Acute graft thrombosis in a patient with factor V Leiden mutation: A case report and review of literature

Abstract

BACKGROUND

Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss. Prompt diagnosis and intervention are essential, particularly in patients with inherited thrombophilias such as factor V Leiden (FVL) mutation.

CASE SUMMARY

A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis. The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries. Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution. Reperfusion was successful with immediate urine output and gradual improvement in renal function. The patient was discharged on direct oral anticoagulation therapy.

CONCLUSION

Early detection and surgical intervention can preserve graft function in post-transplant renal artery thrombosis even in patients at high risk.

Key Words: Acute transplant renal artery thrombosis; Thrombectomy; Factor V Leiden mutation; Inherited thrombophilia; Emergent re-exploration; Living donor kidney; Case report

Core Tip: Vascular thrombosis is an uncommon but serious complication in renal transplantation. Vigilant postoperative monitoring is essential for early detection. We described the successful salvage of a renal allograft with arterial thrombosis in a patient with factor V Leiden mutation, using a technically challenging donor kidney with dual arteries.

INTRODUCTION

Vascular complications in renal transplantation are relatively frequent from either living related or cadaveric donors, occurring in about 3%-15% of cases, and can often result in allograft loss[1,2]. The most common complications include transplant renal artery stenosis, arterial or venous thrombosis, biopsy-related vascular injuries, pseudo-aneurysm formation, and hematomas[1,2]. Among these transplant renal artery thrombosis is particularly devastating. It typically occurs early, presents with severe clinical symptoms, and is a major cause of graft loss[1]. We report our surgical management of early transplant renal artery thrombosis in a patient with a history of factor V Leiden (FVL) mutation.

CASE PRESENTATION

Chief complaints

A 48-year-old male with chronic renal disease secondary to immunoglobulin A (IgA) nephropathy presented for a preemptive living-donor kidney transplantation.

History of present illness

The patient had experienced progressive renal dysfunction over the prior several years. He was evaluated and deemed an appropriate candidate for living-donor renal transplantation. The donor, a 55-year-old male, was a living biological relative, who underwent left-sided donor nephrectomy.

History of past illness

The patient had a known history of chronic kidney disease leading to chronic renal insufficiency along with a documented coagulopathy due to FVL mutation. His medical history also included symptomatic gout, nonspecific acute thyroiditis complicated by hypothyroidism following radioactive iodine therapy, and recurrent venous thrombotic events, as follows. In 2001, the patient developed right popliteal vein thrombosis secondary to nephrotic syndrome (managed with warfarin, to resolution). In 2002, he presented with right superficial thrombophlebitis. In 2003, he experienced recurrent right superficial thrombophlebitis which was associated with a history of undocumented nephrotic syndrome; after this third venous thrombotic episode the patient was maintained on warfarin. There was no history of prior abdominal surgery.

Personal and family history

The patient had no known familial history of hereditary renal diseases. The donor was a healthy biological relative with no history of chronic illness; notably, the donor had a body mass index (BMI) of 27.2 kg/m², consistent with overweight status.

Physical examination

Preoperative physical examination revealed a hemodynamically stable patient for transplant receipt, presenting signs consistent with chronic renal disease and with a BMI of 24 kg/m². There was no evidence of edema, ascites, nor infection. Cardiopulmonary and abdominal examination findings were within normal limits.

Laboratory examinations

The patient’s hemoglobin was mildly decreased (consistent with anemia of chronic disease; 10 g/dL, normal range: 14-18 g/dL). His serum creatinine was elevated (11.0 mg/dL, normal range: 0.7-1.3 mg/dL). The coagulation profile revealed normal fibrinogen, antithrombin III, protein S, and protein C. Tests for lupus anticoagulants and anti-phospholipid antibodies were negative. The crossmatch test was negative, the human leukocyte antigen compatibility test was acceptable, and the panel-reactive antibody test was low.

