Influence of factor XII deficiency on activated partial thromboplastin time (aPTT) in critically ill patients

Abstract

FXII deficiency results in spontaneous prolongation of activated partial thromboplastin time (aPTT), which is widely used to monitor thromboprophylaxis. Misinterpretation of spontaneously prolonged aPTT may result in omission of thromboembolic treatment or even unnecessary transfusion of blood products. This retrospective analysis was performed to calculate a threshold level of FXII resulting in aPTT prolongation. 79 critically ill patients with spontaneous prolongation of aPTT were included. A correlation analysis and a ROC curve for aPTT prolongation predicted by FXII level were created to find the FXII threshold level. Prolongation of aPTT was associated with disease severity. A significant inverse proportionality between FXII and aPTT was seen. A ROC curve for aPTT prolongation, predicted by FXII level (AUC 0.85; CI 0.76–0.93), revealed a FXII threshold level of 42.5%. Of our patients 50.6% experienced a FXII deficiency, in 80.0% of whom we found aPTT to be prolonged without a significantly higher bleeding rate. The FXII deficiency was more common in patients with higher SAPS3 scores, septic shock, transfusion of red blood cells and platelet concentrates as well as in patients receiving renal replacement therapy. Patients with a FXII deficiency and prolonged aPTT less often received anticoagulatory therapy although they were more severely ill. The rate of thromboembolic events was higher in these patients although the difference was not statistically significant. Of all patients with spontaneous aPTT prolongation 50.6% had a FXII level of 42.5% or less. Those patients received insufficient thromboembolic prophylaxis.

C‐reactive protein‐induced activated partial thromboplastin time prolongation in heparinized samples is attenuated by elevated factor VIII

“…Variability in CRP and FVIII levels could be responsible for aPTT/anti‐Xa discrepancy in heparin therapy monitoring, in addition to other previously described factors 11 . Increased contact activation inside the ECMO device could cause activation and consumption of factor XII (FXII) and as many as 50% of critically ill patients develop acquired FXII deficiency accompanied by aPTT prolongation 12 . Recently, three ECMO patients with FXII <40 IU/dL and failure of aPTT to monitor heparin therapy were described 13 …”

Prolonged activated partial thromboplastin time secondary to factor XII deficiency in two surgical patients

“…In contrast, acquired FXII deficiency is frequent as reported by Bachler M et al . in 51% of his 79 critically ill intensive care patients having sepsis, renal failure and following blood transfusion [ 6 ].…”

Facets of individual-specific health signatures determined from longitudinal plasma proteome profiling

“…One striking observation from a precision profiling perspective was to find a single participant with deficiency in F12 among all 101 individuals, and being able to use proteomic and genetic information to pinpoint a possible mechanism of lower levels of circulating F12. A deficiency in F12 is rare and generally non-symptomatic, however, in vitro F12 deficiency results in prolonged activated partial thromboplastin time (aPTT) [37]. Indeed, aPPT is a common screening test for hemostatic function.…”