Management of Recurrent Thrombosis in Liver Transplant Recipients: A Case Report

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doi:10.1016/j.transproceed.2007.11.070 Copyright © 2008 Elsevier Inc. All rights reserved.

Case report

Management of Recurrent Thrombosis in Liver Transplant Recipients: A Case Report

N. Andiça, , , S. Karakuşa, G. Ilhana and M. Haberalb aDepartment of Internal Medicine, Division of Hematology, Faculty of Medicine, Baskent University, Ankara, TurkeybDepartment of General Surgery–Transplantation, Faculty of Medicine, Baskent University, Ankara, Turkey. Available online 6 February 2008.

Abstract

Intra-abdominal thrombotic complications in orthotopic liver transplantation can cause devastating results. The management of these patients after thrombosis remains a difficult clinical problem. We present a case report of a patient who developed recurrent venous, thrombosis after liver transplantation performed because of cirrhosis due to autoimmune hepatitis. She had bleeding episodes during and early after the transplantation procedure and developed portal vein thrombosis after a single dose of recombinant factor VII, which was given for treatment of hemorrhage. She had her second thrombotic attack while she was on warfarin therapy which was initiated after the first bout. No hereditary or immunologic risk factors were found. Management of these patients can be difficult because of the liver’s effect on the coagulation profile.

Article Outline

Case Report Discussion References

Intra-abdominal thrombotic complications in orthotopic liver transplantation (OLT) can have devastating results, reducing graft survival and increasing morbidity and mortality. Mechanical disturbances like a surgically damaged endothelium or decreased flow rates in transplant vessels produce procoagulant states in the postoperative period. Other thrombophilic risk factors, like factor V Leiden mutation, lupus anticoagulant and low levels of natural anticogulants, are also of great importance, since improvement in surgical techniques has reduced the effect of mechanical causes.[1] and [2] Anticoagulation of patients after thrombosis remains a difficult clinical problem. Herein we have reported on a patient who suffered recurrent thrombosis after liver transplantation. Case Report

A 44-year-old female patient underwent cadaveric OLT in December 2006. Her end-stage liver disease over 4 years was due to autoimmune hepatitis. Her international normalized ratio (INR) was 1.7, thrombocytes were within normal range, and fibrinogen level was 108 mg/dL before surgery. She had more bleeding than expected during surgery; 2 consecutive reexplorations had to be performed because of recurrent intra-abdominal hematomas. No source of surgical bleeding was found, the hemorrhage could not be controlled with fibrinogen, thrombocytes, or fresh frozen plasma replacement, so a single 80 μg/kg dose of recombinant factor VII (rFVII) was infused. Although the bleeding stopped, on the day thereafter, ultrasonography revealed portal vein thrombosis. Although the INR was 4 and fibrinogen level was below 150 mg/dL a heparin infusion was started. Five days after heparin, the thrombocyte count fell from 66,000 to 18,000/μL. There was no progression in the thrombosis. Heparin was immediately stopped because of the thrombocytopenia. On follow-up, thrombocyte levels increased, transaminases became normal, and INR fell below 2. These after oral warfarin was started and the patient was discharged. At 12 days thereafter, she was admitted to the hospital with abdominal pain and swelling. Examination revealed massive thrombosis from the inferior vena cava to the renal vein. Urgent thrombectomy was successfully performed, and no residual thrombosis was seen by postthrombectomy Doppler ultrasonography. The patient’s INR was 4 on this second admission; the transaminases were elevated 20-fold. She used warfarin as an outpatient but no INR measurements were performed, so we did not know whether the INR was in a therapeutic range. After thrombectomy she was followed conservatively. The transaminases fell to normal levels and the INR below 2. Warfarin therapy was started again; since then the INR levels have been within therapeutic range. There are no signs of a thrombotic attack. We could not discover any hereditary risk factor; immunologic tests, like lupus anticoagulant, were also negative, and protein S and C activity, which were slightly low before transplantation, dramatically diminished during thrombotic attacks. Discussion

Thrombosis in liver transplant recipients may be due to the type or quality of anastomoses, hereditary components (factor VII Leiden, prothrombin gene mutation), or acquired causes (hyperhomocysteinemia, lupus anticoagulant). Immediate recovery of coagulation factors and delayed recovery of natural anticoagulants like protein C and S in the early postoperative period may induce a hypercoagulable state.3 Most of the time more than one factor is involved in the thrombotic event, making the diagnosis more complicated. In our patient the first thrombotic attack occurred after the single dose rFVII replacement. Although rFVII is believed to be effective and safe to treat coagulopathy among liver transplant cases in large series, in this patient it seemed the most likely etiologic factor for thrombosis.4 Interventional techniques like thrombectomy and angioplasty can be safe and effective solutions, as in our case.5 Anticoagulation is almost always problematic. The second thrombotic attack of this patient was probably due to ineffective anticoagulation. Probably after thrombosis, synthetic function of the liver diminished, elevating the INR. We recommend anticoagulation of liver transplant recipients with thrombosis when their INR is under 2. Low molecular weight heparin can be a suitable choice. Oral warfarin may be used in patients with good liver function. rFVII must be used carefully in the early posttransplantation period, because of the hypercoagulable state during this time. Careful investigation of thrombophilic factors is essential.

References

1 M. Senzolo, P. Burra and E. Cholongitas et al., New insights into the coagulopathy of liver disease and liver transplantation, World J Gastroenterol 12 (2006), p. 7725. View Record in Scopus | Cited By in Scopus (3) 2 P.W. Marks and R. Rosovsky, Hematologic manifestations of systemic disease: liver and renal disease. In: R. Hoffman, Editor, Hematology Basic Principles and Practice (4th Ed.), Elsevier, Philadelphia (2005), p. 2566. 3 R.L. Stahl, A. Duncan and M.A. Hooks et al., A hypercoagulable state follows orthotopic liver transplantation, Hepatology 12 (1990), p. 553. View Record in Scopus | Cited By in Scopus (38) 4 N.M. Gibbs, The place of recombinant activated factor VII in liver transplantation, Int Anesthesiol Clin 44 (2006), p. 99. View Record in Scopus | Cited By in Scopus (2) 5 H. Karakayali, F. Boyvat and M. Coşkun et al., Venous complications after orthotopic liver transplantation, Transplant Proc 38 (2006), p. 604. Abstract | Full Text + Links | PDF (53 K) | View Record in Scopus | Cited By in Scopus (8)

Address reprint requests to Neslihan Andiç, Başkent Universitesi, Hastanesi Hematoloji, Bölümü 79, Sokak 7/5, Bahçelievler, Ankara, Turkey.

Transplantation Proceedings Volume 40, Issue 1, January-February 2008, Pages 322-323