Coagulation Disorders
52
Evaluation of a child with bleeding or
abnormal coagulation screening tests
Meningococcus Purpura fulminans Varicella Pneumococcus Mild DIC Protein C, S or ATIII deficiency ? Child abuse Platelet dysfunction Variant VWD Mild hemophilia or carrier of hemophilia FXIII or mild FXI deficiency
VWD
Mild hemophilia A or carrier
FXI or XII deficiency Mild hemophilia B or carrier Prekallikrein or high-molecular weight kininogen deficiency VWD Hemophilia A or B Severe FXI deficiency
Abnormal PT + PTT Oral anticoagulants Liver disease Vitamin K deficiency Mild DIC FII, V, or X deficiency Only PT abnormal Early in oral anticogulant therapy
FVII deficiency
Abnormal PT, PTT, TT and thrombocytopenia
DIC
Severe liver disease
1:1 mix corrects 7 fibrinogen Dysfibrinogenemia Does not correct Reptilase normal:
Heparin
Reptilase time &: Fibrin split products
Lupus-like anticoagulant Heparin (confirm with & TT + normal reptilase time) Platelet count
History and physical examination 햲
Normal
Coagulation screen PT, PTT, TT
Decreased
(see ‘Evaluation of a child with thrombocytopenia’, p 54) Normal 햳
Acute illness Corrects
Abnormal PT 햷 Abnormal PTT 햶 Bleeding history No Yes Abnormal TT TT PTT Abormal 햴
1:1 mix of patient: normal plasma Does not correct
Bleeding history No Yes – FVIII:C, VWF:RCo, VWFAg + FVIII:C, VWF:RCo, VWFAg Normal
FIX, XI, XII
FVIII:C, VWF:RCo, VWFAg, FIX, FXI Reptilase time 햵 Abnormal Normal
P. de Alarcon · M.J. Manco-Johnson
Evaluation of a child with bleeding or abnormal coagulation screening tests Coagulation Disorders53
쏹햲–– Bleeding in a child can present as petechiae, purpura, epistaxis/mucosal bleeding, hematomas, gastrointestinal and genitourinary bleeding, excessive bleeding with proce- dures and surgery, as well as intracranial hemorrhage. Oth- er children present with an incidental abnormal coagulation screen, often during presurgical screening, in the absence of clinical bleeding. Consider a platelet or vascular disorder if the bleeding is mucosal in nature or a clotting factor defi- ciency if it consists of deep-seated hematomas or
hemarthroses. Nosebleeds and menorrhagia are the most common manifestations of von Willebrand disease (VWD). A family history of bleeding in only males suggests hemo- philia A or B. A palpable, purpuric rash with the typical low- er extremity predominance suggest the vasculitis of Henoch-Schönlein purpura. Less well localized rashes are often seen in viral illnesses, but an acutely ill child with a purpuric rash should be assumed to have me-
ningococcemia or other bacterial septicemia until proven otherwise; although these children may develop DIC with low platelets and abnormal coagulation screen this often is not the case. A purpuric rash which becomes necrotic sug- gests purpura fulminans due to viral or bacterial infection, or a deficiency of a natural anticoagulant (protein C, S or antithrombin). Organomegaly suggests an infiltrative process: either malignancy or a storage disease.
쏹
햳–– A normal platelet count and normal coagulation screen suggests several disorders. If there is an acute illness consider purpura fulminans or mild DIC with infection. If the bleeding history is negative and the child is healthy consider the possibility of a bruising in a normal, active child, or the possibility of child abuse; the appearance of linear bruises or burns is strongly suspicious of abuse. If there is a past history of bleeding consider VWD and obtain factor VIII coagulant (FVIII:C), ristocetin co-factor which is the functional von Willebrand factor assay (VWF:RCo), and von Willebrand antigen (VWFAg) activities. FA100 closure time, if available, may provide an indicator of VWD and other platelet dysfunctions that is more accurate than the bleeding time (see ‘Platelet dysfunction’, p 60). Mild hemo- philia or a hemophiliac carrier may present with normal coagulation studies and a positive history; the PTT may not prolong until the factor level is <30% (normal ~50–150%) so mild deficiencies may be missed. Factor XIII deficiency is a rare coagulation disorder that presents with umbilical stump hemorrhage, soft tissue hematomas and poor
wound healing, but normal coagulation screen; a specific assay is required for this diagnosis. Vascular disorders causing purpura include Henoch-Schönlein purpura, infec- tions, collagen vascular diseases, and collagen deficiencies (Ehlers-Danlos syndrome and Marfan syndrome).
