This multinational, randomized, single-blind trial investigated the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in 74 previously ...treated patients with hemophilia B (FIX activity ≤2 IU/dL). Patients received prophylaxis for 52 weeks, randomized to either 10 IU/kg or 40 IU/kg once weekly or to on-demand treatment of 28 weeks. No patients developed inhibitors, and no safety concerns were identified. Three hundred forty-five bleeding episodes were treated, with an estimated success rate of 92.2%. The median annualized bleeding rates (ABRs) were 1.04 in the 40 IU/kg prophylaxis group, 2.93 in the 10 IU/kg prophylaxis group, and 15.58 in the on-demand treatment group. In the 40 IU/kg group, 10 (66.7%) of 15 patients experienced no bleeding episodes into target joints compared with 1 (7.7%) of 13 patients in the 10 IU/kg group. Health-related quality of life (HR-QoL) assessed with the EuroQoL-5 Dimensions visual analog scale score improved from a median of 75 to 90 in the 40 IU/kg prophylaxis group. Nonacog beta pegol was well tolerated and efficacious for the treatment of bleeding episodes and was associated with low ABRs in patients receiving prophylaxis. Once-weekly prophylaxis with 40 IU/kg resolved target joint bleeds in 66.7% of the affected patients and improved HR-QoL. This trial was registered at www.clinicaltrials.gov as #NCT01333111.
•Nonacog beta pegol, a recombinant glycoPEGylated FIX with extended half-life, was developed to improve care for patients with hemophilia B.•Weekly prophylaxis with nonacog beta pegol was well tolerated and was associated with low bleeding rates and an improved quality of life.
Vaccination with ChAdOx1 n‐CoV‐19 is associated with a rare syndrome called vaccine‐induced immune thrombotic thrombocytopenia (VITT). VITT has been reported mainly in Western countries, whereas the ...report of VITT in Asians is sparse.
To report a case series of VITT following ChAdOx1 n‐CoV‐19 in Thailand and to estimate the incidence of VITT among Asian countries.
We retrieved the number of VITT patients and the total inoculation doses from the database of the Thai Ministry of Public Health. We performed a literature search including published articles and gray literature to estimate the incidence of VITT. The incidences of VITT by countries and respective confidence intervals were calculated.
By the end of August 2021, five VITT cases occurred after 15 million doses of ChAdOx1 n‐CoV‐19 in Thailand. The median age was 31 years, and 60% were women. The incidence of VITT is estimated at 1 in 3 million. In other Asian countries, only a few cases of VITT have been reported. The incidence of VITT is much lower than in those of Western countries, which is estimated at 1 in 100, 000. The fatality rate was 44% in this study.
Although the incidence of VITT in Asians is low, the mortality rate is substantially higher. We urge that public awareness of this syndrome be raised, as early recognition and appropriate treatment of this syndrome following ChAdOx1 n‐CoV‐19 are crucial to improve the outcome.
Hemophilia is an inherited bleeding disorder caused by deficiency of a specific coagulation factor. Factor VIII deficiency is responsible for hemophilia A while factor IX deficiency is responsible ...for hemophilia B. As per the 2020 annual global survey by the World Federation of Hemophilia, only 1828 Thai hemophiliacs have been registered to the national healthcare system. The reason for the low number is the underdiagnosis which is a major concern in the real-world practice among Asian countries. In Thailand, most hemophiliacs are diagnosed by general practitioners, pediatricians or internists at rural hospitals and are referred to hemophilia specialists at the Hemophilia Treatment Centers (HTCs). Despite the challenges pertaining to infrastructure and cost of treatment, Thailand has progressed substantially in providing the required hemophilia care, as evidenced by an evolution in acquiring and sharing knowledge as well as collaborative efforts among multiple stakeholders over the past three decades. In this letter-to-the-editor, the authors have summarized the practices for and challenges faced with hemophilia management in Thailand.
Background
Direct oral anticoagulants (DOACs) are commonly used to prevent stroke and systemic embolism in patients with atrial fibrillation (AF). However, studies into their effectiveness and safety ...in the Thai population have so far been limited.
Objectives
To study the effectiveness and safety of warfarin and DOACs among Thai AF patients
Methods
A retrospective cohort study was conducted on AF patients at Ramathibodi Hospital from 2013 to 2018. All patients were followed for at least 1 year. Relevant clinical information was collected and compared between AF patient groups receiving warfarin, dabigatran, rivaroxaban, and apixaban. The primary outcome was a composite of major bleeding, ischemic stroke, and systemic thromboembolism. The secondary outcomes were all-cause mortality and disease-specific mortality caused by major bleeding, ischemic stroke, and systemic thromboembolism.
