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Acquired Platelet Dysfunction

By

David J. Kuter

, MD, DPhil, Harvard Medical School

Last full review/revision Jun 2020| Content last modified Jun 2020
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Acquired platelet dysfunction, which is common, may result from aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), or systemic disorders.

Acquired abnormalities of platelet function are very common. Causes include

  • Drugs

  • Systemic disorders

  • Cardiopulmonary bypass

Acquired platelet dysfunction is suspected and diagnosed when unusual or prolonged bleeding is observed and other possible diagnoses (eg, thrombocytopenia, coagulation abnormalities) have been eliminated. Platelet aggregation studies are unnecessary.

Drugs

Aspirin, other NSAIDs, inhibitors of the platelet P2Y12 adenosine diphosphate (ADP) receptor (eg, clopidogrel, prasugrel, ticagrelor), and glycoprotein IIb/IIIa receptor inhibitors (eg, abciximab, eptifibatide, tirofiban) may induce platelet dysfunction. Sometimes this effect is incidental (eg, when the drugs are used to relieve pain and inflammation) and sometimes therapeutic (eg, when aspirin or the P2Y12 inhibitors are used for prevention of stroke or coronary thrombosis).

Aspirin and NSAIDs prevent cyclooxygenase-mediated production of thromboxane A2. This effect can last 5 to 7 days. Aspirin modestly increases bleeding in healthy people but may markedly increase bleeding in older patients and those with underlying platelet dysfunction or a severe coagulation disturbance (eg, patients receiving heparin, patients with severe hemophilia Hemophilia Hemophilias are common hereditary bleeding disorders caused by deficiencies of either clotting factor VIII or IX. The extent of factor deficiency determines the probability and severity of bleeding... read more ). Clopidogrel, prasugrel, and ticagrelor all can markedly reduce platelet function and increase bleeding.

Systemic disorders

Many disorders (eg, myeloproliferative neoplasms Overview of Myeloproliferative Neoplasms Myeloproliferative neoplasms are clonal proliferations of bone marrow stem cells, which can manifest as an increased number of platelets, red blood cells (RBCs), or white blood cells (WBCs)... read more , myelodysplastic disorders Myelodysplastic Syndrome (MDS) The myelodysplastic syndrome (MDS) is group of disorders typified by peripheral cytopenia, dysplastic hematopoietic progenitors, a hypercellular or hypocellular bone marrow, and a high risk... read more , uremia, macroglobulinemia Macroglobulinemia Macroglobulinemia is a malignant plasma cell disorder in which B cells produce excessive amounts of IgM M-proteins. Manifestations may include hyperviscosity, bleeding, recurring infections... read more , multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones causing... read more Multiple Myeloma , cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more , systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more Systemic Lupus Erythematosus (SLE) ) can impair platelet function.

Uremia prolongs bleeding via unknown mechanisms. If bleeding is observed clinically in uremic patients, bleeding may be reduced with vigorous dialysis, cryoprecipitate administration, or desmopressin infusion. If necessary, increasing the hemoglobin concentration to > 10 g/dL by transfusion or by giving erythropoietin also reduces bleeding.

Cardiopulmonary bypass

As blood circulates through a pump oxygenator during cardiopulmonary bypass, platelets may become dysfunctional, prolonging bleeding. The mechanism appears to be activation of fibrinolysis on the platelet surface with resultant loss of the glycoprotein Ib/IX binding site for von Willebrand factor. Regardless of platelet count, patients who bleed excessively after cardiopulmonary bypass are often transfused with platelets. Giving an antifibrinolytic agent during bypass may preserve platelet function and reduce the need for transfusion.

General reference

  • Scharf RE: Drugs that affect platelet function. Semin Thromb Hemost 38(8): 865–883, 2012. doi: 10.1055/s-0032-1328881 Epub 2012 Oct 30.

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Overview of Coagulation Disorders
Abnormal bleeding can result from disorders of the coagulation system, of platelets, or of blood vessels. Disorders of the coagulation system can be hereditary or acquired. Of the hereditary disorders of hemostasis, which of the following is the most common? 
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