<prompt> A 5 year old male child presents with continuous bleeding from mouth. He had ho fall early in the morning while playing. No ho bruising or hematoma. He is taking amoxycillin for his middle ear infection. OE he is stable and there is a small laceration in the lower lip with oozing of blood. Hb 12.8g, hematocrit 35.4, WBC count 8400mm3, Platelets 300 X 109L- Prothrombin time 11.5 seconds, aPTT 37.2 seconds. DiagnosisHemophilia AVon Willebrand diseaseGlanzmann thrombastheniaBernard Soulier syndrome  <response>: Answer: b Von Willebrand disease Normal PT and aPTT rules out Hemophilia A Glanzmann thrombasthenia and Bernard Soulier syndrome are qualitative platelet disordersPartial thromboplastin time PTTProthrombin time PTBleeding time BT Tests intrinsic and common pathways of coagulation Normal: 60 - 70 seconds Tests extrinsic common pathways Normal 11-16 seconds Normal 2-8 mins Prolonged aPTT normal 30-40 sProlonged PTProlonged aPTT and PT Deficiencies of factor 1, II, V, VIII, IX, X, XI, XII, Lupus anticoagulant Heparin factors 1, II, V, VII, X Vitamin K deficiency--early Warfarin anticoagulation Factor II, V, X, or fibrinogen Vitamin K deficiency--late Direct thrombin inhibitorsLaboratory findings in Hemostatic disorders Coagulation disordersPlatelet disordersTESTHemophilia A BvW DVit K Liver failureITPTTPHepari nDICAspirinWarfari nBTNNNPlateletNNN-NNPTNNNNNNaPTTNNNNFDP-------VON WILLEBRAND DISEASE Most common inherited bleeding disorders of human Type 1 - AD,. Most common type. Usually. Type 2 - type 2A is AD, qualitative defects in vWF Type 3 - AR. Extremely low levels of vWF. Severe clinical manifestations.Pathogenesis vWF is synthesized by endothelial cells, platelets and megakaryocytes a-granules Weibel-Palade bodies - glue factory of endothelial cells; synthesize P-selectin - adhesion molecule for leukocytes vWF - adhesion molecule for platelets vWF is responsible for platelet adhesion bridge between extracellular collagen matrix and platelet surface receptors GP Ib-IX is a major receptor for vWF vWF acts as a carrier for factor VIII and important for its stability and prolongs half life Factor VIII is synthesized normally but has 4, half-life due to deficiency of carrier moleculeType 1Type 2Type 3 Autosomal dominant Due to missense mutation Most common type Reduced quantity of vWF Mild to moderate bleeding 2A - Autosomal dominant Missense mutations Qualitative defects of vWF Mild to moderate Autosomal recessive Deletions or frame-shift mutations Extremely low levels of vWF Severe clinical manifestationsClinical features Bleeding is uncommon in infancy and manifest in late childhood The most common symptoms - sponatenous mucosal bleedinge.g.epistaxis, excessive bleeding from wounds, menorrhagia Frequently mild vWD manifests first during wisdom tooth extraction or tonsillectomy Defects in platelet function despite normal platelet count Acquired vWD is most commonly seen in MGUS; other conditions - multiple myeloma; Waldenstroms macroglobulinemiaDiagnosis Increased BT Normal aPTT, PT in types 1 and 2 A, B, M Elevated aPTT in types 2N and 3 Plasma level of active vWF, measured as Ristocetin an antibiotic cofactor activity is reducedTreatment Type 1: DDAVP desmopressin IVintranasally For other types - vWF replacement 