Page 2109 - Williams Hematology ( PDFDrive )

2084 Part XII: Hemostasis and Thrombosis Chapter 121: Acquired Qualitative Platelet Disorders 2085

By contrast, some substances found in high concentrations in uremic DDAVP, a vasopressin analogue whose pressor effects are substan-
plasma, such as urea and parathyroid hormone, appear to play no role tially less than its antidiuretic effects, causes the release of VWF from
in platelet dysfunction. 454 tissue stores, has been reported to shorten the bleeding time in 50 to
Concurrent medications and thrombocytopenia must always be 75 percent of patients with uremia. In many cases, surgery has been car-
considered when a patient with renal failure exhibits a bleeding ten- ried out safely after administration of this drug, although no controlled
467
dency. Aspirin can prolong the bleeding time inordinately in uremia. trials have been performed. DDAVP is usually administered intrave-
Unlike aspirin’s effect on COX, this effect is transient and correlates with nously in a dose of 0.3 mcg/kg over 15 to 30 minutes (maximum dose:
467
blood levels of aspirin. 34,35 Bleeding may be potentiated by the admin- 20 mcg) but it is also effective at this dose when given subcutaneously.
468
istration of heparin during hemodialysis; in this situation, the use of Alternatively, the drug can be given intranasally. Improvement in the
an ethylene-vinyl alcohol copolymer hollow fiber dialyzer or intermit- bleeding time is seen within 30 to 60 minutes of administration, lasts
tent saline infusion and high blood flow rates may eliminate the need for approximately 4 hours, and roughly correlates with the rise in the
455
for heparin. β-Lactam antibiotics that prolong the bleeding time may plasma levels of VWF and the appearance in the circulation of high-
467
have a greater effect in uremic patients and increase the occurrence of molecular-weight VWF multimers. In some patients, the drug has
bleeding. 456 been given repeatedly at 12- to 24-hour intervals, although tachyphy-
Mild thrombocytopenia has been reported in chronic renal failure, laxis can occur. 469
457
particularly in patients on dialysis, as a result of diminished marrow Side effects of DDAVP have been mild and uncommon and have
production and decreased platelet survival. Serum thrombopoietin included a 10 to 15 percent decrease in mean arterial pressure, a 20 to
458
levels in hemodialysis patients are increased, 457,459 perhaps reflecting 30 percent increase in pulse rate, facial flushing, water retention, and
increased platelet turnover or a decrease in megakaryocyte mass. But hyponatremia leading to seizures; the latter is more common after
when platelet counts are greater than 100 × 109/L, it is necessary to con- repeated administration and when fluids are given freely. Water reten-
467
sider whether a systemic disease or medication, such as multiple mye- tion and hyponatremia have not been observed in patients whose kid-
loma, systemic vasculitis, hemolytic uremic syndrome, eclampsia, renal neys cannot respond to the hormone. Several uremic and nonuremic
allograft rejection, or heparin, could be responsible for bleeding in a individuals with atherosclerosis have been reported to develop stroke
uremic patient. or myocardial infarction after DDAVP administration, although such
complications appear to be rare. 470,471 If dialysis is not effective, DDAVP
Clinical and Laboratory Features is the treatment of choice for uremic bleeding, particularly if only a
Despite dialysis, abnormal platelet function in uremia remains a clin- short-term effect is required. 467
ical issue because it may contribute to bleeding following surgery or Conjugated estrogens at a dose of 0.6 mg/kg intravenously for
trauma or in conjunction with anatomic lesions of the gastrointestinal 5 days have also been reported to shorten the bleeding time in most,
tract. 441,455 The bleeding time has often been used as an indication of but not all, uremic individuals, both in uncontrolled studies and in ran-
hemorrhagic risk in uremia, but critical reviews of the literature indicate domized, double-blind studies. 34,472–474 They may also be useful in some
475
that it is not appropriate to use for this purpose. 460,461 patients with uremia who bleed from gastrointestinal telangiectasia.
No changes in the plasma levels or multimer distribution of VWF have
Therapy been noted with this treatment and it has been postulated that the active
Abnormal platelet aggregation is common in uremic patients, but by component in conjugated estrogens, 17β-estradiol, acts through an
425
itself is not an indication for therapeutic intervention. The frequency estrogen receptor mechanism. 476
of excessive bleeding after biopsies or other surgical procedures in ure- Lastly, uncontrolled studies suggest that infusions of cryoprecip-
mic patients who have not received specific treatment is not known, itate can shorten the bleeding time in uremic patients and ameliorate
477
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but may be uncommon. Thus, if bleeding does complicate a procedure, bleeding. However, others have reported inconsistent results, and
a thorough search for causes of bleeding other than uremia should be because of concerns of viral contamination, cryoprecipitate is very
initiated without assuming that uremia is the etiology. However, when rarely used for this indication.
therapy for a uremic bleeding diathesis is necessary, the uremic platelet
defect can usually be successfully treated. ANTIPLATELET ANTIBODIES
There are several therapeutic maneuvers that can either partially
or completely correct an abnormal bleeding time in uremic patients and Definition and History
anecdotal observations indicate that they may also improve hemosta- Antibody binding to platelets in several pathologic conditions, includ-
sis. Because prospective studies comparing various treatment regimens ing immune thrombocytopenia (ITP), systemic lupus erythematosus
have not been performed, the choice of therapy should be based on the (SLE), and platelet alloimmunization can cause thrombocytopenia as
severity of the bleeding, the anticipated severity of the hemostatic stress a result of decreased platelet survival. Less commonly, bleeding times
imposed by surgery or trauma, the predicted duration of the therapeutic may be shorter than expected for the degree of thrombocytopenia, sug-
478
effect, and the risks of therapy. gesting enhanced platelet function. On occasion, platelet function is
The mainstay of therapy is dialysis. Intensive dialysis can correct impaired in ITP. 479–483
the bleeding diathesis in many patients, but is only partially effective in
462
others. Peritoneal dialysis and hemodialysis are equally effective. 462,463 Etiology and Pathogenesis
If a patient undergoing dialysis bleeds, it may be worthwhile to increase The mechanism by which autoantibodies or alloantibodies impair
the intensity of the dialysis. platelet function is likely antibody binding to specific platelet GPs. Most
In uremic individuals, increasing the hematocrit by transfusion or antiplatelet antibodies are directed against integrin α β , 479–482 but anti-
IIb 3
treatment with recombinant human EPO to 27 to 32 percent is often bodies directed against GPIb–IX–V, integrin α β , and GPIV have been
2 1
associated with diminished clinical bleeding. 428–430,464,465 A number of detected as well. 484,485 In most instances, the functional consequences
reports suggest that EPO has an effect on platelets independent of an of antibody binding are obscured by the presence of thrombocytope-
increase in hematocrit, perhaps the result of an increase in the num- nia. However, patients have been reported with normal platelet counts,
431
ber of young platelets in the circulation. 466 absent platelet aggregation, autoantibodies against integrin α β ,
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