Elsevier

The Lancet

Volume 355, Issue 9214, 29 April 2000, Pages 1531-1539
The Lancet

Series
Platelets

https://doi.org/10.1016/S0140-6736(00)02175-9Get rights and content

Summary

Section snippets

Platelet production

The development of megakaryocytes and production of platelets are unique processes. Megakaryocyte maturation involves nuclear duplication without cell division, resulting in giant cells. Cytoplasmic organelles are organised into domains representing nascent platelets, demarcated by a network of invaginated plasma membranes. Within the marrow, megakaryocytes are localised next to the sinusoidal walls, which facilitates the exit of large segments of cytoplasm into the circulation. The

Platelet structure and function

On activation, platelets change from the normal disc shape to a compact sphere with long dendritic extensions facilitating adhesion (figure 1). The cytoplasm is rich in actin and myosin which bring about the change in shape and retraction of the clot. There are two classes of secretory granules. The first type are dense granules that secrete ADP and calcium, which reinforce platelet aggregation and platelet-surface coagulation reactions. The second type are α granules, which secrete a vast

Platelet circulation

Platelets survive for about 10 days on average; younger platelets have greater functional ability. The spleen continually but transiently sequesters about a third of circulating platelets. Splenomegaly, particularly when caused by passive congestion due to increased portal venous pressure, greatly increases the fraction of platelets retained in splenic sinusoids, without decreasing overall platelet survival time. This retention causes the mild thrombocytopenia associated with liver cirrhosis

Bleeding disorders

Bleeding can result from defective platelet function or from thrombocytopenia. The abnormalities must be severe for clinically important bleeding to occur, since haemostasis has many redundant functions. For example, the congenital absence of the platelet fibrinogen receptor, glycoprotein IIb-IIIa, has a profound effect on laboratory assessment of platelet function (panel 1), yet patients without this glycoprotein typically have only intermittent and minor bleeding.13 Also the normal platelet

Disorders of platelet function

Although hereditary disorders of platelet function are rare, they define the bleeding symptoms caused by platelet abnormalities.13 Mucocutaneous bleeding, such as purpura, epistaxis, gingival bleeding, and menorrhagia, are prominent features; gastrointestinal bleeding is common; visceral haematomas, haemarthroses, and intracerebral haemorrhage rarely, if ever, occur in the absence of trauma. Even when the genetic defect is severe, as in patients with Glanzmann's thrombasthenia who have

Thrombocytopenia in an otherwise healthy person

Thrombocytopenia may be suspected from bleeding symptoms, or may be discovered by a routine blood count in a person without symptoms. The incidental discovery of thrombocytopenia, which has occurred since platelet counting became routine, has shown the existence of pseudothrombocytopenia and expanded the clinical range of thrombocytopenic disorders to include many symptom-free patients. The investigation and management of patients with isolated thrombocytopenia is illustrated by the algorithm

Thrombocytopenia caused by infection

The most common causes of thrombocytopenia are infections. Thrombocytopenia can occur in infections caused by viruses (eg, HIV, cytomegalovirus, Epstein-Barr virus, hantavirus), mycoplasmas, bacteria, mycobacteria, rickettsiae, or protozoal parasites (eg, malaria). In most cases the mechanism is decreased platelet production, though hypersplenism can contribute. In HIV infection, thrombocytopenia is caused by infection of marrow stromal cells that facilitate haemopoiesis.28 Thrombocytopenia is

Thrombocytopenia associated with pregnancy

The occurrence of thrombocytopenia during pregnancy raises important diagnostic and management issues.23 Mild, symptomless thrombocytopenia (gestational thrombocytopenia), is common at term, occurring in 5% of women.42 If thrombocytopenia is more severe (platelet counts less than 70×109/L) or occurs early in pregnancy, idiopathic thrombocytopenic purpura is diagnosed. This distinction is not precise but nor is it important for management of the woman; severe, symptomatic thrombocytopenia during

Thrombocythaemia

Essential thrombocythaemia is a clonal disorder that originates from a multipotent stem cell and is characterised by an isolated, persistently high platelet count, typically greater than 600×109/L, without the presence of features diagnostic for other myeloproliferative disorders or clinical evidence for reactive thrombocytosis. Many patients have no symptoms, and the diagnosis is made incidentally. Although patients with essential thrombocythaemia do not have the Philadelphia chromosome

Pharmacological inhibition of platelet function to prevent thrombosis

Since the demonstration that aspirin is effective in the primary prevention of myocardial infarction,15 the prophylactic use of aspirin for thrombotic disorders has increased enormously. Aspirin has also become a standard treatment for patients with both cardiovascular and cerebrovascular diseases. However, the use of angioplasty and stent placement to open obstructed coronary arteries has necessitated even more effective antithrombotic agents to prevent restenosis. Ticlopidine, which blocks

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