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It has been controversial whether or not to accept kidneys for transplantation from donors with disseminated intravascular coagulation (DIC). We report two recipients who received the kidneys from a donor with DIC following traumatic head injury. Despite evidence of donor kidney glomerular fibrin deposits and ongoing low-grade DIC in the recipients, which resolved after 5–7 days; both recipients did well suggesting that donors with DIC can be successfully used for renal transplantation.
Disseminated intravascular coagulation (DIC) occurs after brain destruction in head injury patients (1). Evidence of donor DIC may cause certain centers to exclude otherwise viable organs for transplantation. Previous reports have shown primary non-function and/or a high incidence of delayed graft function in such donors (2). In a review of 100 consecutive organ donors at the Pacific Northwest Transplant Bank, Hefty et al. found laboratory evidence of DIC in 29% with the vast majority having clinical evidence of DIC. The 34 recipients of these 29 kidneys did not differ in any way from recipients of non-DIC donor kidneys (3).
We recently accepted kidneys from a 16-year-old male donor with a self-inflicted gunshot wound to the right temple. The donor's history was unremarkable except for depression. Renal function was normal and blood pressure was maintained at greater than 110/50. Initial labs showed: PT 21 s (nl 11–15), PTT 84.9 s (nl 24–36), fibrinogen 111 mg/dL (nl 150–440) and platelets 83 × 109/L. D-dimer was not done. He was found unresponsive and was intubated by paramedics. Pupils were fixed and dilated at the time. During the resuscitation attempt he received four units of fresh frozen plasma and four units of packed red blood cells (HIV, HLTV1 & 2, hepatitis C and hepatitis B serologic testing was negative). Serum creatinine initially was 1.1 mg/dL and rose to a maximum of 1.8 mg/dL 24 h later. At the time of organ procurement, it was 1.3 mg/dL. Urinalysis showed 2+ protein, 4+ blood, 5–10 red cells, 5–10 white cells and was positive for hemoglobin and myoglobin. Hematocrit dropped initially to 23% but stabilized at 33.4%. Platelet count dropped to a low of 79 000 × 109/L, CPK was 1653 units with an MB fraction of 18. PT, PTT and platelet count remained significantly abnormal with a DIC index score ≥ 4 (4). After procurement, the kidneys were biopsied and fibrin thrombi were present in glomeruli on frozen section (Figure 1). Based on the pathology examination, another center turned down the kidneys.
Figure 1. Fibrin thrombi occlude several distended glomerular capillaries (arrows) in the right (right) and left (left) donor kidney biopsies (H&E, 200×). There was no evidence of vascular or tubulointerstitial disease in either donor biopsy. Each had numerous glomeruli, about 25% of which contained from one to five small fibrin thrombi.
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The kidneys were flushed with heparin and transplanted into two recipients. Immunosuppression was basiliximab on day 1 and 4 and mycophenolate mofetil 1 g b.i.d., methylprednisolone 500/250/125 then 1 mg/kg and tacrolimus 0.1 mg/kg beginning on day 4. Each recipient developed transient DIC with thrombocytopenia, which was self-limited.
Recipient 1 was a 55-year-old Caucasian male with end-stage renal disease secondary to type II diabetes. He had had previous coronary artery bypass surgery and had co-morbid hypertension and hyperlipidemia. He achieved immediate graft function with his creatinine reaching a nadir value of 1.5 on post-operative day 6. Pertinent hematologic data are shown in Table 1. There was no evidence of clinical bleeding but his DIC score was 4 at discharge; platelets were normal.
Table 1. Hematologic parameters in the transplant recipients
|Cold ischemia time||Recipient 1||Recipient 2|
|16.7 h||20 h|
|Initial||Post-operative day 4||Initial||Post-operative day 3|
|PT (nl 11–13.5 s)||11.7||12.6||13.3||11.6|
|aPTT (nl 21–31 s)||29.9||22.5||23.9||23.4|
|Fibrinogen (150–499 mg/dL)||295||361|
|D-dimer sensitive (nl 0–499 mg/mL)||4064||2495|
|Platelets × 109/L||161||25||172||46|
|Peripheral blood smear||Many schistocytes, fragmentation, significant thrombocytopenia, nl WBC||Frequent schistocytessignificant thrombocytopenia, nl WBC|
Recipient 2 was a 53-year-old Caucasian male with type II diabetes and chronic hepatitis C secondary to blood transfusions. He also achieved immediate graft function with serum creatinine reaching a nadir value of 1.7 on post-operative day 6. His hematologic parameters are shown in Table 1. He was discharge on post-operative day 7 with normal platelets; his DIC score was 4.
Three months post-transplant both recipients are doing well with stable serum creatinines of 1.2 and 1.5 mg/dL, respectively. Hemograms are normal.
Both lungs and the liver from the donor were used at other institutions and at 3 months are functional. The liver recipient had a coagulopathy not thought to be different from the usual post-operative changes in liver transplantation.
Many centers are reluctant to use kidneys from donors with DIC. Since head injury is frequently complicated by this phenomenon, the presence of low-grade DIC in two recipients is instructive. Although the kidneys were thoroughly flushed prior to implantation, phospholipid surface tissue factor expression on endothelial cells, generation of microparticles from platelets and monocytes plus inflammatory cytokines likely induced consumptive coagulopathy (5,6). Interestingly, CPK was elevated at the same time that DIC occurred in the donor and myoglobin was found in the urine.
Pastural et al. reported a case similar to ours with fibrin thrombi in the glomeruli. Since there were no irreversible lesions on the biopsy in a young donor with normal function, the transplanting center made the decision to go ahead with excellent results (7). These authors found 94 additional cases, four with primary non-function and 26 with delayed graft function. Eighty-six of the 94 had satisfactory long-term graft function. McCall et al. using a database of biopsies between 1 January 1995 and 31 December 2000, showed donor kidney microvascular thrombosis in only 8 of 230 consecutive implantation biopsies (8). While these donors exhibited more delayed graft function compared to other donors, graft survival at 1 and 2 years was similar to non-DIC recipients. Coagulation activation via tissue factor activation, generation of phospholipid surfaces, microparticles and inflammatory cytokines all contribute to sustained thrombin generation and resulting DIC (5). Cytokine release from trauma or induction therapy also could trigger intravascular coagulation (9). In our cases no induction therapy was used. It is possible that many renal transplant recipients develop low-level DIC contributing to mild thrombocytopenia and/or drops in hemoglobin particularly when induction therapy is used. A prospective study of all recipients with and without donor DIC would be necessary to examine this issue.
We conclude that donor kidneys with DIC are suitable for transplant recipients although self-limited DIC without clinical bleeding may result.