Imaging examinations

Preoperative recipient imaging showed normal anatomy of the iliac vessels and no significant vascular calcification. Donor computed tomography (CT) angiography showed the left kidney with two renal arteries and the right kidney with a double renal vein (Figures 1 and 2). We chose the left kidney because it had the least renal function, according to evaluation by scintigraphy, and the most appropriate anatomy.

Figure 1  Computed tomography angiography scan depicted the anatomical configuration of the donor renal arteries.

Figure 2 Three-dimensional reconstruction of computed tomography angiography illustrating the anatomical configuration of the donor renal arteries. A: Anterior view; B: Anterior view with the left renal vein digitally removed to highlight the left renal arteries.

Genetic testing

Analysis of genomic DNA with polymerase chain reaction using specific primers indicated the presence of both guanine and adenine at nucleotide 1691, consistent with heterozygous FVL.

MULTIDISCIPLINARY EXPERT CONSULTATION

A multidisciplinary transplant team including nephrologists, transplant surgeons, and anesthesiologists had evaluated and optimized the patient preoperatively.

FINAL DIAGNOSIS

Chronic kidney disease due to IgA nephropathy and intraoperative vascular challenge due to the presence of an accessory renal artery requiring an additional anastomosis.

TREATMENT

A left donor kidney was retrieved via hand-assisted laparoscopic nephrectomy. Transplantation was performed in the recipient’s right iliac fossa using a pararectal approach. Venous anastomosis was created end-to-side to the fully mobilized right external iliac vein. The main renal artery was anastomosed end-to-side to the external iliac artery, and the inferior polar artery was previously transposed into the main renal artery in the back-table (Figures 3 and 4). Following declamping, the graft reperfused immediately with prompt urine output. No intraoperative complications were noted.

Figure 3 Back-table preparation showed transposition of the inferior polar artery into the main renal artery. A: Schematic Illustration; B: Perioperative image.

Figure 4  Anatomical configuration of the renal allograft in the right iliac fossa, showing end-to-side anastomosis of the renal vein to the external iliac vein and end-to-side anastomose of the main renal artery to the external iliac artery.

The immediate postoperative Doppler ultrasonography showed absent flow in both the main and accessory renal arteries, consistent with allograft renal artery thrombosis. An emergent surgical re-exploration was performed through the same incision. The graft appeared shrunken but viable. Both arteries were occluded with thrombus, and the vein was empty. The arterial anastomosis was dismantled under cold ischemia, and the thrombus was removed (Figure 5). While the graft remained in place, it was flushed with cold heparinized saline and vasodilator solution until pale and cold through venotomy (Figure 6). Separate end-to-side re-anastomoses of the main and inferior polar arteries were performed (Figure 7). Upon reperfusion the graft regained normal color, turgor, and perfusion.

Figure 5 Steps of arterial thrombectomy of the main and inferior polar renal arteries. A: Thrombosed principal and accessory renal arteries; B-D: Dismantling of the arterial anastomosis; E and F: Thrombectomy of both arteries; G: Renal arteries cleared of thrombus.

Figure 6  Cold perfusion of the kidney using heparinized saline combined with a vasodilator solution through a venotomy.

Figure 7 Anatomical configuration of the renal allograft in the right iliac fossa, showing end-to-side anastomosis of the renal vein to the external iliac vein, and separate end-to-side anastomoses of the main renal artery and the inferior polar artery to the external iliac artery. A: Schematic illustration; B: Peri-operative photograph.

Intraoperatively, there were no episodes of hypotension, no requirement for inotropic support, nor any significant blood loss. The total ischemia time was 105 minutes, comprising 60 minutes of warm ischemia and 45 minutes of cold ischemia.

OUTCOME AND FOLLOW-UP

Reperfusion was achieved with immediate restoration of urine output. Postoperative Doppler ultrasonography confirmed patent arterial and venous flows without evidence of thrombosis. The standard immunosuppressive protocol was resumed, and the unfractionated heparin anticoagulant therapy that had been initiated during the preoperative phase was continued in the postoperative phase, with activated cephalin time monitoring.

