Practices and challenges for hemophilia management under resource constraints in Thailand.

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.

Direct oral anticoagulants versus low-molecular-weight heparins for the treatment of acute venous thromboembolism in patients with gastrointestinal cancer: a systematic review and meta-analysis.

BACKGROUND: The association between gastrointestinal (GI) cancer and a high incidence of venous thromboembolism (VTE) is well known. Previous randomized controlled studies demonstrated that direct oral anticoagulants (DOACs) effectively treat cancer-associated thrombosis (CAT). However, some DOACs appeared to increase the risk of bleeding, particularly in patients with GI malignancies. Therefore, the current systematic review and meta-analysis were conducted to evaluate the safety and efficacy of DOACs in GI cancer-associated thrombosis. METHODS: Two investigators individually reviewed all studies that compared DOACs and low-molecular-weight heparins (LMWHs) in GI cancer-associated thrombosis and were published in MEDLINE and EMBASE before February 2022. The effect estimates and 95% confidence intervals (CIs) from each eligible study were combined using the Mantel-Haenszel method. RESULTS: A total of 2226 patients were included in the meta-analysis. The rates of major bleeding in the DOAC and LMWH groups were not significantly different (relative risk [RR]: 1.31; 95% CI: 0.84-2.04; P = 0.23; I2 = 41%). However, the rate of clinically relevant nonmajor bleeding (CRNMB) was significantly higher in the DOAC group (RR: 1.76; 95% CI: 1.24-2.52; P = 0.002; I2 = 8%). The risks of recurrent VTE in the groups did not significantly differ (RR: 0.72; 95% CI: 0.49-1.04; P = 0.08; I2 = 0%). CONCLUSIONS: The current data suggest that treatment of GI cancer-associated thrombosis with DOACs significantly increases the risk of CRNMB. However, the risk of major bleeding was not significantly different. The efficacy of DOACs for preventing recurrent VTE in GI cancer was comparable to that of LMWHs. TRIAL REGISTRATION: INPLASY202180113 .

The efficacy of low-dose warfarin initiation (3 mg versus 5 mg) in newly diagnosed venous thromboembolism patients among a population with a high prevalence of warfarin-sensitive haplotype of the VKORC1 gene: a randomized controlled trial.

OBJECTIVES: The fact that a lower warfarin maintenance dose is required by Asian populations is well-known. Currently, the American College of Chest Physicians recommends commencing warfarin at a dose between 5 and 10 mg for venous thromboembolism (VTE). However, the optimal initiating dose in Asians is unknown. This study aimed to evaluate the efficacy of a 3 mg versus a 5 mg of warfarin initiating dose and a corresponding nomogram in patients with VTE. METHODS: Eligible patients were randomized to receive 3 mg or 5 mg per day warfarin for the first 2 days of treatment. The subsequent dose was adjusted according to the warfarin nomogram. The primary outcome was the number of patients who achieved an INR 2.0-3.0 within 8 days. RESULTS: Fifty-six patients were enrolled. There was no significant difference in baseline characteristics between the groups. Seventeen (60.7%) patients in the 3-mg group and 22 (78.6%) patients in the 5-mg group achieved a therapeutic INR within 8 days (p = 0.146). However, there were significantly more patients in the 5-mg group who achieved the target INR on day 5 (53.6% vs 25.0%, p = 0.029). Furthermore, VKORC1-1639G > A was associated with an increased likelihood to achieve the target INR within 5 days (OR 3.81, 95%CI 1.19-12.16, p = 0.021). CONCLUSIONS: The efficacy of a 3 mg warfarin starting dose with subsequent dose adjustment was similar to that of 5 mg on day 8 after warfarin initiation. However, a 5 mg initiating dose resulted in more patients who achieved therapeutic INR on day 5.

Thrombotic and Hemorrhagic Incidences in Patients After Discharge from COVID-19 Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: The association between coronavirus infection 2019 (COVID-19) and thrombosis has been explicitly shown through numerous reports that demonstrate high rates of thrombotic complications in infected patients. Recently, much evidence has shown that patients who survived COVID-19 might have a high thrombotic risk after hospital discharge. This current systematic review and meta-analysis was conducted to better understand the incidence of thrombosis, bleeding, and mortality rates among patients discharged after COVID-19 hospitalization. METHODS: Using a search strategy that included terms for postdischarge, thrombosis, and COVID-19, 2 investigators independently searched for published articles indexed in the MEDLINE, Embase, and Scopus databases that were published before August 2021. Pooled incidences and 95% confidence intervals were calculated using the DerSimonian-Laird random-effects model with a double arcsine transformation. RESULTS: Twenty articles were included in the meta-analysis. They provided a total of 19 461 patients discharged after COVID-19 hospitalization. The weighted pooled incidence of overall thrombosis among the patients was 1.3% (95 CI, 0. 6-2; I2 90.5), with a pooled incidence of venous thrombosis of 0.7% (95 CI, 0. 4-1; I2 73.9) and a pooled incidence of arterial thrombosis of 0.6% (95 CI, 0. 2-1; I2 88.1). The weighted pooled incidences of bleeding and mortality were 0.9% (95 CI, 0. 1-1.9; I2 95.1) and 2.8% (95 CI, 0. 6-5; I2 98.2), respectively. CONCLUSIONS: The incidences of thrombosis and bleeding in patients discharged after COVID-19 hospitalization are comparable to those of medically ill patients.

