Prolonged Activated Partial Thromboplastin Time

Abstract

To review the diagnostic difficulties of a prolonged activated partial thromboplastin time (aPTT) when 2 inhibitors with opposite clinical presentations coexist, we searched MEDLINE from January 1970 to November 2013 using acquired, factor VIII (FVIII), factor IX, hemophilia A and B, inhibitor, lupus anticoagulant (LA), antiphospholipid, anticardiolipin, anti-β2-glycoprotein I, antibodies, syndrome, bleeding, and thrombosis. We identified 13 articles for a total of 15 cases of possible coexistence of FVIII inhibitor and LA. The presenting clinical manifestation was thrombosis in 6 cases and bleeding in 9 cases. Activated partial thromboplastin time was the presenting laboratory abnormality in all cases, and first-line investigations suggested the coexistence of LA and acquired FVIII inhibitor. None of the articles addressed the diagnostic accuracy of the screening tests by performing "second line" assays. We reviewed the diagnostic pitfalls of the cases under study and provide some guidance for alternative tests when facing a prolonged aPTT that may have a double meaning.

Co-existent Acquired Haemophilia and Lupus Anticoagulant. A Thorny Issue

“…The authors have not quoted the thromboplastin used for their aPTT: (1) a lupus insensitive reagent would have been helpful; (2) factor sensitivity to different thromboplastins modulates the correction of the mixing study. In the presence of auto anti-factor VIII antibodies the Bethesda assay may present with a type II inhibitor pattern but LA may interfere with this assay [2].…”

“…In the scenario given by the authors a chromogenic FVIII should have been done as well as a FVIII inhibitor measured by immune assay though LA could still interfere with the latter. Likewise, the measurement of anticardiolipin or antibeta-2-glycoprotein-1 antibodies may have better supported the presence of a LA the evidence for which relies on an undisclosed DRVVT [2]. However, a FVIII concentration below 0.15 IU/mL may influence the DRVVT result according to the sensitivity of reagents.…”

Characteristics of Acquired Inhibitors to Factor VIII and Von Willebrand Factor Secondary to Systemic Lupus Erythematosus

“…How could these apparently different clinical pictures coexist? Ames et al 25 performed a MEDLINE literature search to investigate the cases of coexistence of LA and acquired FVIII deficiency, and they summarized the clinical presentations. When LA coexisted with FVIII inhibitor, the presentation of thrombosis dominated in 40% of cases.…”

The coexistence of antiβ2 glycoprotein 1 antibody antibody has no effect on hemophilia A patient

“…Therefore, Rampersad et al [2] presented that evaluations of FVIII antibody profiles along with chromogenic Bethesda assay were useful to distinguish FVIII inhibitor from a transient lupus anticoagulant in hemophilia A patients. Therefore, the combination of chromogenic assay and ELISA of lupus anticoagulant testing was recommended to discriminate between FVIII inhibitors and APAs in hemophilia A patients [1,3,4]. However, low titer of anti-β2GP1 seemed not affect the detection of FVIII:C and FVIII inhibitor in this patient.…”

“…Antiphospholipid antibodies (APAs) not only show in APS patients but also occasionally occur in hemophilia A patients [1–3]. To our knowledge, it is the first report of anti-β2GP1 found in Chinese patient with hemophilia A.…”