Blood and endocrine system diseases in children. Lesson Topics: Hemorrhagic disease in children
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- Bu səhifədəki naviqasiya:
- Classification. Diagnostics. Differential diagnosis with other hemorrhagic conditions in
- Transfusion contraindicated
- Intravenous immunoglobulin for
- Frequency
- Fig. 3.
- MEDICATION Prednisone
- Methylprednisolone (Solu-Medrol)
- Immune globulin intravenous
- Adult Dose
- Causes
- Surgical Care
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Blood and endocrine system diseases in children. Lesson 3. Topics: Hemorrhagic disease in children.
thrombocytopathies children. Etiology Pathogenesis. Classification. Diagnostics. Differential diagnosis with other hemorrhagic conditions in children. Treatment. Emergency treatment of bleeding and hemorrhagic conditions requiring treatment. International Guidelines: Clinacal Practice guidelines : Henoch-Schonlein purpura http://www.rch.org.au/clinicalguide/guideline_index/HenochSchonlein_Purpura/
The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia http://www.bloodjournal.org/content/bloodjournal/117/16/4190.full.pdf
GUIDELINES FOR THE MANAGEMENT OF HEMOPHILIA http://www.hemoacademy.cz/dokumenty/guidelines_mng.pdf Introduction: All hemorrhagic diatheses are divided into 3 groups, depending on the type and cause of hemorrhagic syndrome: vasopathies, thrombopathias, coagulopathies.
Autoantibodies against platelet surface Clinical presentation o Typically 1–4 weeks after a nonspecific viral infection o Most 1–4 years of age → sudden onset of petechiae and purpura with or without mucous membrane bleeding o Most resolve within 6 months o <1% with intracranial hemorrhage
o 10–20% develop chronic ITP Labs o Platelets <20,000/mm3 o Platelet size normal to increased o Other cell lines normal o Bone marrow—normal to increased megakaryocytes Treatment o Transfusion contraindicated unless life-threatening bleeding (platelet antibodies will bind to transfused platelets as well) o No specific treatment if platelets >20,000 and no ongoing bleeding o If very low platelets, ongoing bleeding that is difficult to stop or life- threatening: Intravenous immunoglobulin for 1–2 days o If inadequate response, then prednisone o Splenectomy reserved for older child with severe disease
purpura, autoimmune thrombocytopenic purpura, primary thrombocytopenic purpura)
syndrome in which
a decreased number of
circulating platelets (thrombocytopenia) present as a bleeding tendency, easy bruising (purpura), or extravasation of blood from capillaries into skin and mucous membranes (petechiae).
(IgG) with specificity for one or more platelet membrane glycoproteins, binds to circulating platelet membranes. Immunoglobulin-coated platelets induce receptor–mediated phagocytosis by mononuclear macrophages, primarily but not exclusively in the spleen. The spleen is the key organ in the pathophysiology of ITP, not only because platelet autoantibodies are formed in the white pulp, but also because the
immunoglobulin-coated platelets are destroyed by mononuclear macrophages in the red pulp. If bone marrow megakaryocytes are not able to increase production and maintain a normal number of circulating platelets, thrombocytopenia and purpura develop.
1 in 10,000 Mortality/Morbidity: The most frequent cause of death in ITP is spontaneous or accidental, trauma-induced intracranial bleeding in patients whose platelet counts are less than 10,000 per µL. This situation occurs in 1-2% of cases.
children aged 3-5 years. Causes: 1.
Postviral illness. In children, most cases of ITP are acute, and onset seems to occur within a few weeks of recovery from a viral illness. Thrombocytopenia is a recognized complication following Ebstein-Barr virus infection; varicella virus; cytomegalovirus; rubella virus; hepatitis A, B or C; or more typically, a vaguely defined, viral, upper respiratory infection or gastroenteritis. Transient thrombocytopenia often follows recent immunization with attenuated live-virus vaccines. 2.
Human immunodeficiency virus (HIV). Thrombocytopenia may occur during the acute retroviral syndrome coincident with fever, rash, and sore throat. 3.
Drug-induced thrombocytopenia. Persons who have been sensitized (by prior exposure) to quinidine or quinine may develop immune-mediated drug purpura within hours to days of subsequent exposure. ther drugs that have been associated with drug purpura include antibiotics (eg, cephalothins, rifampicin), gold salts, analgesics, neuroleptics, diuretics, antihypertensives, eptifibatide (Integrilin), and, more recently, abciximab (ReoPro), a chimeric monoclonal fragment antigen binding (Fab) antibody fragment directed against the platelet GPIIb/IIIa receptor. CLINICAL Physical: 1.