The postoperative course was uneventful aside from postoperative thrombocytopenia on day 5, raising suspicion of type II heparin-induced thrombocytopenia, prompting a switch to an alternative anticoagulant. The patient was later discharged on long-term direct oral anticoagulation therapy (7.5 mg/day Eliquis; Bristol-Myers Squibb Company). Immunosuppression included thymoglobulin induction that transitioned to tacrolimus on postoperative day 3 along with prednisone, mycophenolate mofetil, sulfamethoxazole/trimethoprim, and valganciclovir.

Imaging follow-up 2 years post-transplantation showed no signs of vascular compromise nor thrombosis. The patient experienced no complications and maintained stable renal function throughout the follow-up period.

DISCUSSION

Renal allograft thrombosis involving either the arterial or venous vasculature is a well-recognized complication of kidney transplantation. It most frequently occurs in the early postoperative period although late onset is also possible. Unfortunately, the prognosis remains poor regardless of the time of onset[3]. Most renal allograft thrombosis occurs early in the postoperative period, peaking within the first 48 h. However, thrombus formation can also be delayed beyond the first week[4].

Transplant renal artery thrombosis manifesting 2 or more weeks post-transplantation is classified as late renal artery thrombosis. This rare complication typically results from severe renal artery stenosis with consequent secondary thrombosis, or iatrogenic intimal injury during percutaneous endovascular procedures, or occurs in the context of graft rejection[5-7]. Delayed diagnosis and management of these complications can lead to significant morbidity with high risks of graft loss and mortality[8]. The incidence of arterial thrombosis ranges from 0.2%-7.5% and venous thrombosis from 0.1%-8.2% with the highest rates observed in pediatric and infant recipients and the lowest in series involving exclusively living donors. Variations in incidence reflect differences in recipient-donor composition, particularly the proportion of deceased donors[9].

Several factors may contribute to the pathogenesis of graft thrombosis, including variables related to the recipient, donor, transplantation, and surgery. Recipient-related factors such as advanced and very young age, history of diabetes mellitus, history of atherosclerosis and heart disease, perioperative or postoperative hemodynamic instability, cytomegalovirus (CMV) infection, toxicity of immunosuppressive agents, primary renal disease, mode of dialysis prior to transplantation, and a hypercoagulative state.

The underlying etiology of end-stage renal disease in the recipient also influences transplantation outcomes. Notably, diabetic nephropathy[10-12] is associated with an elevated risk of thrombosis, likely attributable to diabetic angiopathy. Additionally, atherosclerotic involvement of the vascular structures in either the recipient or the donor further augments this thrombotic risk[13,14].

Intraoperative and postoperative hemodynamic instability constitutes a significant risk factor for the development of graft thrombosis. Many studies identified it as an independent determinant of thrombotic events[10-15]. Pediatric data suggest that this factor may be even more critical in children, with younger patients being particularly susceptible to non-technical thrombosis due to relatively low cardiac output, especially when receiving a disproportionately large graft. This hemodynamic mismatch can result in suboptimal renal perfusion[16]. Accordingly, the implementation of aggressive fluid resuscitation and rigorous cardiovascular monitoring is imperative in such cases. CMV seropositive and seroconverted renal transplant recipients have been reported to exhibit a higher risk of venous thrombosis compared with recipients who are CMV-negative[17].

The incidence of acute transplant renal artery thrombosis has been reported to be higher among recipients treated with cyclosporine, ranging from 1.8%-7.0%, compared with 0%-1.0% in those receiving azathioprine and prednisone[18,19]. While cyclosporine exerts multiple biological effects, its most likely prothrombotic mechanism is the reduction of prostacyclin production by endothelial cells, thereby promoting thrombus formation[20]. Nonetheless, the association between cyclosporine use and renal allograft thrombosis remains controversial. Early clinical and experimental studies reported an increased incidence of renal vascular thrombosis and microvascular injury under cyclosporine-based immunosuppression, potentially related to vasoconstriction and endothelial dysfunction[18,21-24]. Subsequent investigations further described cyclosporine-induced chronic vascular and microvascular damage, which may predispose to thrombotic complications, particularly in the presence of unfavorable donor vascular anatomy[25-30]. However, other studies did not demonstrate a significant increase in renal allograft vascular thrombosis attributable to cyclosporine therapy when compared with alternative immunosuppressive regimens[31-35].

