Low prevalence of heparin-induced thrombocytopenia after cardiac surgery in Thai patients

Introduction

Heparin induced-thrombocytopenia (HIT) has been well recognized in Western countries. However, there are no data in the Thai population. We therefore investigated the prevalence of anti-platelet factor 4 (PF4)/heparin antibodies, HIT, and its thrombotic complications in Thai patients undergoing cardiac surgery using unfractionated heparin.

Materials and methods

Seventy-three consecutive patients were prospectively enrolled in this study. Blood samples before operation and week 1, week 2, and week 3 after operation were collected from each patient for HIT antibody screening by enzyme-linked immunosorbent assay using IgG antibody specific to the PF4/heparin complex. Positive samples were further analyzed by ¹⁴C-serotonin release assay. Complete blood count was performed daily during the first week, then weekly for 3 weeks.

Results

No patient had detectable anti-PF4/heparin antibodies at baseline. Five patients sero-converted during the course of the study for anti-PF4/heparin IgG: 3 (4.1%) at week 1, 4 (5.5%) at week 2, and 5 (6.8%) at week 3 after surgery. However, none of these patients had anti-PF4/heparin antibodies that resulted in ¹⁴C-serotonin release to be considered clinically significant antibodies. Post-operative thrombocytopenia after the operation was found in 35 patients (47.9%), but was not considered to be caused by HIT. Thromboembolic events occurred in 3 patients (4.1%) during follow up; however, none of these patients had positive PF4/heparin antibody tests.

Conclusions

Our study represents the first study to examine Thai patients exposed to heparin in the context of cardiac surgery. We found a lower prevalence of positive anti-PF4/heparin antibodies and clinical HIT than previously published studies.     

Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease 2019: a cross-sectional study

ObjectivesAmid the increasing number of pandemic coronavirus disease 2019 (COVID-19) cases, there is a need for a quick and easy method to obtain a non-invasive sample for the detection of this novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2). We aimed to investigate the potential use of saliva samples as a non-invasive tool for the diagnosis of COVID-19.MethodsFrom 27 March to 4 April 2020, we prospectively collected saliva samples and a standard nasopharyngeal and throat swab in persons seeking care at an acute respiratory infection clinic in a university hospital during the outbreak of COVID-19. Real-time polymerase chain reaction (RT-PCR) was performed, and the results of the two specimens were compared.ResultsTwo-hundred pairs of samples were collected. Sixty-nine (34.5%) individuals were male, and the median (interquartile) age was 36 (28–48) years. Using nasopharyngeal and throat swab RT-PCR as the reference standard, the prevalence of COVID-19 diagnosed by nasopharyngeal and throat swab RT-PCR was 9.5%. The sensitivity and specificity of the saliva sample RT-PCR were 84.2% (95% CI 60.4%–96.6%), and 98.9% (95% CI 96.1%–99.9%), respectively. An analysis of the agreement between the two specimens demonstrated 97.5% observed agreement (κ coefficient 0.851, 95% CI 0.723–0.979; p < 0.001).ConclusionsSaliva might be an alternative specimen for the diagnosis of COVID-19. The collection is non-invasive, and non-aerosol generating. This method could facilitate the diagnosis of the disease, given the simplicity of specimen collection and good diagnostic performance.     

Effect of chewing speed on energy expenditure in healthy subjects

Objective. The aim of the study was to investigate the effect of rate of chewing on energy expenditure in human subjects. Materials and methods. Fourteen healthy subjects (aged 18–24 years) within the normal range of BMI participated in a cross-over experiment consisting of two 6-min sessions of gum chewing, slow (～60 cycles/min) and fast (～120 cycles/min) chewing. The resting energy expenditure (REE) and during gum chewing was measured using a ventilated hood connected to a gas analyzer system. The normality of data was explored using the Shapiro-Wilk test. The energy expenditure rate during chewing and the energy expenditure per chewing cycle were compared between the two chewing speeds using Wilcoxon signed ranks tests. Results. The energy expenditure per chewing cycle during slow chewing (median 1.4, range 5.2 cal; mean 2.1±1.6 cal) was significantly higher than that during fast chewing (median 0.9, range 2.2 cal; mean 1.0±0.7 cal) (p < 0.005). However, the energy expenditure rate was not significantly different between the two chewing speeds (p > 0.05). Conclusions. The results of this study suggest that chewing at a slower speed could increase the energy expenditure per cycle and might affect the total daily energy expenditure.     

