Downloaded 61 times
More Related Content
Similar to Quantitative platelet disorders
Quantitative platelet disorders
- 1.
- 2. Megakaryopoiesis • Platelets arenon-nucleated cellular fragments produced by megakaryocytes within the bone marrow • When the megakaryocyte approaches maturity, budding of the cytoplasm occurs and large numbers of platelets are liberated. • Platelets circulate with a life span of 10-14 days. • Thrombopoietin (TPO) is inversely related with platelet number and megakaryocyte mass.
- 4. Thrombocytopenia • Reduction inplatelet count to <1.5lakhs • Causes • Decreased production-congential /acquired • Sequestration • Increased destruction-immune/nonimmune
- 7. Idiopathic thrombocytopenic purpura • Mostcommon cause • 1 in 20,000 • Peak age is 1-4yr • M=F • Late winter and spring • 1-4week after exposure to a common viral infection(50-65%) an autoantibody directed against the platelet surface • The antibody binds to the platelet surface , circulating antibody-coated platelets are recognized by the Fc receptor on splenic macrophages, ingested, and destroyed • Viruses associated with ITP – EBV and HIV
- 8. • Clinical manifestations •previously healthy 1-4 yr old child with sudden onset of generalized petechiae and purpura • Bleeding from gums and mucous membranes(<1lakh) • Preceding viral infection • Rare-splenomegaly,lymphadenopathy,bone pain,pallor
- 9. • Outcome • Spontaneousresolution occurs within 6months(70-80%) • <1% of patients develop ICH • 20% with acute ITP progress to chronic ITP • Outcome may be related to age • Laboratory findings • Severe thrombocytopenia • Platelet size –normal/increased • Hb,TC,DC-normal • Bone marrow-normal/increased megakaryocytes.Some- immature
- 10. • Indications ofbone marrow aspiration/biopsy • Abnormal TC/DC • unexplained anemia with findings suggestive of a bone marrow failure syndrome or malignancy • Other tests • HIV • Platelet antibody testing • DCT
- 11. • Treatment • Antiplateletantibodies bind to transfused platelets so it is contraindicated • Education and counseling • Single dose of IVIG(0.8-1g/kg) for 1-2days • Prednisolone 1-4mg/kg/day • IV anti-D therapy(50-75microg/kg) • IVH-platelet transfusion,IVIG,high-dose corticosteroids • Splenectomy- • ≥4yr,severe ITP,>1yr • Not easily controlled with therapy • ICH
- 12. Secondary to SLE/HIV •When the onset is insidious, especially in an adolescent, the possibility of a systemic illness, such as systemic lupus erythematosus (SLE), is more likely. • HIV-associated ITP is usually chronic
- 13. Drug-induced thrombocytopenia • Result ofeither an immune process/megakaryocyte injury • Valproic acid, phenytoin, carbamazepine, sulfonamides, vancomycin, and trimethoprim-sulfamethoxazole • Heparin-induced thrombocytopenia occurs after exposure to heparin, the patient has an antibody directed against the heparin–platelet factor 4 complex.
- 14. Maternal ITP • Havelower risk of serious hemorrhage • Treatment • prenatal administration of corticosteroids to the mother • administration of IVIG • sometimes corticosteroids to the infant after delivery • Usually resolves within 2-4months after delivery
- 15. Neonatal alloimmune thrombocytopenic purpura •Development of maternal antibodies against antigens present on fetal platelets that are shared with the father • 1 in 4000-5000 live births • C/F-apparently well child -generalised petechiae and purpura within 1st few days • 30% may have ICH • Diagnosis-presence of maternal alloantibodies directed against the father’s platelets • Treatment -administration of IVIG prenatally to the mother from 2nd trimester throughout pregnancy
- 16. Type 2B VWD •Results from mutations that increase the ability of VWF to bind platelets. • This leads to increased clearance of both VWF and platelets from circulation and results in decreased VWF activity • Diagnosis-direct measurement of the increased platelet binding/increased response to low-dose ristocetin on platelet aggregation testing. • Thrombocytopenia is not always present and may be more prominent during times of stress such as surgery or pregnancy.
