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6 June 2003
Uremic Bleeding:
Pathogenesis and Therapy

麻醉科 林子富
Clinical Manifestations
▪ renal disease and bleeding (Morgagni 1764)
▪ purpura (Bright 1836)
▪ hemorrhagic pleural effusion and hemorrhagic
pericarditis from serosal irritation
▪ characterized by ecchymoses and prolonged
bleeding from puncture sites and mucous
membranes (epistaxis, GI and GU tract bleeding)
▪ Subdural hematoma (hypertension,
anticoagulation with heparin)
▪ Menorrhagia
Laboratory Evaluation
• The only clinically reliable test available to evaluate the
risk of bleeding in uremic patients and their response to
therapeutic interventions is bleeding time.
• Mild thrombocytopenia may develop in uremia, but it is
not sufficient to account for the abnormality in
hemostasis
• Abnormalities in the prothrombin time(PT) or partial
thromboplastin time (PTT) may occur but usually denote
other associated clotting problems or drugs.
Therapy
▪ Dialysis
▪ Uremic plasma elicits changes in the function of platelets from
normal donors. ( toxins, inhibitory peptides)
▪ Peritoneal dialysis: less bleeding risk ( lack of systemic
heparinization and of platelet activation by contact with a
bioincompatible membrane )
▪ preferred over hemodialysis in the high-risk patient with active
bleeding or subdural hematoma
Therapy
▪ Cryoprecipitate
▪ rich in vWf and fibrinogen, was found to improve the uremic
bleeding diathesis
▪ effect is rapid, but not invariably present.
▪ Within 1 hour after infusion of approximately 10 units, there is
normalization of bleeding time in about 50% of uremic
patients.
▪ As many as 50% of patients fail to respond.
▪ risk of transmission of infectious agents
Therapy
▪ Desmopressin (1-deamino-8-D-arginine-vasopressin) or
DDAVP
▪ a derivative of vasopressin with less vasoconstrictor effect,
has been used successfully in some forms of von Willebrand
disease
▪ Intravenous administration of 0.3 to 0.4 µg/kg over 20 to 30
minutes improves bleeding time within 1 hour, and this effect
is maintained for 4 to 8 hours
▪ induces the release of vWf from its endothelial storage pools
▪ Repeated use of desmopressin may deplete these stores of
vWf, resulting in tachyphylaxis after two or three doses
Therapy
▪ Estrogen
▪ von Willebrand disease and hereditary hemorrhagic
telangiectasia sometimes improve during pregnancy
▪ The beneficial effect of high-dose estrogens has been
attributed to the stimulation of an alternative enzymatic route
which reduces the L-arginine concentration in cells.
▪ 0.6 mg/kg per day IV for 4 or 5 days, or oral estrogens, 50
mg/kg per day, cause slower but more sustained
improvements in bleeding time
▪ The onset of action is about 6 hours after the initial intravenous dose
or 2 days after initiation of oral treatment
▪ effect lasts about 2 weeks after completing 5 days of intravenous
treatment, but only 4 or 5 days after oral doses are stopped.
Therapy
▪ Correction of Anemia
▪ Unless there is coincidental severe thrombocytopenia, platelet
transfusions are generally ineffective.
▪ transfusion of red cells corrects the prolonged bleeding time
promptly after a hematocrit of about 30% is reached
▪ The risks associated with repeated red cell transfusions can
be circumvented with human erythropoietin therapy.
▪ 50 to 100 U/kg 3 times per week can improve the anemia of
renal insufficiency to the target hematocrit of 30% in an
average of 6 weeks
Summary
▪ multifactorial nature ; flexible therapeutic strategy
▪ Bleeding time is the best guide to assess the bleeding risk
and to monitor the efficacy of treatment in a given patient.
▪ adequacy of dialysis and the hematocrit influence the bleeding
risk
▪ erythropoietin to avoid the risks associated with transfusions
▪ prophylactic red cell transfusion for actively bleeding or urgent
surgical intervention
▪ desmopressin for short-term interventions such as vascular
access placement or renal biopsy
Summary
▪ recurrent gastrointestinal or other internal hemorrhage
occurs, desmopressin may still be useful acutely, but the
sustained effect of estrogens makes them a more
appealing option
▪ elective surgery, particularly if the risks of bleeding are
high (eg, in orthopedic surgery), pretreatment with
estrogens is usually advisable
▪ Emphasis on dialytic adequacy and appropriate
hematocrit should not be overlooked when therapeutic
interventions such as desmopressin or estrogens are
being implemented.
References
1. Uremic Bleeding: Pathogenesis and
Therapy. The American Journal of the
Medical Sciences. Volume 316(2) August
1998 p 94-1041)
2. Management of Bleeding with Uremia
and Liver Disease. Current Opinion in
Hematology.Volume6(5) Sep.1999 P
329-333
3. Estrogen for Uremic Bleeding.
Hospital Pharmacy.Volume 33(8) Aug.1998
P 999-1005
Have A Nice Day