Incidence and mortality rates of intracranial hemorrhage in hemophilia: a systematic review and meta-analysis
Intracranial hemorrhage (ICH) is a severe complication that is relatively common among hemophilia patients. This systematic review aimed to obtain more precise estimates of ICH incidence and mortality in hemophilia, which may be important for patients, caregivers, researchers and health policy-makers. PubMed and EMBASE were systematically searched using terms related to "hemophilia" and "intracranial hemorrhage" or "mortality". Studies that allowed calculation of ICH incidence or mortality rates in a hemophilia population of at least 50 patients were included. We summarized evidence on ICH incidence and calculated pooled ICH incidence and mortality in three age groups: (1) persons of all ages with hemophilia, (2) children and young adults below 25 years of age with hemophilia and (3) neonates with hemophilia. Incidence and mortality were pooled with a Poisson-Normal model or a Binomial-Normal model. We included 45 studies that represented 54 470 patients, 809 151 person-years and 5326 live births of hemophilia patients. In persons of all ages, the pooled ICH incidence and mortality rates were 2.3 (95% CI 1.2-4.8) and 0.8 (95% CI 0.5-1.2) per 1000 person-years, respectively. In children and young adults, the pooled ICH incidence and mortality rates were 7.4 (95% CI 4.9-11.1) and 0.5 (95% CI 0.3-0.9) per 1000 person-years, respectively. In neonates, the pooled cumulative ICH incidence was 2.1% (95% CI 1.5-2.8) per 100 live births. ICH was classified as spontaneous in 35-58% of cases. Our findings suggest that ICH is an important problem in hemophilia that occurs among all ages, requiring adequate preventive strategies.
A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia
Journal of hematology & oncology. 2021;14(1):37
BACKGROUND Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients. METHODS Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 10(9)/L) after 8 weeks of treatment. RESULTS The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83-68.63; p < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39-86.87; p < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment. CONCLUSIONS In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile. Trial registration Clinical trials.gov NCT03222843 , registered July 19, 2017, retrospectively registered.
The effect of post-operative limb positioning on blood loss and early outcomes after primary total knee arthroplasty: a randomized controlled trial
International Orthopaedics. 2018
INTRODUCTION The purpose of this study was to investigate the benefits of three different post-operative limb positions in primary total knee arthroplasty (TKA). METHODS The trial was a single-surgeon, randomized, controlled trial, and 135 patients following primary TKA were randomized into three groups: group A (45 patients who were treated with the hip fixed at 50 degrees and knee flexed at 90 degrees for 6 hours post-operatively), group B (45 patients who were treated with the hip elevated at 30 degrees and knee flexed at 45 degrees for 6 hours post-operatively), and group C (45 patients in whom the affected knee was fully extended after surgery). Tranexamic acid was used in all patients. RESULTS The total blood loss and hidden blood loss in group A (921 +/- 209 mL, 597 +/- 213 mL) were significantly less than in groups B (1125 +/- 222 mL, 784 +/- 229 mL) and C (1326 +/- 291 mL, 915 +/- 301 mL) and less in group B compared with group C. The drain volume in groups A (158 +/- 35 mL) and B (174 +/- 45 mL) was significantly lower than in group C (249 +/- 31 mL). The maximum haemoglobin drop in group A (3.1 +/- 0.5 g/dL) was statistically significantly less than in groups B (3.6 +/- 0.7 g/dL) and C (4.3 +/- 0.4 g/dL). The range of motion (ROM) in groups A (102 +/- 3 degrees , 105 +/- 2 degrees ) and B (100 +/- 3 degrees , 104 +/- 2 degrees ) was significantly better than in group C (98 +/- 3 degrees , 102 +/- 2 degrees ) at the time of discharge and one month after surgery; it was also significantly less for group A (104.9 +/- 2.1%, 108.0 +/- 2.4%) compared with groups B (106.7 +/- 3.1%, 108.3 +/- 2.7%) and C (108.4 +/- 3.2%, 110.6 +/- 3.0%) with post-operative knee swelling. No differences in transfusion requirements and complications were observed among the three groups. CONCLUSIONS The affected knee flexion position was superior to the use of a fully extended position for blood management, but it only contributed to better early functional recovery up to three months post-operatively in TKA. In addition, by fixing the affected knee at a high flexion position of 90 degrees , patients could achieve less blood loss, lower knee swelling, and better early results for ROM and patient satisfaction than the other two groups.
Blood loss and cost-effectiveness of oral vs intravenous tranexamic acid in primary total hip arthroplasty: A randomized clinical trial
Thrombosis Research. 2018;171:143-148.
