Blood and endocrine system diseases in children. Lesson Topics: Hemorrhagic disease in children
Prednisone (Deltasone, Meticorten, Orasone, Sterapred)
Yüklə 1,02 Mb. Pdf görüntüsü
|
- Bu səhifədəki naviqasiya:
- Further Outpatient Care
- VON WILLEBRAND DISEASE (VWD) Most common hereditary bleeding disorder; autosomal dominant
- Frequency
- Prophylaxis now recommended
- Hemophilia is classified
- Treatment in patients with factor inhibitors
- Recombinant factor VII
- Causes
|
Prednisone (Deltasone, Meticorten, Orasone, Sterapred) Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocyte and antibody production.
Patients with Henoch-Schönlein purpura (HSP) have the potential for severe complications, which may occur precipitously (eg, acute abdomen, acute scrotum, renal failure). Whether or not to admit the patient to the hospital for observation and monitoring depends on the practice of the admitting pediatrician and his or her preference. Further Outpatient Care In all patients, urinalysis and blood pressure monitoring to evaluate for renal involvement should be continued for up to 6 months after presentation, even if initial urinalysis results are normal. Complications Henoch-Schönlein purpura can involve nearly every organ system. GI complications include hydrops of the gallbladder, pancreatitis, and GI bleeding. Surgical complications include intussusception, bowel infarction, and perforation. Overall, 5% of patients develop end-stage renal disease (ESRD). Other potential complications include the following:
Headache
Irritability
Fever
Pulmonary hemorrhage
CNS bleeding
Scrotal edema
Pain Prognosis Most patients have complete resolution of symptoms within 8 weeks. Up to half of all affected patients will have at least 1 recurrence. Younger patients usually have a better prognosis than older patients. As many as 15% of patients may have long-term renal insufficiency, but less than 1% will have end-stage renal disease. Patients with a normal urinalysis at 6 months and without prior renal involvement have not gone on to develop kidney problems. [4]
developing hypertension and proteinuria during pregnancy.
Most common hereditary bleeding disorder; autosomal dominant, but more females affected Normal situation—vWF adheres to subendothelial matrix, and platelets then adhere to this and become activated; also serves as carrier protein for factor VIII Clinical presentation—mucocutaneous bleeding (excessive bruising, epistaxis, menorrhagia, postoperative bleeding) Labs—increased bleeding time and PTT Quantitative assay for vWFAg, vWF activity (ristocetin cofactor activity), plasma factor VIII, determination of vWF structure and platelet count Treatment—need to increase the level of vWF and factor VIII o Most with type 1 DDAVP induces release of vWF o For types 2 or 3 need replacement → plasma-derived vWF-containing concentrates with factor VIII Von Willebrand Disease Although referred to as a single disease, von Willebrand disease (vWD) is in fact a family of bleeding disorders caused by an abnormality of the von Willebrand factor (vWF). vWD is the most common hereditary bleeding disorder. First described by Erik Adolf von Willebrand in 1926, vWD is characterized by a lifelong tendency toward easy bruising, frequent epistaxis, and menorrhagia. Pathophysiology: vWD is due to an abnormality, either quantitative or qualitative, of the vWF, which is a large multimeric glycoprotein that functions as the carrier protein for factor VIII (FVIII). vWF also is required for normal platelet adhesion. As such, vWF functions in both primary (involving platelet adhesion) and secondary (involving FVIII) hemostasis. vWD can be classified into 3 main types, of which 70-80% are considered to be type 1. 1. Type 1 vWD is characterized by a partial quantitative decrease of qualitatively normal vWF and FVIII. 2. vWD type 2 is a variant of the disease with primarily qualitative defects of vWF. 3.
