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].

• Developmental Delay

  Here we present a case in which CAMT appears linked to CNS abnormalities (encephalomalacia, global atrophy) and developmental delay related with intrauterine intracranial hemorrhage. [ncbi.nlm.nih.gov]

  Analyzes chromosomes in newborns and infants for changes that can explain certain birth defects or developmental delays. Multiple testing options providing information on the genetic health of your baby during the first and second trimesters. [integratedgenetics.com]

  Nazareth Martinón‐Torres, Manuel Vázquez‐Donsión, Lourdes Loidi and Jose Miguel Couselo, CAMT in a female with developmental delay, facial malformations and central nervous system anomalies, Pediatric Blood & Cancer, 56, 3, (452-453), (2010). [doi.org]

• Multiple Congenital Anomalies

  Two somewhat similar cases were recently reported, but with multiple congenital anomalies that are not present in our case. [ncbi.nlm.nih.gov]

• Oral Ulcers

  She had Raynaud phenomenon but no skin rashes, oral ulcers, sicca symptoms or photosensitivity. The examination was unremarkable except for minor pedal edema. For last two months, her creatinine had been elevated (3.3 mg/dL). [reumatologiaclinica.org]

• Skin Rash

  This disease is usually diagnosed in infants who often have a skin rash called ‘petechiae’ which represent small bleeds under the skin but there may also be other sites of bleeding. This disease can be inherited and be found in other family members. [childrensmn.org]

  Skin rashes in mononeuritis multiplex are not rare, and the major differentials include collagen vascular diseases, systemic vasculitides, secondary antiphospholipid antibody syndrome, amyloidosis, sarcoidosis, lyme disease, leprosy and postviral syndromes [ruralneuropractice.com]

  She had Raynaud phenomenon but no skin rashes, oral ulcers, sicca symptoms or photosensitivity. The examination was unremarkable except for minor pedal edema. For last two months, her creatinine had been elevated (3.3 mg/dL). [reumatologiaclinica.org]

• Photosensitivity

  She had Raynaud phenomenon but no skin rashes, oral ulcers, sicca symptoms or photosensitivity. The examination was unremarkable except for minor pedal edema. For last two months, her creatinine had been elevated (3.3 mg/dL). [reumatologiaclinica.org]

• Arthralgia

  She had never been worked up for lupus before, given the mild and intermittent nature of her arthralgia, and non-specific symptoms. Anti-nuclear antibody was positive by immunofluorescence in a speckled pattern. [reumatologiaclinica.org]

• Suggestibility

  As previously suggested, c-MPL mutation analysis in CAMT patients helps to predict the clinical course and to provide optimal therapy. [ncbi.nlm.nih.gov]

  Interpretation and Conclusions: These results suggest that therapies, such as hematopoietic stem cell transplantation, which are potentially curative although associated with a risk of treatment-related mortality, should not be postponed even in those [moh-it.pure.elsevier.com]

• Intracranial Hemorrhage

  Here we present a case in which CAMT appears linked to CNS abnormalities (encephalomalacia, global atrophy) and developmental delay related with intrauterine intracranial hemorrhage. [ncbi.nlm.nih.gov]

  Clinical description CAMT manifests since birth, often in the first day or at least within the first month of life, with petechiae, purpura, and gastrointestinal, pulmonary or intracranial hemorrhage due to isolated thrombocytopenia and a near absence [rarediseases.info.nih.gov]

  hemorrhage due to isolated thrombocytopenia and a near absence of megakaryocytes in the bone marrow Two types of CAMT have been identified: Type I-CAMT is the severe form of the disease and is characterized by persistently low platelet counts and early [dovemed.com]

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].

