Heparin-PF4 Antibodies Are Frequent after Vascular Surgery, but Not a Frequent Cause of Graft Thrombosis or Thrombocytopenia.

Surgical intervention for atherosclerotic disease of the aortoiliac and femoral-popliteal arteries has significantly reduced the incidence and complications of peripheral ischemia. However, surgical correction of obstructive arterial lesions can be complicated by either early graft failure due to acute thrombosis or late stenosis of the vascular bypass graft. Despite improvements in surgical technique, early graft failure is still observed in up to 10% of patients and up to 30 % can subsequently develop a graft stenosis. The etiology of early graft closure is less clearly understood. Anatomic or structural defects in the new graft may result in early thrombosis. Underlying prothrombotic conditions have also been suggested as contributing factors to early graft thrombosis. Recently, we have observed recurrent thrombotic events occurring in vascular grafts in two patients who were subsequently diagnosed with the syndrome of Heparin-Induced Thrombocytopenia. Because of these events we undertook an IRB approved, prospective evaluation of HIT antibodies in patients undergoing vascular surgery. Patients undergoing infra-inguinal bypass surgery for atherosclerotic vascular disease were enrolled after informed consent. Blood samples were obtained the day before surgery, day of hospital discharge, at days 14 and 28 after surgery. Platelet counts were obtained on the day of discharge and on post-surgery day 14. Plasma samples were assayed for PFA-heparin antibodies by ELISA (Stago Diagnostica) and platelet activating antibodies by platelet aggregometry. All assays were performed in duplicate.

Seventy-nine patients were enrolled. Six (7.7%) patients provided only the pre-surgical blood specimen and only 68 (86%) patients provided all four blood specimens. All but 5 patients reported previous heparin exposure. Of the 73 patients in which post-surgical blood samples were taken, 28 (38%) became ELISA positive for PF4-Heparin antibodies. When tested for platelet activating antibodies, 7 (10%) were positive. All patients who developed a positive ELISA had antibody detected by day 14. Four patients tested positive by ELISA prior to surgery, with 3/4 having positive aggregation assays. One ELISA negative patient developed early graft closure. No patient developed thrombocytopenia or a 50% or greater decrease in platelet count. Patients undergoing vascular surgery frequently develop PF4-Heparin antibodies of which up to 10% patients have platelet activating antibodies. However, both thrombocytopenia and vascular graft thrombosis due to HIT is a rare event.