Patients with amegakaryocytic thrombocytopenia (AT) characteristically have thrombocytopenia as well as megakaryocytopenia; the latter may not be apparent until a year after birth [1]. They may have bleeding diatheses. Other physical abnormalities are not typical of AT, although a renal failure, hearing and visual loss, mental retardation, cardiac malformations and psychomotor retardation have been reported in some cases [2].

The congenital form of AT is often seen and diagnosed at birth or soon after. During the first week of life, the platelet count may fluctuate between low and normal values. These patients may have a positive family history of the condition, dysmorphic platelets, and thrombocytopenia that is resistant to standard treatment. Congenital AT (CAT) is inherited through various possible mutations in the myeloproliferative leukemia virus (MPL) oncogene, which is responsible for platelet production, giving rise to a range of phenotypic expressions. The mutation may cause a decrease or complete arrest in the production of platelets from hematopoietic stem cells. There are two types of CAT, of which type I is more severe in clinical course, and additional hematological pathologies ensue during infancy [3]. Affected individuals may report with pancytopenia. CAT type II cases rarely suffer from such rapid progression to pancytopenia. Moreover, they have intermittent episodes of less pronounced thrombocytopenia. Eventually, both types lead to bone marrow failure (this occurs earlier in type I).

Hematological pathologies that AT may eventually induce are exemplified by leukemia and aplastic anemia. Patients remain thrombocytopenic for years.

Bleeding may occur in the skin in form of petechiae and purpura. More serious hemorrhage has been described in the literature, taking place in the gastrointestinal tract, such as bleeding per rectum [2]. Intracranial and lung involvement is also documented.

AT can be acquired, and the symptoms are similar to those of the congenital type. Remission is possible, and association with autoimmune diseases such as systemic lupus erythematosus (SLE), and hematologic diseases has been reported [4] [5]. It is thought to be caused by both humoral and cell-mediated immune dysfunction, although the exact process is unknown [6] [7].

• Pathologist

  PMID: 14764528 Assay Assay and technical information Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion [invitae.com]

• Aspiration

  The presence of a normal number of megakaryocytes on an initial bone marrow aspirate should not exclude CAMT from the differential diagnosis of thrombocytopenia within the first year of life. [ncbi.nlm.nih.gov]

  Haematol 2005;131:636 ) Treatment and prognosis Stem cell transplantation 50% evolve to aplastic anemia (at mean age 3.5 years); may evolve to myelodysplastic syndrome or leukemia Microscopic (histologic) images Images hosted on other servers : Bone marrow aspiration [pathologyoutlines.com]

  DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM CODING Diagnostic testing: Definitive diagnostic lab testing includes MPL analysis (genetic testing); bone marrow aspirate, and biopsy specimens showing normal cellularity, with markedly reduced or absent [secure.ssa.gov]

• Severe Clinical Course

  Here we present a girl with severe clinical course of CAMT II having a missense mutation in exon 4 of the c-MPL gene who was admitted to our hospital with intracranial hemorrhage during the newborn period. [ncbi.nlm.nih.gov]

• Orthostatic Hypotension

  No adverse effects have been noted save for orthostatic hypotension, which is ameliorated by a reduction in dosage. [ncbi.nlm.nih.gov]

• Suggestibility

  These data suggest that HoxA11 inhibition of differentiation may involve nonhomeodomain sequences. [ncbi.nlm.nih.gov]

Certain molecular tests are conducted to diagnose AT. Samples taken from bone marrow aspiration show hypoplasia as well as the absence of Mpl messenger ribonucleic acid (mRNA) in the cells, this is indicative of AT [8]. Full blood count and serum thrombopoietin (TPO) measurements may reveal thrombocytopenia or pancytopenia, as well as high TPO titers [9]. There may be other signs of dysfunction in the thrombopoietin pathway.

Further studies that can prove useful are - fluorescent in-situ hybridization, skin fibroblast culture, and gene and chromosome analysis [10].

A platelet count of less than 50x109/L supports the diagnosis of AT.

In addition to depleted megakaryocytes in bone marrow, the presence of anti-thrombopoietin immunoglobulin G (IgG) antibodies is consistent with the diagnosis of acquired AT [6] [7].

1. Rose MJ, Nicol KK, Skeens MA, Gross TG, Kerlin BA. Congenital amegakaryocytic thrombocytopenia: the diagnostic importance of combining pathology with molecular genetics. Pediatr Blood Cancer. 2008;50(6):1263-1265.
2. Cines DB, Bussel JB, McMillan RB, Zehnder JL. Congenital and acquired thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2004:390-406.
3. King S, Germeshausen M, Strauss G, Welte K, Ballmaier M. Congenital amegakaryocytic thrombocytopenia: a retrospective clinical analysis of 20 patients. Br J Haematol. 2005;131(5):636-644.
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7. Colovic M, Pavlovic S, Kraguljac N, et al. Acquired amegakaryocytic thrombocytopenia associated with proliferation of γ/δ TCR+ T-lymphocytes and a BCR-ABL (p210) fusion transcript. Eur J Haematol. 2004;73(5):372–375.
8. Pemberton LC, Levett D, Skinner R, Hall AG, Hanley JP. Novel mutations in a child with congenital amegakaryocytic thrombocytopenia. Br J Hematol. 2006;135(5):742–746.
9. Ballmaier M, Germeshausen M, Schulze H, et al. C-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia. Blood. 2001;97(1):139–146.
10. Maserati E, Panarello C, Morerio C, et al. Clonal chromosome anomalies and propensity to myeloid malignancies in congenital amegakaryocytic thrombocytopenia (OMIM 604498). Haematologica. 2008;93(8):1271-1273.