Control of bleeding in severely uremic
patients undergoing oral surgery
David J. Buckley, B.D.S.,* Anthony P. Barrett. B.D.Sc.. Ph.D.,**
Jerry Koutts, M.D., B.S., F.R.A.C.P., F.R.C.P.A.,***
John H. Stewart, A4.B.Ch.B.. F.R.C.P.. F.R.A.C.P.,****
Westmead, New South Wales, Australia
WESTMEAD HOSPITAL DENTAL CLINICAL
The roles of hemodialysis and I-deamino-8-D-arginine
following oral surgery in a severely uremic patient are described.
(ORAL SURC. ORAL MED. ORAL PATHOL. 61546-549,
P rolonged bleeding is commonly encountered in
patients requiring hemodialysis for the severe uremia
of end-stage renal failure. There are three key
factors that predispose to this bleeding tendency.
First, the anticoagulation involved in the procedure
of hemodialysis-and in the outpatient maintenance
of prosthetic shunt patency-is generally considered
to provoke bleeding following oral surgery. Indeed,
the role of anticoagulation appears to be the princi-
pal concern expressed in the dental literature. Sec-
ond, it is significant that approximately 10% of
patients with severe uremia have mild (or occasion-
ally severe) thrombocytopenia as a result of impaired
platelet production.2 Furthermore, significant throm-
bocytopenia may be associated with the procedure of
hemodialysis itself. Third, abnormal platelet func-
tion is now well established as an important factor in
most patients with severe uremia.4,5
Although dialysis remains the mainstay for the
prevention of prolonged bleeding in uremia, it is not
always effective.6 Adjunctive measures may need to
be employed to secure hemostasis. The synthetic
analogue of the antidiuretic hormone vasopressin,
1-deamino-8-D-arginine vasopressin (DDAVP), has
previously been recommended in the management of
bleeding in severe uremia. 38 The aim of this article is
to examine the role of hemodialysis and DDAVP in
the prevention of bleeding following sequential den-
tal extractions in a severely uremic patient.
*Registrar, Oral Diagnosis.
**Staff Specialist, Oral Diagnosis.
***Head of Unit (Clinical Hematology).
****Head of Unit (Renal Medicine).
546
and
SCHOOL AND DEPARTMENT OF MEDICINE
vasopressin (DDAVP) in the control of hemorrhage
1986)
CASEREPORT
A 38-year-old white man was referred to the Westmead
Hospital Dental Clinical School for assessment in prepara-
tion for cadaveric renal transplantation. One year previ-
ously the patient experienced the onset of progressive renal
failure due to reflux nephropathy. Maintenance hemodial-
ysis therapy with a cuprophane hollow-fiber dialyzer began
5 weeks prior to referral. Vascular access was via a
surgically constructed forearm arteriovenous fistula. Sys-
temic anticoagulation involved adjustment of the whole
blood partial thromboplastin time to one and one half
times that of established laboratory controls. This was
achieved with an initial loading dose of 1,500 IU heparin
and maintained by heparin infusion at a rate of approxi-
mately 1,500 IU per hour. Current medication included
hydralazine hydrochloride, 50 mg, labetalol hydrochloride,
200 mg, and aluminum hydroxide, 600 mg twice daily, as
well as calcium carbonate, 1.2 g three times daily. The
patients medical history was otherwise unremarkable.
Physical examination revealed significant pallor of the
skin and mucosae, reflecting a severe underlying chronic
anemia (Hb:5.9g/dl at initial presentation). The patient
was partially dentate, and his oral hygiene was poor.
Radiographic evidence of bony changes,9 commonly
reported in long-term hemodialysis patients, was not evi-
dent.
Nine extractions were performed in three stages, follow-
ing induction of local anesthesia with lignocaine hydro-
chloride 2% with 1:200,000 epinephrine. Each extraction
session was planned for 14 hours following dialysis. Imme-
diately prior to and 24 hours after each extraction session,
a full blood count and skin bleeding time (SBT) determi-
nation (by the Simplate II method) were performed. Since
there is evidence to suggest that DDAVP may encourage
hemostasis through the elevation of various factor VIII
levels*, the following standard assays for factor VIII
activity were performed: (1) factor VIII coagulant activity
Volume 6I Control of bleeding in severely uremic oral surgery patients 547
Number 6

