Thrombosis in renal disease: Transplantation

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Thrombosis in renal diseaseTransplantation

• Ryszard Grenda MD,PhD
• Prof.Head
• Dept. of Nephrology, Kidney TransplantationHypert
  ension
• Childrens Memorial Health Institute, Warsaw,
  Poland

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Urgent imaging
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Renal transplant thrombosis

• Incidence, timing, clinical importance
• Risk factors
• Prophylaxis Treatment
• Outcome

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Timing NAPRTCS data
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• 3.1

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Risk factors -
donor - procedure
- recipient related
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Risk factors- confirmed and/or suggested

• Donor- related
• age lt 5 years
• multiple vessels
• laparoscopic technique of kidney harvesting
• Procedure related
• prolonged CIT (gt24 hours)
• prolonged ATN (gt 7 days)
• surgical complications

• Recipient-related
• age lt 5 years
• congenital or acquired thrombophilia
• specific primary renal disease (e.g. congenital
  nephrotic syndrome)
• PD as pre-transplant RRT modality
• pre-emptive transplantation
• clinicaly silent acute rejection

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INCIDENCE OF HEREDITARY AND ACQUIRED
THROMBOPHILIA IN A PEDIATRIC POPULATION
UNDERGOING KIDNEY TRANSPLANTATION.Joshua J
Zaritsky, Pornpimol Rianthavorn, Jennifer L
Marik, Jennifer S Singer, H Albin Gritcsh, Guy
Young, Mohammed Malekzadeh, Robert B Ettenger.
Abstract WCT, Boston 2006
Incidence of Thrombophilias
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• Overall incidence 10
• lt 2 years of age 18
• gt 10 years of age 4
• Significant risk factors
• young age of donor
• young age of recipient
• increased CIT
• intra-procedure surgical complications
• Non-significant factors
• LRD vs deceased donor
• gender of recipient and donor
• multiple vessels
• left vs right placement
• Iliac artery vs aorta

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NAPRTCS data
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Graft thrombosis in pediatric renal transplant
recipients. A report of the North American
Pediatric Renal Transplant Cooperative
Study. Harmon WE, Stablein D, Alexander SR,
Tejani A. Transplantation. 1991
Feb51(2)406-12
1045 renal transplants
Thrombosis occurred in 2.6 of all transplants
and accounted for 22.5 (27/120) of all graft
failures that occurred in the first 60 days
following transplantation
In recipients less than 6 years old, the
thrombosis rate for those who received
transplants without prior dialysis was 4/32
(12.5) versus 3/109 (2.8) with prior dialysis.
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Living-unrelated renal transplantation in
children a report of the North American
Pediatric Renal Transplant Cooperative Study
Al-Uzri A, Sullivan EK, Fine RN, Harmon WE.
Pediatr Transplant. 1998 May2(2)139-44
Experience with 38 LURD transplants for children
Twenty nine were primary Tx, seven were second
Tx, and two were third Tx.
There were 12 LURD graft failures, including 3
due to vascular thrombosis (7,9)
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Renal transplantation in children with congenital
nephrotic syndrome a report of the North
American Pediatric Renal Transplant Cooperative
Study (NAPRTCS). Kim MS, Stablein D,
Harmon WE.
Pediatr Transplant. 1998 Nov2(4)305-8.
132 transplant recipients with the primary
diagnosis of CNS
Graft failures attributed to vascular thrombosis
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Pretransplant dialysis status and outcome of
renal transplantation in North American
childrena NAPRTCS Study.
Vats AN, Donaldson L, Fine RN, Chavers BM.
Transplantation. 2000 Apr 1569(7)1414-9.
Primary Tx was performed in 2495 children
The major single cause of graft failure in each
group was PD vascular thrombosis 20 HD
chronic rejection 27
CONCLUSION
Graft loss resulting from vascular thrombosis is
more common in children who receive PD than in
those receiving HD.
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The role of pretransplantation renal replacement
therapy modality in kidney allograft and
recipient survival.
Goldfarb-Rumyantzev AS, Hurdle JF, Scandling JD,
Baird BC, Cheung AK.
Am J Kidney Dis. 2005 Sep46(3)537-49
US Renal Data System records from January 1,
1990, to December 31, 1999, with a follow-up
period through December 31, 2000 (n 92,844)
CONCLUSION
compared with PD, HD as an RRT modality, is
associated with increased risk for graft failure
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Impact of immunosuppression protocols
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Is dose of cyclosporine important factor?
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TAC vs CsA
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NAPRTCS data ATG induction and risk of thrombosis
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Prophylaxis
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• Standard unfractioned heparin 5000 u/sc.
  b.i.d. during hospitalisation
• Intensified LMWH 5000 u/sc once daily, 6 weeks

