The hemostatic system consists of platelets, coagulation factors, and the endothelial cells lining the blood vessels. The platelets arise from the fragmentation of the cytoplasm megakaryocytes in the bone marrow and circulate in blood as disc-shaped anucleate particles Under normal circumstances, the resistance of the endothelial cell lining to interactions with platelets and coagulation factors prevents thrombosis. Platelets play a primary role in this process, interacting with subendothelium-bound von Willebrand factor (vWf) via the membrane glycoprotein (GP) Ib complex.

Normal hemostasis. On resting platelets, GP IIb/IIIa is unable to bind fibrinogen or vWf. Platelet activation allows binding of these proteins, which bridges adjacent platelets. Morphologically, the platelets change dramatically from discs to spiny spheres in a process called shape change The alpha granules contain hemostatic proteins such as fibrinogen, vWf, and growth factors (eg, platelet-derived growth factor).

During activation, the granules are centralized and their contents are discharged into the lumen of the open canalicular system, from which they are then released to the exterior (the release reaction) Following activation, platelets have 2 major mechanisms to recruit additional platelets to the growing hemostatic plug. They release proaggregatory materials (eg, ADP) by the release reaction, and they synthesize thromboxane A2from arachidonic acid.

Thus, the release reaction and prostaglandin synthesis act to consolidate the initial hemostatic plug by promoting the participation of other platelets in the growing hemostatic plug. In addition, when platelets are activated, negatively charged phospholipids move from the inner to the outer leaflet of the membrane bilayer. Platelet disorders lead to defects in primary hemostasis and have signs and symptoms different from coagulation factor deficiencies (disorders of secondary hemostasis).

The body's reaction to vessel wall injury is rapid adhesion of platelets to the subendothelium. The initial hemostatic plug, composed primarily of platelets, is stabilized further by a fibrin mesh generated in secondary hemostasis. The arrest of bleeding in a superficial wound, such as the bleeding time wound, almost exclusively results from the primary hemostatic plug In comparison, defects in secondary hemostasis exhibit delayed deep bleeding (eg, muscles and joints) and the characteristic physical examination finding is hemarthrosis.

Autoimmune thrombocytopenias 7 . Immune thrombocytopenic purpura 1 , 2 , 3 . Immune thrombocytopenic purpura (ITP) is one of the most common autoimmune disorders. ITP is caused by autoantibodies to platelets. Platelets with antibodies on their surface are trapped in the spleen, where they are efficiently removed by splenic macrophages. The mechanism of origin of these antibodies is not known.

These antibodies may be directed toward the viral antigens and then cross-react with platelet antigens. They persist because of the failure of immune surveillance mechanisms to repress these antibodies.

. Acute ITP is a disease that occurs exclusively in children. It affects both sexes equally and has a peak incidence in children aged 3-5 years. Most patients have a history of an antecedent acute viral syndrome The onset is sudden, with symptoms and signs depending on the platelet count. Bleeding is usually mild, unless the platelet count drops below 20,000/?L. With platelet counts from 20,000/?L to 50,000/?L, petechiae and ecchymoses are observed following mild trauma.

With platelet counts less than 10,000/?L, generalized petechiae, ecchymoses, and mucosal bleeding occur. With platelet counts less than 2000/?L, widespread ecchymoses, hemorrhagic bullae, and retinal hemorrhage occur Physical examination reveals only the presence of petechiae and ecchymoses. The presence of lymphadenopathy or splenomegaly suggests other secondary causes of thrombocytopenia rather than ITP.

Spurious thrombocytopenia.

. Platelet GP IIb/IIIa is a major antigen in platelets and is polymorphic. Most individuals have leucine at position 33 (phospholipase A1 [PLA1]/PLA1 or human platelet alloantigen [HPA]&8211;1a). A small number of individuals, approximately 1-3% of random populations, have proline at position 33. Homozygotes with proline are termed phospholipase-negative (or HPA-1b, PLA2/PLA2), and, when they receive blood products from HPA-1a&8211;positive individuals, they produce an antibody reactive against HPA-1a.

This alloantibody destroys the transfused platelets and the patient's own platelets, leading to a severe form of thrombocytopenia that lasts for several weeks and, sometimes, several months Posttransfusion purpura typically occurs 10 days following a transfusion. This syndrome can be induced by a small amount of platelets contaminating a red blood cell transfusion or, occasionally, following fresh frozen plasma (FFP) transfusion.

The thrombocytopenia responds to intravenous immunoglobulin (IVIG). Other platelet alloantigens are occasionally implicated in posttransfusion purpura . Neonatal alloimmune thrombocytopenia 8 .

Causes. Platelet defects can be considered either as a decreased number of platelets (thrombocytopenia) or as defective platelets. Platelet aggregation tests are useful in differentiating various disorders of platelet function. Spurious thrombocytopenia can occur due to aggregates forming in the specimen. Also, dilutional thrombocytopenia may occur in situations of fluid replacement or blood component replacement without platelet support.

In all cases of thrombocytopenia, the peripheral blood smear must be reviewed to confirm the thrombocytopenia. This review is crucial. Thrombocytopenia can be further divided into increased destruction or decreased production. Thrombocytopenia resulting from increased destruction occurs either by an immune mechanism or increased consumption. Platelets are consumed intravascularly by the activation of the coagulation process ( diffuse/disseminated intravascular coagulation [DIC] ) or by deposition on damaged endothelial cells (microangiopathy).

Production defects result from those diseases that cause bone marrow failure , such as aplastic anemia , infiltration by leukemia or another malignancy, fibrosis or granulomatous disorders, or tuberculosis. Functional disorders of platelets can be inherited (rare) or acquired (common). Causes of thrombocytopenia related to increased destruction include (1) immune thrombocytopenias (eg, autoimmune, alloimmune, drug-induced) and (2) increased consumption (eg, DIC, TTP).

Causes of thrombocytopenia related to decreased production include bone marrow depression. Disorders of platelet function are as follows Disorders of platelet adhesion (von Willebrand disease, Bernard-Soulier syndrome). Disorders of secretion. Disorders of thromboxane synthesis.

Thrombasthenia [in the Pediatrics: General Medicine section]. Thrombocytosis, Secondary. Clinical Trials The Genetics and Functional Basis of Inherited Platelet, White Blood Cell, Red Blood Cell, and Blood Clotting Disorders. Once-Daily Oral E5501 Tablets Used in Subjects With Chronic Liver Diseases and Thrombocytopenia Prior to Elective Surgical or Diagnostic Procedures. Sequestration of Platelets Prior to Bypass Reduces Bleeding After Cardiac Surgery.

Study of ADAMTS-13 Activity, Von Willebrand Factor and Platelet-Monocyte Aggregation in Coronary Artery Disease. Study of Megakaryocytes From Patients With Abnormal Platelet Vesicles.

Thrombocytopenia.

American College of Chest Physicians evidence-based clinical practice guidelines (8th edition).

Medical Editor.

Thrombocytopenia in Pregnancy (Obstetrics and Gynecology). Alpha2-Plasmin Inhibitor Deficiency (Hematology).

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