered the ChAdOx1 vaccine. PATIENTS/METHODS: A total of 521 vaccinated and 146 nonvaccinated subjects were enrolled. Blood samples were collected to determine platelet counts, anti-PF4 Abs using ELISA and D-dimer levels 5 to 30 days after the first vaccination. RESULTS: None of the participants developed thrombocytopenia or had significantly decreased platelet counts from baseline after ChAdOx1 vaccination. The frequencies of anti-PF4 Abs between vaccinated (16/521; 3.1%; 95% confidence interval [CI], 1.8-4.9) and nonvaccinated Thai people (6/146; 4.1%; 95% CI, 1.5-8.7) were similar. None of the detectable anti-PF4 Abs activated platelets in vitro. The average D-dimer levels between vaccinated and control groups were similar (282.2 ± 286.3 vs 267.8 ± 219.3 ng/mL; P = 0.58). Four vaccinated and one nonvaccinated participants had markedly elevated D-dimer levels >2000 ng/mL without detectable anti-PF4 Abs. Imaging studies of these asymptomatic subjects revealed incidental pulmonary embolism in a vaccinated elderly woman. CONCLUSIONS: This study demonstrated a low prevalence of thrombocytopenia and pathogenic anti-PF4 Abs after ChAdOx1 vaccination. D-dimer testing revealed no significant coagulation activation. Routine tests for platelet counts, anti-PF4 Abs, and D-dimer levels are not recommended for VITT screening without clinical suspicion.

Heparin-induced thrombocytopenia in patients with COVID-19: a systematic review and meta-analysis.

Heparin thromboprophylaxis is routinely administered during hospitalization for COVID-19. Because of the immune stimulation related to COVID-19, there is ongoing concern regarding a heightened incidence of heparin-induced thrombocytopenia (HIT). We performed a literature search using PubMed, EMBASE, Cochrane, and medRxiv database to identify studies that reported clinical and laboratory characteristics and/or the incidence of HIT in patients with COVID-19. The primary aim was to systematically review the clinical features and outcomes of patients with COVID-19 with confirmed HIT. The secondary objective was to perform a meta-analysis to estimate the incidence of HIT in hospitalized patients with COVID-19. A meta-analysis of 7 studies including 5849 patients revealed the pooled incidence of HIT in COVID-19 of 0.8% (95% confidence interval [CI], 0.2%-3.2%; I2 = 89%). The estimated incidences were 1.2% (95% CI, 0.3%-3.9%; I2 = 65%) vs 0.1% (95% CI, 0.0%-0.4%; I2 = 0%) in therapeutic vs prophylactic heparin subgroups, respectively. The pooled incidences of HIT were higher in critically ill patients with COVID-19 (2.2%; 95% CI, 0.6%-8.3%; I2 = 72.5%) compared with noncritically ill patients (0.1%; 95% CI, 0.0%-0.4%: I2 = 0%). There were 19 cases of confirmed HIT and 1 with autoimmune HIT for clinical and laboratory characterization. The median time from heparin initiation to HIT diagnosis was 13.5 days (interquartile range, 10.75-16.25 days). Twelve (63%) developed thromboembolism after heparin therapy. In conclusion, the incidence of HIT in patients with COVID-19 was comparable to patients without COVID-19, with higher incidences with therapeutic anticoagulation and in critically ill patients.

Direct Oral Anticoagulants in Asian Patients with Atrial Fibrillation: Consensus Recommendations by the Asian Pacific Society of Cardiology on Strategies for Thrombotic and Bleeding Risk Management.

The disease burden of AF is greater in Asia-Pacific than other areas of the world. Direct oral anticoagulants (DOACs) have emerged as effective alternatives to vitamin K antagonists (VKA) for preventing thromboembolic events in patients with AF. The Asian Pacific Society of Cardiology developed this consensus statement to guide physicians in the management of AF in Asian populations. Statements were developed by an expert consensus panel who reviewed the available data from patients in Asia-Pacific. Consensus statements were developed then put to an online vote. The resulting 17 statements provide guidance on the assessment of stroke risk of AF patients in the region, the appropriate use of DOACs in these patients, as well as the concomitant use of DOACs and antiplatelets, and the transition to DOACs from VKAs and vice versa. The periprocedural management of patients on DOAC therapy and the management of patients with bleeding while on DOACs are also discussed.

Acute bilateral angle closure induced by monoclonal antibody (Daratumumab) infusion.

PURPOSE: To report a case of daratumumab-induced bilateral angle closure glaucoma and myopia that showed no recurrence after repeated drug administration with prophylactic cycloplegia. OBSERVATIONS: A 63-year-old man with relapsing multiple myeloma presented with acute bilateral eye pain and blurred vision 14 hours after first daratumumab infusion. Eye examination revealed raised intraocular pressure and shallow anterior chamber. Anterior segment ocular coherence tomography and ultrasound biomicroscopy showed ciliochoroidal effusions in both eyes. The diagnosis of bilateral acute angle closure glaucoma and induced myopia was made. Cycloplegia- and intraocular-pressure-lowering medications were given, which gradually deepened the anterior chambers and normalized intraocular pressure and refraction. The ciliochoroidal effusions completely resolved on day 14. The cycloplegic was given as a premedication for subsequent infusions. There was no recurrence of effusion throughout his 6-month daratumumab treatment course. CONCLUSIONS AND IMPORTANCE: Daratumumab can induce ciliochoroidal effusion, which results in acute secondary angle closure and myopia. The potential prophylactic effect of the cycloplegic drug may enable continuation of daratumumab infusion under close monitoring.