BACKGROUND To assess the blood loss and cost-effectiveness of the oral and intravenous (IV) administration of tranexamic acid (TXA) for the treatment of primary total hip arthroplasty (THA). METHODS From January 2017 to August 2017, 100 patients undergoing primary THA were enrolled and randomly divided into two groups. In the oral TXA group (N=50), 1g of TXA (2 tablets of 500mg) was given 2h before the incision, and the same dose was repeated 3h and 6h postoperatively. In the IV TXA group (N=50), 1g of TXA was administered 10min before the incision, and the same dose was repeated 3h and 6h postoperatively. The total follow-up period was 6months. RESULTS There were no statistically significant differences in total blood loss (863.3+/-272.5mL and 886.1+/-200.2mL, P=0.66), maximum Hb drop (2.9+/-0.6g/dl and 3.1+/-0.8g/dl, P=0.17), maximum Hct drop (7.4+/-2.1% and 7.7+/-1.8%, P=0.48), transfusion rates (1 and 2, P=1.00) and transfusion units (1.5 u and 3 u, P=0.56) between the two groups. However, the costs of TXA in the oral group were significantly lower than those in the IV TXA group ( yen600 and yen3150, P<0.01). There was no difference in the Hb levels on postoperative days 1 and 3. No significant differences were found for operating time, hospital length of stay, DVT and/or PE, and wound complications in the postoperative follow-up. CONCLUSIONS The study demonstrated that the oral and IV administration of TXA in patients undergoing THA was proved to be an equivalent and effective method in reducing blood loss and transfusion rates. However, oral TXA is more cost-effectiveness than IV TXA, and it may be an alternative to the IV form.
Multiple boluses of intravenous tranexamic acid to reduce hidden blood loss and the inflammatory response following enhanced-recovery primary total hip arthroplasty: a randomised clinical trial
The Bone & Joint Journal. 2017;99 B.C.((11)):1442-1449.
AIMS: The aim of this study was to examine the efficacy and safety of multiple boluses of intravenous (IV) tranexamic acid (TXA) on the hidden blood loss (HBL) and inflammatory response following primary total hip arthroplasty (THA). PATIENTS AND METHODS A total of 150 patients were allocated randomly to receive a single bolus of 20 mg/kg IV TXA before the incision (group A), a single bolus followed by a second bolus of 1 g IV-TXA three hours later (group B) or a single bolus followed by two boluses of 1 g IV-TXA three and six hours later (group C). All patients were treated using a standard peri-operative enhanced recovery protocol. Primary outcomes were HBL and the level of haemoglobin (Hb) as well as the levels of C-reactive protein (CRP) and interleukin-6 (IL-6) as markers of inflammation. Secondary outcomes included the length of stay in hospital and the incidence of venous thromboembolism (VTE). RESULTS The mean HBL was significantly lower in group C (402.13 ml standard deviation (sd) 225.97) than group A (679.28 ml sd 277.16, p < 0.001) or B (560.62 ml sd 295.22, p = 0.010). The decrease in the level of Hb between the pre-operative baseline and the level on the third post-operative day was 30.82 g/L (sd 6.31 g/L) in group A, 27.16 g/L (sd 6.83) in group B and 21.98 g/L (sd 3.72) in group C. This decrease differed significantly among the three groups (p < 0.01). The mean level of CRP was significantly lower in group C than in the other two groups on the second (p ≤ 0.034) and third post-operative days (p ≤ 0.014). The levels of IL-6 were significantly lower in group C than group A on the first three post-operative days (p = 0.023). The mean length of stay was significantly lower in group C than group A (p = 0.023). No VTE or other adverse events occurred. CONCLUSION Multiple boluses of IV-TXA can effectively reduce HBL following primary THA. A regime of three boluses leads to a smaller decrease in the level of Hb, less post-operative inflammation and a shorter length of stay in hospital than a single bolus. Cite this article: Bone Joint J 2017;99-B:1442-9.
Comparison of intravenous versus topical tranexamic acid in primary total hip and knee arthroplasty: an updated meta-analysis
Thrombosis Research. 2017;153:28-36.
BACKGROUND The appropriate route for administering tranexamic acid in primary total hip (THA) and knee arthroplasty (TKA) remains controversial. The purpose of this meta-analysis was to compare the efficacy and safety of topical or intravenous tranexamic acid. METHODS PubMed, EMBASE, and the Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) comparing topical and intravenous tranexamic acid following primary THA or TKA. Primary outcomes were transfusion frequency and maximum drop in hemoglobin. Other parameters included total blood loss (TBL), hidden blood loss, drainage volume, hemoglobin level on postoperative day 1 (POD 1), deep vein thrombosis (DVT), pulmonary embolism (PE), wound complications and other adverse events. Data were analyzed using Rev Man 5.2. RESULTS A total of 18 RCTs involving TKA and 4 RCTs involving THA, corresponding to approximately 2260 patients, were included in the meta-analysis. No significant difference between topical and intravenous tranexamic acid was found in transfusion requirement (RR 1.14, 95%CI 0.87 to 1.50, p=0.35). The maximum drop in hemoglobin was significantly smaller in the intravenous group than in the topical group (MD 0.33g/dL, 95%CI 0.07 to 0.58, p=0.01); similar results were observed for the subset of studies involving THA (MD 0.49g/dL, 95%CI 0.28 to 0.70, p<0.001) and the subset involving TKA (MD 0.30g/dL, 95%CI 0.02 to 0.59, p=0.04). The topical and intravenous groups did not differ significantly in TBL, drainage volume, hemoglobin level on POD 1, DVT, PE, wound complications or other adverse events. CONCLUSION The available evidence indicates similar transfusion requirements and safety for topical and intravenous tranexamic acid in THA and TKA. However, intravenous injection seems to be associated with a smaller maximum drop in hemoglobin.