Results
A total of 1680 AF patients were enrolled in the study (warfarin 1193, apixaban 140, dabigatran 193, rivaroxaban 114). The estimated incidence of composite outcome was 16% 95% CI, 14−18% and 12.4% 95% CI, 9.4−15.3% in the warfarin and DOAC group, respectively, given a number needed to treat of 28 95% CI, 3−52. Compared with warfarin, DOACs were associated with both lower rate of all-cause mortality (4.9% 22/447 vs 8% 98/1193) and lower disease-specific mortality (0.4% 2/447 and 1% 12/1193).
Conclusions
This study suggests DOACs were associated with a lower risk of major bleeding, ischemic stroke, and systemic thromboembolism compared to warfarin in Thai patients with AF. Patients receiving DOAC also had a lower rate of all-cause mortality and disease-specific mortality.
There is limited information on the influence of body mass index (BMI) on clinical outcomes in patients with venous thromboembolism (VTE).
Investigate the influence of BMI on baseline ...characteristics, treatment patterns, and 24-month outcomes in VTE patients.
GARFIELD-VTE is a prospective, non-interventional study of 10 869 patients with objectively confirmed VTE. Patients were grouped according to BMI: <18.5 (underweight; n = 214); 18.5-24.9 (normal; n = 2866); 25.0-29.9 (overweight; n = 3326); ≥30 (obese; n = 3073).
Compared with patients with a normal BMI, obese patients were more frequently Caucasian (77.4% vs. 57.9%), treated in the outpatient setting (30.4% vs. 23.1%), and had previous VTE (17.5% vs. 11.7%). Active cancer was associated with lower BMI (underweight: 30.4%, normal: 13.5%, overweight: 9.4%, obese: 7.0%). At baseline, overweight and obese patients less often received parenteral therapy alone (16.7% and 14.4%) compared with those with an underweight or normal BMI (30.8% and 21.6%). Obese patients more commonly remained on anticoagulants for ≥2-years compared to those with a normal BMI (52.3% vs. 37.7%). After 24-months, the risk of all-cause mortality was lower in overweight and obese patients than in those with normal BMI (adjusted hazard ratio 95% CI; 0.75 0.63-0.89 and 0.59 0.49-0.72, respectively). Underweight patients more often experienced major bleeding (2.45 1.41-4.26) and all-cause mortality (1.90 1.43-2.53) than patients with a normal BMI. Recurrent VTE was comparable among groups.
Underweight VTE patients have the highest risk of mortality and major bleeding. The risk of mortality in obese VTE patients is lower than that in VTE patients with a normal BMI.
Immunization stress-related responses presenting as stroke-like symptoms could develop following COVID-19 vaccination. Therefore, this study aimed to describe the clinical characteristics of ...immunization stress-related responses causing stroke-like events following COVID-19 vaccination in Thailand. We conducted a retrospective study of the secondary data of reported adverse events after COVID-19 immunization that presented with neurologic manifestations. Between March 1 and July 31, 2021, we collected and analyzed the medical records of 221 patients diagnosed with stroke-like symptoms following immunization. Two majority types of vaccines were used at the beginning of the vaccination campaign, including CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca). Demographic and medical data included sex, age, vaccine type, sequence dose, time to event, laboratory data, and recovery status as defined by the modified Rankin score. The affected side was evaluated for associations with the injection site. Overall, 221 patients were diagnosed with immunization stress-related responses (stroke-like symptoms) following CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca) vaccinations. Most patients (83.7%) were women. The median (interquartile range) age of onset was 34 (28-42) years in patients receiving CoronaVac and 46 (33.5-60) years in those receiving ChAdOx1. The median interval between vaccination and symptom onset for each vaccine type was 60 (16-960) min and 30 (8.8-750) min, respectively. Sensory symptoms were the most common symptomology. Most patients (68.9%) developed symptoms on the left side of the body; 99.5% of the patients receiving CoronaVac and 100% of those receiving ChAdOx1 had a good outcome (modified Rankin scores less than or equal to2, indicating slight or no disability). Immunization stress-related responses presenting as stroke-like symptoms can develop after COVID-19 vaccination. Symptoms more likely to occur on the injection side are transient (i.e., without permanent pathological deficits). Public education and preparedness are important for administering successful COVID-19 vaccination programs.
Heavy menstrual bleeding (HMB) is common among reproductive‐aged women receiving oral antithrombotics and frequently results in a negative impact on quality of life.
We translated the Menstrual ...Bleeding Questionnaire (MBQ) into Thai by forward translation, back‐translation, pretesting, and cognitive interviewing. The translated questionnaire was content validated by a gynecologist. A validation study was conducted for the translated MBQ and defined the optimal score for the diagnosis of HMB. We then performed a cross‐sectional study to determine the prevalence of HMB using the translated MBQ. Reproductive‐aged Thai women who visited outpatient clinics receiving oral antithrombotics were asked to assess menstrual characteristics after receiving antithrombotics. The impact of menstruation on quality of life was assessed by using the MBQ.
