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Abnormal Bleeding, Pediatric

Basics

Description

- Thrombocytopenia: increased destruction - Idiopathic thrombocytopenia - Neonatal alloimmune thrombocytopenia - Maternal autoimmune thrombocytopenia - Drug-induced (heparin, sulfonamides, digoxin, chloroquine) - Disseminated intravascular coagulation - Infection: viral, bacterial, fungal, rickettsial - Microangiopathic process (e.g., thrombotic thrombocytopenic purpura or hemolytic uremic syndrome) - Kasabach-Merritt syndrome

- Thrombocytopenia: sequestration - Platelet function disorders - Storage pool disorders (e.g., dense granule deficiency, Hermansky-Pudlak or Chediak-Higashi syndrome) - Platelet receptor abnormalities (e.g., Glanzmann thrombasthenia, adenosine 5"²-diphosphate receptor defect) - Drugs (e.g., aspirin, NSAIDs, guaifenesin, antihistamines, phenothiazines, anticonvulsants) - Uremia - Paraproteinemia

- Prolongation of PT and aPTT - Liver disease, severe - Disseminated intravascular coagulation - Severe vitamin K deficiency - Hemorrhagic disease of the newborn - Deficiency of factors II, V, or X or fibrinogen - Dysfibrinogenemia - Hypoprothrombinemia associated with a lupus anticoagulant

- Normal screening (PT, aPTT) laboratory tests - Von Willebrand disease - Factor XIII deficiency - Alpha-2-antiplasmin deficiency - Plasminogen activator inhibitor-I deficiency

- Vessel wall disorders - Congenital - Hereditary hemorrhagic telangiectasia - Ehlers-Danlos syndrome - Marfan syndrome

- Phase 1 - Includes a thorough history and physical exam - Familial history specifically of bleeding or consanguinity - Standard screening laboratory tests include PT, aPTT, and platelet count.

- Test: Phase 3: discriminating laboratory studies for abnormal phase 1 or 2 tests - When thrombocytopenia is present: - Inspection of blood smear - Mean platelet volume (may be normal or elevated in destructive causes, elevated in congenital macrothrombocytopenias, low in Wiskott-Aldrich syndrome) - Bone marrow aspiration (rarely necessary)

- Prolonged PT and aPTT - Factor assays: II (prothrombin), V, X, and fibrinogen - Potential other causes: disseminated intravascular coagulation, liver disease, and fibrinogen disorders, as described previously - Vitamin K deficiency, moderate to severe

Abnormal bleeding may present as

  • Frequent or significant mucocutaneous bleeding (epistaxis, bruising, gum bleeding, or menorrhagia)
  • Bleeding in unusual sites such as muscles, joints, or internal organs
  • Excessive postsurgical bleeding

Etiology

Abnormal bleeding can be the result of a coagulation factor deficiency, an acquired or congenital disorder of platelet number or function, or inherited or acquired collagen vascular disorders.

Diagnosis

Differential Diagnosis

Platelet disorders may be quantitative or qualitative, collagen vascular disorders can be acquired or inherited, and disorders of coagulation factors can be congenital or acquired.

  • Thrombocytopenia: defective productionCongenital/geneticThrombocytopenia with absent radii syndromeAmegakaryocytic thrombocytopeniaFanconi anemiaMetabolic disordersWiskott-Aldrich syndromeBernard-Soulier syndromeOther rare familial syndromes (e.g., MYH9-related disorders, RUNX1 mutations)AcquiredAplastic anemiaDrug-associated marrow suppressionVirus-associated marrow suppressionChemotherapyRadiation injuryNutritional deficiencies (e.g., vitamin B12 and folate)Marrow infiltrationNeoplasia (e.g., leukemia, solid tumor)HistiocytosisOsteopetrosisMyelofibrosisHemophagocytic syndromesStorage diseases
  • Thrombocytopenia: increased destructionIdiopathic thrombocytopeniaNeonatal alloimmune thrombocytopeniaMaternal autoimmune thrombocytopeniaDrug-induced (heparin, sulfonamides, digoxin, chloroquine)Disseminated intravascular coagulationInfection: viral, bacterial, fungal, rickettsialMicroangiopathic process (e.g., thrombotic thrombocytopenic purpura or hemolytic uremic syndrome)Kasabach-Merritt syndrome
  • Thrombocytopenia: sequestration
  • Platelet function disordersStorage pool disorders (e.g., dense granule deficiency, Hermansky-Pudlak or Chediak-Higashi syndrome)Platelet receptor abnormalities (e.g., Glanzmann thrombasthenia, adenosine 5"²-diphosphate receptor defect)Drugs (e.g., aspirin, NSAIDs, guaifenesin, antihistamines, phenothiazines, anticonvulsants)UremiaParaproteinemia
  • Coagulation disordersProlongation of activated partial thromboplastin time (aPTT)Deficiency of factors VIII, IX, XI, or XII; prekallikrein; or high-molecular-weight kininogenAcquired inhibitor or lupus anticoagulantProlongation of prothrombin time (PT)Deficiency of factor VIIMild vitamin K deficiencyLiver disease, mild to moderateProlongation of PT and aPTTLiver disease, severeDisseminated intravascular coagulationSevere vitamin K deficiencyHemorrhagic disease of the newbornDeficiency of factors II, V, or X or fibrinogenDysfibrinogenemiaHypoprothrombinemia associated with a lupus anticoagulantNormal screening (PT, aPTT) laboratory testsVon Willebrand diseaseFactor XIII deficiencyAlpha-2-antiplasmin deficiencyPlasminogen activator inhibitor-I deficiency
  • Vessel wall disordersCongenitalHereditary hemorrhagic telangiectasiaEhlers-Danlos syndromeMarfan syndromeAcquiredVasculitis (systemic lupus erythematosus, Henoch-Sch ¶nlein purpura, and others)Scurvy (vitamin C deficiency)