Skin and mucous membranes. The presence of widespread petechiae and ecchymoses, oozing from a venepuncture site, gingival bleeding, or hemorrhagic bullae indicates that the patient is at risk for a serious bleeding complication (Fig. 1). If the patient's blood pressure was taken recently, petechiae may be observed under and distal to the area where the cuff was placed and inflated (Fig. 2). Similarly, suction-type ECG leads may induce petechiae. 2. Abdomen. The spleen is palpable in less than 10% of children with ITP. In children with acute ITP, the presence of a readily palpable spleen is not typical. Fig. 1. Haemorrhagic rush in idiopathic thrombocytopenic purpura.
Fig. 2. “Cuff” symptrom in thrombocytopenic purpura.
Fig. 3. Petechiae and purpura from immune thrombocytopenic purpura
Complete blood count. The hallmark of ITP is isolated thrombocytopenia. Peripheral blood smear 1. The morphology of red cells and leukocytes is normal. 2. The morphology of platelets is typically normal, with varying numbers of large platelets. 3.
Clumps of platelets on a peripheral smear prepared from ethylenediaminetetraacetic acid (EDTA)-anticoagulated blood are evidence of pseudothrombocytopenia. Antiplatelet antibody. Assays for platelet antigen-specific antibodies, platelet-associated immunoglobulin, or other antiplatelet antibodies are available in some medical centers and certain mail-in reference laboratories. Imaging Studies: Computer-assisted tomographic (CT) scanning or magnetic resonance imaging (MRI) Use them promptly when the medical history or physical examination suggests serious internal bleeding. Procedures: The primary diagnostic evaluation is the bone marrow aspirate and biopsy. In ITP, a normal-to-increased number of megakaryocytes exist in the absence of other significant abnormalities. Spleen. No specific findings exist in the spleen. Medical Care: 1.
The goal of medical care is to increase the platelet count to a safe level, permitting patients with ITP to live normal lives while awaiting spontaneous or treatment-induced remission. After 6 months, if the platelet count cannot be maintained at a safe level or it cannot be maintained at a safe level with medication without serious treatment-related toxicity, consider splenectomy. 2.
Corticosteroids (oral prednisone, IV methylprednisolone) are the drugs of choice for initial management of ITP. 3. Intravenous immune globulin (IVIG) has been the drug of second choice for many years. However, recent studies indicate that for patients who are Rh(D) positive with ITP, intravenous Rho immune globulin (RhIG) offers comparable efficacy, less toxicity, greater ease of administration, and a lower cost than IVIG. 4. The limitation of using IV RhIG is the lack of efficacy in patients who are Rh(D) negative or splenectomized. Also, IV RhIG induces immune hemolysis in persons who are Rh(D) positive and should not be used when the hemoglobin concentration is less than 8.0 g/dL. Medical care in children 1. The initial treatment of ITP depends on whether the risk of severe hemorrhage, such as intracranial bleeding, is estimated to be low, moderate, or high.
2. Children whose platelet count is greater than 30,000/ L typically only have mild purpura, and the risk of a severe hemorrhage is low. They may be managed as outpatients without specific treatment. 3. Children whose platelet count is less than 20,000/ L may have more significant purpura and mucosal bleeding. Oral prednisone is conservative treatment, and the addition of IV RhIG for patients who are Rh(D) positive or IVIG for patients who are Rh(D) negative is a more aggressive treatment. 4. Children whose platelet count is less than 10,000/ L are likely to have a significant bleeding tendency and a high risk of serious hemorrhage. Initial treatment with IV methylprednisolone and either IV RhIG or IVIG is appropriate. 5. Platelet transfusions may be required for overt bleeding but are not recommended for prophylaxis. Chronic or treatment-resistant ITP 1. For those patients whose platelet counts do not or no longer respond to treatment with tolerable doses of corticosteroids, IV RhIG, IVIG, or splenectomy, other treatments are available. 2. Data supporting these options are based on relatively few case studies and response rates are comparatively lower. 3.
Before concluding that a patient has failed both medical management and splenectomy, necessitating treatment with alternative options, perform an imaging study to ensure that the problem is not associated with the presence of an accessory spleen. 4. Among the medical treatment options in these circumstances are cyclophosphamide, azathioprine, and danazol. 5.
Interventions of uncertain efficacy include vinblastine, vincristine, ascorbic acid, colchicine, or interferon-alpha, for which conflicting reports of efficacy in the medical literature exist.
complete, and lifelong clinical remission. In chronic ITP, the results of splenectomy typically are less predictable. Platelet counts may not revert to fully normal values, and relapses are not uncommon. Splenectomy results in a lifelong increased risk of sepsis from infection by encapsulated bacteria. In children, the risk of bacterial sepsis after splenectomy is estimated to be 1-2%. Many pediatricians recommend delaying splenectomy until children are aged 5 years.