The translated MBQ had excellent reliability (intraclass correlation coefficient = 0.93) and discriminated between women with and without HMB (area under the receiver operating characteristic curve = 0.93). A score of 21.5 had 82.9% sensitivity and 83.1% specificity in the diagnosis of HMB. The mean (standard deviation) of the score was significantly higher in the HMB group than in the normal menstrual bleeding group (30.4 9.4 vs 15.4 5.6; P < .001, respectively). Of the 49 women, the prevalence of HMB in patients receiving warfarin (n = 29), direct oral anticoagulants (n = 4), or antiplatelet agents (n = 16) was 27.6%, 25.0%, and 25.0%, respectively.
MBQ is a simple and valid tool that can be applied to screen women experiencing HMB. One‐fourth of reproductive‐aged women who received oral antithrombotics experienced HMB that impacted their quality of life.
Abstract Blood coagulation activation is frequently found in patients with malaria. Clinically apparent bleeding or disseminated intravascular coagulation (DIC) is associated with very severe disease ...and a high mortality. Protein C, protein S, and antithrombin levels were found to be low in P. falciparum , but were normal in P. vivax infection. Plasma levels of plasminogen activator inhibitor-1 were high in cases of P. falciparum infection whereas tissue plasminogen activator levels were low. Elevated plasma levels of von Willebrand factor (vWF) and vWF propeptide, thrombomodulin, endothelial microparticles have been reported in P. falciparum -infected patients. It has been demonstrated that severe P. falciparum infection is associated with acute endothelial cell (EC) activation, abnormal circulating ultralarge vWF multimers, and a significant reduction in plasma ADAMTS13 function. These changes may result in intravascular platelet aggregation, thrombocytopenia, and microvascular disease. It has also been shown that P. falciparum -parasitized red blood cells (pRBCs) induce tissue factor (TF) expression in microvascular ECs in vitro . Recently, loss of endothelial protein C receptor (EPCR) localized to sites of cytoadherent pRBCs in cerebral malaria has been demonstrated. Severe malaria is associated with parasite binding to EPCR. The cornerstone of the treatment of coagulopathy in malaria is the use of effective anti-malarial agents. DIC with spontaneous systemic bleeding should be treated with screened blood products. Study in Thailand has shown that for patients who presented with parasitemia > 30% and severe systemic complications such as acute renal failure and ARDS, survival was superior in the group who received exchange transfusion. The use of heparin is generally restricted to patients with DIC and extensive deposition of fibrin, as occurs with purpura fulminans or acral ischemia. Antiplatelet agents interfere with the protective effect of platelets against malaria and should be avoided.
Abstract
Background
The prevalence of anti-platelet factor 4 (PF4)/polyanionic antibodies occurring after vaccination with ChAdOx1 nCoV-19 is low. Most of these antibodies are not associated with ...vaccine-induced thrombotic thrombocytopenia. It remains unknown whether these antibodies are preexisting or occur as a result of vaccination. In this study, we demonstrated the incidence of anti-PF4/polyanionic antibodies, thrombocytopenia, and thrombosis after vaccination with ChAdOx1 nCoV-19 in a large cohort of Thais.
Methods
We conducted a prospective study in a cohort of health care workers and members of the general population who received COVID-19 vaccination with ChAdOx1 nCoV-19. Blood collection for complete blood count, D-dimer, and anti-PF4/polyanionic antibodies was performed before vaccination (day 0), day 10, and day 28 after vaccination. Anti-PF4/polyanionic antibodies were detected using enzyme-link immunosorbent assay (ELISA). Functional assay was performed for all positive ELISA tests.
Results
A total of 720 participants were included in the study. 214 participants received both the first and second doses, 91 participants received only the first, 51 received only the second, and 364 received the third booster dose of ChAdOx1 nCoV-19. Median age was 42 years (IQR, 34–53). 67% of participants were female. Three participants developed seroconversion, yielding an incidence of vaccination-induced anti-PF4/polyanionic antibodies of 0.42% (95% confidence interval 0.08, 1.23). Fourteen (1.9%) participants had preexisting anti-PF4/polyanionic antibodies before the vaccination but their optical density of anti-PF4/polyanionic antibodies did not significantly increase over time. None of the anti-PF4/polyanionic positive sera induced platelet aggregation. Abnormal D-dimer levels following vaccination were not different among the positive and negative anti-PF4/polyanionic groups (11.8% vs. 13.2%, p = 0.86). Thrombocytopenia occurred in one person with negative anti-PF4/polyanionic antibodies. No clinical thrombosis or bleeding occurred.
Conclusion
We found a low incidence of seroconversion of anti-PF4/polyanionic antibodies after vaccination with ChAdOx1 nCoV-19 in Thais. Most of the anti-PF4/polyanionic antibodies were preexisting and did not significantly increase after vaccination with ChAdOx1 nCoV-19. Following vaccination, some participants with anti-PF4/polyanionic antibodies had elevated D-dimer levels, while only one developed thrombocytopenia and no thrombotic events were observed.
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