Renal artery graft thrombosis may also be precipitated by the administration of the monoclonal antibody OKT3, which has been shown to induce procoagulant activity[36,37]. The risk is further elevated in patients pretreated with high-dose intravenous methylprednisolone as this may activate the tissue factor/factor VII pathway[38]. Consequently, the recommended premedication dose of methylprednisolone should not exceed 8 mg/kg[39].

Pre-transplant peritoneal dialysis has been reported to be associated with a higher incidence of transplant renal artery thrombosis. Epidemiological data indicate a higher thrombotic risk among recipients who underwent re-transplant and in patients who underwent peritoneal dialysis prior to transplantation compared with those maintained on hemodialysis[10,14,40-43].

The pathophysiological basis may involve an acquired thrombophilic state, potentially resulting from selective protein losses into the peritoneal fluid, analogous to nephrotic syndrome. Additionally, patient selection factors may contribute; individuals switched from hemodialysis to peritoneal dialysis due to vascular access complications (often suggestive of underlying atherosclerosis) have been shown to have a greater thrombotic risk with the switch itself posing more risk than peritoneal dialysis alone[11].

Hypercoagulative states, also referred to as thrombophilias, comprise hereditary or acquired conditions that predispose individuals to thrombosis. Thrombophilias are classified as congenital (inherited), acquired (secondary), or both (mixed) conditions[44].

The presence of anti-phospholipid antibodies has been recognized as an important risk factor for early allograft failure[45]. While anti-phospholipid antibodies are found in approximately 10% of patients awaiting renal transplantation, the rate of clinical events in these patients is far less. The observation that only a fraction of patients with anti-phospholipid antibodies experience thrombotic complications led to the description of anti-phospholipid antibody syndrome, defined by the presence of anti-phospholipid antibodies and a clinical history of thrombosis.

Anti-phospholipid antibodies include not only the lupus anticoagulant and anticardiolipin antibodies but also more recently recognized subgroups of anti-phospholipid antibodies (antibodies against beta-2-glycoprotein-I) and antibodies to phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylcholine, and anti-annexin-V.

Patients with anti-phospholipid antibodies in association with other autoimmune diseases, most commonly lupus, are classified as having secondary anti-phospholipid syndrome. Approximately 40% of patients with systemic lupus erythematosus have an anti-phospholipid (anti-cardiolipin) antibody (lupus anticoagulant). The presence of anti-phospholipid antibodies has been recognized as an important risk factor for early allograft failure[46].

However, risk factors for arterial thrombosis are not limited to anti-phospholipid antibodies and lupus anticoagulants. Other hypercoagulable states include FVL mutation[47], antithrombin deficiency[48], methylene tetrahydrofolate reductase mutation, and hyperhomocysteinemia[49]. Furthermore, infectious and inflammatory states such as polyarteritis nodosa[50], Takayasu arteritis[51], and Behcet disease[52] are associated with renal artery thrombosis. These diseases might still possibly endanger acute thrombosis of a transplanted renal artery.

The FVL mutation, characterized by activated protein C (APC) resistance, represents the most prevalent inherited thrombophilic disorder. It is present in approximately 5%-8% of the general population, observed in 20% of individuals experiencing a first venous thrombotic event, and identified in up to 50% of patients with a personal or family history of recurrent thrombosis[53].

