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

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-b

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

Initial treatment in patients without significant bleeding symptoms, severe thrombocytopenia (<5000/µL), or signs of impending bleeding (such as retinal hemorrhage or large oral mucosal hemorrhages) can be instituted as an outpatient using single agents Traditionally this has been prednisone at 1 mg/kg, although

Rh0(D) immune globulin therapy (WinRho SDF) at 50–75 µg/kg is also being

used in this setting Rh0(D) immune globulin must be used only in Rh+ patients as the mechanism of action is production of limited hemolysis, with antibody-coated cells "saturating" the Fc receptors, inhibiting Fc receptor function Hemoglobin levels usually decrease (mean 1.7 g/dL), although severe intravascular hemolysis

is a rare complication Doses are reduced if given to anemic patients Intravenous gamma globulin (IVIgG), which is pooled, primarily IgG antibodies, also blocks the Fc receptor system, but appears to work primarily through different mechanism(s) IVIgG has more efficacy than anti-Rh0(D) in post-splenectomized patients IVIgG is dosed at 2 g/kg total, given in divided doses over 2–5 days Side effects are usually related to the volume of infusion and infrequently include aseptic meningitis and renal failure All immunoglobulin preparations are derived from human plasma and undergo treatment for viral inactivation

For patients with severe ITP and/or symptoms of bleeding, hospital admission and combined modality therapy are given using high-dose glucocorticoids with IVIgG or anti-Rh0D therapy, and, as needed, additional immunosuppressive agents Rituximab, an anti-CD20 (B cell) antibody, has shown efficacy in the treatment of refractory ITP

Splenectomy has been used for treatment of patients who relapse after glucocorticoids 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 with

anti-Rh0(D) or IVIgG may be a reasonable approach to see if the ITP will resolve Vaccination against encapsulated organisms (especially pneumococcus, but also

menningococcus and Haemophilus influenzae, depending on patient age and

potential exposure) is recommended before splenectomy Accessory spleen(s) are

a very rare cause of relapse

New drugs for ITP include TPO receptor agonists This approach to treatment of ITP stems from the finding that many patients with ITP do not have increased TPO levels, as was previously hypothesized, nor do they all have increased platelet destruction Two agents, one administered subcutaneously and another orally, have shown response in many patients with refractory ITP Roles for these agents in ITP treatment are not fully defined

Inherited Thrombocytopenia

Thrombocytopenia is rarely inherited, either as an isolated finding or as part

of a syndrome, and may be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern Many forms of autosomal dominant thrombocytopenia are now known to be associated with mutations in the

nonmuscle myosin heavy chain MYH9 gene Interestingly, these include the

May-Hegglin anomaly and Sebastian, Epstein's, and Fechtner syndromes, all of which have distinct distinguishing features A common feature of these disorders is large

platelets (Fig 109-1C) Autosomal recessive disorders include congenital

amegakaryocytic thrombocytopenia, thrombocytopenia with absent radii, and Bernard Soulier syndrome The latter is primarily a functional platelet disorder due

to absence of GPIb-IX-V, the vWF adhesion receptor X-linked disorders include Wiskott-Aldrich syndrome and a dyshematopoietic syndrome resulting from a mutation in GATA-1, an important transcriptional regulator of hematopoiesis

Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome

Thrombotic thrombocytopenic microangiopathies are a group of disorders characterized by thrombocytopenia, a microangiopathic hemolytic anemia evident

by fragmented RBCs (Fig 109-1D) and laboratory evidence of hemolysis, and

microvascular thrombosis This includes thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), as well as syndromes complicating bone marrow transplantation, certain medications and infections, pregnancy, and vasculitis In DIC, while thrombocytopenia and microangiopathy are seen, a coagulopathy predominates, with consumption of clotting factors and fibrinogen resulting in an elevated prothrombin time (PT) and often activated partial thromboplastin time (aPTT) The PT and aPTT are characteristically normal in TTP or HUS