type 3 vWD is characterized by marked deficiencies of both vWF and FVIIIc in the plasma, the absence of vWF from both platelets and endothelial cells, and a lack of the secondary transfusion response and the response to DDAVP
Frequency: Prevalence worldwide is estimated at 0.9-1.3%. Sex: vWD affects males and females in equal numbers. History: Many children with vWD are asymptomatic and are diagnosed as a result of a positive family history or during routine preoperative screening (eg, prolonged bleeding time). Importantly, remember that a wide variation in clinical manifestations exists, even for members of the same family. The history may reveal the following: Increased or easy bruising Recurrent epistaxis Menorrhagia Postoperative bleeding (particularly after tonsillectomy or dental extractions) Family history of a bleeding diathesis Bleeding from wounds Gingival bleeding Postpartum bleeding Medical Care: Minor bleeding problems, such as bruising or a brief nosebleed, may not require specific treatment. For more serious bleeding, medications that can raise the vWF level and, thereby, limit bleeding are available. The goal of therapy is to correct the defect in platelet adhesiveness (by raising the level of effective vWF) and the defect in blood coagulation (by raising the FVIII level). In recent years, desmopressin (1-deamine-8-D-arginine vasopressin, DDAVP) has become a mainstay of therapy for most patients with mild vWD.
For patients with vWF who do not respond to desmopressin, and for individuals with the rare types 2B or 3 vWD, plasma-derived Factor VIII (FVIII) concentrates that contain vWF in high molecular weight can be used. Pediatric Dose 20-50 U/kg; base the dose on the weight of the patient, the baseline FVIII level, and the severity of the bleeding.
85% are A and 15% B; no racial or ethnic predisposition X-linked Clot formation is delayed and not robust → slowing of rate of clot formation With crawling and walking—easy bruising Hallmark is hemarthroses—earliest in ankles; in older child, knees and elbows
vague groin pain and hypovolemic shock Vital structure bleeding—life-threatening Labs
2× to 3× increase in PTT (all others normal) Correction with mixing studies Specific assay confirms: o Ratio of VIII:vWF sometimes used to diagnose carrier state o Normal platelets, PT, bleeding time, and vW Factor Treatment Replace specific factor Prophylaxis now recommended for young children with severe bleeding (intravenous via a central line every 2–3 days); prevents chronic joint disease
For mild bleed—patient’s endogenous factor can be released with desmopressin (may use intranasal form) Avoid antiplatelet and aspirin medications DDAVP increases factor VIII levels in mild disease .
of clotting factor VIII (F VIII) and factor IX (F IX), respectively. They account for 90-95% of severe congenital coagulation deficiencies. The 2 disorders are considered together because of their similar clinical pictures and similar patterns of inheritance. Hemophilia is one of the oldest described genetic diseases. An inherited bleeding disorder in males was recognized in Talmudic records of the second century. The modern history of hemophilia began in 1803 with the description of hemophilic kindred by John Otto, followed by the first review of hemophilia by Nasse in 1820. Wright demonstrated evidence of laboratory defects in blood clotting in 1893; however, FVIII was not identified until 1937 when Patek and Taylor isolated a clotting factor from the blood, which they called antihemophilia factor (AHF). A bioassay of FVIII was introduced in 1950. Pathophysiology: F VIII and F IX circulate in an inactive form. When activated, these 2 factors cooperate to cleave and activate factor X, a key enzyme that controls the conversion of fibrinogen to fibrin. Therefore, the lack of either of these factors may significantly alter clot formation and clinical bleeding. Frequency: Hemophilia has a worldwide distribution. Sex: Both Hemophilia A and B are X-linked recessive disorders; therefore, they affect males almost exclusively. Physical: Only 30-50% of patients with severe hemophilia present with manifestations of neonatal bleeding (eg, after circumcision). Approximately 1-2% of neonates have intracranial hemorrhage. At birth, other neonates may present with severe hematoma and prolonged bleeding from the cord or umbilical area. After the immediate neonatal period, bleeding is uncommon in infants until they become toddlers. When trauma-related soft-tissue hemorrhage occurs, young children may have oral bleeding when their teeth are erupting. Bleeding from gum and tongue lacerations often is troublesome because the oozing of blood may continue for a long time despite local measures. As physical activity increases in
children, hemarthrosis and hematomas occur. Chronic arthropathy is a late complication of recurrent hemarthrosis in a target joint. Traumatic intracranial hemorrhage is a serious life-threatening complication that requires urgent diagnosis and intervention.