A molecular aberration in the factor V gene has been identified as the cause of the majority of APC resistance cases[54]. Physiologically, APC in conjunction with its cofactor protein S regulates coagulation by proteolytically inactivating the activated coagulation factors V and VIII (Va and VIIIa)[55]. A single point mutation in the factor V gene, a guanine-to-adenine substitution at nucleotide position 1691 (G1691A), results in a variant factor V protein that is resistant to inactivation by APC[56-58]. This mutated protein, known as FVL, contains a glutamine (Q) residue at amino acid position 506 (codon CAA) in place of the normal arginine (R; codon CGA). This mutation, also referred to as R506Q at the protein level, impairs the inactivation of factor Va by APC. Additionally, FVL impairs the proteolytic degradation of factor VIIIa, a mechanism thought to exacerbate the prothrombotic phenotype associated with this mutation[59].

The hypercoagulable condition associated with the FVL mutation exhibits variable penetrance[60]. While some carriers remain asymptomatic throughout their lives, others require the presence of additional risk factors, such as oral contraceptive use or anti-phospholipid antibodies, to precipitate a thromboembolic manifestation[61].

The FVL mutation has been associated with an increased risk of transplant renal vein thrombosis, with multiple cases reported in recipients who are FVL-positive across various studies[62-67]. Irish et al[63] identified a four-fold elevated risk of allograft thrombosis linked to FVL while noting that the mutation does not significantly increase the risk of arterial thrombosis, such as myocardial infarction, within this patient population. Therefore, the FVL mutation does not appear to confer an increased risk for arterial thrombosis.

The FVL mutation does not appear to predispose individuals to arterial thrombosis, including renal arterial thrombosis. Consistently, reports of renal arterial thrombosis in patients with the FVL mutation are exceedingly rare in the literature. Le Moine et al[68] documented a single case of renal artery thrombosis in a patient with heterozygous FVL while Klein et al[47] described another case of acute renal artery occlusion presenting as renal colic in an individual positive for FVL. Notably, the latter patient also tested positive for anti-phospholipid antibodies, suggesting that heterozygosity for FVL alone may be insufficient to induce renal arterial thrombosis. These observations underscore the variable penetrance of the FVL mutation and highlight the requirement for additional prothrombotic factors to precipitate such events.

In the context of renal transplantation, the donor kidney endothelium acquires a prothrombotic phenotype as a result of reperfusion injury, surgical trauma, inflammatory activation, and tissue factor expression, compounded by the recipient’s immune response. When this endothelial activation coincides with an inherited or acquired predisposition to hypercoagulability, the likelihood of thrombotic complications is substantially increased[69,70].

Donor-related risk factors reported in the literature include age over 60 years, very young donors under 5 years of age, marginal donors (e.g., multiple renal arteries, right kidney procurement), and pre-existing donor renal artery lesions such as atherosclerosis. An elevated risk of graft thrombosis has been documented in kidney transplant from elderly donors[12,71], likely attributable to donor hypotension combined with ischemia-reperfusion injury, which may promote procoagulant activity through cytokine release and the recipient’s immune response in atherosclerotic vessels[70]. Similarly, pediatric recipients receiving kidneys from cadaveric donors younger than 5 years exhibit a significantly higher incidence of thrombosis compared to those receiving grafts from older donors[72], a risk largely attributed to the marked size mismatch between donor and recipient vessels[73].

Historically, renal grafts with multiple arteries were considered to carry a higher risk of thrombosis[74]; however, this association appears less relevant in the modern transplant era[10,12-14,75-80] with reports of successful implantation even in grafts containing up to six arteries[81]. Accessory renal arteries are present in approximately 10%-20% of the population. Successful transplantation in such cases necessitates a highly skilled surgeon with comprehensive knowledge of renal arterial anatomical variations and advanced proficiency in microsurgical vascular reconstruction[81].

Regarding donor-related risk factors for graft thrombosis, Amézquita et al[73] suggested that the use of the right donor kidney as opposed to the left may predispose to early vascular thrombosis[73]. This association had been previously reported in earlier analyses[10]. Anatomical considerations largely account for this increased risk. The right kidney typically has a shorter renal vein and a longer renal artery, both of which present distinct technical challenges during transplantation. The longer artery is more susceptible to kinking while the shorter vein can complicate anastomosis. Furthermore, postoperative swelling whether due to ischemic injury, acute tubular necrosis, or urinary obstruction may result in compression of the renal vein by the graft itself[10,15,82]. The positioning of the right kidney is further complicated when multiple renal arteries are present, thereby increasing the technical complexity of the procedure[10].

