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Disorders of platelet number and function 

Disorders of platelet number and function

Chapter:
Disorders of platelet number and function
Author(s):

Kathryn E. Webert

and John G. Kelton

DOI:
10.1093/med/9780199204854.003.220603
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date: 29 April 2017

Platelets are released from megakaryocytes in the bone marrow and circulate for 5 to 10 days before being cleared by the cells of the reticuloendothelial system. They play a critical role in haemostasis, with key features being (1) adhesion—when the wall of a blood vessel is damaged, platelets adhere to exposed collagen and other components of the subendothelium via the glycoprotein Ib receptor and other adhesive receptors; followed by (2) activation—release of thrombin, adenosine diphosphate, and arachidonic acid, which is converted by a cascade of enzymes into platelet activating agents including thromboxane A2; and (3) aggregation—glycoprotein IIb/IIIa undergoes conformational changes, making it able to bind fibrinogen and resulting in the formation of the haemostatic plug

Thrombocytopenia

Thrombocytopenia is defined as a reduction in the number of circulating platelets to less than 150 × 109/litre. Bleeding is uncommon unless the platelet count falls below 10 to 20 × 109/litre, or unless there is abnormal platelet function.

Increased platelet destruction: autoimmune thrombocytopenia—mediated by antibodies that bind to individual platelet glycoproteins, most frequently glycoprotein IIb/IIIa. May be (1) Primary (idiopathic thrombocytopenic purpura, ITP)—a disorder of children and (typically) young or middle-aged women. May present in adults with incidentally discovered thrombocytopenia, a long history of easy bruising, or acute onset of petechiae, purpura, and bleeding. Many patients will not require specific treatment, but those with severe thrombocytopenia (platelets <10 × 109/litre) and/or significant haemostatic impairment are treated with corticosteroids, typically oral prednisone (1 mg/kg). Second-line treatments include high-dose intravenous immunoglobulin, splenectomy, and danazol. (2) Secondary—conditions that can cause immune thrombocytopenia include systemic lupus erythematosus, drug induced (most commonly heparin, quinidine, sulfonamides, valproic acid, and gold), chronic lymphocytic leukaemia, post-transfusion purpura, and infections (e.g. HIV, varicella, Epstein–Barr virus).

Increased platelet destruction: nonimmune thrombocytopenia—disorders associated with both thrombocytopenia and fragmentation haemolysis include (1) Thrombotic thrombocytopenic purpura—manifestations include thrombocytopenia, microangiopathic haemolytic anaemia, renal impairment, fever, and ischaemic neurological findings; may be related to a deficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin-1-like domains); treatment is with plasmapheresis. (2) Haemolytic uraemic syndrome—presents as renal failure, microangiopathic haemolytic anaemia, and thrombocytopenia. May be epidemic in association with a diarrhoeal illness caused by enterohaemorrhagic or verotoxigenic Escherichia coli serotype O157:H7 or Shigella dysenteriae serotype I; can also be hereditary or sporadic, sometimes in association with noninfectious conditions. Aside from supportive care, treatment is usually with plasmapheresis. (3) Disseminated intravascular coagulation—patients are usually very unwell and present with fulminant bleeding and organ dysfunction, most often in the context of sepsis; characterized by large amounts of thrombin that overwhelm the physiological inhibitors of coagulation; replacement therapy with fresh frozen plasma, cryoprecipitate, and platelets should be considered.

Decreased platelet production—may rarely be congenital, but most cases are acquired, with common or important causes being (1) toxins—drugs (e.g. chemotherapeutic agents, chloramphenicol, nonsteroidal anti-inflammatory drugs, antiepileptic medications, gold), alcohol; (2) nutritional deficiencies—folate or vitamin B12; (3) bone marrow infiltration; (4) myelodysplastic syndrome.

Disorders of platelet distribution and platelet sequestration—these include (1) splenomegaly and hypersplenism; (2) haemodilution—in patients who have received large volumes of crystalloid solutions or blood products; (3) extracorporeal circulation; (4) hypothermia.

Thrombocytosis

Thrombocytosis is defined as an increase in the number of circulating platelets to more than 600 × 109/litre.

Primary thrombocytosis (thrombocythaemia)—a chronic myeloproliferative disorder often caused by mutation in the JAK2 tyrosine kinase. Presentation may be with thrombosis or bleeding. Young, asymptomatic patients do not require treatment. Low-dose aspirin can prevent thrombosis and may relieve symptoms such as headache and erythromelagia, but it may unmask bleeding tendencies and hence should be avoided in patients with a history of bleeding. Hydroxyurea will lower the platelet count and usually reduces thrombohaemorrhagic complications.

Secondary thrombocytosis—causes include infections, malignancy, chronic inflammatory bowel disease, rheumatoid arthritis, iron deficiency, and hyposplenism.

Disorders of platelet function

Congenital disorders—these can affect platelet (1) adhesion and aggregation—e.g. Bernard–Soulier syndrome, caused by a deficiency or abnormality of platelet glycoprotein Ib/IX; (2) secretion; and (3) procoagulant activity.

Acquired disorders—most common causes of platelet dysfunction are (1) medications and toxins—e.g. aspirin, nonsteroidal anti-inflammatory agents, ticlopidine, clopidrogel, glycoprotein IIb/IIIa inhibitors; (2) systemic disorders—e.g. chronic renal failure; and (3) haematological diseases—e.g. chronic myeloproliferative disorders, myelodysplastic syndromes, dysproteinaemias.

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