쏹
햴–– Normal platelet count and abnormal coagulation screen suggests a clotting factor deficiency or an anticoa- gulant. Repeating the abnormal test with a mixture of 1 part of patient plasma with 1 part normal plasma will normalize the test when a deficiency of a factor is present, but the screening test will remain abnormal after mixing if an anti- coagulant is present. Lupus-like anticoagulants in children are frequent and transient postviral asymptomatic auto- immune reactions. Rarely, they cause thromboembolic dis- ease and even less often bleeding problems. Lupus-like anticoagulants usually prolong the PTT. In the rare child in whom the anticoagulant results in acquired prothrombin deficiency, a bleeding tendency occurs and the PT is pro- longed. The presence of a lupus-like anticoagulant should be confirmed by other phospholipid correction studies, in- cluding the platelet neutralization test and the Russell Viper venom test (RVVT). Heparin in the patient, or more often simply contaminating the sample, is frequent in the hospi- tal setting.
쏹
햵–– If heparin is present in the patient (or simply the labo- ratory sample), the TT will always be prolonged if the PTT is (the PT may be but is less sensitive to heparin). The repti- lase (or Ancrod) time utilizes a snake enzyme which per- forms exactly like thrombin except that it is not inhibited by heparin. Therefore, a prolonged TT and a normal reptilase time confirm the presence of heparin. Prolongation of both the TT and reptilase times are consistent with a fibrinogen defect or increased FSP.
쏹
햶–– If the coagulation screening test corrects with a 1:1 mix of patient and normal plasma, there is a factor deficien- cy. A markedly abnormal PTT with no history of bleeding suggests factor XII deficiency. Mild abnormalities of the PTT alone are most often due to vWD, given the 1% incidence of this disorder in the general population, but can also be due to mild factor deficiencies in mild hemophilia A or B or in carriers, or due to factor XI deficiency. Severe prolonga- tions of the PTT due to factor deficiencies are usually due to hemophilia, but consider DIC in acutely ill patients.
쏹
햷–– A prolonged PT is usually associated with a prolonged PTT, most often due to oral anticoagulants, liver disease, and vitamin K deficiency, and rarely to isolated deficiencies of factors II, V or X. The TT will be normal with oral anti- coagulants and vitamin K deficiency, but may be abnormal in liver disease because of hypofibrinogenemia and/or elevated FSP. Rare isolated factor VII deficiency can cause an isolated prolongation of the PT, but this is usually seen at the beginning of oral anticoagulation therapy or vitamin K deficiency; FVII, which is only measured by the PT, falls much faster (half-life 3–6 h) than the other vitamin K- and hepatic-dependent factors. Prolongation of the PTT should be noted within 24–48 h. An abnormal TT suggests heparin effect or fibrinogen defects.
Selected reading
Brogan PA, Raffles A: The management of fever and petechiae: Making sense of rash decisions. Arch Dis Child 2000;83:506–507.
Cohen AJ, Kessler CM: Treatment of inherited coagula- tion disorders. Am J Med 1995;99:675–682.
Leung AK, Chan KW: Evaluating the child with purpura. Am Fam Physician 2001;64:419–428.
Saulsbury FT: Henoch-Schonlein purpura in children: Report of 100 patients and review of the literature (review). Medicine 1999;78:395–409.
Wells LC, Smith JC, Weston VC, Collier J, Rutter N: The child with a non-blanching rash: How likely is meningococcal disease? Arch Dis Child 2001;85:218–222. Werner EJ: von Willebrand disease in children and adolescents (review; 131 refs). Pediatr Clin North Am 1996; 43:683–707.