Successful venous thromboprophylaxis in a patient with vaccine-induced immune thrombotic thrombocytopenia (VITT): a case report of the first reported case in Thailand.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but fatal complication of the Coronavirus Disease 2019 vaccine. The many reports of VITT have mostly been in the Caucasian population. Here, we present the first reported case in an Asian population. CASE PRESENTATION: A 26-year-old female had severe headache and severe thrombocytopenia 8 days after administration of the ChAdOx1 nCoV-19 vaccine developed by AstraZeneca. Although no thrombosis was demonstrated by imaging studies, she had very highly elevated d-dimer levels during hospitalization. Serology for antibodies against platelet factor 4 was positive on several days with very high optical density readings. We found that the antibody could induce spontaneous platelet aggregation without the presence of heparin. We decided to treat her with intravenous immunoglobulin, high-dose dexamethasone, and a prophylactic dose of apixaban. She improved rapidly and was discharged from the hospital 6 days after admission. Neither thrombocytopenia nor thrombosis was subsequently detected at the three-week follow-up. CONCLUSIONS: Despite the lower rate of thrombosis, VITT can occur in the Asian population. Early detection and prompt treatment of VITT can improve the patient's clinical outcome. Thromboprophylaxis with nonheparin anticoagulants also prevents clot formation.

Risk of perioperative bleeding related to highly selective cyclooxygenase-2 inhibitors: A systematic review and meta-analysis.

BACKGROUND: Several literatures reported that highly selective cycloxygenase-2 inhibitors (COX-2 inhibitors) had no effect on platelet function. However, some experts suggested stopping all non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors at least five elimination half-lives prior to surgery. We, therefore, systematically summarized the risk of clinical bleeding or platelet dysfunction in healthy or surgical subjects who received COX-2 inhibitors. METHODS: Two electronic databases, MEDLINE and EMBASE, were searched for randomized, controlled studies published during 1980-December 2015. Additionally, manual search was performed to identify potential eligible studies. Intervention was perioperative use of any available COX-2 inhibitors in current practice (celecoxib, parecoxib, or etoricoxib), compared to non-selective NSAIDs, analgesics, or placebo. Two independent reviewers selected eligible studies, extracted the data, and assessed the quality of the included studies. The primary outcome was postoperative bleeding. All analyses were performed using RevMan-5.3. RESULTS: Of 3900 abstracts reviewed, 35 studies met the inclusion criteria. The data from 16 out of 35 studies were used in this meta-analysis, and outcomes of other 19 remaining studies were descriptively summarized. COX-2 inhibitors did not significantly increase the risk of postoperative bleeding events (relative risk or RR = 0.92; 95% confidence interval or CI: 0.63-1.33; p = 0.65), intraoperative blood loss (mL) (weighted mean difference or WMD = -4.38; 95% CI: -14.69 to 5.92; p = 0.4), postoperative blood loss (mL) (WMD = -13.89; 95% CI: -30.24 to 2.47; p = 0.10), and 24-h postoperative hemoglobin loss (g/dL) (WMD = 0.47; 95% CI: -0.14 to 1.09; p = 0.13). Platelet function analyzer closure time (second) significantly decreased with the use of COX-2 inhibitors (WMD = -22.22; 95% CI: -44.03 to -0.41; p < 0.00001). In the 19 remaining studies, COX-2 inhibitors did not significantly increase risk of bleeding in both clinical and laboratory outcomes. CONCLUSION: Highly selective COX-2 inhibitors did not significantly increase the risk of intraoperative, postoperative bleeding, or blood loss. They also had no significant effect on platelet function. Therefore, perioperative, single dose, or short course of COX-2 inhibitors can be safely used in individuals who are undergoing surgery.

The efficacy of 3-mg warfarin initiating dose in adult Thai patients, who required long-term anticoagulant therapy.

