The Pediatric Page
Approach to the Child with a Bleeding Disorder - March 2006
Pediatricians frequently see patients who have increased bruising, nosebleeds or prolonged bleeding from circumcision or from tonsillectomy. These may or may not be manifestations of a bleeding disorder. Initial work-up always involves taking a careful bleeding history. The child’s age, sex, clinical presentation, past history and family history may suggest a diagnosis. Mucocutaneous bleeding (i.e. petechiae, purpura, epistaxis, subconjunctival hemorrhages) is characteristic of platelet and blood vessel disorders. Soft tissue, muscle or joint bleeding is suggestive of hemophilia. Early childhood bleeding occurs most frequently in congenital disorders, while later presentation is more likely associated with acquired disorders. A child who is clinically ill may have disseminated intravascular coagulation (DIC) and sepsis.
A complete history is followed by laboratory evaluation. Initial laboratory evaluation includes a CBC, PT/PTT, and a 1:1 mixing study (see algorithm [PDF, 24KB]). The 1:1 mixing study evaluates whether the problem results from a factor deficiency or inhibitor. I do not routinely obtain bleeding times because of the difficulty in interpretation.
A low platelet count with an otherwise normal CBC, normal PT/PTT and large platelets on the peripheral smear points to idiopathic thrombocytopenic purpura (ITP). The peak age of occurrence of acute ITP is at 2-4 years. ITP is a disorder involving a patient’s antibody production, typically IgG, against the platelet antigen GPIIb/IIIa. The patient may have a history of a viral syndrome 10-14 days prior to the presentation of bleeding symptoms. The bleeding symptoms include increased bruising, petechiae and mucosal bleeding, such as epistaxis, gum bleeding or subconjunctival hemorrhages. The child is typically otherwise clinically well. If not, then other concerning diagnoses presenting with isolated thrombocytopenia must be evaluated. These include DIC, leukemia, hemolytic uremic syndrome, Wiskott-Aldrich syndrome or infection (HIV, EBV, CMV).
Once diagnosis is established based on clinical picture and laboratory evaluation, then treatment to prevent intracranial hemorrhage and stop active bleeding may be initiated. Treatment is not indicated for platelet counts greater than 10,000 with no active bleeding. If the platelet count is less than 10,000 or if the patient has active bleeding, particularly from the mucous membranes, then we start with IVIG, 1gm/kg for 1-2 days. Other therapies may include Win-rho (anti-Rh antibody) or steroids (prednisone or dexamethasone). Our practice is to perform bone marrow aspirate and biopsy prior to initiating steroids, due to a very small risk of steroids masking an early leukemia. If isolated thrombocytopenia persists beyond 6 months, the patient has chronic ITP. We search for a possible underlying cause of the thrombocytopenia, such as an autoimmune disorder, IgA deficiency, HIV, EBV or CMV. Splenectomy or rituximab (anti CD-20 monoclonal antibody) is discussed with the family, depending on the age of the patient and baseline platelet counts.
If the platelet count is normal and the PT is normal and the PTT is mildly elevated or normal, then von Willebrand disease (vWD) is a likely diagnosis. Once von Willebrand disease is suspected, referral to a hematologist is warranted. vWD is the most common inherited bleeding disorder, with an estimated prevalence of 1 in 100. Von Willebrand factor is best known for its role as a carrier protein for factor VIII in fibrin clot formation. There are three major types. Types 1 and 3 are quantitative deficiencies of vW factor, while type 2 defects are qualitative. Type 1 is the most common and has a wide range of bleeding presentations. Many patients are never diagnosed if their disease is mild enough. Since it is most commonly inherited as an autosomal dominant disorder, a family history of increased bleeding is frequently elicited. VWD must be suspected in any patient who has frequent and prolonged nosebleeds, easy bruising, prolonged bleeding from mucosal surgery or dental procedures, or heavy menses. The patient may even have an iron deficiency anemia resulting from their chronic bleeding symptoms.
Laboratory evaluation may be initiated if the bleeding history appears to be consistent with vWD, and includes a vW factor antigen level, ristocetin cofactor activity (vW factor activity level) and factor VIII activity level. All three values are low in type 1 disease and nonexistent in type 3 disease. Type 2 subtypes usually have normal vW antigen levels and low vW activity and Factor VIII activity. Unfortunately, other factors such as illness, anxiety/crying, recent bleeding, medications and age of the specimen all affect outcome of the laboratory values, giving falsely high and falsely low values. We therefore recommend repeating the studies as confirmation of initial results. Type 1 vWD is treated with DDAVP, which releases stored vW factor from reticuloendothelial cells. Each patient must undergo a DDAVP challenge to establish their responsiveness to the medication prior to using it as a therapy to prevent or halt bleeding. If the patient is not responsive to DDAVP, then Humate-P, a factor VIII concentrate with vW factor, may be given. Therapy is administered prior to surgical and dental procedures with bleeding risk and whenever there is uncontrolled bleeding.
Joint and Muscular Bleeding
Hemophilia A and B are X-linked congenital bleeding disorders affecting male infants, usually diagnosed through family history and prolonged PTT. Undiagnosed hemophilia may cause severe bleeding with circumcision. It can also result in significant ecchymosis with minimal trauma or joint and muscle bleeding, usually by the end of infancy or in early childhood. These children have a significantly prolonged PTT and normal PT. Diagnosis is made through measurement of Factor VIII activity for Hemophilia A and Factor IX activity for Hemophilia B. It is important to remember that the PTT is prolonged normally during first several days of life. Rarely, female children can show hemophilia-like bleeding symptoms due to low factor level resulting from carrier state with incomplete lyonization. Treatment involves recombinant factor replacement with bleeding episodes.
Elevated PTT without History of Bleeding
Frequently we see elevated PTT in otherwise normal children undergoing routine coagulation screening prior to elective surgery. This usually is attributed to transient antiphospholipid antibody from a previous or current infection. Even though it may never result in active bleeding or increased thromboembolism, elective surgery needs to be delayed until a full work up is completed. The transient antiphospholipid antibody is confirmed by lack of the correction of PTT with a 1:1 mixing study, a positive PNP (platelet neutralizing protein) and a dRVVT (dilute Russell Viper Venom Time). It normally disappears within 4 to 6 weeks after resolution of the infection.
This information provided by Louise Lo, M.D.
Division of Pediatric Hematology & Oncology