Alert

Always consider nonaccidental injury as a cause of increased bruising.

Approach to the Patient

  • Phase 1Includes a thorough history and physical examFamilial history specifically of bleeding or consanguinityStandard screening laboratory tests include PT, aPTT, and platelet count.
  • Phase 2If a bleeding disorder is suspected but the initial screening tests are negative, testing for von Willebrand disease, qualitative platelet disorders, dysfibrinogenemia, or factor XIII deficiency is warranted.
  • Phase 3Any abnormal screening tests need further evaluation with additional testing to define the specific disorder (e.g., factor assays).

History

By taking into account the patient's age, sex, clinical presentation, past medical history, and family history, the most likely cause of bleeding can be usually determined.

  • Hemophilia is X-linked, most common in males.
  • A family history of bleeding suggests an inherited bleeding disorder.
  • Bleeding in unusual places without significant trauma (intracranial, joints) indicates a significant bleeding disorder.
  • Persistent palpable bruising is highly suggestive of a bleeding disorder.
  • Several surgeries without bleeding makes an inherited bleeding disorder less likely.
  • Mucocutaneous bleeding (gum bleeding, bruises, epistaxis, recurrent petechiae, menorrhagia) may indicate thrombocytopenia, a platelet disorder, or von Willebrand disease.
  • The use of aspirin and NSAIDs (e.g., ibuprofen) negatively affect platelet function and result in an acquired bleeding disorder.

Physical Exam

  • Children with bleeding disorders are more likely to have large bruises (>5 cm), palpable bruises, and bruises on more than one body part.
  • Uncommon sites for bruising for all ages include the back, buttocks, arms, and abdomen.
  • Finding: Petechiae in skin and mucous membranes?
  • Significance: Disorder of platelet number or function, von Willebrand disease, or vasculitis
  • Finding: Bruises in unusual places?
  • Significance: Possible platelet disorder or von Willebrand disease
  • Finding: Large bruises or palpable bruises?
  • Significance: Coagulation deficiencies, severe platelet disorders, or von Willebrand disease
  • Finding: Delayed wound healing?
  • Significance: Factor XIII deficiency or dysfibrinogenemia
  • Finding: Purpura localized to lower body (buttocks, legs, ankles)?
  • Significance: Henoch-Sch ¶nlein purpura

Diagnostic Tests & Interpretation

  • The aPTT may be extremely prolonged in patients with deficiencies of the contact factors (prekallikrein, high molecular weight kininogen, factor XII). These deficiencies do not result in bleeding.
  • Improper specimen collection including heparin contamination or underfilling of the specimen tube can result in artificially prolonged clotting times.
  • Test: Phase 1: initial laboratory screeningPlatelet countPT and aPTT
  • Test: Phase 2
  • Test for von Willebrand diseaseFactor VIII:CVon Willebrand factor antigen (VIIIR:Ag)Von Willebrand factor activity (ristocetin cofactor)Von Willebrand factor multimeric analysis-only send after the diagnosis of von Willebrand disease has been establishedThrombin time and fibrinogen assay to screen for afibrinogenemia and dysfibrinogenemiaDefinitive platelet testing includes platelet aggregation and secretion studies with specific agonists.Factor XIII deficiency suspected: factor XIII assay (Urea clot lysis study is a screening test.)
  • Test: Phase 3: discriminating laboratory studies for abnormal phase 1 or 2 tests
  • When thrombocytopenia is present:Inspection of blood smearMean platelet volume (may be normal or elevated in destructive causes, elevated in congenital macrothrombocytopenias, low in Wiskott-Aldrich syndrome)Bone marrow aspiration (rarely necessary)
  • Prolonged aPTTInhibitor screen (50:50 mixing study of patient's and normal plasma)If aPTT fully corrects with mixing, this is consistent with a factor deficiency:Assess for specific factor deficiencies: factors VIII, IX, XI, or XII; prekallikrein; and high-molecular-weight kininogenIf partial or no correction after mixing study:Inhibitor is present.Confirmatory test for the presence of a lupus anticoagulant with a platelet-neutralizing procedure or dilute Russel viper venom time (DRVVT)
  • Prolonged PTInhibitor screen should also be considered for prolonged PT.Specific factor level (VII)
  • Prolonged PT and aPTTFactor assays: II (prothrombin), V, X, and fibrinogenPotential other causes: disseminated intravascular coagulation, liver disease, and fibrinogen disorders, as described previouslyVitamin K deficiency, moderate to severe

