ROTEM®-guided coagulation factor concentrate therapy in trauma: 2-year experience in Venice, Italy

Abstract Abstract 626 Introduction: The treatment of hemophilia A (HA) requires infusions of factor VIII (FVIII) concentrates. The number of FVIII units infused in order to obtain a specific circulating FVIII level is calculated with the formula: [body weight (BW) (kg) × desired FVIII increase (%)]/2, with the assumption that each unit of FVIII infused per kg of BW increases the circulating FVIII level by 2 %. The aim of the present study was to evaluate the impact of several morphometrical parameters (BW, body mass index (BMI), fat mass index (FMI), difference between BW and ideal BW, height), age and type of coagulation factor concentrate on the FVIII recovery in a large group of patients with severe haemophilia who had previously taken part in pharmacokinetic studies using Advate®, Kogenate FS® or ReFacto AF/Xyntha®. Methods: A total of 201 adults (> 18 yr) with severe HA carefully selected from 8 clinical trials using three recombinant FVIII concentrates were included in the analysis (Fig. 1). The FVIII recovery was calculated using the maximum FVIII concentration measured at 15 or 30 minutes after infusion. Regression tree (RT) was used to identify predictors of FVIII recovery. RT-based models are non-linear and non-parametric alternatives to linear models for regression problems. Continuous variables were compared using the Kruskal-Wallis test. Results: The median FVIII recovery was 2.16 for all patients and was significantly different between the 3 coagulation factor groups in univariate analysis. However, the BW, difference between BW and IBW, BMI and FMI were also significantly different between coagulation factor groups. In multivariate analysis, 5 groups were created by RT (Fig. 2 and Fig. 3): patients with a BMI < 20.3 kg/m2 (Group 2; Median FVIII recovery: 1.60), patients with a BMI between 20.3 and 29.5 kg/m2 (Group 4; Median FVIII recovery: 2.14) and patients with a BMI ≥ 29.6 kg/m2 (Group 5; Median FVIII recovery: 2.70). Group 1 and group 3 were made up of 2 outlier patients. The FVIII recovery was significantly different between group 2, group 4 and group 5 (P<0.001) (Fig. 2 and Fig. 3). The random forest associated with this RT shows that the age and the type of coagulation factor concentrate had no influence on FVIII recovery. Conclusions: The type of coagulation factor concentrate first emerged as a univariate predictor of FVIII recovery in our study. It later appeared to have no influence in the multivariate model, as opposed to the BMI which emerged as the strongest predictor of FVIII recovery. These results are consistent with previous crossover studies which have demonstrated comparable FVIII recovery of different concentrates (Haemophilia 2007;13:124–30, Haemophilia 2009;15(4):869–80). Our findings also support that dose calculation of FVIII to reach a specific FVIII target level should be adapted in underweight and overweight patients. Taking the ideal BW instead of the actual BW in the dose calculation should be implemented since only a small fraction of FVIII distributes outside the vascular system. Disclosures: No relevant conflicts of interest to declare.

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Coagulation Factor Concentrate Usage and the Risk of Lymphadenopathy: A Prospective Study

The American Journal of the Medical Sciences ◽

10.1097/00000441-198609000-00004 ◽

1986 ◽

Vol 292 (3) ◽

pp. 142-146 ◽

Cited By ~ 2

Author(s):

W. Abe Andes ◽

K.M. Wulff ◽

D. Mercer ◽

K. Ohene Frempong ◽

J. Patin

Keyword(s):

Prospective Study ◽

Coagulation Factor ◽

A Prospective Study ◽

Factor Concentrate

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Thrombotic complications in patients with hereditary bleeding disorders

Thrombosis and Haemostasis ◽

10.1160/th04-03-0148 ◽

2004 ◽

Vol 92 (08) ◽

pp. 298-304 ◽

Cited By ~ 46

Author(s):

Massimo Franchini

Keyword(s):