Anticoagulation and In-Hospital Mortality From Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

Hypercoagulability in coronavirus disease 2019 (COVID-19) may aggravate disease severity during hospitalization but the reported survival benefits from anticoagulation (AC) vary among studies. We performed a literature research to estimate pooled odds ratios (ORs) of in-hospital mortality and major bleeding comparing among intermediate-to-therapeutic dose AC, prophylactic dose AC, and no AC. Until October 22, 2020, PubMed, EMBASE, and Cochrane Library Database were searched for studies reporting AC utilization and mortality in COVID-19. Studies with suspected risk of bias were excluded before the synthesis of pooled ORs with 95% confidence intervals (CIs) using random-effects models. Of 37 identified studies (N = 19,510), 17 (N = 17,833) were aggregated in the meta-analysis. The overall mortality rate was 23.1% (95% CI 18.7-28.2). The pooled odds of mortality comparing anticoagulated to non-anticoagulated patients were similar, but lower in prophylactic dose AC group (OR 0.83; 95% CI 0.73-0.95). Notably, intermediate-to-therapeutic dose AC increased mortality (OR 1.60; 95% CI 1.11-2.31) and major bleeding compared to prophylactic dose AC (OR 3.33; 95% CI 2.34-4.72). Our findings support the optimal efficacy and safety profiles of prophylactic dose AC in hospitalized COVID-19 patients.

Causes and outcomes of hypereosinophilia in a tropical country.

BACKGROUND: Hypereosinophilia (HE), defined by blood eosinophils > 1.5 ? 109/L persisting over one month, is commonly found in clinical practice. OBJECTIVE: This study aimed to explore etiologies, clinical characteristics, and outcome of HE. METHODS: The HE patients from a single center in Thailand during 2014-2019 were retrospectively reviewed. RESULTS: Among 166 HE patients, 102 (61.5%) cases had reactive HE (HER) of which 52% was due to parasitic infestations. Two-thirds of these patients were diagnosed based on the patients' response to empirical anti-parasite therapy. Without secondary causes, eosinophil-related symptoms were found in 20 (12.0%) patients (Hypereosinophilic syndrome: HES) of which three of them had myeloid neoplasms (HESN) and one case had lymphocytic variant HES (L-HES). Among 11 of 16 idiopathic HES (HESI) patients who were treated with systemic steroid, nine (81.8%) patients responded well, and two cases obtained symptom improvement with stable eosinophilia. There was 44 (26.5%) asymptomatic HE of undetermined significance (HEUS) and 37 (84.1%) of them had HE for more than 6 months before diagnosis. Marked eosinophilia (> 10 ? 109/L) was more common in HES (37.5%), but it was also found in HER (16.7%) and HEUS (11.4%). During the median follow-up period of 16 months, 82.9% (34/41) of HEUS cases remained asymptomatic while seven (17.1%) patients spontaneously recovered. CONCLUSIONS: A therapeutic trial of anti-parasite is reasonable for asymptomatic HE in tropical countries. Most HESI responded to systemic corticosteroids and HEUS showed benign courses without therapy.

Systemic Coagulopathy in Hospitalized Patients With Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

Coagulation activation has been reported in several cohorts of patients Coronavirus Disease 2019 (COVID-19). However, the true burden of systemic coagulopathy in COVID-19 remains unknown. In this systematic review and meta-analysis, we performed a literature search using PubMed, EMBASE, and Cochrane Database to identify studies that reported the prevalence of systemic coagulopathy using established criteria in patients with COVID-19. The primary outcome was the prevalence of systemic coagulopathy (disseminated intravascular coagulation [DIC] and/or sepsis-induced coagulopathy [SIC]). Pooled prevalences and 95% confidence intervals [CIs] were calculated using random-effects model. A total of 5 studies including 1210 patients with confirmed COVID-19 were included. The pooled prevalence of systemic coagulopathy was 7.1% (95%CI: 3.2%,15.3%, I2 = 93%). The pooled prevalence of DIC (N = 721) and SIC (N = 639) were 4.3% (95%CI 1.7%, 10.4%, I2 = 84%) and 16.2% (95%CI: 9.3%, 26.8%, I2 = 74%), respectively. Only 2 studies reported the prevalence of elevated D-dimer levels with the pooled prevalence of 84.6% (95%CI: 52.0%,96.5%, I2 = 94%). Average D-dimer and fibrinogen levels were remarkably increased, while platelet counts, PT, and aPTT ratios were minimally affected in COVID-19. The estimated prevalence of systemic coagulopathy in patients with COVID-19 was low despite D-dimer elevation in most patients. Relatively low systemic coagulopathy in COVID-19 may contribute to the high incidence of thrombosis rather than bleeding in patients with COVID-19.