Alert

Pitfalls of testing:

  • PFA-100Low specificity and sensitivityAffected by medications (NSAIDs)Not recommended as a screening test
  • Bleeding timeProlonged when platelets <100,000/mm3Affected by medications such as aspirin, NSAIDs, antihistaminesDoes not correlate with bleeding riskHighly operator dependentNot recommended as a screening test
  • PT and aPTTNormal ranges are age-dependent.Polycythemia (hematocrit 65%) or underfilling of the specimen tube may result in a spuriously prolonged result.Heparin contamination results in a spuriously prolonged result.
  • Von Willebrand disease studiesValues fluctuate over time and may be periodically normal in affected individuals.May require repeated testing to make diagnosis

EMERGENCY CARE

  • Pressure, elevation, and ice are generally helpful for most bleeding disorders when active bleeding is present.
  • More definitive care is dictated by the nature of the underlying hemostatic defect:Platelet transfusions are useful in disorders of thrombocytopenia owing to decreased production and for intrinsic qualitative platelet disorders but not for immune platelet disorders.Frozen plasma should be used only in severe cases when the exact diagnosis is not readily available but a defect in coagulation is suspected.
  • Head injuries in patients with thrombocytopenia or hemophilia require immediate medical attention.

Treatment

General Measures

  • Pressure on wound
  • Elevation
  • Topical application of thrombin
  • Topical application of clot-activating polymers

Additional Reading

  • Buchanan GR. Bleeding signs in children with idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2003;25(Suppl 1):S42-S46. [View Abstract]
  • Khair K, Liesner R. Bruising and bleeding in infants and children: a practical approach. Br J Haematol. 2006;133(3):221-231. [View Abstract]
  • Koreth R, Weinert C, Weisdorf DJ, et al. Measurement of bleeding severity: a critical review. Transfusion. 2004;44(4):605-617. [View Abstract]
  • Lillicrap D, Nair SC, Srivastava A, et al. Laboratory issues in bleeding disorders. Haemophilia. 2006;12(Suppl 3):68-75. [View Abstract]
  • Sarnaik A, Kamat D, Kannikeswaran N. Diagnosis and management of bleeding disorder in a child. Clin Pediatr. 2010;49(5):422-431. [View Abstract]

Codes

ICD09

  • 286.9 Other and unspecified coagulation defects
  • 784.7 Epistaxis
  • 924.9 Contusion of unspecified site
  • 287.1 Qualitative platelet defects
  • 626.2 Excessive or frequent menstruation
  • 287.5 Thrombocytopenia, unspecified

ICD10

  • D68.9 Coagulation defect, unspecified
  • R04.0 Epistaxis
  • T14.8 Other injury of unspecified body region
  • D69.1 Qualitative platelet defects
  • D69.6 Thrombocytopenia, unspecified
  • N92.0 Excessive and frequent menstruation with regular cycle

SNOMED

  • 64779008 Blood coagulation disorder (disorder)
  • 12441001 Epistaxis (disorder)
  • 125667009 contusion (disorder)
  • 267532001 Qualitative platelet disorder (disorder)
  • 386692008 Menorrhagia (finding)
  • 302215000 Thrombocytopenic disorder (disorder)

FAQ

  • Q: What are the proper preoperative screening tests for bleeding disorders prior to elective surgery such as tonsillectomy?
  • A: A thorough personal history, familial history, and physical exam are by far the most important screening tests. A bleeding time or PFA-100 is not recommended. A CBC, PT, and aPTT are often requested by the surgeon, but normal results do not ensure that a bleeding complication will not occur. Overall, the sensitivity and specificity of these screening tests is poor.
  • Q: Bruising is a normal part of childhood. How does one know when bruising is "too much"¯?
  • A: Small bruises on boney prominences on the front of the body are common in children and probably reflect trauma rather than a bleeding disorder. Children with bleeding disorders are more likely to have large bruises (>5 cm), palpable (raised) bruises, and bruises on more than one body part. Uncommon sites for bruising for all ages include the back, buttocks, arms, and abdomen.