Diseases of Platelet Number: Immune Thrombocytopenia, Neonatal Alloimmune Thrombocytopenia, and Posttransfusion Purpura

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Chapter 56 Diseases of Platelet Number

Immune Thrombocytopenia, Neonatal Alloimmune Thrombocytopenia, and Posttransfusion Purpura

Donald M. Arnold, Christopher Patriquin, Lisa J. Toltl, Ishac Nazi, James Smith, John Kelton

Table 56-1 Antibody-Mediated Thrombocytopenic Disorders Caused by Autoantibodies (Immune Thrombocytopenia), Alloantibodies (Neonatal Alloimmune Thrombocytopenia) or Potentially Both (Posttransfusion Purpura)

GP, Glycoprotein; HPA, human platelet antigen; RBC, red blood cell.

Table 56-2 Standardized Terminology and Definitions for Immune Thrombocytopenia Proposed by the International Working Group (Vicenza Consensus Conference) in 2009

Terminology	Definition
ITP	Immune thrombocytopenia (rather than idiopathic or immune thrombocytopenic purpura)
Platelet threshold for ITP diagnosis	<100 × 10⁹/L
Primary ITP	ITP with no associated cause (diagnosis of exclusion)
Secondary ITP	ITP in the setting of an underlying cause such as drugs, HIV, or SLE
Newly diagnosed ITP	Designation for patients at diagnosis (rather than “acute” ITP).
Persistent ITP	Sustained or recurrent thrombocytopenia lasting 3-12 months
Chronic ITP	Thrombocytopenia lasting >12 months
Complete response	Achievement of a platelet count of ≥100 × 10⁹/L in the absence of bleeding
Response	Achievement of a platelet count of ≥30 × 10⁹/L and at least a twofold increase from baseline in the absence of bleeding
Refractory ITP	Failure to achieve a response or relapse after splenectomy* and requirement for treatment(s) to minimize the risk of clinically significant bleeding.

ITP, Immune thrombocytopenia; SLE, systemic lupus erythematosus.

^*Splenectomy failure may not be applicable in children.

Figure 56-1 BLOOD FILM EXAMINATIONS FROM PATIENTS WITH THROMBOCYTOPENIA.

A, Pseudothrombocytopenia showing marked platelet clumping. B, Schistocytes (fragmented red blood cells) and reticulocytosis in a patient with thrombotic thrombocytopenic purpura. C, Macrothrombocyte (left panel) and neutrophil-containing cytoplasmic inclusions (Döhle bodies, right panel) in a patient with May-Hegglin anomaly. D, A patient with immune thrombocytopenia with low platelets and postsplenectomy Howell-Jolly bodies (arrows).

First-Line Therapy

An 8-year-old girl is brought to the emergency department because her mother noticed bruising on her legs. She has had a sore throat and fever for the past 7 days but is otherwise well and not taking any medications. On physical examination, there are a few small bruises on her legs but no petechiae on her skin or purpura in her mouth. Neurologic examination findings are normal, and the spleen is not palpable. The platelet count is 23 × 10⁹/L. The presumed diagnosis is ITP without significant bleeding; thus the decision is made to observe the child in the hospital with no specific treatment. The next day, the platelet count is 33 × 10⁹/L. On day 2, it is 37 × 10⁹/L, and the child is discharged home. One week later, the platelet count is 66 × 10⁹/L, and 1 month later, it is up to 155 × 10⁹/L.

Table 56-3 Differential Diagnosis of Thrombocytopenia in Newborns

Long-Term Follow-Up

The best treatment of patients with ITP who fail first-line therapy remains controversial and depends on the severity of symptoms, side effect profile, and patient preference. Splenectomy has been used for many years and is the treatment option most likely to be associated with durable remissions. Rituximab may achieve a platelet count response in up to 60% of patients, but responses are rarely sustained past 6 to 12 months. TPO receptor agonists (romiplostim or eltrombopag) are associated with a platelet count response in up to 60% of patients as long as treatment is maintained. These drugs are generally well tolerated; however, long-term safety data beyond 5 years are not yet available.

Neonatal Alloimmune Thrombocytopenia Versus Hemolytic Disease of the Newborn

NAIT can be viewed as the platelet equivalent of HDN with some important differences: (1) maternal sensitization by fetal platelet antigens can occur early in the first trimester, (2) NAIT can affect first pregnancies, (3) women at risk for NAIT are not easily identifiable before sensitization and thus are not amenable to universal screening programs, and (4) a specific therapy that targets prevention of platelet antigen sensitization is lacking (e.g., Rh-immune globulin that target RBC antigen exposure).

Figure 56-2 DIAGNOSTIC TESTING ALGORITHM FOR INVESTIGATION OF NEONATAL ALLOIMMUNE THROMBOCYTOPENIA (NAIT) AND MANAGEMENT RECOMMENDATIONS BASED ON RESULTS OF TESTING (CURRENTLY USED BY THE ONTARIO PROVINCIAL PLATELET LABORATORY AT MCMASTER UNIVERSITY PLATELET IMMUNOLOGY REFERENCE LABORATORY, 2012).

Maternal blood samples are tested for platelet antigens (phenotyping and polymerase chain reaction genotyping) and platelet alloantibodies. Amniocentesis and fetal genotyping are recommended when the father is known to be heterozygous for the incompatible antigen. HPA, Human platelet antigen.

(Modified from Arnold DM, Smith JW, Kelton JG: Diagnosis and management of neonatal alloimmune thrombocytopenia. Transfus Med Rev 22:255, 2008, with permission.)