BACKGROUND: Warfarin anticoagulation is the standard treatment for patients with thromboembolic diseases. Prior studies recommended commencing warfarin with the initial doses between 5 mg and 10 mg for the first 1 or 2 days. However, lower warfarin loading dose is advised for the elderly and patients with co-morbid diseases. Moreover, warfarin requirement is also affected by several genetic factors, which differ among various ethnic populations. Currently, the optimal initiating dose of warfarin in Thai patients is unknown. However, based on the observation of the clinical practice at Siriraj hospital, a lower starting dose (3 mg/day) of warfarin was commonly given to patients who required long-term anticoagulant therapy. OBJECTIVE: To investigate the efficacy and safety of 3-mg warfarin initiating dose. MATERIAL AND METHOD: A retrospective study of inpatients who received warfarin 3 mg/day for the first two days of oral anticoagulation therapy with the target INR of 2.0-3.0 at Siriraj hospital from January 2004-December 2007 was performed. The efficacy of 3-mg warfarin loading dose was determined by assessing the proportion of patients who achieved the target INR of 2.0-3.0 between day 3 and day 5 of warfarin treatment. RESULTS: Total of 164 patients was included in the study. Eighty-six patients (52.4%) were males. The mean age was 55.1 + 16.8 years (range 16-88 years). The mean body weight and serum albumin were 61.5 +/- 12.2 kg and 3.7 +/- 0.7 g/dl, respectively. Prosthetic heart valve replacement was the most common indication for warfarin anticoagulation therapy (36%), followed by deep vein thrombosis (32.3%). The mean cumulative weekly dose of warfarin was 22.3 +/- 5.8 mg. The median time to therapeutic INR (2.0-3.0) was 6 days. Forty-seven patients (29%) achieved therapeutic INR between day 3 and day 5 of warfarin treatment. Time to therapeutic INR was not affected by age, gender, body weight, serum albumin, or concomitant medication use. Interestingly, patients who received warfarin due to prosthetic heart valve replacement were more likely to achieve therapeutic INR between day 3 and day 5 when compared to those with other indications with adjusted OR 16.25 (95% CI 5.13-51.44, p < 0.001). Bleeding complication was rare (0.6%) and was not associated with excessive anticoagulation. CONCLUSION: 3-mg warfarin initiating dose appeared to be safe in adult Thai patients. However, the efficacy of 3-mg starting dose as determined by the proportion of patients who achieved the target INR between day 3 and day 5 of warfarin treatment was relatively less efficient when compared with that previously reported with a 5-mg loading dose. Further randomized, prospective study is required to examine the efficacy of 3-mg versus higher warfarin starting dose in Thai patients.

Two patients with rare causes of Weber's syndrome.

We report two patients with rare causes of Weber's syndrome and review the relevant literature. The first patient presented with Weber's syndrome caused by a partially thrombosed giant aneurysm of the posterior cerebral artery. The second patient was an immunocompetent patient who presented with progressive hemiparesis and subsequently developed Weber's syndrome. Primary central nervous system lymphoma (PCNSL) was eventually diagnosed. To our knowledge, the association between Weber's syndrome and PCNSL is rare.

5-azacitidine: An alternative treatment of myelodysplastic syndromes in patient with refractory response to hematopoietic growth factor, a case report and review of literatures.

Myelodysplastic Syndrome (MDS) comprises a heterogeneous group of clonal hemopathies derived from an abnormality affecting a multipotent hematopoietic stem cell and characterized by maturation defects resulting in ineffective hematopoiesis. It most frequently occurs in elderly patients. Despite trials testing numerous agents in patients with MDS, no single drug has yet emerged as the accepted standard of treatment. Most MDS patients, due to their age and co morbidity, are not eligible for allogeneic hematopoietic stem cell transplantation; the only established curative regimen. The effect of available lineage-specific growth factors is limited to improvement of single lineages and has not resulting in the survival benefit. Treatment with low dose Ara-C is disappointing in regard to response rate or duration. No benefit has been demonstrated in differentiation inducers such as retinoids and Vitamin D3 as single agents. We report a case of a patient with transfusion dependent MDS who was not a candidate for allogeneic stem cell transplantation or cytotoxic chemotherapy, who also failed to response to erythropoietin support but had a favorable response to 5-azacitidine. His blood transfusion requirement reduced significantly, and was correlated with the remarkable improvement of the pancytopenia, particularly anemia and thrombocytopenia after receiving the investigational therapy with 5-azacitidine. In summary, 5-azacitidine appears to be a promising alternative therapy for patient with refractory anemia secondary to MDS.