Page 2499 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 152 Hematologic Manifestations of Childhood Illness 2231

parvovirus B19 polymerase chain reaction (PCR), with results being Delayed Posttransplant Thrombocytopenia
positive in 85% of cases; IgM results were positive in 78% and IgG
in 39%. Treatment with IVIg was used in 84% of patients, and there Delayed thrombocytopenia is not a major problem after solid organ
was a recurrence in 28%. The three deaths occurred only in patients transplant, and most of the data are published in adult series. In one
after liver transplant who developed myocarditis and cardiogenic retrospective study of 36 adult liver transplant recipients, mild
shock. Of interest, in a prospective study of 47 solid organ transplant thrombocytopenia (<140,000/µL) was seen in 54% of patients at 1
347
recipients, none were found to have molecular evidence of parvovirus year and 25% at 3 years after transplant. However, severe throm-
B19 in the first year after transplant. 339 bocytopenia (<50,000/µL) was seen in only 9% of patients at 1 year
In a review of parvovirus B19 infection in children after transplant, and in no patients at 3 years after transplant. The thrombocytopenia
there were 16 case reports: 5 each after liver, heart, and renal trans- was associated with splenomegaly in some patients. No clinical bleed-
340
plant and 1 after bone marrow transplant. The onset was at a ing problems were noted after 1 year from transplant. In one report,
median of 8 months, with a range of 1 to 24 months. Although only 3 (12%) of 25 pediatric liver transplant recipients were found to have
312
3 of 14 tested were IgM positive, all were PCR positive. There were isolated thrombocytopenia. The etiology of the thrombocytopenia
no associated symptoms in 7 of 14, but other reported symptoms in these children was cavernous transformation of the portal vein,
include cytopenias, rash, myocarditis, and pneumonia. All 10 patients autoimmune, and unknown. In two other children in this series,
who received IVIg treatment were cured, although recurrences have thrombocytopenia was associated with additional cytopenias, and the
been reported. cause was possibly related to TAC. In an additional study of 126
children who underwent cardiothoracic transplant, 9 (8%) were
noted to have isolated thrombocytopenia. Infection was the most
Platelets common etiology (n = 262). In patients with combined cytopenias,
including thrombocytopenia, two-thirds were related to either infec-
Problems with platelets, including thrombocytopenia and thrombo- tion or PTLD and 20% possibly secondary to TAC.
cytopathy, have been reported after transplant, primarily in adults. Sirolimus has been associated with mild thrombocytopenia in
After liver transplant, almost all patients develop a transient throm- adults, although the reported frequency has varied. In a study of
bocytopenia. Delayed thrombocytopenia is much less frequent. It has renal transplant recipients, 23% were reported to have mild throm-
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348
been reported in 12% of children after liver transplant, 8% after bocytopenia, but no liver transplant patients taking the drug were
349
308
cardiothoracic transplant, and outside the setting of HUS/MAHA found to be thrombocytopenic. In 66 pediatric kidney transplant
very infrequently after kidney transplant. Causes of platelet problems recipients taking sirolimus, there were no reported cases of throm-
350
posttransplant include medication effect, immune etiology, HUS/ bocytopenia. Low platelet counts are usually seen within the first
MAHA, infection, and other miscellaneous causes. 4 weeks of treatment and are associated with higher sirolimus blood
levels. 351,352 Similarly to TAC and CsA, sirolimus has been shown
Immediate Thrombocytopenia to potentiate agonist-induced platelet aggregation, although this is
353
not the proven explanation for the thrombocytopenia. A 25% to
After Liver Transplant 50% dose reduction is often effective in resolving sirolimus-mediated
thrombocytopenia.
More than 90% of adults have been reported to have thrombocyto-
penia within the first week after liver transplant. 341–345 Nadir counts
usually occur between days 4 and 6 posttransplant, with an average Immune-Mediated Thrombocytopenia
count of 58,000/µL (range, 19,000 to 330,000/µL). An increase in Posttransplant
thrombopoietin is seen on days 4 to 6, and increased reticulated
platelets are noted on days 7 and 8. There are few reported clinical There are many case series of immune-mediated thrombocytopenia
sequelae from the mild thrombocytopenia, although the lowest after all types of solid organ transplant in children and adults and
331
platelet counts have been associated with the most severe and com- either alone or in combination with other cytopenias. Eight adults
plicated posttransplant course. Resolution is usually seen in 2 weeks. after liver transplant were reported to have immune thrombocytope-
354
Lack of resolution is associated with a poor prognosis for graft and nia (incidence, 0.7%). The low platelets were seen 53 months after
overall survival. In a study of children who received a living donor transplant on average, with a range of 1.9 to 173 months. Three
liver transplant, preoperative platelet count, graft-to-recipient weight patients had demonstrable antiplatelet antibodies. Steroids provided
ratio, and acute rejection were identified as risk factors for developing effective therapy in four and rituximab in four, although splenectomy
early thrombocytopenia in multivariate analysis. 346 was ultimately necessary in three. Seven of the eight survived with
There is controversy regarding the etiology of this transient normal platelet counts. Five children were reported to have severe
thrombocytopenia. One theory is that it is a nonimmune consump- thrombocytopenia (<10,000/µL) within 2 to 4 months after starting
345
tive process reflected by increased markers of thrombin generation. TAC. 334,355 All were documented to have antiplatelet antibodies.
The liver may be the site of platelet sequestration. A second theory Responses were seen to steroids, rituximab, or anti-RhD.
is that it is unlikely to be a consumptive process because of the lack Two cases after heart or lung transplant in adults have been
356
of platelet activation after day 1. The thrombocytopenia is more likely reported. These cases occurred 60 to 460 days after transplant and
a result of low levels of thrombopoietin seen pretransplant. With new responded to prednisone and IVIg. Acquired Glanzmann thrombo-
production and rising levels of thrombopoietin from the new liver, asthenia has been reported in two children after cardiac trans-
there is a subsequent increase in platelet production, resulting in plant. 335,357 Both were receiving TAC and had demonstrable antibodies
normalization of the platelet count soon after transplant. Although against glycoprotein IIb/IIIa. One patient had multiple autoantibod-
the specific etiology has not been clarified, there is general consensus ies, and the other subsequently developed additional antiplatelet
that it is not immune mediated. antibodies. One child responded to prednisone therapy and switching
Lymphocyte-depleting antibodies such as rabbit antithymocyte from TAC to CsA. The other responded to rituximab after prednisone
globulin (rATG) are being used with increasing frequency as and IVIg therapy failed.
induction-type therapy in pediatric liver and intestine transplants. Alloimmune thrombocytopenia was reported in three recipients
358
rATG does exacerbate the transient thrombocytopenia seen immedi- of organs from the same donor (two kidneys and a liver). Develop-
A1
ately after solid organ transplant but resolves in a similar 1- to 2-week ment of human platelet antigen-1a (HPA-1a; Pl ) antibodies from
period. Treatment of this transient thrombocytopenia is supportive. donor B cells were documented in an example of passenger lympho-
Platelet transfusions are of uncertain benefit. Although originally cyte syndrome. The thrombocytopenia in these cases was particularly
azathioprine was believed to be a cause of this thrombocytopenia, refractory to standard treatment, except transfusion of HPA-1a–
there is no evidence that alteration of azathioprine dose is necessary. negative platelets. One patient died, another required splenectomy,