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Chapter 130 Acquired Disorders of Platelet Function 1933

TABLE Acquired Disorders of Platelet Function platelet, bind to its receptor on the platelet membrane, and reinforce
130.1 aggregation by promoting secretion from α and dense granules.
Aspirin-treated platelets stimulated with these agonists demonstrate
Drugs, Foods, and Additives only a primary, reversible wave of aggregation without granule secre-
Drugs: see Table 130.2 tion. Stronger agonists (high concentrations of thrombin and colla-
Food and additives: omega-3 fatty acids, ethanol, ginger, onion, garlic, gen) do not require TXA 2 synthesis to cause platelet secretion and
black tree fungus, Gingko biloba, cumin, turmeric, tonic water, irreversible aggregation, and thus some hemostatic function is main-
caffeine, pineapple, others tained in aspirin-treated patients.
Clonal Disorders Aspirin may also have COX-independent actions that may affect
Clonal hematologic diseases coagulation. At the site of microvascular injury, platelets bind to
Myeloproliferative neoplasms exposed collagen, and coagulation is initiated by tissue factor con-
Paroxysmal nocturnal hemoglobinuria currently. It was reported that low-dose aspirin (30 mg/day for 7
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Paraproteinemias days) decreased thrombin formation in healthy volunteers. Undas
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Leukemias and myelodysplastic syndromes et al used the same microvascular injury model and showed that
Solid tumors aspirin at 75 mg/day for 7 days decreased the velocity of prothrombin
Systemic Metabolic Disorders consumption by 29%, thrombin generation by 29%, and delayed
End-stage renal disease both activation and maximum cleavage of factor XIII by thrombin.
Liver diseases Interestingly, high cholesterol levels (>240 mg/dL) impaired the
Diabetes and hyperlipidemias antithrombotic effect of low-dose aspirin in a microvascular injury
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Platelet Dysfunction Related With Extracorporeal Circuits model.
In contrast to the antiplatelet effect of aspirin, which appears
Miscellaneous unrelated to the dose above small threshold doses, GI mucosal toxic-
Hypothermia ity is dose related. The mechanism of mucosal injury appears to be
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Scurvy distinct from the effect on hemostasis, involving ionic trapping of
Acquired platelet dysfunction with eosinophilia 17
aspirin within gut mucosal cells and diminished synthesis of protec-
tive gut prostaglandins. 18,19 The inhibitory effect of even a single dose
of aspirin on gastric prostaglandin synthesis is prolonged, with one
study showing that gastric COX activity was still 57% suppressed 72
TABLE Drug-Induced Platelet Dysfunction hours after a single 325-mg dose of aspirin. Bleeding may originate
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130.2 from discrete ulcers or diffuse mucosal damage and is more common
Anti-Platelet Drugs to arise from the upper GI tract. The risk of bleeding is increased
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COX inhibitors: aspirin even with doses of aspirin as low as 10–30 mg/day; the protective
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ADP receptor antagonists effect of resistant coatings is unproven. The GI risk of aspirin is
Thienopyridines: clopidogrel, ticlopidine, prasugrel increased in elderly adults (older than 65 years of age) and in those
Nonthienopyridines: ticagrelor, cangrelor with concomitant medical conditions, such as cardiovascular disease,
α IIb β 3 inhibitors: abciximab, eptifibatide, tirofiban as well as in those taking certain other medications, such as other
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PDE inhibitors NSAIDs. Aspirin appears to delay the healing of gastric ulcers,
Nonselective PDE inhibitors: pentoxifylline, caffeine, theophylline possibly because it interferes with the release of growth factors from
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PDE3 inhibitors: cilostazol, milrinone, anagrelide platelets, such as endostatin and vascular endothelial growth factor.
PDE5 inhibitors: dipyridamole, sildenafil Regular use of aspirin (≥75 mg) impairs primary hemostasis dose-
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Adenyl cyclase stimulators: epoprostenol, iloprost, beraprost dependently. Aspirin treatment was associated with a small but sig-
Drugs that adversely affect platelet function nificant increase in mucocutaneous bleeding as evidenced by easy
NSAIDs: ibuprofen, naproxen, indomethacin, bruising, hematemesis, melena, epistaxis, and an increased frequency
Cardiovascular agents of blood transfusion surrounding surgeries. Because low doses have
Calcium channel blockers: nifedipine, diltiazem, verapamil been shown to be effective in preventing thrombosis, it is likely that
β-Blockers: propranolol the risk of bleeding can be reduced while maintaining an antiplatelet
Vasodilators: nitrates, nitroprusside effect.
Diuretics: furosemide Aspirin may unmask mild hereditary disorders of platelet func-
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Angiotensin II receptor antagonist: losartan, valsartan, and tion. For example, patients with mild von Willebrand disease often
olmesartan have a normal bleeding time that becomes markedly increased with
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Antibiotics: β-lactams, amphotericin, hydroxychloroquine, aspirin therapy. The bleeding risk associated with aspirin is increased
nitrofurantoin in the presence of other hemostatic defects, or if aspirin is given
Antifungal drugs: Miconazole, amphotericin B simultaneously with anticoagulant drugs.
Psychiatric drugs: TCAs, fluoxetine, chlorpromazine, promethazine,
trifluoperazine
Oncologic drugs: mithramycin, daunorubicin, BCNU, asparaginase, Aspirin Resistance
vincristine, dasatinib, ibritunib
Anesthetics: dibucaine, procaine, halothane, sevoflurane, propofol The response to aspirin therapy varies among individuals. Every day,
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Plasma expanders: dextran, hydroxyl ethyl starch the human body can produce approximately 10 × 10 platelets, and
Heparins and thrombolytic agents this production can increase 10-fold if needed. The life span of
Miscellaneous: clofibrate, statins, cocaine, ketanserin, radiographic platelets is 8–10 days, and every day nearly 10%–12% of the platelets
contrast agents, antihistamines, immunosuppressive drugs are replaced by new platelets. The capacity of the bone marrow to
produce new platelets, the aspirin dosage, the aspirin exposure time
ADP, Adenosine diphosphate; BCNU, carmustine; COX, cyclooxygenase; (spot doses or regular use), and individual parameters will determine
NSAID, nonsteroidal antiinflammatory drug; PDE, phosphodiesterase; TCA,
tricyclic antidepressant. the antihemostatic effect of aspirin in any particular individual.
The issue of aspirin resistance is hotly debated, with reported
incidence rates varying from 0% to 57%. 25–28 The presence of aspirin
resistance is associated with high rates of cardiovascular events. 27,28
The most important issue in determining whether laboratory
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aspirin resistance is real is compliance. Schwartz et al evaluated 190