• Cytopenia

  Most of the patients develop a severe aplastic anemia and trilineage cytopenia during the first years of life and hematopoietic stem cell transplantation is the only curative treatment. [ncbi.nlm.nih.gov]

  […] with Unilineage Dysplasia (RCUD) + Refractory Anemia with Ringed Sideroblasts (RARS) + Refractory Cytopenia with Multilineage Dysplasia (RCMD) + Refractory Anemia with Excess Blats (RAEB) + MDS with Isolated 5q Deletion (5q-syndrome) + Myelodysplastic [atlases.muni.cz]

  Bussel Fetal and neonatal cytopenias: what have we learned? [29.] C. Kaplan Neonatal alloimmune thrombocytopenia [ [ [ [33.] J. Kjeldsen-Kragh, M. Kim, M.K. Killie, A. Husebekk, J. Freedman, J.W. [apcontinuada.com]

  Yoshinari Bone marrow findings in systemic lupus erythematosus patients with peripheral cytopenias Clin Rheumatol, 17 (1998), pp. 219-222 [10] H. Chang, T.C. [reumatologiaclinica.org]

• Lymphopenia

  This time she had thrombocytopenia of (10,000/mm 3 ) and lymphopenia (300/mm 3 ). The diagnostic possibilities considered were lupus disease activity, Macrophage Activation Syndrome (MAS) and viral fever. [reumatologiaclinica.org]

  [45, 47, 48] As first course, Horse ATG (h-ATG) is used in the immunosuppressive combination, however for refractory and relapse cases further courses are given using rabbit ATG (r-ATG). r-ATG appears to be more immunosuppressive as a more prolonged lymphopenia [emedicine.medscape.com]

The clinical bleeding tendency resolved after treatment for 4 weeks and complete remission was documented after 6 weeks. Azathioprine treatment for AAMT is low risk, convenient, and cost-effective. [ncbi.nlm.nih.gov]

Diagnosis - Acquired amegakaryocytic thrombocytopenia Prognosis - Acquired amegakaryocytic thrombocytopenia The long-term outlook (prognosis) for people with acquired amegakaryocytic thrombocytopenia varies based on the underlying cause. [checkorphan.org]

The prognosis of this heritable disorder is poor and bone marrow transplantation is the only effective treatment. [ncbi.nlm.nih.gov]

Prognosis Prognosis is poor and with supportive therapy, progression to full marrow failure (tri-linear marrow aplasia) occurs during the first years of life. 30% of patients with CAMT die due to bleeding complications before the HSCT and 20% due to the [rarediseases.info.nih.gov]

[…] decreased marrow megakaryocytes and high serum TPO levels Red cell macrocytosis with normal hemoglobin level Bone marrow initially normocellular Mucocutaneous or GI bleeding, variable physical abnormalities ( Br J Haematol 2005;131:636 ) Treatment and prognosis [pathologyoutlines.com]

[…] of Pathology Thrombocytopenia Microchapters Home Patient Information Overview Historical Perspective Classification Pathophysiology Causes Differentiating Thrombocytopenia from other Diseases Risk Factors Screening Natural History, Complications and Prognosis [wikidoc.org]

Since it is a syndrome of diverse etiologies, the optimal treatment is often uncertain. In a patient with longstanding AATP, a complete remission was obtained with antithymocyte globulin. [ncbi.nlm.nih.gov]

Epidemiology The exact prevalence is unknown and less than 100 cases have been reported in the literature. In addition, the incidence may be underestimated due to difficult and inconsistent diagnosis of the disease. [rarediseases.info.nih.gov]

This review will summarize the diagnosis, pathophysiology, and management of CAMT. Copyright © 2011 Wiley-Liss, Inc. [ncbi.nlm.nih.gov]

Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology Thrombocytopenia Microchapters Home Patient Information Overview Historical Perspective Classification Pathophysiology [wikidoc.org]

Treatment for CAMT involves treating and preventing bleeding with platelet transfusion. In most cases, bone marrow or stem cell transplant is required for cure. [childrensmn.org]

Treatment Initial treatment is directed at stopping or preventing bleeding with platelet transfusions. [verywellhealth.com]

How can Congenital Amegakaryocytic Thrombocytopenia be Prevented? Currently, Congenital Amegakaryocytic Thrombocytopenia may not be preventable, since it is a genetic disorder. [dovemed.com]

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