Hemophilia is classified according to the clinical severity as mild, moderate, or severe. Patients with severe disease usually have less than 1% factor activity. It is characterized by spontaneous hemarthrosis and soft tissue bleeding in the absence of precipitating trauma. Patients with moderate disease have 1-5% factor activity and bleed with minimal trauma. Patients with mild hemophilia have more than 5% FVIII activity and bleed only after significant trauma or surgery. Lab Studies: Usually, the activated partial thromboplastin time (aPTT) is prolonged. Bleeding times, prothrombin times, and platelet counts are normal. The diagnosis is based on functional assay results for FVIII and FIX. It is usual to also measure von Willebrand factor which, when combined with low factor VIII, may indicate vWF deficiency as the primary diagnosis. TREATMENT Ambulatory replacement therapy for bleeding episodes is essential for preventing chronic arthropathy and deformities. Home treatment and infusion by the family or patient is possible in most cases. Prompt and appropriate treatment of hemorrhage is important to prevent long-term complications and disability. For most mild hemorrhages, dose calculations are directed toward achieving an FVIII activity level of 30-40% or FIX activity levels of 30% and clotting factor activity of at least 50% in severe bleeds (eg, major dental surgery, major surgery or trauma), and 80-100% activity in life-threatening hemorrhage. Hospitalization is reserved for severe or life-threatening bleeds, such as large soft tissue bleeds; retroperitoneal hemorrhage; and hemorrhage related to head injury, surgery, or dental work. Patients are treated with prophylaxis or intermittent therapy (demand) for bleeding events. Prophylaxis has been shown in many studies to prevent or at least reduce the progression of damage to target sites, such as joints. In most countries with access to recombinant product, prophylaxis is primary recommended beginning as early as 1 year of age and continuing into adolescence. A cost benefit analysis indicates that this approach reduces overall factor use and significantly reduces morbidity. In situations in which this is not feasible, secondary prophylaxis, ie, therapy after a target joint has been established to prevent worsening of the joint, is instituted for a defined period.
Dosing is designed to maintain levels greater than 2% at the trough. This requires thrice weekly factor VIII or twice weekly factor IX to achieve. The treatment of hemophilia may involve the management of hemostasis, management of bleeding episodes, use of factor replacement products and medications, and treatment of patients with factor inhibitors.
therapy aimed at correcting the coagulation factor deficiency. Management of bleeding episodes Musculoskeletal bleeding Immobilization of the affected limb and the application of ice packs are helpful in diminishing swelling and pain. Early infusion upon the recognition of pain often may eliminate the need for a second infusion by preventing the inflammatory reaction in the joint. Cases in which treatment begins late or causes no response may require repeated infusions for 2-3 days. Do not aspirate hemarthroses unless they are severe and involve significant pain and synovial tension. Infusion must be aimed at maintaining a normal level of FVIII or FIX. Other interventions include elevation of the affected part to enhance venous return and, rarely, surgical decompression. Oral bleeding Oral bleeding from the frenulum and bleeding after tooth extractions are not uncommon. Bleeding is aggravated by the increased fibrinolytic activity of the saliva. Combine adequate replacement therapy with an antifibrinolytic agent (e- aminocaproic acid [EACA]) to neutralize the fibrinolytic activity in the oral cavity. GI bleeding Manage GI hemorrhage with repeated or continuous infusions to maintain nearly normal circulating levels of FVIII coagulant or FIX. Intracranial bleeding If CNS hemorrhage is suspected, immediately begin an infusion prior to radiologic confirmation. Maintain the factor level in the normal range for 7-10 days until a permanent clot is established.
therapy. Fresh frozen plasma and cryoprecipitate no longer are used in hemophilia A and B because of the lack of safe viral elimination and concerns regarding volume overload. Many plasma-derived FVIII concentrates are commercially available. Many recombinant FVIII concentrates are now available. The advantage of such products is the elimination of viral contamination. The effectiveness of these products appears comparable to that of plasma-derived concentrates. Concerns regarding higher incidences of the presence of inhibitor appear to be unwarranted.