Table I. Key parameters measured

Skin 7rnre
bleeding sirw
Facror VIII assay (U/d11
time Platelets Urea Creatinint, dial~~.si.c
Stage of treatment (min) (X 10~////) V1II.C VIII: VWF VIlItAg (mmol/li (mmol/l) (/VI

Sesiitm I
Pre-DDAVP 10 240 180 68 180 18 x43 14
Post-DDAVP (I hr) 6.5 230 260 105 195 19.8 886 I5
Post-DDAVP (24 hr) >I5 228 150 94 205 24.3 1100 3x
Sessiorl II
Pre-extraction 6 237 120 85 I80 17.6 818 I4
Postextraction (24 hr) >I5 224 I48 95 I85 26.3 III9 3x
Session 111
Pre-extraction 5 261 I65 89 125 20.0 861 14
Postextraction (24 hr) 9.5 204 160 82 210 29.2 1093 ix
(pre-DDAVP)
Post-DDAVP (I hr) >I5 212 170 100 172 33.9 II54 40
Normal range of values 2-9.5 150-400 50-150 50-150 50-150 2.5-6.5 ho- 125

(F VIII:C), (2) factor VIII-related antigen (F VIII:Ag),
and (3) factor VIII von Willebrand (F VIILVWF) (Table
I). Multiple biochemicalanalyses(MBA12) were also
performedand includedserumurea and serumcreatinine
levels. Prothrombin time and activated partial thrombo-
plastin times were determinedsimilarly throughout and
were within normal limits.
Prior to the first extraction session,the SBT was 10
minutes-marginally above the upper limit of normal in
this laboratory (range, 2 to 9.5 minutes). DDAVP was
administeredin 50 ml of isotonic saline solution (by
intravenous infusion over 30 minutes) at a dose of 0.3
pg/kg. One hour following the administrationof DDAVP,
and immediatelyprior to surgery, thesetestswererepeat-
ed. The SBT was reduced to 6.5 minutes. Four teeth
(upper left first and third molarsand lower left first and
secondpremolars)wereextracted and the socketssecured
with mattresssutures,as were all subsequentextraction
sockets.Abnormal postoperativebleedingdid not occur.
Prior to the secondextraction session,which includedtwo
teeth (lower left first and secondmolars), the SBT was
within normal limits (6 minutes)and, therefore, DDAVP
was not administered.Abnormal postoperativebleeding
did not occur. Twenty-four hours following eachof these
extraction sessions, the SBT was>15 minutes.
Prior to the third session-whenthree teeth (upper left
lateral incisorand cuspidand upper right first molar) were
extracted-the SBT was again within normal limits (5
minutes)and DDAVP wasnot administered.However,the
socketsbeganto bleedfreely 18 hoursafter extraction (32
hours after dialysis). Six hours following the onset of
bleeding,the patient returned. The socketsof the three
recently extracted teeth were bleeding freely, with no
evidenceof clot formation, despite seeminglyadequate
localpressure.Eventhoughthe SBT at this stage(38 hours
after dialysis) wasonly at the upper limit of normal (9.5
minutes), the decisionwas made to initiate DDAVP as
previously described.Bleeding did not cease,however,
following the infusionof DDAVP-the SBT having actu-
ally risen (SBT > 15 minutes) 1 hour following infusion.
Hemodialysiswasreinstituted. Bleedingfrom all sockets
ceasedabruptly 3 hourslater. Ten hoursfollowingcomple-
tion of hemodialysis,there wasno evidenceof bleedingor
soft tissuehematoma.Subsequenthealingwasuneventful,
as with all other extractions.
DISCUSSION
This report clearly demonstrates the potential for
patients with end-stage renal disease to bleed postop-
eratively following dental surgery. Of the three key
factors that predispose to the bleeding tendency in
uremia, heparinization and thrombocytopenia did
not appear important in this patient. First, the
anticoagulant effect of heparinization was unlikely
to provoke postoperative bleeding, as each extraction
session was scheduled for 14 hours following hemo-
dialysis, and the duration of action of heparin is
reported to be on the order of 2 to 4 hours only.O As
heparinization is the principal concern expressed in
the dental literature, it is generally recommended
that invasive dental and oral surgical procedures be
performed on the day following hemodialysis. In the
present case, however, effective hemostasis occurred
during active anticoagulation with heparin. This
probably reflects, in part, the increasingly pre-
cise control of anticoagulation possible during con-
temporary hemodialysis, which tends to over-
come the past complications of less efficient
heparinization.
Second, platelet counts throughout the study were
never below 200 X 109/1. Therefore, as with the
anticoagulation effects of heparin, thrombocytopenia
appeared similarly unimportant. By exclusion, plate-
let dysfunction appeared to be the most likely cause
of postoperative bleeding in the present case.
548 Buckley et al. Oral Surg.
June, 1986