MEDICATION Prednisone 4-8 mg/kg/d PO; however, a reduced dose of 1.5-2.0 mg/kg/d may be adequate for management of nonurgent situations or when risk of adverse effects is high because of predisposing factor, such as diabetes or psychiatric illness Methylprednisolone (Solu-Medrol) 30 mg/kg/d IV for initial management of a severe bleeding tendency in ITP. IV methylprednisolone recommended when most rapid and reliable treatment of ITP is required. In this situation, combine methylprednisolone with IV RhIG in qualified patients who are Rh(D) positive or IVIG in patients who are Rh(D) negative or unqualified patients who are Rh(D) positive. Intravenous Rho immune globulin (WinRho SDF) -- Specialized immunoglobulin product manufactured from pools of plasma from persons who are Rh(D) negative and have been alloimmunized to the D blood group antigen. A single infusion of 50 µg/kg, followed by a second dose, if required, of 20-40 µg/kg, is recommended; an off-label dose of 75 µg/kg in patients whose hemoglobin concentration is at least 8.0 g/dL may increase efficacy without adverse effect Not recommended for persons whose Rh blood type is Rh(D)- negative or who have had a splenectomy; IV RhIG should not be used for persons whose hemoglobin concentration is <8.0g/dL; persons with known IgA deficiency and anti-IgA are at risk of an anaphylactic/anaphylactoid reaction to all plasma- containing biologicals, including IV RhIG
Sandoglobulin) Begin with 1.0 g/kg infused IV at starting rate of 0.5 mL/kg/h (5% solution) to a maximum rate of 4.0 mL/kg/h; repeat dose at 3-4 wk intervals when indicated by decreasing platelet count Immunosuppressive antimetabolite -- Used in patients with ITP to reduce production of abnormal autoantibody. Azathioprine (Imuran) -- May be effective in some patients with ITP who do not or no longer respond to corticosteroids, IV RhIG, or IVIG. May be used in conjunction with prednisone to reduce dose of prednisone, or it may be used as another oral medication to delay splenectomy. Adult Dose 2 mg/kg/d PO/IV Pediatric Dose 50mg/daily Synthetic antineoplastic drugs (chemically related to nitrogen mustards) -- Inhibit cell growth and proliferation. Cyclophosphamide (Cytoxan) -- May be useful in some patients who do not or no longer respond to corticosteroids, IV RhIG, IVIG, or splenectomy. Induces less of a decrease in platelet count compared to other immunosuppressive alkylating agents. 2 mg/kg/d PO or 1.0-1.5 g/m
2 q2-4mo as a bolus IV infusion; occasionally, patients require more frequent dosing
spontaneous recovery with completely normal platelet counts in 2-8 weeks. Fatal bleeding occurred in 0.9% on initial presentation. Fatal intracerebral hemorrhage occurs rarely in children who have been treated with prednisone and IV RhIG or IVIG for at least 2 days.
constitutional thrombopathy, hereditary hemorrhagic thrombopathy Background: Glanzmann initially described thrombasthenia in 1918 when he noted purpuric bleeding in patients with platelet counts within the reference range. Glanzmann thrombasthenia is one of several inherited disorders of platelet function. athophysiology: Glanzmann thrombasthenia is an autosomal recessive trait whereby the production and assembly of the platelet membrane glycoprotein (GP) IIb-IIIa is altered, preventing the aggregation of platelets and subsequent clot formation. Mortality/Morbidity: The probability of death following bleeding is estimated at approximately 5%. ] Age: Patients with Glanzmann thrombasthenia are typically diagnosed in infancy; all individuals with the disorder are recognized by age 5 years. Physical: Most patients with thrombasthenia present with signs of purpura or bleeding. The diagnosis is made in patients with refractory hemorrhage and appropriate findings on the diagnostic laboratory studies Causes: Trauma and pressure remain the most frequent causes of bleeding in persons with thrombasthenia. Lab Studies: 1.
A history of prolonged bleeding, a prolonged bleeding time, and failure of platelets to aggregate in response to any of the usual agonists are diagnostic of thrombasthenia. 2.
A CBC may also suggest the degree of bleeding. Patients who are thrombasthenic have platelet counts within the reference range and, on blood smear, normal platelet morphology. 3.
Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are within reference ranges. 4. A urinalysis may demonstrate proteinuria and microscopic hematuria. 5. The diagnosis is confirmed by documenting the absence of GP IIb- IIIa via sodium dodecyl sulfate-polyacrylamide gel electrophoresis of radiolabeled platelet proteins. Medical Care: 1.
