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2086 Part XII: Hemostasis and Thrombosis Chapter 121: Acquired Qualitative Platelet Disorders 2087

A number of maneuvers have been taken to reduce the hemostatic “rebalanced,” although it remains unstable, with patients prone to both
abnormalities associated with cardiac surgery. These include coating the bleeding and thrombosis. Chronic liver disease can be associated with
artificial surfaces of cardiopulmonary bypass devices with heparin, 543–547 a prolonged bleeding time and reduced platelet aggregation and proco-
548
using centrifugal rather than roller pumps, use of a number of phar- agulant activity, 567,570,571 but there is no evidence for a platelet function
549
572
macologic agents, and performing coronary artery surgery without defect specific to liver disease. Rather, they are the result of multiple
bypass. 301,550 Off-pump coronary artery bypass surgery appears to pre- factors, including thrombocytopenia, hypofibrinogenemia, and anemia,
573
serve platelet function, but concerns have been raised about adverse none of which imply an intrinsic defect in platelet function. Regard-
thromboembolic events postsurgery because of the concurrence of nor- less, the prolonged bleeding in these patients may respond to infusion
mal platelet function, late thrombin generation, and reduced fibrinoly- of DDAVP, but clinical relevance of this observation is uncertain. 575
574
sis. 551–553 Several pharmacologic maneuvers have been tried to assist in Patients with DIC may exhibit reduced platelet aggregation and
the management of postoperative bleeding. Postoperative patients with acquired storage pool deficiency. 576,577 These result from platelet activa-
a prolonged bleeding time and excessive blood loss may respond to tion in vivo by thrombin or other agonists. Alternatively, elevated levels
DDAVP, as evidenced by a shortening of the bleeding time. However, of fibrin(ogen) degradation products and the low fibrinogen levels that
results of trials using this agent have been contradictory, some stud- accompany DIC may contribute to the platelet defect. Although puri-
ies showing a reduced blood loss and most showing no benefit. 554–556 fied low-molecular-weight fibrinogen-degradation products can impair
Based on the assumption that platelet activation during bypass could be platelet aggregation, this effect requires concentrations of degradation
578
a major cause of postoperative platelet dysfunction, infusion of platelet products unlikely to occur in vivo. Moreover, it is difficult to assess the
activation inhibitors such as PGE , PGI , or stable PGI analogues have significance of platelet dysfunction in most patients with DIC because
1
2
2
been carried out in animal models and in humans. By increasing plate- of the simultaneous presence of thrombocytopenia and other hemo-
let cAMP and reducing platelet responsiveness, these agents prevent static defects.
bypass-induced thrombocytopenia and platelet dysfunction. However, Decreased platelet aggregation and secretion in response to ADP
randomized trials using PGI and its analogue, iloprost, have not shown and epinephrine has been reported in Bartter syndrome, a group of rare
2
a clear overall benefit, in part because of significant toxicity, including inherited disorders characterized by severe restrictions of salt reabsorp-
hypotension. 123,557 Recombinant factor VIIa has been recommended to tion by the thick ascending limb of Henle, perhaps caused by excessive
treat uncontrolled postoperative bleeding that has not responded to PGE synthesis. 579–582 However, reviews of series of patients with Bartter
2
580
558
routine hemostatic therapy. However, the off-label use of recombinant syndrome make no mention of hemostatic problems so that the clin-
factor VIIa is associated with an increased risk for arterial and venous ical significance of the platelet aggregation abnormalities is doubtful.
thromboembolism and a retrospective case-matched review of patients In addition to thrombocytopenia, platelet dysfunction has been
559
who had received recombinant factor VIIa perioperatively during major observed in some patients with hemorrhagic fevers caused by Dengue,
cardiac surgery indicated that it was associated with worse survival. Hanta, Lassa, Junín, and Ebola viruses. There are also isolated reports
583
223
Nonetheless, it remains a potentially useful therapeutic consideration of a slight prolongation of the bleeding time and/or ex vivo platelet func-
in view of the prognosis of uncontrolled postoperative hemorrhage. tion defects in a number of other clinical conditions. These include non-
560
Based primarily on the cardiovascular complications encountered by thrombocytopenic purpura with eosinophilia, 584–586 atopic asthma and
587
patients in two randomized studies of the use of parecoxib/valdecoxib hay fever, acute respiratory failure, and Wilms tumor elaborating
588
to treat pain after cardiac surgery, the use of coxibs as well as traditional hyaluronic acid. The clinical significance of these associations is not clear.