The precise pathogenesis of the platelet dysfunc- postoperative bleeding in the present case was due to
tion in uremia is unclear, but it is considered to be disordered platelet function resulting from the
associated with a number of factors, including reten- increased accumulation of dialyzable platelet toxins
tion of platelet toxins6 and abnormal factor VIII following hemodialysis. We recommend, therefore,
activity. I2 The retention of dialyzable platelet toxins, that in cooperation with the renal physician and
normally excreted by the kidney, has long been hematologist, the dentist or oral surgeon perform
considered a cause of platelet dysfunction.6B3 From invasive dental and oral surgical procedures 2 to 4
Table I it is clear that rising levels of serum urea and hours following hemodialysis, to allow for elimina-
creatinine are related to time following completion of tion of any potential residual influence of heparin. As
hemodialysis. Therefore, it appears reasonable that a the SBT is acknowledged to be the most valuable test
similar time-related increase in the concentration of for demonstrating platelet dysfunction,* it should be
platelet toxins could be anticipated. This may be performed routinely prior to treatment. If it is
reflected in the increased SBT, seen on each occasion prolonged following hemodialysis, DDAVP may be
24 hours following extractions (38 hours following beneficial in reducing it to normal levels prior to
hemodialysis). The observation that the postopera- surgery. If the SBT is not reduced-or if postopera-
tive bleeding in this patient ceased once dialysis was tive bleeding occurs, as seen following the third
instituted further supports a role of dialyzable plate- extraction session reported here-then further hemo-
let toxins in uremia. dialysis should be instituted.
The von Willebrand portion of the factorVII1 We wish to acknowledge the cooperation and excellent
complex is essential for normal platelet function. A technical assistance of Mrs. Mary Sartor, Department of
deficiency of this factor, as seen in von Willebrands Hematology, Institute of Clinical Pathology and Medical
disease, is characterized by a prolongation of the Research, Westmead Hospital.
SBT and decreased platelet adhesiveness.14 A possi-
ble pathogenic role of factor VIII in the etiology of
platelet dysfunction in uremia is suggested, but it has REFERENCES
yet to be clearly demonstrated.5, I2 In fact, factor VIII 1. Sowell SB: Dental care for patients with renal failure and
activity in persons with renal failure is generally renal transplants. J Am Dent Assoc 104: 171-177, 1982.
normal or increased.15 DDAVP has been used suc- 2. Stewart JH: Platelet numbers and life span in acute and
chronic renal failure. Thromb Diath Haemorrh 17: 532-542.
cessfully to facilitate hemostasis in mild to moderate 1967.
von Willebrands disease by increasing factor VIII- 3. Vicks SL, Gross ML, Schmitt GW: Massive hemorrhage due
to hemodialysis-associated thrombocytopenia. Am J Nephrol
related activity and, therefore, apparently correcting 3: 30-33, 1983.
platelet dysfunction. K It has been proposed that 4. Castaldi PA, Rozenberg MC, Stewart JH: The bleeding
boosting factor VIII activity above normal in uremia disorder of uremia-a qualitative platelet disorder. Lancet 2:
may similarly facilitate hemostasis.,* In one study 66-69, 1966.
5. Deykin D: Uremic bleeding. Kidney Int 24: 698-705, 1983.
by Mannucci and colleagues,8 major surgery was 6. Stewart JH, Castaldi PA: Uraemic bleeding: A reversible
made possible in uremic patients with a hemorrhagic platelet defect corrected by dialysis. Q J Med 30: 409-423,
tendency. Infusion of DDAVP was associated with 1967.
1. Watson AJS, Keogh JAB: Effect of I-deamino-8-D-arginine
an increased factor VIII-related activity and a short- vasopressin on the prolonged bleeding time in chronic renal
ened SBT. A similar effect was seen during the first failure. Nephron 32: 49-52, 1982.
8. Mannucci PM, Remuzzi G, Pusineri F, Lombardi R, Valsec-
extraction session in this study when DDAVP was chi C, Mecca G, Zimmerman TS: Deamino-8-D-arginine
administered 14 hours after hemodialysis (Table I). vasopressin shortens the bleeding time in uremia. N Engl J
A study performed by Vincente and colleagues,18 Med 308: 8-12, 1983.
however, failed to demonstrate these effects. Follow- 9. Kelly WH, Mirahmadi MK, Simon JHS, Gorman JT: Radio-
graphic changes of the jawbones in end-stage renal disease.
ing the third extraction session in the reported case, ORAL SURG ORAL MED ORAL PATHOL 50: 372-38 I, 1980.
DDAVP-this time administered 38 hours after 10. Precious DS, Laba JP, Hinrichsen GJ: Dental considerations
hemodialysis-failed to significantly boost factor for patients on chronic dialysis and renal transplant recipi-
ents. Can Dent Assoc J 9: 595-599, 1981.
VIII-related activity. The SBT was not shortened, 11. Farrell PC, Ward RA, Schindhelm K, Gotch FA: PreciZe
and the patient continued to bleed. The reason for anticoagulation for routine hemodialysis. J Lab Clin Med 92:
this apparently inconsistent action of DDAVP is 164-176, 1978.
12. Kazatchkine M, Sultan Y, Caen JP, Bariety J: Bleeding in
unclear, but it is probably influenced by a number of renal failure: a possible cause. Br Med J 2: 612-615, 1976.
factors, particularly the levels of dialyzable platelet 13. Horowitz HI: Uremic toxins and platelet function. Arch
toxins. Other possible factors may include lowered Intern Med 126: 823-826, 1970.
14. Mammen EF: Congenital coagulation disorders. Semin
hematocrit19 and increased prostacyclin activity.*O Thromb Hemost 9: 22-27, 1983.
In conclusion, we propose that the major cause of 15. Wegmuller E, Gruninger U, Furlan M, Beck EA. Hodler J,
Volume 61 Control of bleeding in severely uremic oral surgery patients 549
Number 6

