Page 2203 - Hematology_ Basic Principles and Practice ( PDFDrive )

1950 Part XII Hemostasis and Thrombosis

platelet count response in up to 60% of patients, but responses are TABLE Differential Diagnosis of Thrombocytopenia in
rarely sustained past 6–12 months. TPO receptor agonists (romip- 131.3 Newborns
lostim or eltrombopag) are associated with a platelet count response
in up to 60% of patients as long as treatment is maintained. These Perinatal Hypoxemia
drugs are generally well tolerated; however, long-term safety data Placental Insufficiency
beyond 5 years are not yet available and long-term maintenance Congenital Infection
therapy is expensive since either agent costs approximately $3,000 Sepsis
per month. Toxoplasmosis
Rubella
Cytomegalovirus
Treatment of Refractory Immune Thrombocytopenia Autoimmune
Maternal immune thrombocytopenia
As suggested by the International Working Group on standardization Maternal systemic lupus erythematosus
of terminology in ITP, the term refractory ITP is used to define Disseminated Intravascular Coagulation
patients who have failed splenectomy or relapsed thereafter and either Maternal Drug Exposure
exhibit severe thrombocytopenia or have a risk of bleeding that neces- Congenital Heart Disease
sitates therapy (see Table 131.2). 3 Hereditary Thrombocytopenia
Evidence to help guide management of patients with chronic MYH9 macrothrombocytopenia (including May-Hegglin anomaly)
refractory ITP after splenectomy is limited, and treatment has been Thrombocytopenia absent radii syndrome
mainly unsatisfactory. However, TPO receptor agonists provide a Amegakaryocytic thrombocytopenia
new and effective option for this challenging group of patients. The Wiskott-Aldrich syndrome
overarching principle of therapy for this population is to prevent Fanconi anemia
bleeding with the achievement of a stable, although not necessarily Hemangioma with Thrombocytopenia
normal, platelet count, and that combination therapy may be more Kasabach-Merritt syndrome
effective than single agent treatment for achievement of this goal. Bone marrow Infiltration
In randomized trials, nonsplenectomized patients with ITP tended Congenital leukemia
to show better platelet count responses to TPO receptor agonists
than splenectomized patients; however, the difference was small, and
response rates in splenectomized patients approached 50%. Although thrombocytopenia may last for days, but occasionally, it can be severe
some patients included in the trials had failed up to five prior thera- and can persist for many weeks. Bleeding symptoms range from
pies, the results may not be applicable to all patients with refractory petechiae and bruising to gastrointestinal or intracranial hemorrhage.
ITP seen in clinical practice. Bleeding occurs in up to 20% of neonates with NAIT and can occur
Before the availability of TPO receptor agonists, a systematic review early in pregnancy. For infants with severe thrombocytopenia, mor-
identified rituximab, azathioprine, and cyclophosphamide as the agents tality estimates of 10% have been reported and infants with intra-
most often associated with complete responses in patients with refrac- cranial bleeding may be left with developmental delays and permanent
tory ITP. Good response rates have also been reported with a combina- neurologic deficits.
tion of cyclosporine, azathioprine, and mycophenolate (CellCept).
Similarly, a combination of IVIg, intravenous methylprednisolone,
vincristine, or intravenous anti-D followed by maintenance therapy Pathophysiology
with danazol and azathioprine have shown good response rates. Other
treatment options include low-dose or alternate-day corticosteroids, Fetal and neonatal thrombocytopenia in NAIT reflects the clearance
repeated doses of IVIg, high-dose chemotherapy, or dapsone. High- of IgG-sensitized fetal platelets by maternal alloantibodies directed
dose chemotherapy followed by stem cell transplantation has also been against fetal/paternal platelet-specific antigens. The syndrome can be
used successfully in this population, but with the advent of TPO considered analogous to the destruction of fetal RBCs in hemolytic
receptor agonists, transplantation is no longer used. disease of the newborn (HDN) but with several differences. Perhaps
most importantly, NAIT often presents in a first pregnancy, possibly
because of early maternal sensitization to paternally derived antigens
NEONATAL ALLOIMMUNE THROMBOCYTOPENIA expressed on fetal platelets. In contrast, it is uncommon for HDN to
occur in a first pregnancy without previous sensitization to the Rh
NAIT is an uncommon but serious thrombocytopenic disorder that antigen. This difference suggests that unlike RBCs, transplacental
can cause fetal or neonatal bleeding resulting in death or disability. passage of fetal platelets or platelet antigens into the maternal circula-
It is important to recognize this disorder because treatment may tion occurs early in pregnancy. Another difference is that pregnant
prevent recurrence in subsequent pregnancies. With NAIT, intra- women at risk for HDN (e.g., those who are Rh negative) can be
cranial bleeding can occur during the neonatal period or in utero, in identified early by screening and treatment with anti-Rh immune
which case the diagnosis is first suspected after abnormal fetal ultra- globulin reduces the risk of sensitization. To date, screening programs
sonography. The incidence of NAIT has been estimated to range for NAIT have not been widely implemented because women at risk
from 1 : 1000–1 : 5000 births; however, it is often underdiagnosed. are not readily identifiable before sensitization has occurred, and
therapies to prevent maternal alloimmunization are not currently
available. Screening programs for NAIT continue to be an active area
Clinical Presentation of research (see box on Neonatal Alloimmune Thrombocytopenia
Versus Hemolytic Disease of the Newborn).
Thrombocytopenia may be severe in infants affected by NAIT and
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often the platelet count is less than 10–20 × 10 /L shortly after birth.
The differential diagnosis is broad and includes septicemia, hypoxia, Laboratory Investigation of Suspected Neonatal
and birth trauma, among other factors (Table 131.3). Typically, Alloimmune Thrombocytopenia
NAIT presents as severe thrombocytopenia, possibly with associated
bleeding, in an otherwise healthy neonate with no other explanation The diagnosis of NAIT is established by documenting the presence
for the low platelet count. The thrombocytopenia often worsens of platelet-specific antigen incompatibility between mother and infant
hours or days after delivery, likely reflecting increased RES function (or mother and father) and the presence of maternal antiplatelet allo-
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in the newborn, particularly within the lungs. Without treatment, antibodies directed against the incompatible antigen (Fig. 131.3).