Transplantation-related factors include cold ischemia time of the donor kidney > 24 hours, immune induction protocol, and rejection reactions. Several studies with larger cohorts report an increased incidence of thrombosis associated with prolonged cold ischemia time, particularly when exceeding 24 hours[42,80,83,84]. Surgery-related risk factors are primarily defined by technical challenges during graft procurement, back-table preparation, and implantation that may compromise the arterial lumen and disrupt normal blood flow. These include donor artery intimal injury incurred during graft retrieval, suboptimal vascular anastomosis, particularly in small grafts, as well as misalignment, torsion, or kinking of the renal artery.

Although intimal injury is uncommon, Nerli et al[85] reported a case of renal artery thrombosis resulting from such damage that led to impaired intraoperative blood flow across the anastomosis. This underscores the importance of using atraumatic perfusion needles and equipment, carefully inspecting the cut vessel ends for injury, monitoring graft turgidity, and closely observing the appearance of the transplanted kidney during surgery[85,86].

In renal transplantation the two predominant arterial anastomotic techniques are the end-to-end anastomosis of the renal artery to the hypogastric artery and the end-to-side anastomosis to the external iliac artery[87]. The end-to-end approach is generally favored due to its technical simplicity and shorter operative duration as well as its advantage in preserving lower limb perfusion. However, it is associated with a higher incidence of stenosis compared with the end-to-side anastomosis[88]. Allograft positioning in kidney transplantation can be challenging and may lead to torsion, an early or late complication. This often causes arterial kinking, typically due to an excessively long renal artery twisting from graft or pelvic shifts[89].

Post-transplant graft thrombosis typically presents with a sudden decrease in urine output accompanied by severe pain and tenderness over the graft site. Thrombocytopenia may develop within hours due to platelet accumulation in the thrombus. Prompt investigation is essential as early detection may allow for corrective intervention, whereas delayed diagnosis or treatment often results in graft loss[6].

A Doppler ultrasound is a rapid, reliable, and noninvasive first-line modality for identifying renal artery or vein thrombosis[90,91], demonstrating absent flow in both the main and intrarenal arterial branches[92]. Characteristic findings include a rapid decline in systolic frequency shifts, a retrograde diastolic plateau in the main renal artery and its proximal branches, and the absence of venous Doppler signals. Additional modalities, such as angiography, scintigraphy, CT, and magnetic resonance imaging, may also be employed to detect or confirm vascular thrombosis[5].

Transplant renal artery thrombosis represents a surgical emergency with the only viable chance of salvaging the graft being prompt exploration and restoration of renal perfusion. Therapeutic approaches for acute transplant renal artery thrombosis include open surgical thrombectomy or endovascular interventions, including catheter-directed thrombolysis and pharmacomechanical thrombectomy with or without adjunctive angioplasty or stent placement.

The therapeutic role of catheter-directed thrombolysis and percutaneous thrombectomy in early transplant renal artery thrombosis has not been clearly established. However, successful outcomes have been documented following percutaneous interventions for late-onset renal artery thrombosis[2]. A limited number of cases have documented successful graft salvage in acute transplant renal artery thrombosis through endovascular catheter-directed thrombolysis, either alone or in combination with adjunctive angioplasty[2,93].

The administration of thrombolytic agents during the early post-transplant period warrants careful consideration due to the heightened risk of severe hemorrhagic complications[1]. Hedegard et al[94] strongly advised the avoidance of thrombolytic therapy within the initial 2 weeks following graft implantation. In cases where endovascular thrombolysis was successfully employed to treat renal artery thrombosis, a comprehensive evaluation to identify and address the underlying cause was imperative to prevent recurrence[93]. In most cases by the time the diagnosis is confirmed, it is already too late for graft salvage, leaving graft nephrectomy the only viable intervention. Nephrectomy performed for renal artery thrombosis is associated with a high mortality rate, with sepsis constituting the principal cause of death[15].