Reubi FC: Factor VIII activity in chronic renal disease. effect of red cell transfusions. Lancet 2: 1013-1015, 1982.
Nephron 28: 157-162, 1981. 20. Remuzzi G, Cavenaghi AE, Mecca G, Donati MB, De
16. Mannucci PM, Ruggeri ZM, Pareti Fl, Capitanio A: I- Gaetano G: Prostacyclin-like activity and bleeding in renal
deamino-8-D-arginine vasopressin: a new pharmacological failure. Lancet 2: 1195-I 197, 1977.
approach to the management of haemophilia and van Wille- 21. Steiner RW, Coggins C, Carvalho ACA: Bleeding time in
brands disease. Lancet 1: 869-872, 1977. uremia: a useful test to assess clinical bleeding. Am J
17. Menon C, Berry EW, Ockelford P: Beneficial effect of Hematol 7: 107-I 17, 1979.
D.D.A.V.P. on bleeding time in von Willebrands disease.
Lancet 2: 743-744, 1978.
18. Vincente V, Alberta I, Macias JF, Lopez Borrasca A: Reprint requests to:
DDAVP in uremia. Nephron 36: 145-146, 1984. Dr. D.J. Buckley
19. Livio M. Gotti E, Marchesi D, Mecca G, Remuzzi G, De Westmead Hospital Dental Clinical School
Gaetano G: Uraemic bleeding: role of anaemia and beneficial Westmead, New South Wales, 2145, Australia

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