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Own experience (1984-2003) Childrens Memorial
Health Institute, Warsaw, Poland Prokurat S,
Grenda R, Latoszynska J et al.Renal
transplantation in children undergoing peritoneal
dialysis-20 years of experience,
Ped.Transpl,2005,9,6,59

• Overall 318 renal graft recipients, at mean age
  of 12,6 ymean duration of dialysis prior to Tx
  31 months
• Incidence of thrombosis 10/318 3.1
• 4.6 among patients previously on PD vs 2.2
  among patients on HD
• Overall 9/10 clotted grafts were lost
• LMW-heparin prophylaxis (50 u/kg sc. q.o.d, mean
  duration 14 days) introduced as routine in 161
  consequtive patients
• Thrombotic events among PD pts. 2 events on
  prophylaxis (vs 4 in pts. without heparin),
  among HD 0 events on prophylaxis (vs 4 events
  in pts. without heparin)
• __________________________________________________
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Pre-heparin era vascular thrombosis complicated
7 out of 176 transplants (4.0)
Only one graft was rescued with local
thrombolytic therapy (streptokinase).
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Typical and atypical complications of
anticoagulants post- renal transplantation

• Bleeding increased requirement for blood
  tranfusion and formation of haematomas
• Increased risk of lymphocoele (?) Lundin C et
  al..Low molecular heparin prophylaxis increases
  the incidence of lymphocoele after kidney
  transplantation. Ups J Med. Sci,2002,107 (1),9-15

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Bleeding and thrombosis in high-risk renal
transplantation candidates using heparin.
Ann Pharmacother. 2004 Apr38(4)537-43.
Mathis AS, Dave N, Shah NK, Friedman GS.
Twenty-eight (3.86) of 725 consecutive renal
transplant recipients received heparin to prevent
renal thrombosis. Eighteen patients (64.3) had
clinically important bleeding (including 14 major
bleeding).
Bleeding occurred at a mean PTT (partial
thromboplastin time) ratio of 2.5 /- 1, higher
than the overall mean in bleeders and nonbleeders
(p 0.001).
Prolonged surgical antibiotic prophylaxis (p
0.053), particularly with cefotetan (p 0.091),
trended toward a significant association with
bleeding
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Outcome in high risk patients
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Hypercoagulable states in renal transplant
candidates impact of anticoagulation upon
incidence of renal allograft thrombosis.
Friedman GS, Meier-Kriesche HU, Kaplan B, et al
Transplantation. 2001 Sep 2772(6)1073-8.
Patients who were at hypercoagulable states in
the study cohort received i.v. heparin
immediately after transplant and p.o. warfarin as
outpatients
CONCLUSIONS Long-term allograft function has
been achieved in 90 of study patients when
prophylactically anticoagulating study patients
with hypercoagulable states. A 2.6-fold
reduction in the expected incidence of allograft
thrombosis was observed in anticoagulated
patients with hypercoagulable states.
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Treatment
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Long-term sequele of successful thrombolysis
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ACUTE THROMBOSIS OF RENAL TRANSPLANT ARTERY
Graft Salvage by Means of Intra-Arterial
Fibrinolysis Rouvière Olivier, Berger Pascal,
Béziat Christophe, Garnier Jane-Luce, Lefrançois,
Nicole, Martin Xavier, Lyonnet Denis
Transplantation, 2002, 73(3), 403-409
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Summary

• Renal transplant thrombosis remains a significant
  cause of early graft loss, mainly in young
  recipients.
• Several inherited and acquired risk factors have
  been identified.
• There is no clear evidence, that routine
  heparin-based prophylaxis is univocally effective
  under all multifactorial circumstances. Special
  risk groups gain the highest benefit.
• Combined management, aimed to specific,
  transplantation procedure-related targets
  probably lowers the overall risk.
• The safety of long-term prophylaxis, based on
  oral vitamin-K dependent anticoagulants
  (dicumarole-derivatives), probably should be
  re-evaluated.
• Selective local thrombolysis (urokinase/alteplase)
  may be effective as rescue therapy mostly in
  early detected renal vein thrombosis. Artery
  clotting is occasionally treatable event.