Monitoring of hemostatic status in four patients being treated with recombinant factor VIIa.
Recombinant Factor VIIa (rVIIa) is a potent hemostatic agent for the management of refractory bleeding in patients with Factor VII deficiency or Factor VIII inhibitors. While the current recommended dose is usually effective, the most appropriate dose remains a subject of debate. Since factor VII levels and shortening of the pro-thrombin time do not appear to correlate with response, an appropriate laboratory marker of clinical response has not been identified. In this article we report changes noted in thrombin generation, platelet function and clot structure in blood from patients treated with rVIIa. Thrombin generation was assessed via a thrombin generation time (TGT) assay using a Hemodyne HAS instrument. Changes in clot structure were assessed as changes in clot elastic modulus in the HAS, changes in maximum amplitude in the TEG and changes in maximum clot firmness in the ROTEG. The cases presented confirmed improvement in thrombin generation with administration of rVIIa. The cases also illustrate that: a) in the factor VII deficient patient, 25% of the 90 microg/kg dose is sufficient to totally correct the defect, b) patients with high level factor VIII inhibitors may require significantly more than the recommended dose of 90 microg/kg, c) thrombin generation may not be completely corrected despite dramatic shortening of the prothrombin time, and d) increasing rVIIa doses does not by itself ensure improved thrombin generation.
Coagulation Special Studies Laboratory, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0230, USA. mcarr@hsc.vcu.edu
Marcus E
ME
Carr
Erika J
EJ
Martin
Jan G
JG
Kuhn
Heather
H
Ambrose
Stephen
S
Fern
Paulette C
PC
Bryant
D000368:Aged; D015415:Biomarkers; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D001778:Blood Coagulation Disorders / Q000188:drug therapy* / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002648:Child; D016903:Drug Monitoring; D004548:Elasticity / Q000187:drug effects; D005167:Factor VII / Q000627:therapeutic use*; D005168:Factor VII Deficiency / Q000188:drug therapy / Q000378:metabolism; D005169:Factor VIII / Q000037:antagonists & inhibitors; D015942:Factor VIIa; D005260:Female; D006487:Hemostasis / Q000187:drug effects; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013917:Thrombin / Q000187:drug effects / Q000378:metabolism
D015415:Biomarkers; D006490:Hemostatics; D011994:Recombinant Proteins; D005167:Factor VII; D005169:Factor VIII; C103587:recombinant FVIIa; D015942:Factor VIIa; D013917:Thrombin