Primary prophylaxis has significantly reduced the number of orthopedic surgical procedures performed on patients with hemophilia (PWH) worldwide. However, studies on orthopedic surgery in PWH are still being published in the medical literature.
The aim of this article is to determine the types of orthopedic surgical interventions in PWH published between 2020 and 2023 and the countries in which they are published.
The following orthopedic surgical procedures are still performed on PWH: total knee, ankle, elbow and hip arthroplasty, ankle fusion, ankle distraction, and the surgical removal of hemophilic pseudotumors. The countries in which articles on orthopedic surgery in hemophilia have been published in the period 2000-2023 include China (14 articles); Republic of Korea and U.S.A. (3 articles each); Germany, Italy, Japan, Poland and Turkey (2 articles each); and 1 article each in the following countries: Austria, Belgium, Chile, France, Ireland, New Zealand, Russia, and The Netherlands. These data suggest that primary prophylaxis should be improved and extended to all patients globally.

How to optimize perioperative factor VIII (FVIII) replacement through hemostatic monitoring is critically important to manage hemophilia A patients. The bispecific antibody emicizumab binds activated FIX (FIXa) and FX to functionally mimic FVIIIa. While being used for hemostatic control in hemophilia A, this therapeutic antibody inconveniently interferes with coagulation tests using human FIXa and FX, such as activated partial thromboplastin time (APTT) and FVIII activity measurement based on one-stage clotting assays. Clot waveform analysis (CWA) extends the interpretation of measurement curves for coagulation time to provide global information. We performed APTT-CWA to monitor perioperative hemostasis in a hemophilia A patient on emicizumab undergoing liver transplantation. Plasma samples were treated with anti-idiotype monoclonal antibodies against emicizumab to enable accurate coagulation assays. Kinetics of maximum coagulation velocity and acceleration mimicked that of FVIII activity. These CWA parameters better correlated with FVIII activity than APTT. The plateaus of them were observed at FVIII activity of 100% or more, supporting the protocol for perioperative FVIII replacement. Thus, CWA may measure coagulation potential in hemophilia A patients undergoing liver transplantation, aiding in optimizing perioperative hemostasis.

Type 3 von Willebrand disease (VWD), a rare and severe subtype, can produce inhibitors in roughly 5% to 10% of cases. We present a case of type 3 VWD with inhibitors in late pregnancy, which was successfully managed with a combination of neutralization and factor (F)VIII replacement during cesarean delivery. The patient, a 30-year-old woman, had no history of inhibitors despite over 100 exposures to VWF/FVIII. She developed inhibitors after 28 weeks of weekly pd VWF/FVIII prophylaxis for recurrent urolithiasis-associated hematuria during pregnancy. Genetic analysis detected two novel frameshift mutations: VWF Exon7 c.777_784dup and Exon14 c.1625_1646del. Titers of inhibitors to factors VIII and VWF using the Bethesda assay were 1.2 and 1.1 BU/mL, respectively. Pharmacokinetics revealed significantly low in vivo recovery of FVIII:C and VWF:Rcof and shortened half-life. During cesarean delivery, a combination of bolus pd VWF/FVIII once daily for neutralizing inhibitors plus continuous infusion of recombinant FVIII Fc fusion protein resulted in minimal bleeding without allergic reactions. Both VWF:Rcof and FVIII:C levels increased transiently during the 7-h of combination therapy without thrombotic events. In conclusion, combination therapy with neutralization and continuous FVIII replacement was effective for hemostasis with a low VWD inhibitor titer, though further optimization is required.

The use of colloids may impair hemostatic capacity. However, it remains unclear whether this also holds true when colloids are administered in a goal-directed manner. The aim of the present study was to assess the effect of goal-directed fluid management with 6% hydroxyethyl starch 130/0.4 on hemostasis compared to lactated Ringer\'s solution in patients undergoing partial hepatectomy. We included 50 patients in this prospective, randomized, controlled trial. According to randomization, patients received boluses of either hydroxyethyl starch or lactated Ringer\'s solution within the scope of goal-directed fluid management. Minimum perioperative FIBTEM maximum clot firmness (MCF) served as the primary outcome parameter. Secondary outcome parameters included fibrinogen levels and estimated blood loss. In the hydroxyethyl starch (HES) group the minimum FIBTEM MCF value was significantly lower (effect size -6 mm, 95% CI -10 to -3, p < 0.001) in comparison to the lactated Ringer\'s solution (RL) group. These results returned to normal within 24 h. We observed no difference in plasma fibrinogen levels (RL 3.08 ± 0.37 g L-1 vs HES 2.65 ± 0.64 g L-1, p = 0.18) or the amount of blood loss between the two groups (RL 470 ± 299 mL vs HES 604 ± 351 mL, p = 0.18). We showed that goal-directed use of HES impairs fibrin polymerization in a dose-dependent manner when compared with RL. Results returned to normal on the first postoperative day without administration of procoagulant drugs and no differences in blood loss were observed.

Introduction: People with hemophilia (PWH) may require some surgical procedures (orthopedic surgery, cardiac surgery, neurosurgery, et cetera) throughout their lives.Areas covered: Articles on surgery and hemophilia published during the year 2020 were analyzed. The principal inclusion factor was a focal point on surgery in hemophilia. Articles that did not concentrate on this subject were not included.Expert opinion: Turoctocog alfa pegol appears to be efficacious for perioperative hemostatic treatment of all kind of surgical operations (minor and major) in PWH A. Long-acting recombinant coagulation factor IX (FIX) albumin fusion protein (rIX-FP) seems to facilitate perioperative management in PWH B. In people suffering from von Willebrand disease (VWD), the utilization of concentrates of von Willebrand factor (VWF) is commonly used for the decrease of exaggerated bleeding during surgical operations. On-demand management with 30-60 IU/kg may keep hemostasis under control during all kind of surgical operations. Factor concentrates with extended half-life (EHL) are a good option to standard half-life (SHL) products in PWH undergoing surgery, permitting diminished number of infusions and inferior consuming, particularly for EHL factor IX (FIX). Supplementary factor VIII (FVIII) and/or bypassing management have demonstrated to be secure and efficacious in association with emicizumab for major surgical procedures.