Abnormal bleeding in children J Kiwanuka

GENERAL INTRODUCTION

Introduction Disambiguation: abnormal bleeding (a presentation) vs. bleeding disorder (a conclusion/diagnosis) Bleeding can be normal – following (the right amount of) trauma – Stopping spontaneously within the expected time Abnormal bleeding – Unprovoked – Too prolonged – Excessive

Introduction Bleeding and bruising, external and internal – therefore, bleeding and bruising disorders Congenital bleeding disorders may be undiagnosed until adulthood Haemostatic function may need to be assessed in the context of (apparently normal) traumatic bleeding Not all bleeding episodes suggest a generalized bleeding disorder

Scope Basic physiology of haemostasis Common clinical presentations of bleeding disorders The differential diagnosis Approach to diagnostic evaluation Summary of management options

DIFFERENTIAL DIAGNOSIS

Haemostasis – summary of factors Normal vasculature – structure, resistance, contractility Normal platelet activity – number and quality (function) Adequate coagulation system – clotting factors Clot stability – factors Balance between coagulation and anticoagulation

Classification INHERITEDACQUIRED PRIMARY o Vascular defects o Platelet defects o Platelet-vessel interaction defects SECONDARY o Clotting factor defects

Primary haemostatis defects - Platelets Quantitative - thrombocytopenia – Immune thrombocytopenic purpura (ITP) (and neonatal alloimmune thrombocytopenia) – Hemolytic uremic syndrome (HUS) – Thrombotic thrombocytopenic purpura (TTP) – Medications e.g. Heparin, bone marrow suppressive drugs – Marrow failure (leukemia, aplastic anemia) – Platelet sequestration, consumption and dilution e.g. Kasabach-Merritt, hypersplenism, FBs, etc

Primary haemostatis defects - Platelets More rare stuff – Congenital amegakaryocytic thrombocytopenia – Thrombocytopenia absent radii – Wiskott-Aldrich syndrome

Primary haemostatis defects - Platelets Qualitative (poor platelet function) – with or without associated thrombocytopenia – Inherited platelet aggregation defect Glanzmann thromboasthenia – normal platelet count Bernard-Soulier disease – platelets usually decreased Storage pool defects – normal platelet count – Drug effect: e.g. Aspirin, NSAIDs, valproate – Systemic conditions e.g. Liver failure, uraemia

Secondary haemostatis defects Congenital factor deficiency – Hemophilia A (factor VIII deficiency) and B (factor IX deficiency) – von Willebrand disease von Willebrand factor is a cofactor for platelet adhesion and a carrier protein for factor VIII (therefore affects both primary and secondary haemostasis) vW disease not one homogenous entity – 3 types – Other factor deficiencies: V, XI, XII, XIII (generally very rare)

Secondary haemostatis defects Acquired factor deficiency – Vitamin K deficiency – decreased synthesis of factors II, VII, IX and X – Liver failure – decreased synthesis of clotting factors (but also often causes some thrombocytopenia) – DIC – consumption of clotting factors (and platelets) – Circulating inhibitors and Antiphospholipid antibody

MANAGEMENT

Context Previously undiagnosed bleeding disorder vs. the patient with a known (congenital) defect External bleeding vs. internal and bruising Active, life-threatening bleeding vs. signs of abnormal bleeding that is not severe Suspected CNS bleeding Long-term maintenance and preventive therapy Planned interventions and surgery

General principles Control bleeding – pressure, compression Resuscitation – Check and ensure patent airway, breathing – Evaluate for shock etc – Volume expansion using normal saline – Blood transfusion If the patient has a known specific haemostatic defect, specific treatment should be administered as soon as possible

General principles Patients with established haemophilia should carry an alert bracelet bearing their diagnosis Patients with known severe haemophilia need to be treated promptly whenever CNS bleeding is suspected or possible, e.g. after head trauma, even if there is no obvious sign of bleeding. – Treatment should be administered prior to imaging studies

General principles Patients with on-going disorders are best managed by a specialized unit – Including supervised home care Avoid intramuscular (IM) injections Advice on limitation of severe contact sports if not on adequate replacement therapy

Products Fresh frozen plasma – Use for disorders for which factor concentrates are not available Cryoprecipitate – Use for afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, factor XIII deficiency in situations where FFP is contraindicated due to volume overload concerns – has a higher risk of HIV and/or hepatitis C transmission relative to FFP Desmopressin (DDAVP) – Increased release of vWF and factor VIII

Products Virally inactivated and recombinant factor concentrates – Wherever possible, recombinant products should be used because these have lower treatment risks Fibrogammin P (FXIII concentrate) Fibrin glue – May be used for small to moderate lacerations and dental extraction – but this should be done with caution, as it may lead to the development of thrombin inhibitors.

Products Amicar (epsilon-aminocaproic acid): – an anti-fibrinolytic agent that helps stabilize the fibrin clot. – Most useful for mucous membrane bleeding, especially nasal, oral, and gastrointestinal tract bleeding, where enzymes contained in secretions can accelerate clot degradation. – Can be administered orally or parenterally and should be given every six hours for 7-10 days.

Products Platelet concentrates – Avoid platelet transfusions, as these are likely to be destroyed by the underlying immune process – if CNS bleeding or occurs continuous platelet infusion should be considered. I.V. Immunoglobulin (IVIG) Corticosteroids Plasmapheresis Rituximab