Chapter 109. Disorders of Platelets and Vessel Wall (Part 6)

Immune Thrombocytopenic Purpura: Treatment The treatment of ITP utilizes drugs that decrease reticuloendothelial uptake of the antibody-bound platelet and/or decrease antibody production. However, the diagnosis of ITP does not necessarily mean that treatment must be instituted. Patients with platelet counts 30,000/µL appear not to have increased mortality related to the thrombocytopenia.
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Chapter 109. Disorders of Platelets and Vessel Wall (Part 6) Chapter 109. Disorders of Platelets and Vessel Wall (Part 6) Immune Thrombocytopenic Purpura: Treatment The treatment of ITP utilizes drugs that decrease reticuloendothelial uptakeof the antibody-bound platelet and/or decrease antibody production. However, thediagnosis of ITP does not necessarily mean that treatment must be instituted.Patients with platelet counts >30,000/µL appear not to have increased mortalityrelated to the thrombocytopenia. Initial treatment in patients without significant bleeding symptoms, severethrombocytopenia (used in this setting. Rh0(D) immune globulin must be used only in Rh+ patients asthe mechanism of action is production of limited hemolysis, with antibody-coatedcells saturating the Fc receptors, inhibiting Fc receptor function. Hemoglobinlevels usually decrease (mean 1.7 g/dL), although severe intravascular hemolysisis a rare complication. Doses are reduced if given to anemic patients. Intravenousgamma globulin (IVIgG), which is pooled, primarily IgG antibodies, also blocksthe Fc receptor system, but appears to work primarily through differentmechanism(s). IVIgG has more efficacy than anti-Rh0(D) in post-splenectomizedpatients. IVIgG is dosed at 2 g/kg total, given in divided doses over 2–5 days. Sideeffects are usually related to the volume of infusion and infrequently includeaseptic meningitis and renal failure. All immunoglobulin preparations are derivedfrom human plasma and undergo treatment for viral inactivation. For patients with severe ITP and/or symptoms of bleeding, hospitaladmission and combined modality therapy are given using high-doseglucocorticoids with IVIgG or anti-Rh0D therapy, and, as needed, additionalimmunosuppressive agents. Rituximab, an anti-CD20 (B cell) antibody, has shownefficacy in the treatment of refractory ITP. Splenectomy has been used for treatment of patients who relapse afterglucocorticoids are tapered. Splenectomy remains an important treatment option;however, more patients than previously thought will go into a remission over time.Observation, if the platelet count is high enough, or intermittent treatment withanti-Rh0(D) or IVIgG may be a reasonable approach to see if the ITP will resolve.Vaccination against encapsulated organisms (especially pneumococcus, but alsomenningococcus and Haemophilus influenzae, depending on patient age andpotential exposure) is recommended before splenectomy. Accessory spleen(s) area very rare cause of relapse. New drugs for ITP include TPO receptor agonists. This approach totreatment of ITP stems from the finding that many patients with ITP do not haveincreased TPO levels, as was previously hypothesized, nor do they all haveincreased platelet destruction. Two agents, one administered subcutaneously andanother orally, have shown response in many patients with refractory ITP. Rolesfor these agents in ITP treatment are not fully defined. Inherited Thrombocytopenia Thrombocytopenia is rarely inherited, either as an isolated finding or as partof a syndrome, and may be inherited in an autosomal dominant, autosomalrecessive, or X-linked pattern. Many forms of autosomal dominantthrombocytopenia are now known to be associated with mutations in thenonmuscle myosin heavy chain MYH9 gene. Interestingly, these include the May-Hegglin anomaly and Sebastian, Epsteins, and Fechtner syndromes, all of whichhave distinct distinguishing features. A common feature of these disorders is largeplatelets (Fig. 109-1C). Autosomal recessive disorders include congenitalamegakaryocytic thrombocytopenia, thrombocytopenia with absent radii, andBernard Soulier syndrome. The latter is primarily a functional platelet disorder dueto absence of GPIb-IX-V, the vWF adhesion receptor. X-linked disorders includeWiskott-Aldrich syndrome and a dyshematopoietic syndrome resulting from amutation in GATA-1, an important transcriptional regulator of hematopoiesis. Thrombotic Thrombocytopenic Purpura and Hemolytic UremicSyndrome Thrombotic thrombocytopenic microangiopathies are a group of disorderscharacterized by thrombocytopenia, a microangiopathic hemolytic anemia evidentby fragmented RBCs (Fig. 109-1D) and laboratory evidence of hemolysis, andmicrovascular thrombosis. This includes thrombotic thrombocytopenic purpura(TTP) and hemolytic uremic syndrome (HUS), as well as syndromes complicatingbone marrow transplantation, certain medications and infections, pregnancy, andvasculitis. In DIC, while thrombocytopenia and microangiopathy are seen, acoagulopathy predominates, with consumption of clotting factors and fibrinogenresulting in an elevated prothrombin time (PT) and often activated partialthromboplastin time (aPTT). The PT and aPTT are characteristically normal inTTP or HUS.