Thrombosis and anticoagulation: clinical issues of special importance to hematologists who practice in Asia

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Effects of posterior condylar osteophytes on gap balancing in computer-assisted total knee arthroplasty with posterior cruciate ligament sacrifice

Objective

Gap planning in navigated total knee arthroplasty (TKA) is a critical concern. Osteophytes are normally removed prior to gap planning, with the exception of posterior condylar osteophytes of the femur, which are removed after posterior condylar resection. This study investigated how posterior condylar osteophytes affect gap balancing during surgery.

Methods

This prospective study was conducted on 40 primary varus osteoarthritic knees with a posterior condylar osteophyte that underwent TKA navigation. For all knees, computed tomography (CT) was performed to evaluate osteophyte position. The extension gap and flexion gap were determined under navigation using a tension device with a distraction force of 44 lb. The extension gap and flexion gap were measured before and after osteophyte removal.

Results

This study revealed that the average osteophyte thickness after removal was 7.75 ± 5.34 mm. The average extension gap change was 0.64 ± 0.80 mm, and the average flexion gap change was 0.85 ± 1.12 mm. With respect to increases in the medial extension gap, lateral extension gap, medial flexion gap and lateral flexion gap, the average effects of posterior condylar osteophyte removal were 0.74 ± 0.81 mm, 0.53 ± 0.96 mm, 0.71 ± 0.97 mm and 1.00 ± 1.41 mm, respectively. Posterior condylar osteophyte thickness was also significantly associated with increases in the lateral extension gap (R² = 0.107, p = 0.03), medial flexion gap (R² = 0.101, p = 0.04) and lateral flexion gap (R² = 0.107, p = 0.04).

Conclusion

These results indicated that posterior condylar osteophytes of the femur affect gap balancing during TKA navigation.

     

Combined De-Novo Mutation and Non-Random X-Chromosome Inactivation Causing Wiskott-Aldrich Syndrome in a Female with Thrombocytopenia

Objective

Disorders linked to mutations in the X chromosomes typically affect males. The aim of the study is to decipher the mechanism of disease expression in a female patient with a heterozygous mutation on the X-chromosome.

Patients and Methods

Clinical data was extracted from the Canadian Inherited Marrow Failure Registry. Genomic ribonucleic acid (DNA) and complementary DNA (cDNA) underwent Sanger sequencing. Protein analysis was performed by flow cytometry. X-inactivation patterns were analyzed by evaluating the DNA methylation status and cDNA clonal expression of several genes on the X-chromosome. SNP array was used for molecular karyotyping of the X-chromosome.

Results

A female with thrombocytopenia, eczema and mild T-lymphocyte abnormalities with extensive negative diagnostic testing, was suspected to have Wiskott-Aldrich syndrome (WAS)/X-linked thrombocytopenia. Although the girl had a mutation (c.397G?>?A, p.E133K) in only one allele, she was found to have an extremely skewed X-inactivation pattern and no expression of the WAS protein. Family studies using DNA methylation analysis and cDNA clonal expression of several genes on the X-chromosome demonstrated that the patient developed de-novo non-random inactivation of the X-chromosome that does not carry the mutation. Genome-wide high-density molecular karyotyping excluded deletions and amplifications as a cause for the non-random inactivation of one X-chromosome.

Conclusions

Our study emphasizes the need to test selected female patients with complete or incomplete disease expression for X-linked disorders even in the absence of a family history.     

