Pathophysiology, Clinical Manifestations and Diagnosis of Immune Thrombocytopenia: Contextualization from a Historical Perspective
Abstract
:1. History of Immune Thrombocytopenia and Platelets
2. Pathophysiology of ITP
2.1. Autoantibodies
2.2. T Lymphocytes
2.3. Thrombopoietin
2.4. Current Pathophysiological Model in ITP
3. Terminology
4. Epidemiology
5. Clinical Manifestations
6. Diagnosis
Differential Diagnosis
7. Prognosis
8. Areas for Future Work and Direction
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Year | Author | Discovery |
---|---|---|
1735 | Werlhof [2] | “Morbus maculosus hemorrhagicus” (ITP) identified |
1841 | Addison [3] | The first-time platelets were referred to (“extremely minute…granules”) |
1865 | Schultze [5] | First accurate description of platelets |
1882 | Bizzozero [6] | Introduced the name “platelets” Role of platelets in hemostasis |
1883 | Brohm [8] | Association between thrombocytopenia and the Werlhof syndrome |
1889 | Hayem [10] | First platelet count documenting thrombocytopenia in this purpura |
1890 | Howell [11] | Description of megakaryocytes |
1906 | Wright [12,13] | Platelets as fragments of the cytoplasm of megakaryocytes |
1915 | Frank [14] | A toxic substance produced by the spleen causes thrombocytopenia |
1916 | Kaznelson [15] | Increased platelet destruction in the spleen First splenectomy |
1946 | Dameshek and Miller [16] | Increase in the total number of megakaryocytes in the bone marrow. Most of these cells did not produce platelets |
1951 | Harrington et al. [19] | “Humoral factor” (Immune etiology) |
1951 | Evans et al. [20] | Anti-platelet autoantibodies |
1958 | Kelemen et al. [41] | The first to coin the term “thrombopoietin” |
1965 | Shulman et al. [21] | The humoral factor causing thrombocytopenia is an immunoglobulin G |
1978 | McMillan et al. [28] | Anti-megakaryocyte autoantibodies |
1982 | Van Leeuwen et al. [22] | Anti-glycoprotein autoantibodies |
1991 | Semple et al. [34] | T cell abnormalities |
1994 | Bartley et al. [42] Kuter et al. [43] Lok et al. [44] | Purification and cloning of thrombopoietin |
1996 | Emmons et al. [45] Kosugi et al. [46] | TPO levels in ITP are low compared to central thrombocytopenia |
2003 | Chang et al. [31] | Anti-megakaryocyte autoantibodies |
2004 | McMillan et al. [32] | Anti-megakaryocyte autoantibodies |
2004 | Houwezijl et al. [33] | Megakaryocytic abnormalities |
2015 | Grozovsky et al. [48,49] | Desialylated platelets are removed from the circulation in hepatocytes via AMR |
Mandatory |
Patient history, family history, physical examination, CBC and reticulocytes, peripheral blood smear, basic coagulation test, liver function, folic acid and vitamin B12, immunoglobulin levels, serology (HIV, HBV, HCV) |
Recommended |
Anti-phospholipid antibodies, anti-thyroid antibodies and thyroid function, antinuclear antibodies, serum proteinogram |
Tests of potential utility |
Anti-glycoprotein antibodies, reticulated/immature platelet fraction, H. pylori, bone marrow examination (in selected patients), Viral PCR for EBV, CMV, and parvovirus, blood group and Rh, direct antiglobulin test, pregnancy test |
Tests of unproven or uncertain benefit |
TPO levels, bleeding time, serum complement |
Bone marrow diseases, including myelodysplastic syndromes, leukemias, other neoplasms, metastatic disease, aplastic anemia, myelofibrosis, and Gaucher disease |
Liver disease (including cirrhosis or portal hypertension) |
Hereditary thrombocytopenia |
Secondary immune thrombocytopenia, due to infections (HIV, HCV, HBV, H. pylori), autoimmune disorders/immunodeficiency (CVID, systemic lupus erythematosus, hyperthyroidism or APS), malignancy (for example, lymphoproliferative disorders) |
Splenomegaly (Hypersplenism) |
Drugs including heparin, alemtuzumab, PD-1 inhibitors, abciximab, valproate, alcohol abuse, quinine use, exposure to environmental toxins or chemotherapy, herbal products |
Other microangiopathic disorders (DIC, TTP, HUS), Evans syndrome |
Recent transfusions (post-transfusion purpura) and vaccinations |
Others: vitamin B12 or folate deficiency, pregnancy, giant hemangiomas |
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Martínez-Carballeira, D.; Bernardo, Á.; Caro, A.; Soto, I.; Gutiérrez, L. Pathophysiology, Clinical Manifestations and Diagnosis of Immune Thrombocytopenia: Contextualization from a Historical Perspective. Hematol. Rep. 2024, 16, 204-219. https://doi.org/10.3390/hematolrep16020021
Martínez-Carballeira D, Bernardo Á, Caro A, Soto I, Gutiérrez L. Pathophysiology, Clinical Manifestations and Diagnosis of Immune Thrombocytopenia: Contextualization from a Historical Perspective. Hematology Reports. 2024; 16(2):204-219. https://doi.org/10.3390/hematolrep16020021
Chicago/Turabian StyleMartínez-Carballeira, Daniel, Ángel Bernardo, Alberto Caro, Inmaculada Soto, and Laura Gutiérrez. 2024. "Pathophysiology, Clinical Manifestations and Diagnosis of Immune Thrombocytopenia: Contextualization from a Historical Perspective" Hematology Reports 16, no. 2: 204-219. https://doi.org/10.3390/hematolrep16020021