Risk Factors ◽

Gene Mutations ◽

Coagulation Factor ◽

Venous Catheter ◽

Bleeding Tendency ◽

Bleeding Disorders ◽

Central Venous ◽

Prothrombotic Risk Factors ◽

Thrombotic Complications ◽

Factor Concentrate

SummaryThromboses in patients with hereditary bleeding disorders are uncommon. However, in some cases, the co-existence of prothrombotic risk factors may increase the likelihood of developing thrombotic complications in such patients. This review summarizes the cases of thrombosis reported in the literature and analyzes the most important risk factors for thrombosis in patients with a congenital bleeding tendency. In particular we focus on central venous catheter (CVC)-associated thrombosis, on the thrombotic complications of coagulation factor concentrate therapy and on the presence of prothrom-botic gene mutations. Data were identified by searches of the published literature, including PubMed, references from reviews and abstracts from the most important meetings on this topic. In conclusion, there is increasing evidence that thrombotic complications in patients with hereditary bleeding disorders have a multifactorial pathogenesis, depending on exogenous (coagulation factor replacement therapy, CVC, HIV infection) and/or endogenous (prothrombotic gene mutations) risk factors.

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Management of Perioperative Anticoagulation in Patients with VWD

Blood ◽

10.1182/blood.v126.23.1100.1100 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1100-1100

Author(s):

Mario Von Depka ◽

Carsten Detering ◽

Stefanie Döpke ◽

Mahnaz Ekhlasi-Hundrieser

Keyword(s):

Risk Factors ◽

Body Weight ◽

Surgical Procedures ◽

Thrombotic Event ◽

Coagulation Factor ◽

Post Surgery ◽

Thrombosis Risk ◽

Perioperative Anticoagulation ◽

Factor Concentrate ◽

Von Willebrand

Abstract Objectives: von Willebrand disease (VWD) is the most common hereditary bleeding disorder. This study reviews the management of perioperative anticoagulation in patients with VWD undergoing surgical procedures. Risk factors for VTE with von Willebrand factor (VWF) concentrate use are older age, previous VTE, obesity, surgery, hormone replacement therapy use, antifibrinolytic therapy use and high post infusion FVIII levels. Currently, there are few data from randomized clinical trials assessing efficacy and possible complications of perioperative VTE prophylaxis in VWD patients. Methods: A total number of 116 surgeries were performed (minor: n=64 and major: n=52) in this retrospective, single-centre study. They were divided into groups of perioperative non-anticoagulation (n=54) and perioperative anticoagulation (n=62), who all received coagulation factor concentrate (CFC). Sub-analyses were done according to the type of concentrate used. Anticoagulation was performed using different low molecular weight heparins (LMWH) according to standard protocols or body-weight adapted doses in patients with either elevated body-mass-index or additional thrombosis risk factors. Blood samples had been collected pre- and post-surgery (up to 21 days) to analyse PT, aPTT, PFA, and trough levels of FVIII coagulant activity (FVIII:C), VWF activity (VWF:GPIbM) and antigen (VWF:Ag), respectively. Furthermore, the median doses of CFC/kg and the median total number of infusions were calculated. The rates of clinically overt thrombosis as well as bleeding were assessed during the post-operative phase. Results: The majority of patients suffered from VWD type 1 (104), 9 patients with type 2A, 2 with type 2M and 1 with type 3 VWD. Humate-P (H) was used in 55 patients and 61 patients received Wilate (W). Using W, we found parallel curves for FVIII:C, VWF-antigen and VWF:GPIbM, respectively. Using H, less concordance between VWF:Ag and VWF:GPIbM was visible and FVIII:C tends to increase between D3 to D10 in spite of decreasing VWF:Ag and VWF:GPIbM. This observation was visible in minor as well as major surgical procedures. LMWH (Enoxaparin, Nadroparin and Certaparin) were used in doses between 30 and 100 mg/injection (mean 46.0 ± 18.5 mg/injection) and a mean of 32.2 ± 24.6 injections in total (range: 8-112). In one patient a significant haematoma occurred (1/116; 0.9%), also one thrombotic event was documented in a different patient (1/116; 0.9%). Conclusion: Using standard dose LMWH in patients with no overt increased thrombosis risk as well as body-weight-adapted LMWH in high risk patients seem to be safe and effective in VWD patients receiving coagulation factor concentrate perioperatively. However, prospective randomized comparative studies are required to determine the optimal indication as well as type of anticoagulation according to the CFC treatment regimen in this setting. Disclosures No relevant conflicts of interest to declare.

