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Proposed Relationship Between Intravenous Immunoglobulin and Thrombosis in Renal Transplant Recipients

Transplant Pharmacy Resident, Transplant Department, Henry Ford Hospital Transplant Institute, Detroit, MI

Iman Bajjoka, PharmD BCPS

Director of Pharmacy Research, Transplant Pharmacotherapy Specialist, Transplant Department, Henry Ford Hospital Transplant Institute

Lama Hsaiky, PharmD BCPS

Transplant Pharmacotherapy Specialist, Transplant Department, Henry Ford Hospital Transplant Institute

Ravi Parasuraman, MD

Senior Staff, Nephrology/Hypertension Department, Henry Ford Hospital Transplant Institute

Reprints: Dr. Bajjoka, Henry Ford Transplant Institute, 2799 W. Grand Blvd., CFP 219, Detroit, MI 48202, fax 313/916-3433, ibajjok1{at}hfhs.org

OBJECTIVE: To report 2 cases of intravenous human immunoglobulin (IVIG)-associated thrombosis in kidney transplant patients.

CASE SUMMARY: Both cases involved female patients presenting to Henry Ford Hospital in Detroit for renal transplantation. Patient 1 presented with systemic lupus erythematosus, positive for both anticardiolipin and anti-DNA antibody. Patient 2, postnephrectomy, was found to have moderate hyperhomocysteinemia, with a total plasma homocysteine level of 3.9 mg/L. Both patients were considered highly sensitized and at high risk for rejection due to the presence of either high panel reactive antibody or a positive B cell flow cytometry crossmatch, in addition to other risk factors. Therefore, IVIG was considered a viable treatment option to be included in induction therapy. IVIG was administered both peri- and postoperatively, and both patients experienced immediate graft function with good urine output. Within 24 hours following transplantation, elevations in serum creatinine and decreases in urine output were seen. Subsequently, kidney exploration was performed and palpable thrombi in renal arteries and veins were detected. Immediate nephrectomy was performed in both cases.

DISCUSSION: Currently, evidence derived from case reports highlights numerous risk factors for IVIG-associated thrombosis, one of which appears to be a hypercoagulable state. It has also been reported that some IVIG products contain amounts of anticardiolipin antibodies; these antibodies may potentiate thrombosis in the presence of hypercoagulable states, such as hyperhomocysteinemia or antiphospholipid syndrome. In these 2 patients, the Naranjo probability scale indicated that there was a possible association between the thrombotic events and the use of IVIG.

CONCLUSIONS: Prospective trials evaluating the safety of IVIG in highly sensitized transplant patients are scarce. Therefore, it is imperative that the benefits and risks be weighed when considering the use of IVIG in highly sensitized transplant patients.

Key Words: intravenous immunoglobulin, renal transplantation, thrombosis

Published Online, January 30, 2007. www.theannals.com, DOI 10.1345/aph.1H434