Approach to the child with bleeding symptoms
- Donald L Yee, MD
Donald L Yee, MD
- Associate Professor of Pediatrics
- Baylor College of Medicine
Pediatricians will be confronted with an infant, child, or adolescent either with overt bruising or bleeding or with a history of increased bleeding sometime during their busy clinical practice. This topic review will discuss the approach to such patients, including selection of the most appropriate laboratory tests to arrive at a working diagnosis. An approach to the adult with bleeding symptoms and neonatal thrombocytopenia are discussed separately. (See "Approach to the adult patient with a bleeding diathesis" and "Causes of neonatal thrombocytopenia".)
Clinical evaluation of a patient with bleeding symptoms begins with taking a careful history, taking into account the child's age, sex, clinical presentation, past history, and family history.
Bleeding history — In assessing the patient's bleeding history, it is important to ask about prior bleeding episodes and to characterize the type of bleeding (table 1):
●Bleeding into the skin and mucous membranes is characteristic of disorders of platelets and blood vessels (purpuric disorders) and may be manifested as petechiae and/or ecchymoses.
●Bleeding into soft tissue, muscle, and joints suggests the presence of hemophilia or other disorders of coagulation proteins.
- Khair K, Liesner R. Bruising and bleeding in infants and children--a practical approach. Br J Haematol 2006; 133:221.
- Hsieh L, Nugent D. Factor XIII deficiency. Haemophilia 2008; 14:1190.
- Plummer ES, Crary SE, Buchanan GR. Prominent forehead hematomas ("goose-eggs") as an initial manifestation of hemophilia. J Pediatr 2013; 163:1781.
- Sadowitz D, Souid AK, Terndrup TE. Idiopathic thrombocytopenic purpura in children: recognition and management. Pediatr Emerg Care 1996; 12:222.
- Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011; 117:4190.
- Vesely S, Buchanan GR, Cohen A, et al. Self-reported diagnostic and management strategies in childhood idiopathic thrombocytopenic purpura: results of a survey of practicing pediatric hematology/oncology specialists. J Pediatr Hematol Oncol 2000; 22:55.
- Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med 2002; 346:995.
- Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115:168.
- Blanchette V, Bolton-Maggs P. Childhood immune thrombocytopenic purpura: diagnosis and management. Hematol Oncol Clin North Am 2010; 24:249.
- Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand's disease. Blood 1987; 69:454.
- Hoyer LW. Hemophilia A. N Engl J Med 1994; 330:38.
- Haitjema T, Westermann CJ, Overtoom TT, et al. Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease): new insights in pathogenesis, complications, and treatment. Arch Intern Med 1996; 156:714.
- Triplett DA, Brandt JT, Batard MA, et al. Hereditary factor VII deficiency: heterogeneity defined by combined functional and immunochemical analysis. Blood 1985; 66:1284.
- Ghauri AJ, Abbott J, Shah P, Gardiner P. Bleeding risks associated with herbal medicine in children. Glob Adv Health Med 2014; 3:5.
- World Federation of Hemophilia. www.wfh.org/en/page.aspx?pid=639 (Accessed on March 06, 2016).
- Monagle P, Barnes C, Ignjatovic V, et al. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost 2006; 95:362.
- Hillman C, Lusher JM. Tests of blood coagulation technical points of clinical relevance. In: Acquired Bleeding Disorders in Children, Lusher JM, Barhart MI (Eds), Masson, New York 1981. Vol 2, p.107.
- Payne BA, Pierre RV. Pseudothrombocytopenia: a laboratory artifact with potentially serious consequences. Mayo Clin Proc 1984; 59:123.
- Lippi U, Schinella M, Nicoli M, et al. EDTA-induced platelet aggregation can be avoided by a new anticoagulant also suitable for automated complete blood count. Haematologica 1990; 75:38.
- Lossing TS, Kasper CK, Feinstein DI. Detection of factor VIII inhibitors with the partial thromboplastin time. Blood 1977; 49:793.
- Exner T, Triplett DA, Taberner D, Machin SJ. Guidelines for testing and revised criteria for lupus anticoagulants. SSC Subcommittee for the Standardization of Lupus Anticoagulants. Thromb Haemost 1991; 65:320.
- Greenberg CS, Devine DV, McCrae KM. Measurement of plasma fibrin D-dimer levels with the use of a monoclonal antibody coupled to latex beads. Am J Clin Pathol 1987; 87:94.
- Lind SE. The bleeding time does not predict surgical bleeding. Blood 1991; 77:2547.