Prevention plays a pivotal role in reducing the risk of vascular thrombosis and necessitates the integration of multiple measures. These include minimizing cold and warm ischemia times, ensuring meticulous surgical technique, such as excising traumatized segments of the donor artery during procurement, performing endarterectomy on atherosclerotic recipient vessels, and avoiding size mismatch between donor and recipient vessels, maintaining adequate intravascular volume to prevent perioperative hypotension, utilizing effective preservation solutions, and ensuring prompt, effective management of rejection. Collectively, these measures constitute key elements of a comprehensive prevention strategy[15,95].

Furthermore, identification and management of thrombophilic disorders may help prevent renal vascular thrombosis, potentially requiring routine screening and targeted therapy. However, no consensus guidelines exist. Screening is recommended for candidates with personal or family histories of thrombosis or recurrent catheter occlusions or those undergoing preemptive living donor transplantation.

The identification and management of thrombophilic conditions may serve as a preventive strategy against renal vascular thrombosis. This could involve routine screening and targeted therapy aimed at reducing the risk of thrombosis and subsequent graft loss; however, no consensus guidelines have yet been established. Previous studies suggest that laboratory evaluation should be considered for potential recipients with a personal or family history of thrombotic events, such as deep or superficial vein thrombosis, pulmonary embolism, thrombosed fistulas, or multiple occlusions of central venous dialysis catheters, or for patients undergoing preemptive transplantation with a living donor kidney[89].

Balancing the risk of thrombosis and hemorrhage is essential in recipients of renal transplants. In patients with known thrombophilia and prior thrombotic events, perioperative heparinization followed by long-term anticoagulation with warfarin has demonstrated favorable outcomes, including successful re-transplantation. However, the limited prospective randomized studies evaluating heparin use in this population have yielded conflicting results, underscoring the need for a standardized preoperative assessment of thrombotic and hemorrhagic risks and the development of consensus guidelines. Specifically, intravenous heparin has been effective in preventing graft thrombosis in patients with anti-phospholipid antibodies or congenital coagulation disorders. To minimize bleeding complications while maintaining anti-thrombotic efficacy, it is advisable to maintain the partial thromboplastin time ratio between 1.5 and 2.0. Long-term anticoagulation with warfarin or low-dose heparin should also be considered, targeting an international normalized ratio of approximately 2.5[89,96-98].

In our case the patient presented two major risk factors for renal graft thrombosis: A history of FVL mutation; and the presence of multiple donor renal arteries that created a technically challenging situation with increased surgical complexity and prolonged warm and cold ischemia times. The precise cause of the thrombosis cannot be definitively determined as a preventive strategy was implemented, including perioperative heparin anticoagulation, planned continuation of postoperative anticoagulation, and back-table transposition of the accessory renal artery into the main renal artery to reduce warm ischemia time. However, the back-table transposition of the inferior polar artery to the main renal artery may have contributed to the development of transplant renal artery thrombosis due to intimal injury.

The expertise of our surgical team in managing complex transplantation scenarios combined with prompt diagnosis and immediate re-exploration with thrombectomy enabled successful graft salvage.

CONCLUSION

We reported herein a rare case of acute transplant renal artery thrombosis in a patient with a hypercoagulable state due to FVL mutation, resulting in a long-term, well-functioning renal graft. Given the challenges associated in managing thrombosis and the high likelihood of graft loss, implementing comprehensive preventive strategies is essential. These measures should be particularly emphasized in patients with known additional thrombotic risk factors such as FVL mutation as the case of our patient. Early detection, prompt diagnosis, and timely intervention for post-transplant vascular complications, particularly renal transplant thrombosis, are critical to improving patient outcomes and enhancing graft survival.