Rae Kerlin from the Ohio State University Werner Medical Center wants to provide coagulation testing for a patient who has type I cryoglobulinemia [monoclonal IgM kappa]. Rae’s team team ordered a PFA but they were unable to obtain results due to hyperviscosity. PT/PTT = 13.9/24.7. They are planning to test FVIII via the 0ne-stage clotting assay, VWF Ag by Liatest, and a ristocetin cofactor by platelet agglutination. Rae is concerned that at least the VWF Ag and the VWF:RCo could be inaccurate due to the protein changes. Rae also asked if we could perform clot-based testing on pheresis plasma.
I [Geo] reached out to several experts. Bob Gosselin [SOCAL] responded as follows.
Hey GF, likely the apheresis process has some sort of anticoagulation going on, so any residual effect from that process will certainly interfere with coag testing. In an unpublished study, we did see residual heparin anticoagulation in some patients, but typically coag testing is not performed, so likely testing and neutralizing may be in order. [Geo adds, you could use Hepsorb if the anticoagulant is heparin, and citrate anticoagulant would be no different than collecting in a blue-closure tube.]
Otherwise, one may be limited to what testing can be done with hyperviscosity. They can certainly consider isolated tests that use two-stage chromogenic methods like FVIII, FIX, and FBG, as one can manually dilute the plasma in saline and correct for the dilution. Not sure how viable any clot-based assay would be, but certainly can try manual diluting as it is unclear whether auto-dilution is affected by viscosity yielding incorrect sample volume. Use an appropriate diluent such as saline, buffer, or deficient plasma. We are kinda fishing since the cause of the bleeding is unclear.
I suspect viscoelastic testing [VET] would be problematic as well, but I have no experience with these patients. It seems plausible since we are looking for changes in clotting blood. Maybe the newer platforms such as the TEG 6S, ROTEM Delta or Quantra would give better results than the original ROTEM and the TEG 5000. BG
And here is a response from Dr. Emmanuel Favaloro [Sydney, NSW]:
Limited personal experience, but I would concur with what has been said so far; not sure how accurate routine coag tests would be in this setting, and even if you got clot times, how those would equate to bleeding risk. Factor assays may be more successful, since done at dilution, but might be impacted by whatever is causing the hyperviscosity. We are publishing a review on whole blood viscosity in STH soon, but that is on whole blood viscosity, so the main players for that are RBCs, platelets, and fibrinogen; in specific plasma hyperviscosity syndromes, yes, more likely a paraprotein or cryoglobulin; paraproteins are notorious for inhibiting coagulation. The docs should be evaluating for paraprotein or cryoglobulin and treating accordingly. As BG also indicates, there is a potential anticoagulant around as well.
Dave McGlasson offers this publication: Surov S, Ovsepyan R, Vysochin I, et al. Procoagulant impact of the plasmapheresis procedure on coagulation state of collected plasma.Blood Transfus 2015; 13: 651-5 DOI 10.2450/2015.0315-14. The authors seem to imply that at least in normal subjects, pheresis plasma and pre-pheresis plasma results match up well.
We are stretched by questions like this and invite additional comments from our experienced participants.