Rotational Thromboelastometry for Assessing Bleeding Complications and Factor XIII Deficiency in Cardiac Surgery Patients.

We aimed to detect alterations and deficits in hemostasis during cardiac surgery with cardiopulmonary bypass (CPB) using point-of-care-supported coagulation analysis (rotational thromboelastometry, impedance aggregometry), in addition to single factor assays for the measurement of fibrinogen (FI) and factor XIII (FXIII) levels. Forty-one patients scheduled for elective cardiac surgery with CPB were enrolled in this observational study. Perioperative measurement (pre-, postheparin, 30-minutes before the end of bypass, 1-hourpostoperatively) of standard laboratory variables, additional rotational thromboelastometry (ROTEM; International GmbH, Munich, Germany), Multiplate analysis (Roche, Switzerland), and an assay of FXIII activity were performed as well as the collection of epidemiological data and blood loss. The FI and FXIII levels as well as the measured ROTEM and Multiplate parameters correlated weakly with the blood loss. Clotting time and maximum clot firmness (MCF) of the intrinsically activated ROTEM showed a good correlation (rCT-INTEM = 0.378; P < .05, rMCF-INTEM = 0.305; P < .05) with postoperative drainage loss, suggesting a dependence of blood loss on the initial intrinsic activity. Additionally, perioperative FI or FIBTEM levels and the FXIII levels correlated with each other. Intrinsically activated ROTEM showed a good correlation with postoperative drainage loss, thus suggesting a dependence of blood loss on the initial intrinsic activity and therefore facilitating clinicians to assess postoperative bleeding complications. Based on the FI level or the MCFFIBTEM measured by ROTEM, it may also be possible to assess the FXIII concentration. Especially in chronically ill and massive bleeding cardiac surgery patients with significantly decreased FXIII levels, the knowledge of FXIII deficiency may help clinicians to treat coagulation disorders more adequately.

Recombinant FXIII (rFXIII-A2) Prophylaxis Prevents Bleeding and Allows for Surgery in Patients with Congenital FXIII A-Subunit Deficiency.

Recombinant factor XIII-A2 (rFXIII-A2) was developed for prophylaxis and treatment of bleeds in patients with congenital FXIII A-subunit deficiency. mentor™2 (NCT00978380), a multinational, open-label, single-arm, multiple-dosing extension to the pivotal mentor™1 trial, assessed long-term safety and efficacy of rFXIII-A2 prophylaxis in eligible patients (patients with severe [<0.05 IU/mL] congenital FXIII subunit A deficiency) aged ≥6 years. Patients received 35 IU/kg rFXIII-A2 (exact dosing) every 28 ± 2 days for ≥52 weeks. Primary endpoint was safety (adverse events including immunogenicity); secondary endpoints were rate of bleeds requiring FXIII treatment, haemostatic response after one 35 IU/kg rFXIII-A2 dose for breakthrough bleeds and withdrawals due to lack of rFXIII-A2 efficacy. Steady-state pharmacokinetic variables were also summarized. Elective surgery was permitted during the treatment period. Sixty patients were exposed to rFXIII-A2; their median age was 26.0 years (range: 7.0-77.0). rFXIII-A2 was well tolerated without any safety concerns. No non-neutralizing or neutralizing antibodies (inhibitors) against FXIII were detected. Mean annualized bleeding rate (ABR) was 0.043/patient-year. Mean spontaneous ABR was 0.011/patient-year. No patients withdrew due to lack of efficacy. Geometric mean FXIII trough level was 0.17 IU/mL. Geometric terminal half-life was 13.7 days. rFXIII-A2 prophylaxis provided sufficient haemostatic coverage for 12 minor surgeries without the need for additional FXIII therapy; eight procedures were performed within 7 days of the patient's last scheduled rFXIII-A2 dose, and four were performed 10 to 21 days after the last dose.

A large case series on surgical outcomes in congenital factor XIII deficiency patients in Iran.

Essentials Data on surgery in factor XIII (FXIII) deficiency patients are scarce and lack standardized guidelines. Variable dosage of 10-50 U kg-1 was given to FXIII deficiency patients undergoing surgery. Surgical outcomes showed excellent hemostasis with a minimal risk of post-operative complications. Surgery can be performed safely in FXIII deficiency patients following FXIII administration. SUMMARY: Background The lack of accepted standardized surgical guidelines leads to dependence on the treating physicians' and centers' experiences. Aim Our aim is to evaluate the surgical outcomes of a large group of congenital factor XIII deficiency (FXIIID) patients. Methods A case series study was conducted prior to surgery on congenital FXIIID patients in two major referral centers located in Iran from 2010 to 2016. All patients were on prophylaxis using plasma factor XIII concentrate (10 U kg-1 , every 28 days) except for three patients. Single doses of 10 U kg-1 or 30 U kg-1 plasma factor XIII concentrate were given before a minor procedure and circumcision, respectively. Two doses of plasma factor XIII concentrate, one 30 U kg-1 prior to the procedure and the second dose of 30 U kg-1 on postoperative day 3, were given for major surgery. The dose was 50 U kg-1 both before and after neurosurgical procedures. Results One hundred and sixty-two FXIIID patients underwent minor, major and obstetrical/gynecological surgeries. Median age of the patients was 14 years (ages ranged 15 days to 47 years). The male-to-female ratio was 89/73. Five postoperative complications, two bleeding and three thrombosis, were recorded. Conclusion Our study showed excellent hemostasis in FXIIID patients undergoing surgeries. During the period of these surgeries, we observed only 1.8% postoperative complications. Surgery can be performed safely in FXIIID patients, and our proposed treatment regimens lead to adequate hemostatic coverage with minimal risk, for both minor and major surgeries.