589
NSAIDs appears contraindicated in this setting. 561,562
Inhibiting fibrinolysis using ε-aminocaproic acid or tranexamic
acid during cardiopulmonary bypass can reduce mediastinal blood REFERENCES
549
loss and transfusion requirements. Aprotinin (Trasylol), a broad-
spectrum protease inhibitor, was also used for this purpose, but obser- 1. Hayward CP: Diagnostic evaluation of platelet function disorders. Blood Rev 25(4):169–
vational studies, 563–565 as well as a blinded clinical trial, revealed that its 173, 2011.
566
use is associated with serious end-organ damage and a higher mortality 2. Nurden P, Nurden A, Jandrot-Perrus M: Diagnostic assessment of platelet function, in
Quality in Laboratory Hemostasis and Thrombosis, edited by S Kitchen, JD Olson, FE
than the use of ε-aminocaproic acid or no antifibrinolytic agent. Preston, pp 159–173. Blackwell Publishing, London, 2013.
The most important determinant of blood loss following cardio- 3. Wisloff F, Godal H: Prolonged bleeding time with adequate platelet count in hospital
patients. Scand J Haematol 27(1):45–50, 1981.
pulmonary surgery is the surgical procedure itself. If excessive nonsur- 4. Patrono C: Aspirin as an antiplatelet drug. N Engl J Med 330(18):1287–1294, 1981.
gical postoperative bleeding occurs, one should verify that the patient is 5. Smith WL, DeWitt DL, Garavito RM: Cyclooxygenases: Structural, cellular, and molec-
no longer hypothermic and that heparin has been fully reversed. At this ular biology. Annu Rev Biochem 69:145–182, 2000.
point, the administration of pharmacologic agents, along with judicious 6. Kis B, Snipes JA, Busija DW: Acetaminophen and the cyclooxygenase-3 puzzle: Sorting
out facts, fictions, and uncertainties. J Pharmacol Exp Ther 315(1):1–7, 2005.
transfusions of platelets, cryoprecipitate, fresh frozen plasma and red 7. Smith W, Garavito R, DeWitt D: Prostaglandin endoperoxide H synthases (cyclooxyge-
blood cells is appropriate. nases)-1 and -2. Biol Chem 271:33157, 1996.
8. Chandrasekharan NV, Dai H, Roos KL, et al: COX-3, a cyclooxygenase-1 variant inhib-
ited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and
expression. Proc Natl Acad Sci U S A99(21):13926–13931, 2002.
MISCELLANEOUS DISORDERS 9. Weiss H, Aledort L: Impaired platelet/connective tissue reaction in man after aspirin
ingestion. Lancet 2:495, 1967.
Measurements of hemostatic function are frequently abnormal in 10. O’Brien JR. Effect of salicylates on human platelets. Lancet 1(7557):1431, 1968.
patients with end-stage and fulminant liver disease and result from 11. Grosser T, Fries S, FitzGerald GA: Biological basis for the cardiovascular consequences
decreased coagulation factor production, fibrinolysis, dysfibrinogen- of COX-2 inhibition: Therapeutic challenges and opportunities. J Clin Invest 116(1):4–
emia, thrombocytopenia as a result of hypersplenism and thrombo- 15, 2006.
poietin deficiency, as well as disseminated intravascular coagulation 12. Kyrle PA, Eichler HG, Jager U, Lechner K: Inhibition of prostacyclin and thromboxane
A2 generation by low-dose aspirin at the site of plug formation in man in vivo. Circula-
(DIC). 425,567 However, the clinical consequences of these laboratory tion 75(5):1025–1029, 1987.
abnormalities have been reassessed because they do not take into 13. Jaffe EA, Weksler BB: Recovery of endothelial cell prostacyclin production after inhibi-
tion by low doses of aspirin. J Clin Invest 63(3):532–535, 1979.
account that both anti- and prohemostatic pathways are perturbed in 14. Marcus AJ, Safier LB: Thromboregulation: Multicellular modulation of platelet reactiv-
liver disease. 568,569 Thus, hemostasis in liver disease is considered to be ity in hemostasis and thrombosis. FASEB J 7(6):516–522, 1993.
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