The risk of variant Creutzfeldt-Jakob disease among UK patients with bleeding disorders, known to have received potentially contaminated plasma products

Abstract

The risk of variant Creutzfeldt-Jakob disease (vCJD) from potentially infected plasma products remains unquantified. This risk has been assessed for 787 UK patients with an inherited bleeding disorder prospectively followed-up for 10-20 years through the UK Haemophilia Centre Doctors' Organisation (UKHCDO) Surveillance Study. These patients had been treated with any of 25 'implicated' clotting factor batches from 1987 to 1999, which included in their manufacture, plasma from eight donors who subsequently developed clinical vCJD. Variant CJD infectivity of these batches was estimated using plasma fraction infectivity estimates and batch-manufacturing data. Total potential vCJD infectivity received by each patient has been estimated by cumulating estimated infectivity from all doses received during their lifetime. Of 787 patients, 604 (77%) were followed-up for over 13 years following exposure to an implicated batch. For these 604 patients, the estimated vCJD risk is ≥ 1% for 595, ≥ 50% for 164 and 100% for 51. This is additional to background UK population risk due to dietary exposure. Of 604 patients, 94 (16%) received implicated batches linked to donors who developed clinical vCJD within 6 months of their donations. One hundred and fifty-one (25%) had received their first dose when under 10 years of age. By 1st January 2009, none of these patients had developed clinical vCJD. The absence of clinical vCJD cases in this cohort to date suggests that either plasma fraction infectivity estimates are overly precautionary, or the incubation period is longer for this cohort than for implicated cellular blood product recipients. Further follow-up of this cohort is needed.

Dealing with the uncertain risk of variant Creutzfeldt‐Jakob disease transmission by coagulation replacement products

“…Prior to 2004, all cases of vCJD had been attributable to dietary exposure to BSE, however four cases of vCJD infection transmitted by transfusion of non-leucodepleted red cells from asymptomatic donors infected with vCJD have since been recognised (Health Protection Agency [HPA] 2006; Llewelyn et al, 2004;Peden et al, 2004;Wroe et al, 2006). Plasma from these and other donors who subsequently developed vCJD contributed to plasma pools that were used to manufacture factors VIII and IX (FVIII and FIX), which are used in the treatment of patients with haemophilia A, haemophilia B and the severe forms of von Willebrand disease (Zaman et al, 2011), as well as factor XI, antithrombin and prothrombin complex concentrates. Over 20 000 patients with inherited bleeding disorders are currently registered in the UK, of whom around one-fifth have received coagulation replacement products manufactured from pooled plasma concentrates.…”

Safety surveillance in haemophilia and allied disorders

“…At present, plasma-derived concentrates undergo two separate viral inactivation steps and are known to be free from HIV, HBV and HCV viruses [5]. However, two viruses continue to cause concern; parvovirus B19 cannot be entirely destroyed by current methods and its elimination depends on testing plasma mini-pools with PCR [6], whereas there are currently no tests for or methods for destroying variant Creutzfeldt-Jakob disease (vCJD), hence the avoidance of using plasma from areas in which vCJD is endemic [7]. vCJD is a particular concern in the UK where a patient with haemophilia was shown to have prions in the spleen at autopsy.…”

“…However, this patient received multiple blood transfusions as well as FVIII concentrate and the relevant contribution of each is uncertain [8]. Significant uncertainty about the transmissibility of vCJD by concentrates remains, and the UK population of haemophiliac patients remains under close surveillance for the development of this infection [7,9].…”

Induced Pluripotent Stem Cells: Therapeutic Applications in Monogenic and Metabolic Diseases, and Regulatory and Bioethical Considerations

“…Such research focuses on the detection and subsequent inactivation of emerging bloodborne pathogens in donors such as the prions causing variant Creutzfeldt-Jakob disease, or other potential emerging agents [52][53][54]. It is also important to increase the efficiency of recombinant factors increasing their half-life (by PEGylating the factor molecule or using fusion proteins [55][56][57][58] and attenuating their immunogenic capacity to produce inhibitors, by chemically modifying them [59] or by developing recombinant factors of human origin [60].…”