- Mammen EF, Comp PC, Gosselin R, et al. PFA-100 system: a new method for assessment of platelet dysfunction. Semin Thromb Hemost 1998; 24:195.
- Favaloro EJ, Facey D, Henniker A. Use of a novel platelet function analyzer (PFA-100) with high sensitivity to disturbances in von Willebrand factor to screen for von Willebrand's disease and other disorders. Am J Hematol 1999; 62:165.
- Dean JA, Blanchette VS, Carcao MD, et al. von Willebrand disease in a pediatric-based population--comparison of type 1 diagnostic criteria and use of the PFA-100 and a von Willebrand factor/collagen-binding assay. Thromb Haemost 2000; 84:401.
- Podda GM, Bucciarelli P, Lussana F, et al. Usefulness of PFA-100 testing in the diagnostic screening of patients with suspected abnormalities of hemostasis: comparison with the bleeding time. J Thromb Haemost 2007; 5:2393.
- Nichols WL, Hultin MB, James AH, et al. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia 2008; 14:171.
- Hayward CP, Harrison P, Cattaneo M, et al. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function. J Thromb Haemost 2006; 4:312.
- Montgomery RR, Gill JC, Scott JP. Hemophilia and von Willebrand's Disease. In: Nathan and Oski's Hematology of Infancy and Childhood, 6th, Nathan DG, Orkin SH, Ginsberg D, Look AT (Eds), WB Saunders, Philadelphia 2003. p.1547.
- Gomez K, Bolton-Maggs P. Factor XI deficiency. Haemophilia 2008; 14:1183.
- Perry DJ. Factor VII Deficiency. Br J Haematol 2002; 118:689.
- Bajaj SP, Rapaport SI, Barclay S, Herbst KD. Acquired hypoprothrombinemia due to non-neutralizing antibodies to prothrombin: mechanism and management. Blood 1985; 65:1538.
- Furie B, Greene E, Furie BC. Syndrome of acquired factor X deficiency and systemic amyloidosis in vivo studies of the metabolic fate of factor X. N Engl J Med 1977; 297:81.
- Bomgaars L, Carberry K, Fraser C, et al. Development of factor V and thrombin inhibitors in children following bovine thrombin exposure during cardiac surgery: a report of three cases. Congenit Heart Dis 2010; 5:303.
- Chua JD, Friedenberg WR. Superwarfarin poisoning. Arch Intern Med 1998; 158:1929.
- Park CH, Seo JY, Kim HJ, et al. A diagnostic challenge: mild hemophilia B with normal activated partial thromboplastin time. Blood Coagul Fibrinolysis 2010; 21:368.
- Duncan EM, Rodgers SE, McRae SJ. Diagnostic testing for mild hemophilia a in patients with discrepant one-stage, two-stage, and chromogenic factor VIII:C assays. Semin Thromb Hemost 2013; 39:272.
- Hayward CP. Diagnostic approach to platelet function disorders. Transfus Apher Sci 2008; 38:65.
- Israels SJ, Kahr WH, Blanchette VS, et al. Platelet disorders in children: A diagnostic approach. Pediatr Blood Cancer 2011; 56:975.
- Phillips DR, Agin PP. Platelet membrane defects in Glanzmann's thrombasthenia. Evidence for decreased amounts of two major glycoproteins. J Clin Invest 1977; 60:535.
- Nurden AT. Qualitative disorders of platelets and megakaryocytes. J Thromb Haemost 2005; 3:1773.
- Warrier I, Lusher JM. Congenital thrombocytopenias. Curr Opin Hematol 1995; 2:395.
- Bleeding history
- Clinical features
- Family history
- LABORATORY EVALUATION
- Initial testing
- - Platelet count and the peripheral smear
- - Prothrombin time (PT)
- - Activated partial thromboplastin time (aPTT)
- - Fibrinogen
- Second tier testing
- - Thrombin time and reptilase time
- - Tests for specific factor deficiencies and inhibitors
- - Antiphospholipid antibodies
- - Clot solubility in urea and factor XIII activity testing
- - Tests for fibrinolysis
- - Bleeding time and PFA-100
- DIAGNOSTIC APPROACH
- Abnormal initial testing
- - Pancytopenia
- - Thrombocytopenia
- - Normal PT and prolonged aPTT
- - Prolonged PT and normal aPTT
- - Prolonged PT and aPTT
- Well child
- Sick child
- Normal initial testing
- - Von Willebrand disease
- - Some cases of hemophilia
- - Factor XIII deficiency and other fibrinolytic disorders
- - Platelet function disorders
- - Vascular purpuras
- - Undetermined etiologies
- SUMMARY AND RECOMMENDATIONS