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Effects of coagulation factor concentrate prophylaxis in moderate and severe hemophilia A patients at a single hemophilia center in Korea

Korean Journal of Pediatrics ◽

10.3345/kjp.2013.56.7.291 ◽

2013 ◽

Vol 56 (7) ◽

pp. 291 ◽

Cited By ~ 2

Author(s):

Byung Suk Moon ◽

Jun Seok Choi ◽

Chur Woo You

Keyword(s):

Hemophilia A ◽

Coagulation Factor ◽

Severe Hemophilia ◽

Factor Concentrate

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INTRACRANIAL HAEMORRHAGE IN LOW-BIRTH-WEIGHT INFANTS AND PROPHYLACTIC ADMINISTRATION OF COAGULATION-FACTOR CONCENTRATE

The Lancet ◽

10.1016/s0140-6736(73)91297-x ◽

1973 ◽

Vol 301 (7815) ◽

pp. 1284-1286 ◽

Cited By ~ 31

Author(s):

H. Waltl ◽

R. Kurz ◽

G. Mitterstieler ◽

H.J. Födisch ◽

L. Hohenauer ◽

...

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Intracranial Haemorrhage ◽

Coagulation Factor ◽

Low Birth Weight Infants ◽

Prophylactic Administration ◽

Factor Concentrate

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Transfusion in trauma: thromboelastometry-guided coagulation factor concentrate-based therapy versus standard fresh frozen plasma-based therapy

Critical Care ◽

10.1186/cc10078 ◽

2011 ◽

Vol 15 (2) ◽

pp. R83 ◽

Cited By ~ 280

Author(s):

Herbert Schöchl ◽

Ulrike Nienaber ◽

Marc Maegele ◽

Gerald Hochleitner ◽

Florian Primavesi ◽

...

Keyword(s):

Coagulation Factor ◽

Fresh Frozen Plasma ◽

Fresh Frozen ◽

Factor Concentrate ◽

Frozen Plasma

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Prevalence of hepatitis C virus antibody in a cohort of hemophilia patients [see comments]

Blood ◽

10.1182/blood.v76.1.254.254 ◽

1990 ◽

Vol 76 (1) ◽

pp. 254-256 ◽

Cited By ~ 124

Author(s):

DB Brettler ◽

HJ Alter ◽

JL Dienstag ◽

AD Forsberg ◽

PH Levine

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

New England ◽

Coagulation Factor ◽

Positive Association ◽

Core Antigen ◽

Viral Inactivation ◽

Significant Difference ◽

Hcv Antibody ◽

Factor Concentrate

Abstract One hundred thirty-one patients followed at the New England Hemophilia Center (Worcester, MA) were tested for antibody to hepatitis C virus (HCV). All but two had used factor concentrate that had not undergone viral inactivation; two patients had used only cryoprecipitate. The overall prevalence of HCV antibody positivity was 76.3%. There was no significant difference in age or the amount of non-heat-treated factor concentrate used between the group that was HCV antibody positive and negative. There was also no significant difference between aminotransferase levels in the two groups. There was a positive association between HCV antibody and the presence of antibody to hepatitis B core antigen and antibody to human immunodeficiency virus. A group of 31 patients were tested twice for HCV antibody at intervals of 35 to 71 months. In this subset, 25 were repeatedly seropositive, 4 were repeatedly seronegative, and 2 went from seropositive to seronegative. These data confirm the previous impression that non-A, non-B hepatitis is a major sequela to the use of pooled coagulation factor concentrates. HCV infection may account for most of the chronic liver disease observed in this population. Anti-HCV testing of plasma donors and improved methods of viral inactivation should prevent new cases from developing.

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