Refractory bleeding in individuals with thrombasthenia requires the transfusion of normal platelets. 2. E-aminocaproic acid may be useful in controlling bleeding after dental extraction. 3.
Corticosteroids are not helpful in persons with acute bleeding. 4.
Other more rare therapies cited were bone marrow transplants and recombinant factor VIIa. Surgical Care: Patients with severe menorrhagia may require hysterectomy. Vasculitis and Thrombophlebitis Vasculitis is a descriptive term associated with a heterogeneous group of diseases that results in inflammation of blood vessels. Arteries and veins of any size in any organ may be affected, leading to ischemic damage to organs. The pattern of vessel involvement is highly variable, leading to innumerable clinical presentations. The most common vasculitides of childhood are Henoch-Schцnlein purpura and Kawasaki disease. See articles on Kawasaki Disease, Infantile Polyarteritis Nodosa, Polyarteritis Nodosa, and Takayasu Arteritis. For the clinician, diagnosing the cause of vasculitis is a difficult task that involves distinguishing disease entities with possibly overlapping clinical presentations. Classification criteria have been established for a number of distinct clinical syndromes, but these are less useful in making a diagnosis in patients who do not meet all the criteria of any one disease. While groups of patients with unifying features can be identified, a patient with vasculitis often presents initially with nonspecific constitutional findings. Various classification schemes for vasculitis have been proposed, most recently by an international consensus conference in Chapel Hill, North Carolina in 1994. This classification is as follows: Large-sized vessel vasculitis 1. Temporal arteritis - Granulomatous arteritis of the aorta and major branches, especially the extracranial branches of the carotid artery that usually occurs in patients older than 50 years 2. Takayasu arteritis - Granulomatous arteritis of the aorta and major branches that usually occurs in patients younger than 50 years Medium-sized vessel vasculitis 1. Polyarteritis nodosa - Necrotizing vasculitis of medium- or small- sized arteries without involvement of large arteries, veins, or venules; renal involvement without glomerulonephritis 2. Kawasaki disease - Medium- and small-sized arteritis of childhood associated with mucocutaneous lymph node syndrome; most commonly affects coronary arteries, although veins and aorta may be involved (Lesions of the aorta have been found on autopsy.) Small-sized vessel vasculitis 1.
Wegener granulomatosis - Granulomatous inflammation of small- to medium-sized vessels involving the respiratory tract; necrotizing glomerulonephritis common 2.
Churg-Strauss syndrome - Eosinophil-rich and granulomatous inflammation involving the respiratory tract and necrotizing vasculitis of small- to medium-sized vessels; associated with asthma and eosinophilia (Under the classification of the American College of Rheumatology and traditional classifications, Wegener granulomatosis and Churg-Strauss syndrome are grouped together with polyarteritis nodosa under medium-sized vessel vasculitis.) 3. Microscopic polyangiitis (MPA) - Pauci-immune necrotizing vasculitis involving small- and
medium-sized vessels; necrotizing glomerulonephritis common; pulmonary capillaritis frequent 4. Schönlein-Henoch disease: Small-vessel vasculitis with
immunoglobulin A (IgA) immune accumulation; involvement of skin, gut, and glomeruli typical; associated with arthritis or arthralgia 5. Essential cryoglobulinemic vasculitis - Vasculitis with cryoglobulin immune accumulation affecting arterioles and venules; associated with serum cryoglobulins; skin and glomeruli often involved 6. Cutaneous leukocytoclastic vasculitis - Isolated cutaneous vasculitis without systemic vasculitis or glomerulonephritis 7.
Possible thrombophlebitis, or superficial venous thrombosis - Resulting from vasculitic lesions with endothelial activation; in children, more often due to hypercoagulable states or catheter instrumentation
Idiopathic thrombocytopenic purpura (ITP), also known as primary immune thrombocytopenic purpura and autoimmune thrombocytopenic purpura, is defined as isolated thrombocytopenia with normal bone marrow and the absence of other causes of thrombocytopenia. The 2 distinct clinical syndromes manifest as an acute condition in children and a chronic condition in adults. ITP is a decrease in the number of circulating platelets in the absence of toxic exposure or a disease associated with a low platelet count.
ITP is primarily a disease of increased peripheral platelet destruction, with most patients having antibodies to specific platelet membrane glycoproteins. Relative marrow failure may contribute to this condition, since studies show that most patients have either normal or diminished platelet production. Acute ITP often follows an acute infection and has a spontaneous resolution within 2 months. Chronic ITP persists longer than 6 months without a specific cause.
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