compromise, iliopsoas bleeding, and preparation for surgery. Desmopressin vasopressin analog, or 1-deamino-8-D-arginine vasopressin (DDAVP) DDAVP is considered the treatment of choice for mild and moderate hemophilia A. It is not effective in the treatment of severe hemophilia. It stimulates a transient increase in plasma FVIII levels and results in sufficient hemostasis to stop a bleeding episode or to prepare patients for dental and minor surgical procedures. It can be administered intravenously at a dose of 0.3 mcg per kilogram of body weight. Its peak effect is observed in 30-60 minutes. Several doses of DDAVP may need to be infused every 12-24 hours before tachyphylaxis is observed. Treatment in patients with factor inhibitors Inhibitors to FVIII develop in 25-35% of children with severe hemophilia A, and inhibitors to FIX develop in 1-3% in children with hemophilia B. Inhibitors develop in relatively young children, usually within their first 50 exposures to FVIII. In the treatment of patients with low-titer FVIII inhibitors (<5 Bodansky units [BU]), bleeding can be controlled with human FVIII administered at standard or higher doses. In patients with high-titer inhibitors, immune tolerance induction (ITI) may be used to reduce or suppress the inhibitor. Therapeutic options include standard or activated prothrombin complex concentrate (PCC); recombinant factor VIIa (NovoSeven); and porcine FVIII (Hyate:C), if no cross- reacting antibodies are present. In patients with high-titer FIX inhibitors, ITI usually is less successful compared with that in patients with FVIII inhibitors. Therapeutic options are the same for these patients as for those with FVIII inhibitors, with the same doses. Patients with hemophilia B and inhibitors can have anaphylactic reactions to FIX infusions.
may be used (eg, 50-75 U/kg with high inhibitor titers); individualize doses according to clinical situation; may administer more frequently in special circumstances FIX Complex Dose 20-50 U/kg IV; individualize doses according to clinical situation; may administered higher doses and qd or more frequently in special cases Patients with FVIII: 75-100 U/kg IV q6-12h
treatment for bleeding episodes in patients with hemophilia A or B and inhibitors. Dose 90 mcg/kg IV q2h until hemostasis is achieved or treatment is judged inadequate; for patients with or without inhibitors; may use 35-120 mcg/kg, depending on the severity of the clinical situation; duration of administration has not been well established Hemophilia C Hemophilia C can be distinguished from hemophilias A (deficiency of factor VIII) and B (deficiency of factor IX) by the absence of bleeding into joints and muscles and by its occurrence in individuals of either sex. Unlike hemophilias A and B in which the bleeding tendency clearly is related to factor level, the bleeding risk in hemophilia C is not always influenced by the severity of the deficiency, especially in individuals with partial deficiency. This unpredictable nature of the disease makes it more difficult to manage than hemophilia A or B. Causes: Congenital deficiency of factor XI clotting activity is caused by mutations in the factor XI gene. Pathophysiology: The severity of the deficiency is based on plasma factor XIC (clotting) activity. Frequency: Hemophilia C has a high prevalence among Ashkenazi Jews (in Israel, estimated at 8%). Sex: The inheritance of factor XI is autosomal, affecting males and females equally. History: Bleeding after surgery or after injury is the usual presenting symptom in individuals prone to bleeding. The following presentations have been reported: Massive hemothorax Cerebral hemorrhage Subarachnoid hemorrhage Spinal epidural hematoma with the Brown-Sequard syndrome Hematuria and spontaneous hemarthrosis are rare. In women, menorrhagia is an important finding. Physical: Physical examination usually is normal except when bleeding occurs. Bruising may occur at unusual sites. The patient may have signs of pallor, fatigue, and tachycardia with excessive bleeding.
aPTT is prolonged in factor XI deficiency, whereas the PT and TT are normal. Genetic analysis for the mutation in factor XI is helpful in determining which mutation has caused the deficiency. Yüklə 1,02 Mb. Dostları ilə paylaş:
|