The added-up albumin enhances the diuretic effect of furosemide in patients with hypoalbuminemic chronic kidney disease: a randomized controlled study

ABSTRACT: BACKGROUND: Chronic kidney disease (CKD) with edema is a common clinical problem resulting from defects in water and solute excretion. Furosemide is the drug of choice for treatment. In theory, good perfusion and albumin are required for the furosemide to be secreted at the tubular lumen. Thus, in the situation of low glomerular filtration rate (GFR) and hypoalbuminemia, the efficacy of furosemide alone might be limited. There has been no study to validate the effectiveness of the combination of furosemide and albumin in this condition. METHODS: We conducted a randomized controlled crossover study to compare the efficacy of diuretics between furosemide alone and the combination of furosemide plus albumin in stable hypoalbuminemic CKD patients by measuring urine output and sodium. The baseline urine output/sodium at 6 and 24 hours were recorded. The increment of urine output/sodium after treatment at 6 and 24 hours were calculated by using post-treatment minus baseline urine output/sodium at the corresponding period. RESULTS: Twenty-four CKD patients (GFR = 31.0 [PLUS-MINUS SIGN] 13.8 mL/min) with hypoalbuminemia (2.98 [PLUS-MINUS SIGN] 0.30 g/dL) were enrolled. At 6 hours, there were significant differences in the increment of urine volume (0.47 [PLUS-MINUS SIGN] 0.40 vs 0.67 [PLUS-MINUS SIGN] 0.31 L, P < 0.02) and urine sodium (37.5 [PLUS-MINUS SIGN] 29.3 vs 55.0 [PLUS-MINUS SIGN] 26.7 mEq, P < 0.01) between treatment with furosemide alone and with furosemide plus albumin. However, at 24 hours, there were no significant differences in the increment of urine volume (0.49 [PLUS-MINUS SIGN] 0.47 vs 0.59 [PLUS-MINUS SIGN] 0.50 L, P = 0.46) and urine sodium (65.3 [PLUS-MINUS SIGN] 47.5 vs 76.1 [PLUS-MINUS SIGN] 50.1 mEq, P = 0.32) between the two groups. CONCLUSION: The combination of furosemide and albumin has a superior short-term efficacy over furosemide alone in enhancing water and sodium diuresis in hypoalbuminemic CKD patients.Trial registrationThe Australian New Zealand Clinical Trials Registration (ANZCTR12611000480987).     

Reduced‐dose direct oral anticoagulants in the extended treatment of venous thromboembolism: a systematic review and meta‐analysis

Essentials

• In venous thromboembolism (VTE), benefits of extended treatment are balanced by bleeding risks.
• This is a meta‐analysis of reduced‐dose direct oral anticoagulants (DOACs) in extended treatment.
• Reduced‐dose DOACs are as effective as full anticoagulation with bleeding risks similar to placebo.
• Reduced‐dose DOACs are an attractive option for patients in the extended phase of VTE treatment.

Summary

Background

Extended‐duration anticoagulation is beneficial for preventing recurrent venous thromboembolism (VTE). Reduced‐dose direct oral anticoagulants (DOACs) may be preferable if they preserve efficacy and cause less bleeding. We conducted a systematic review and meta‐analysis of trials comparing reduced‐dose DOACs with full‐dose DOACs and aspirin or placebo in the extended phase of VTE treatment.

Methods

A literature search was conducted by use of the MEDLINE, EMBASE and CINAHL databases, supplemented by hand‐searching. One thousand three hundred and ninety‐nine titles were screened, with data from accepted studies being extracted by two independent reviewers. Major outcomes analyzed included recurrent VTE and major and clinically relevant non‐major bleeding events, presented as risk ratios (RRs) and 95% confidence intervals (CI).

Results

Two trials met the prespecified inclusion criteria. Data from 5847 patients were analyzed for efficacy outcomes, and from 5842 patients for safety outcomes. Reduced‐dose DOACs were as effective as full‐dose treatment in preventing recurrent VTE at 1 year (RR 1.12 [95% CI 0.67–1.87]), and more effective than aspirin or placebo (RR 0.26 [95% CI 0.14–0.46]). Rates of major or clinically relevant non‐major bleeding events were similar between patients receiving reduced‐dose DOACs and and those receiving aspirin or placebo (RR 1.19 [95% CI 0.81–1.77]). There was a trend towards less bleeding when reduced‐dose and full‐dose DOACs were compared (RR 0.74 [95% CI 0.52–1.05]).

Conclusions

Extended‐duration treatment of VTE with reduced‐dose DOACs may be as efficacious as full‐dose treatment, with rates of major bleeding being similar to those in patients receiving treatment with aspirin or placebo, but further long‐term studies are needed.