thrombotic microangiopathy in which there is red cell destruction and a consumptive thrombocytopenia caused by platelet and fibrin deposition in the microvasculature
This acute disease usually follows an episode of acute gastroenteritis, often triggered by Escherichia coli 0157:H7. Shortly thereafter, signs and symptoms of hemolytic anemia, thrombocytopenia, and acute renal failure ensue. Sometimes neurologic symptoms are associated with these findings. E.coli 0157:H7 produces a specific toxin (verotoxin) that binds to and damages renal endothelial cells preferentially.
The association of a giant hemangioma with localized intravascular coagulation causing thrombocytopenia and hypofibrinogenemia is called the Kasabach-Merritt syndrome. In most patients the site of the hemangioma is obvious, but retroperitoneal and intra-abdominal hemangiomas may require body imaging for detection. Inside the hemangioma there is platelet trapping and activation of coagulation with fibrinogen consumption and generation of fibrin(ogen) degradation products. Arteriovenous malformation within the lesions can cause heart failure.The peripheral blood smear shows microangiopathic changes. Multiple modalities have been used to treat Kasabach-Merritt syndrome, including surgical excision , laser photocoagulation, corticosteroids in high doses, local x-ray therapy, and antiangiogenic agents such as interferon a2 . Over time most patients who present in infancy have regression of the hemangioma.
Congenital amegakaryocytic thrombocytopenia is caused by a rare defect in hematopoiesis that usually manifests within the first few days to weeks of life, when the child presents with petechiae and purpura caused by profound thrombocytopenia. Other than skin and mucous membrane findings, the physical examination is normal.
syndrome consists of thrombocytopenia that presents in early infancy with radial anomalies of variable severity from mild changes to marked limb shortening. In many such individuals there are also other skeletal abnormalities of the lower extremities.Intolerance to formula may complicate management by triggering gastrointestinal bleeding.
microcephaly, microphthalmia, epicanthal folds, dangling thumbs, site of ureteralreimplantation, congenital dislocated hips, and rocker bottom feet. (Alter BP, Young NS. The bone marrow failure syndromes.
is characterized by thrombocytopenia with tiny platelets, eczema, and recurrent infections due to immune deficiency. WAS is inherited as an X-linked disorder. The WAS protein appears to play an integral role in regulating the cytoskeletal architecture of both platelets and T lymphocytes in response to receptor-mediated cell signaling. The WAS protein is common to all cells of hematopoietic lineage. Molecular analysis of families with X-linked thrombocytopenia has shown that many members have a point mutation within the WAS gene, whereas individuals with the full manifestation of WAS have large gene deletions. Examination of the bone marrow in WAS shows the normal number of megakaryocytes, although the megakaryocytes may have bizarre morphology. Transfused platelets have a normal life span. Splenectomy often corrects the thrombocytopenia, suggesting that the platelets formed in WAS have accelerated destruction. About 5% of WAS patients develop lymphoreticular malignancies. Successful bone marrow transplantation cures WAS.
Causes of Thrombocytopenia in pediatrics other than ITP
Causes ofThrombocytopeniain pediatrics otherthan ITPPrepared by:-Asmaa Rabie Abdel MonemA 5th grade med studentAlexandria University Faculty of Medicine
Causes of thrombocytopeniaincreased destruction Immune mechanism Iodopathic (ITP) Secodary to infection, drugs, SLE Non-immune mechanism platelet consumption DIC ,HUS microangiopathic hemolyticanemia platelet destruction Hypersplenism , drugs Prothetic heart valve sequesteration Large spleenDecreased production Bone marrow depression Hereditary Fanconi anemia TAR syndrome Acquired Drugs , chemotherapy Inefction, hepatitis ,HIV,EBV Bone marrow infiltration Leukemia ,neuroblastoma Storage disease
Secondary immune mechanismDrug-Induced Thrombocytopenia•A number of drugs are associatedwith immune thrombocytopenia asthe result of either an immuneprocess or a megakaryocyte injury.
Heparin-induced hrombocytopenia (and rarely thrombosis) is seldom seen inpediatrics but occurs when, after exposure to heparin, the patient developsan antibody directed against the heparin/ platelet factor IV complex.
Non immune Platelet Destructionincrease platelet consumptionDIChemolytic-uremic syndromethromboticthrombocytopenic purpuraThe syndromes of DIC, hemolytic-uremic syndrome, and thromboticthrombocytopenic purpura share the hematologic picture ofThe microangiopathic hemolytic anemia is characterized by thepresence of RBC fragments, including helmetcells, schistocytes, spherocytes, and burr cells.
Hemolytic-Uremic Syndrome (HUS)Abnormal red cell morphologyNormal numbers ofmegakaryocytes.
Combined Platelet and Fibrinogen Consumption SyndromesKasabach-Merritt SyndromeHemangiomaplatelet trapping and activation ofcoagulation with fibrinogenconsumption and generation offibrin(ogen)
Non immune Platelet DestructionSequestration•Individuals with massive splenomegalydevelop thrombocytopenia, since thespleen acts as a sponge for plateletsand sequesters large numbers.•Most such patients will also have mildleukopenia and anemia on the CBC.Individuals who havethrombocytopenia caused by splenicsequestration should undergo a work-up to diagnose the etiology ofsplenomegaly, includinginfectious, infiltrative, neoplastic, obstructive, and hemolytic causes.
Thrombocytopenia–absent radius(TAR)The thrombocytopenia of TARsyndrome frequently remitsover the first few years of life.
Fanconi anemiaAplastic anemia not presentat birth, develops about 6yr of age; fatal withoutbone marrow transplant;chromosomal breakagechallenge test available forearly diagnosis.
Wiskott-Aldrich syndrome (WAS)MicrothrombocytopeniaEczemaRecurrent infectionsX-linkedNormal number ofmegakaryocytesSuccessful bonemarrowtransplantation curesWAS.Microthrombocytes
Refrences1. Nelson textbook of pediatrics 19th edition,Chapter 476.2. Dan L. Longo, HARRISON’S Hematology andOncology;3. Childhood idiopathic thrombocytopenic purpura(itp): over 40 year of experiences; MedicalJournal of Islamic World Academy of Sciences19:4, 151-160, 2011.-http://www.uptodate.com/contents/clinical.4-of-evaluation-and-manifestationschildren-in-thrombocytopenia