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Thrombocytopenia maybe defined as a subnormal number of platelets in the circulating blood. It is the most common cause of abnormal bleeding. In general, the severity and frequency of hemorrhagic manifestations correlate to the platelet count. Platelet counts below 20× 0!"# usually are associated with spontaneous hemorrhage. Thrombocytopenia results from three processes$ % & deficient platelet production. Those that depopulate the stem cell or mega'aryocyte compartments are the most common, e.g., marrow in(ury by myelosuppressive drugs or irradiation and aplastic anemia.%2& accelerated platelet destrucion, utili)aton or loss, e.g., idiopathic thrombocytopenia purpura, diffuse intravascular coagulaton, thrombotic thrombocytopenia purpura. %*& abnormal distribution or pooling of the platelets within the body. This type of thrombocytopenia is seen in the various disorders associated with splenomegaly. Idiopathic thrombocytopenic purpura Idiopathic thrombocytopenic purpura ia an acquired disease of children and adults characteri)ed by a low platelet count ,an normal or increased numbers of mega'aryocytes in the bone marrow, and absence of evidence for other disease. +lthough this disease is also referred to as immune thrombocytopenic purpura and autoimmune thrombocytopenic purpura, idiopathic thrombocytopenic purpura remains the most common designation. The clinical syndromes of ITP are divided into acute and chronic types. ,-tiology and pathogenesis. -vidence is mow convincing that the syndrome of ITP is caused by platelet destruction as the result of an immunologic process. . Platelet survival Platelet survival is greatly shortened in ITP. The survival time of isologous platelets labeled with / 0r1chromate ranges from 2 to *days to a matter of minutes. 2. Platelet antibodies Thrombocytopenia in ITP appears to result from the action of a platelet antibody. The infusion of plasma from patients with ITP predictably induces thrombocytopenia in normal recipients. The responsible factor is an immunoglobulin of the Ig2 class that is species specific. Increased quantities of Ig2 have been demonstrated on the platelet surface, and the
Immune comple3es The frequency with which acute ITP is associated with antecedent viral infection have led to the suggestion that a viral antigen1antibody comple3. +cute ITP +cute ITP occurs most frequently in children 2 t0 9 years. . the onset of the disorder usually is sudden. 7epatic sequestration of platelets has been demonstrated in association with ITP. but it is relatively more common between puberty and /0 years of age. 0onceivably. usually in patients with severe thrombocytopenia and mar'edly shortened platelet survival. an immunoglobulin has been demonstrated on the surface of the mega'aryocytes by means of immunofluorescence and other techniques. 0hronic ITP 0hronic ITP affects persons of all ages. It occurs more frequently in women than in men. 8plenic tissue from patients with ITP produces more immunoglobulin than that of normal control sub(ects.0linical features. it rarely affects adults and has no gender predilection. may be responsible for platelet sensiti)ation and destruction in this form of the disorder. 5ole of the spleen 6hen / 0r1chromate1labeled isologous platelets are administered to patients with ITP. Impaired thrombopoiesis In chronic ITP. and a significant percentage of that formed binds to homologous platelets. The duration of the disease ranges from a few days to a few months. . +cute ITP usually is self1limited: spontaneous remissions occur in as many as !*. 4. The spleen also is important in ITP as a site of production of platelet antibodies. a ratio of 2 . + history of infection preceding the onset of bleeding has been documented repeatedly. *. 2. /. the attachment of antibody may impair platelet production. of patients. e3ternal scintillation counting reveals a rapid accumulation of radioactivity predominantly in the spleen. total mega'aryocyte mass and the platelet turnover rate were several times greater than normal. Platelet phagocytosis by splenic leu'ocytes has been demonstrated in vitro.rate of platelet destruction in ITP is proportional to levels of such platelet1associated Ig2. with an average of 4 to 9 wee's. In patients with acute ITP. Thus.