- 17. Platelet-type VWD • Mutationin platelet GPIb causes spontaneous binding to VWF • Presents with decreased VWF activity, loss of high-molecular- weight multimers, and thrombocytopenia similar to type 2B VWD. • Treatment-platelet transfusion
- 19. Thrombocytopenia-absent radius syndrome • Thrombocytopenia(absence or hypoplasia of megakaryocytes) that presents in early infancy • Bilateral radial anomalies of variable severity, ranging from mild changes to marked limb shortening
- 21. Wiskott-aldrich syndrome • Characterizedby eczema, and recurrent infection as a consequence of immune deficiency. • It is inherited as an X-linked disorder. • Splenectomy often corrects the thrombocytopenia X-linked thrombocytopenia • point mutation within the WAS gene
- 22. Congenital amegakaryocytic thrombocytopenia • Manifestswithin the 1st few days to week of life • Child presents with petechiae and purpura caused by profound thrombocytopenia. • A rare defect in hematopoiesis as a result of a mutation in the stem cell TPO receptor. • Bone marrow shows an absence of megakaryocytes. • Often progress to marrow failure (aplasia) over time. • Hematopoietic stem cell transplantation is curative
- 24. Microangiopathy • DIC,HUS,TTP • RBCdestruction and consumptive thrombocytopenia due to platelet and fibrin deposition in the microvasculature • Presence of RBC fragments including helmet cells,schistocytes,spherocytes and burr cells
- 25. Hemolytic uremic syndrome •It is a common cause of community acquired AKI • Triad-microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency • Most common - toxin-producing Escherichia coli that causes prodromal acute enteritis (diarrhea-associated HUS) • Asia,southern Africa-Shigella dysenteriae type 1 • Western countries-verotoxin or Shiga-like toxin producing E. coli (STEC) • Genetic –deficiencies of vWF cleaving protease/complement factor H, I, or B, and defects in vitamin B12 metabolism(absence of preceding diarrhea prodrome)
- 26. • Pathogenesis • Microvascularinjury with endothelial cell damage • Endogenous IgM recognises T antigen causing microvascular angiopathy • Clinical manifestations • E.coli • Fever,vomiting,abdominal pain and diarrhea • Pallor,irritability,weakness and lethargy • oliguria • Pneumococci • Pneumonia,empyema,bacteremia • Majority –irritability,lethargy,encephalopathy,seizures
- 27. • Treatment • promptcorrection of volume deficit • control of hypertension • early institution of dialysis
- 28. Thrombotic thrombocytopenic purpura • Pentadof • Fever • Microangiopathic hemolytic anemia • Thrombocytopenia • Abnormal renal function • Central nervous system changes • Microvascular thrombi within the central nervous system cause subtle neurologic signs • Initial manifestations are often nonspecific • Diagnosis-microangiopathic hemolytic anemia characterized by morphologically abnormal RBCs, with schistocytes, spherocytes, helmet cells, elevated reticulocyte count
- 29. • Treatment-plasmapheresis (effectivein 80-95% of cases) based on thrombocytopenia and microangiopathic hemolytic anemia • Rituximab, corticosteroids, and splenectomy are reserved for refractory cases. • The majority of cases of TTP are caused by an autoantibody– mediated deficiency of a metalloproteinase (ADAMTS-13) that is responsible for cleaving the high-molecular-weight multimers of VWF • ADAMTS- 13 deficiency can be treated by repeated infusions of fresh-frozen plasma.
- 31. Sequestration • Thrombocytopenia developsin individuals with massive splenomegaly because the spleen acts as a sponge for platelets and sequesters large numbers. • Most such patients also have mild leukopenia and anemia on CBC. • Individuals who have thrombocytopenia caused by splenic sequestration should be diagnosed for etiology of splenomegaly, including infections, inflammatory, infiltrative, neoplastic, obstructive, and hemolytic causes.
- 32. Kasabach –Merritt syndrome •The association of a giant hemangioma with localized intravascular coagulation causing thrombocytopenia and hypofibrinogenemia • In most patients, the site of the hemangioma is obvious, but retroperitoneal and intraabdominal hemangiomas may require body imaging for detection. • Inside the hemangioma there is platelet trapping and activation of coagulation, with fibrinogen consumption and generation of fibrinogen degradation products.
- 34. Thrombocytopenia from acquired disorders •Infiltrative disorders like malignancies(ALL),histiocytosis, lymphomas, and storage disease • Aplastic processes may present as isolated thrombocytopenia or along with leukopenia, neutropenia, anemia, or macrocytosis • Bone marrow examination should be performed when thrombocytopenia is associated with abnormalities found on physical examination or on examination of the other blood cell lines.
- 35. Thrombocytosis • Increased plateletcount above normal >4 lakhs • Primary • Myeloproliferative disorders • Essential thrombocythemia,PCV,CML,idiopathic myelofibrosis • Leucocytosis,immature white cells,nucleated red cells,defective platelet function,splenomegaly • Secondary • Hemorrhage ,trauma ,infections ,iron deficiency ,malignancy , splenectomy ,chronic inflammatory disease • Features of underlying causative disorder are evident
- 36.
- 37. Fanconi anemia • Radialanomalies • Short stature • Microcephaly • Hyperpigmentation