A message from Vilas Hiremath:
Dear George, hello. Female 30 yrs underwent laparoscopy, started bleeding. Prothrombin time (PT) and partial thromboplastin time (APTT, PT) prolonged, both mixing study 1:1 corrected. Normal fibrinogen and thrombin time (TT). Factor X, VIII. II normal, factor V is 6.0%. Dilute Russell viper venom time (DRVVT) screen and confirm both prolonged, unable to get ratio. My question is 1) why DRVVT is sensitive to factor V deficiency being snake venom, and 2) whether antiphospholipid antibody (APL) involved with activated protein C (resistance?) APC (R?) (resistance and “R” added by Geo.) Whether a case of thrombosis presented with bleeding. Your comments please.
Hello, Vilas, and thank you for your questions. In the DRVVT assay, Russell viper venom activates factor X, driving the common coagulation pathway, so the DRVVT is prolonged by deficiencies of X, V, II, and fibrinogen (when fibrinogen is <100 mg/dL). Thus the factor V deficiency may be expected to prolong the assay and invalidate the DRVVT ratio when testing for lupus anticoagulant.
A factor V deficiency could also invalidate the activated protein C resistance ratio when screening for factor V Leiden mutation.
There are documented instances of anti-phospholipid antibodies specific for thrombin that are associated with thrombocytopenia and mild bleeding, see for example, Forastiero R. Bleeding in the antiphospholipid syndrome. Hematology. 2012;17 Suppl 1:S153–5. Though the normal factor II (prothrombin) assay and the corrected PT and PTT appear to rule this out, you may wish to check the platelet count and order the anti-prothrombin antibody immunoassay alongside anti-cardiolipin and anti-beta-2-glycoprotein I to rule out the presence of an anti-phospholipid antibody.
The simplest explanation appears to be an isolated congenital factor V deficiency. I am curious, as this is an uncommon autosomal recessive disorder associated in some instances with consanguinity. It is a mild bleeding disorder, fitting your patient’s described symptoms. Factor V deficiency is more often associated with liver disease, though usually concomitant with other factor deficiencies, and it may be the consequence of the use of surgical fibrin glue, as some fibrin glue uses bovine thrombin, eliciting an alloantibody that cross-reacts with human thrombin and factor V. Again, your results seem to rule out the anti-bovine antibody, as factor II is normal and there is no evidence for an inhibitor.
A true factor V deficiency would be relatively easily managed with fresh-frozen plasma, if the bleeding symptoms call for treatment. I’ll be interested to see follow-up information on your patient, and I invite our participants to suggest other explanations.