partial thromboplastin time. and occur most in dependent region. =thers 5epeated bleeding may lead to anemia of iron deficiency type. epista3is. 8ymptoms and signs are predictable from the 'nown pattern of bleeding associated with platelet disorders$ purpura. but it is the most common cause of death and may occur acutely or at any time during a prolonged course. * to 4μm in diameter. *.g.g. ?giant@forms % 0 μm or more in diameter&. Patients usually have a fluctuating clinical course. The white blood cell count and hemoglobin concentration are usually normal unless significant hemorrhage due to the thrombocytopenia has occurred. The blood Isolated thrombocytopenia is the essential abnormality.. The platelets often are abnormally large.laboratory >inding. and gingival bleeding are common: gastrointestinal bleeding and hematuria are less common. The results of tests of blood coagulation. such as a prolonged bleeding time.. e. and deeply stained forms.g. The marrow * . The spleen is occasionally palpable on deep inspiration but never greater. are normal in patients with uncomplicated thrombocytopenia. and may be intermittent or even cyclic. Intracerebral hemorrhage is uncommon. e. . 4.appro3imately *$ having been found repeatedly. =ther morphologic changes may be seen in some patients.. -pisodes of bleeding may last a few days of a few wee's. . and reveal more than normal variation in si)e and shape. Tests of hemostasis and blood coagulation reveal only changes attributable to thrombocytopenia. +bnormalities in platelet si)e and morphologic appearance are common. but this is more common in the acute ITP of childhood. absent or deficient clot retraction. and deficient prothrombin consumption. not palpable. The onset of the chronic form of the disorder usually is insidious. bi)arre shapes. <leeding manifestation <leeding into the s'in in the form of petechiae is characteristec. Petechiae are asymptomatic. a positive reaction to the tourniquet test. e. and coagulation time. menorrhagia. 8pontaneous remissions are uncommon and are li'ely to be incomplete. 2. -osinophilia of blood and marrow may be noted. prothrombin time.
myelodysplastic syndrome. P+Ig2 is increased in patients with ITP. Increased marrow mega'aryocytes with a shift to younger. 20140 years of age *$ . platelet1producing mega'aryocytes has been commonly reported. aplastic anemia. . The diagnosis of ITP is made by e3cluding other causes of thrombocytopenia. with the e3ception of the normoblastic hyperplasia that may develop as the results of blood loss. Physical activity should be restricted to minimi)e the ha)ards of trauma.+lterations in the bone marrow are limited to the mega'aryocytes.Aifferential diagnosis. Table. acute infectious illness. =bservation$ Fost patients who are incidentally discovered to have asymptomatic mild 4 +cute ITP 0hildren 219 years of age Bone 0ommon 1* wee's before onset +brupt in Present in severe cases D20× 0!"# 219 wee's: rarely longer =ccur in E0. disseminated intravascular coagulation. Tests for platelet antibodies +ssays of P+Ig2 represent the first sensitive and reproducible method for demonstrating antibodies in ITP. and the magnitude of increase is greater in patients with more severe thrombocytopenia. its prognosis.Treatment. >eatures of acute and chronic ITP >eatures Pea' age incidence 8e3 predilection +ntecedent infection =nset of bleeding 7emorrhagic bullae mouth Platelet count Auration 8pontaneous remissions . acute leu'emia. female to male patients Cnusual Insidious Csually absent *01E0× 0!"# Fonths or years Cncommon: fluctuating course common . Arugs that impair platelet functions should be avoided. e. systemic lupus erythematous. hypersplenism. and the results of therapy %see Table&. of cases 0hronic ITP +dults. 8everal differences e3ist between acute ITP and chronic ITP that are of particular significance in the interpretation of data concerning the incidence of the disorder.g. *.. less polyploid mega'aryocytes and fewer mature. <lood loss should be treated as otherwise indicated. particularly head in(ury.
