Haemophilia : the official journal of the World Federation of Hemophilia
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Optimal doses of von Willebrand Factor/Factor VIII (VWF/FVIII) concentrates for surgical procedures in patients with VWD need to be determined. A prospective, multicenter study was performed that included an initial pharmacokinetic (PK) assessment following a standard dose of VWF/FVIII concentrate (Humate-P®) to determine individual PK parameters and guide therapeutic dosing during surgery. Forty one subjects received 60 IU kg⁻¹ VWF: RCo. ⋯ When analysing individual recovery values on repeated infusions, a very weak correlation was observed between presurgery IVR and IVR for both VWF:RCo and FVIII, measured at various times just prior to and after the surgical procedure. Although group median values were fairly consistent among repeated IVR measurements, the intra-individual IVR values for FVIII and VWF:RCo with repeated infusions showed a large degree of variability. IVR values obtained from pharmacokinetic analyses performed in advance of anticipated surgery do not reliably predict postinfusion circulating levels of VWF:RCo or FVIII attained preoperatively or with subsequent peri-operative infusions.
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Haemophilia A replacement therapy is dosed according to patient's weight and plasma FVIII activity (FVIII:C). The FVIII interacts with platelet membrane but limited data on the impact of platelet procoagulant activity (PCA) are available in haemophilia A. Our aim was to characterize individual PCA in vitro in 20 adult haemophilia A patients at various FVIII:C levels. ⋯ In haemophilia A, the variability in thrombin generation is partially related to plasma FVIII:C, but mainly dependent on platelet procoagulant capacity. Annexin V binding and PCA in response to activation by collagen receptors contribute to this variability. In all, platelet PCA at least following collagen interaction significantly impacts thrombin generation in haemophilia A.
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Defective hemostasis in haemophilia patients with FVIII inhibitors results in a dramatic decrease in thrombin generation forming unstable fibrin clots that are susceptible to fibrinolyisis. In this study we tested whether the combination of plasma derived activated prothrombin complex concentrate (pd-aPCC) with tranexamic acid (TXA) may improve fibrin clot stability in FVIII inhibitor plasma. A microplate assay for clot lysis time was used to assess clot stability in FVIII inhibitor plasma. ⋯ The effect of pd-aPCC and TXA on clot stability was then tested and verified in plasma samples from ten patients with severe haemophilia A and inhibitors. The combination of TXA (10 mg mL⁻¹) and pd-aPCC (0.5 U mL⁻¹) significantly increased clot lysis time compared to TXA alone. Our results suggest that the combination of pd-aPCC with TXA improves clot stability in FVIII inhibitor plasma without additional increases in thrombin generation.
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Pregnancy, labour and delivery present intrinsic haemostatic challenges to women with and carriers of bleeding disorders and their offspring. Deficiency of fibrinogen and factor XIII are associated with miscarriage, placental abruption and foetal loss. The risk of antenatal complications including antepartum haemorrhage is unknown in women with other bleeding disorders. ⋯ The optimal management of pregnancy in women with inherited bleeding disorders requires a multidisciplinary approach and advanced individualized management plan taking into consideration obstetric and bleeding risk factors. Women with mild or moderate bleeding disorders can be managed at their local maternity unit in close collaboration with a tertiary centre. However, those with severe or rare disorders or carrying an affected infant should be managed in a tertiary centre with an onsite Haemophilia centre.
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Patients with congenital haemophilia with inhibitors are at risk of peri-operative bleeding complications, since replacement of the missing coagulation factor is ineffective, presenting a therapeutic challenge in elective or emergency surgery. Therefore, the management of peri-operative bleeding requires the use of bypassing agents, such as recombinant activated FVII (rFVIIa, NovoSeven(®) ). This article presents an updated evaluation of the safety and effectiveness of rFVIIa in the treatment of peri-operative bleeding in this patient population. ⋯ Recombinant FVIIa has consistently demonstrated effectiveness in treatment of bleeding in these patients during such procedures. Thrombotic events were rare. This analysis confirms the value of corroborating clinical trial results with post-marketing surveillance registries to assess small patient populations with clinically challenging management decisions.