Qualitative Platelet Disorders

General Principles

Qualitative platelet disorders present with mucocutaneous bleeding and excessive bruising with an adequate platelet count, PT, and aPTT and normal screening tests for vWD. Most potent platelet defects produce prolonged PFA-100 closure times. However, a normal PFA-100 does not exclude qualitative platelet disorders, and high clinical suspicion of a disorder should lead to further testing.

Classification

  • Inherited disorders of platelet function include receptor, signal transduction, cyclooxygenase (COX), secretory (e.g., storage pool disease), adhesion, or aggregation defects. In vitro platelet aggregation studies can identify patterns of agonist responses consistent with a particular defect, such as the rare autosomal recessive disorders of adhesion in Bernard–Soulier syndrome (lack of GP Ib/IX [vWF receptor]) and aggregation in Glanzmann thrombasthenia (lack of GP IIb/IIIa [fibrinogen receptor]).
  • Acquired platelet defects are more common than hereditary platelet qualitative disorders.
    • Conditions associated with acquired qualitative defects include metabolic disorders (uremia, liver failure), myeloproliferative diseases, myelodysplasia, acute leukemia, monoclonal gammopathy, and cardiopulmonary bypass platelet trauma.
    • Drug-induced platelet dysfunction is a side effect of many drugs, including high-dose penicillin, aspirin (ASA) and other NSAIDs, and ethanol. Other drug classes, such as β-lactam antibiotics, β-blockers, calcium channel blockers, nitrates, antihistamines, psychotropic drugs, tricyclic antidepressants, and selective serotonin reuptake inhibitors, cause platelet dysfunction in vitro, but they rarely cause bleeding.
    • Certain foods and herbal products may affect platelet function including omega-3 fatty acids, garlic and onion extracts, ginger, gingko, ginseng, and black tree fungus. Patients should stop using herbal medications and dietary supplements ≥1 week before major surgery.1,2

Treatment

  • Treatment of uremic platelet dysfunction can include dialysis to improve uremia; desmopressin (DDAVP) 0.3 μg/kg IV to stimulate release of vWF from endothelial cells; or conjugated estrogens (0.6 mg/kg IV daily for 5 days)3 and platelet transfusions in actively bleeding patients, although transfused platelets rapidly acquire the uremic defect. Transfusion or erythropoietin (EPO) to increase a hematocrit toward 30% might assist in hemostasis.4,5
  • Antifibrinolytic agents such as aminocaproic acid or tranexamic acid are commonly used as adjunct therapies with DDAVP for procedures or bleeding complications.
  • Reserve platelet transfusions for major bleeding episodes. Anecdotal reports have described successful control of severe bleeding with recombinant factor VIIa (rFVIIa).
  • Reversal of drug-induced platelet dysfunction
    • NSAIDs other than ASA reversibly inhibit COX. Their effects only last several days. COX-2 inhibitors have antiplatelet activity in large doses, but they have a minimal effect on platelets at therapeutic doses.
    • Aspirin irreversibly inhibits COX-1 and COX-2. Its effects diminish over 7–10 days because of new platelet production.
    • Thienopyridines inhibit platelet aggregation by irreversibly (clopidogrel and prasugrel) or reversibly (ticagrelor) blocking platelet adenosine diphosphate receptor P2Y12.
    • Dipyridamole, alone or in combination with ASA (Aggrenox), inhibits platelet function by increasing intracellular cyclic adenosine monophosphate (cAMP).
    • Abciximab, eptifibatide, and tirofiban block platelet IIb/IIIa–dependent aggregation (see Chapter 4, Ischemic Heart Disease).
    • Platelet transfusion compensates for drug-induced platelet dysfunction, except immediately following tirofiban and eptifibatide therapy.
    • Hold antiplatelet agents for 7 days before elective invasive procedures.

References

  1. Basila D, Yuan CS. Effects of dietary supplements on coagulation and platelet function. Thromb Res. 2005;117(1-2):49-53.  [PMID:15913714]
  2. Hodges PJ, Kam PC. The peri-operative implications of herbal medicines. Anaesthesia. 2002;57(9):889-899.  [PMID:12190754]
  3. Hedges SJ, Dehoney SB, Hooper JS, Amanzadeh J, Busti AJ. Evidence-based treatment recommendations for uremic bleeding. Nat Clin Pract Nephrol. 2007;3(3):138-153.  [PMID:17322926]
  4. Viganò G, Benigni A, Mendogni D, Mingardi G, Mecca G, Remuzzi G. Recombinant human erythropoietin to correct uremic bleeding. Am J Kidney Dis. 1991;18(1):44-49.  [PMID:2063854]
  5. Fernandez F, Goudable C, Sie P, et al. Low haematocrit and prolonged bleeding time in uraemic patients: effect of red cell transfusions. Br J Haematol. 1985;59(1):139-148.  [PMID:3918557]

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