2. %*& difficulty in assuring adequate follow1up care. or the necessity of high doses for maintenance of a clinical status free of serious hemorrhage. %4& in many cases of ITP in pregnant women. Fechanism of action$ % & significantly diminish immunoglobulin synthesis. because of the frequency of spontaneous remissions. especially in children. =ne commonly used in initiation therapy consists of administering 40 to 90mg of prednisone daily to adults. followed by a gradual tapering of the dosage. %*& impair reticuloendothelial function and thereby to diminish platelet destruction. %2& inhibit the binding of antibodies to platelets. 7owever. 0omplete and sustained remissions have occurred after splenectomy in from /0 to over !0. %/& in patients with acute ITP and ma(or uncontrolled bleeding in whom the mortality rate after splenectomy is high. of patients with ITP who receive adrenal corticosteroid therapy. 8ome increase in platelet numbers and a favorable clinical response can be e3pected in G0 to !0. a reasonable rule of thumb being 9 months at most. %2& removal of a ma(or site of antibody synthesis. . %2& failure to respond to steroid therapy. The initial course of steroids should be maintained for * to 4 wee's.or moderate thrombocytopenia can safely be followed with no treatment. 8teroid therapy should not be maintained for long periods. in whom the ha)ard of fulminating infection after splenectomy is greater than at a later age. of / . 0orticosteroids 0orticosteroids are widely used as the initial means of therapy. %4& overriding contraindications due to the use of steroids. 8plenectomy is contraindicated in the following situations$ % & early in the first episode of bleeding. %2& in patients with cardiac or other complications who are at ris' of serious sequelae from any ma(or surgical procedure. The indications for splenectomy in patients with ITP may be stated as follows$ % & failure of spontaneous remission to occur after 9 months of observation in patients with moderate or severe bleeding. and mg"'g body weight to children. relapse after discontinuance of steroid therapy or reduction in the dosage. Fost patients who will respond to splenectomy do so within several days. %*& in children under 2 years of age. most patients will relapse when prednisone is tapered or discontinued. 8plenectomy The ma(or effects of splenectomy are twofold$ % & removal of the ma(or site of destruction of antibody1sensiti)ed platelets.
and IHIg. preoperative platelet transfusions are not indicated. and in some patients who are refractory to all other modes of treatment. but most evidence points to bloc'ade of the >c receptors of the reticuloendothelial cells. and other immunosuppressive agents. -mergency treatment of acute bleeding In patients with severe bleeding. but act more rapidly. Treatment with immunoglobulin appears to be effective in patients who failed to respond to splenectomy. often diminish bleeding for a time. subarachnoid hemorrhage. actinomycin.patients. Immunosuppressive drugs 0yclophosphamide %/0 to 200mg"day orally or *00 to 900 mg"m2 intravenously every 2 wee's& has induced remissions in from 44 to //. high1dose parenteral glucocorticoids. have been administered to patients with ITP. 9 . and can be effective in the management of serious complications. +ll of these immunosuppressive agents may be leu'emogenic and"or carcinogenic. Hincristine %0. + regimen of 400mg"'g"day for / days usually is recommended. e.0 2/mg"'g&. of patients. and perhaps neutrali)ation of antiplatelet autoantibodies by antiidiotypic antibodies in the preparations. In patients with platelet counts above /0× 0!"#. appear to be as effective as cyclophosphamide. Platelet transfusions$ Platelet transfusions may produce some increase in platelet numbers in many patients. administered intravenously at wee'ly intervals.g. 7igh1dose immunoglobulin. with variable success. appropriate treatment includes platelet transfusions. <y measuring the pattern of splenic versus hepatic sequestration with radiolabeled platelets may predict the response to splenectomy. They should be reserved for such life1threatening emergencies or for the immediate preoperative treatment of patients with serious hemorrhage before splenectomy. 4.02/mg"'g not to e3ceed a total dose of 2mg& and vinblastine %0. *. in addition to conventional critical care measures. Platelet replacement should be avoided in patients with chronic ITP because of the possible development of alloantibodies. +)athioprine. in pregnant women. The mechanism of this therapeutic effect is not entirely clear.. either alone or in combination with corticosteroids.
Intravenous 5h %A& immune globulin has been studied in children with acute ITP and refractory chronic ITP as an alternative to intravenous Ig. -3change plasmapheresis. 0hildren respond better than adults. G . possibly by diminishing >c %Ig2& receptors. In doses of 400 to E00mg"day. The only clinically important side effect of anti15h%A& is the predictable alloimmune hemolysis. it is believed that the antibody coats the red blood cells of 5h1positive patients and either bloc's the reticuloendothelial clearance of the patients platelets or modulates the immune system. =thers Aana)ol. It may be valuable in critically ill patients. an androgen with minimal virili)ing side effects.7igh doses of glucocorticoids. /. resulting in an increase in the platelet count. and may be particularly effective in children. The mechanism of action is un'nown: however. +nti1A. such as g of methylprednisolone given by intravenous infusion daily for * days. and nonsplenectomi)ed patients respond better than splenectomi)ed patients. has proved effective in the treatment of ITP. presumably acts by inducing reticuloendothelial dysfunction. may also cause a rapid increase of the platelet count and may ameliorate bleeding even if platelet counts remain low due to an effect on the vasculature.
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