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Evaluation of Abnormal Bleeding

Evaluation of Abnormal Bleeding. Ambulatory Medicine Clerkship 01/11/2010 Kofi-Buaku Atsina YSM III. Learning Objectives. List the differential diagnoses of abnormal bleeding in an adult. Describe the appropriate diagnostic evaluation for abnormal bleeding in an adult.

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Evaluation of Abnormal Bleeding

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  1. Evaluation of Abnormal Bleeding Ambulatory Medicine Clerkship 01/11/2010 Kofi-Buaku Atsina YSM III

  2. Learning Objectives • List the differential diagnoses of abnormal bleeding in an adult. • Describe the appropriate diagnostic evaluation for abnormal bleeding in an adult. • Interpret coagulation assays and understand their role in refining differential diagnosis • Understand the coagulation cascade • Describe the physiologic role of von Willebrand factor in clotting

  3. Case 1 • HPI: A 62 y/o mildly overweight black woman with h/o hypertension presents with gingival bleeding after periodontal scaling of her lower-right second molar 5 hours prior to the episode. Her bleeding had persisted despite application of ice and pressure. She reports a similar episode 6 months earlier, also after a periodontal procedure, in which bleeding stopped only after the application of firm pressure for 6 hours. She is otherwise in her USOH and denies any easy bruising, epistaxis, rectal bleeding, hemturia, weakness, fatigue, lightheadedness, fever, arthralgia, dyspnea, jaundice, adbominal pain, back pain, rash or confusion.

  4. PMH/PSH • Deep-vein thrombosis in the legs (20 years ago) • Cosmetic blepharoplasty, w/o bleeding complications (@ age 20) • Arthroscopic repair of meniscal tear in the left knee without bleeding complications (1 year ago) • Uncomplicated vaginal delivery • SH • Former smoker, quit 30 years ago • Consumes alcohol infrequently • FH • Father died of lung cancer at age 62 • Mother still living and in good health at age 88 • Brother had colorectal cancer at age 57 • No h/o bleeding diathesis • Meds Thiazide diuretic • Allergies • NKDA

  5. Physical Exam • Gen: NAD • Vitals: BP: 128/76 mm Hg, P: 80 and regular, RR: 16, O2 saturation 98% on ambient air. • HEENT: Oral cavity revealed blood slowly oozing from the vicinityof the lower-right second molar, with no visible mucosal laceration.But no oral petechiae, bullae, or ulcers. Mild conjunctivalpallor was noted, but no scleral icterus. There was no lymphadenopathy. • RESP: Clear to auscultation and percussion. • Cor: Mild lateral apical displacement; RRR, no murmur, rub, or gallop. • Abd: Soft and not tender; normal bowel sounds and no hepatosplenomegalyor masses detected. Rectal examination revealed no masses anda scant amount of brown stool that was negative for occult blood. • EXT: Her extremities were warm, with brisk capillary refill, and no clubbing, cyanosis, or edema. No rashes, petechiae,ecchymoses, or telangiectasias were noted. • Neuro: cranial nerves intact, 5/5 muscle strength, normal sensation,3/5 deep-tendon reflexes, normal coordination, and gait.

  6. Differential diagnosis? • Acquired • Trauma • Drugs: Aspirin, wafarin, heparin • Platelet disorder: ITP, TTP/HUS, HIT • Clotting factor deficiency • Liver disease, malnutrition, clotting factor inhibitor, acquired von willebrand disease • Combined platelet and clotting factor disorder: DIC • Vessel wall disease: acquired vasculitides • Genetic • Platelet disorder • Bernard Soulier syndrome, Glanzmann’s thrombasthenia, storage pool disorders • Clotting factor deficiency • Hemophilia A, Hemophilia B, von Willebrand disease • Vessel wall abnormalities: Ehlers-Danlos syndrome

  7. Acquired or Genetic? • Acquired • Based on history: • Generally healthy person • PMH/PSH • Cosmetic blepharoplasty, w/o bleeding complications • Arthroscopic repair of meniscal tear in the left knee without bleeding complications • Uncomplicated vaginal delivery

  8. Nature of Bleeding • Mucosal Bleeding (petechiae, purpura), menorrhagia, prolonged bleeding from minor wounds --> Platelet disorder/ vWF disorder • Deep Tissue Bleeding (Hemathrosis, hematomas, ecchymosis, prolonged post-surgical bleeding ) --> Coagulation factor defect/deficiency

  9. Platelet/vWF disorder or Coagulation disorder? • Acquired: • Platelet Disorder • Quantitative: • Bone marrow diseases e.g. aplastic anemia, marrow infiltration (leukemia), drug induced e.g alcohol, thiazides, infection (HIV, measles) • Infections eg. HIV, CMV, infectious mononucleosis • Immunological e.g. ITP • Nonimmunologic e.g.TTP/HUS • Drug induced e.g. Heparin, quinidine, sulfa compounds • Hypersplenism • Qualitative: • Aspirin/NSAID • Uremia • Acquired von Willebrand Disease • Hypothyroidism, Mechanical/Shear stress, Lymphoproliferative diseases, Pancreatitis, DIC,Decompensated cirrhosis

  10. Effectors of Hemostasis • Vessel Wall Integrity • vWF • Platelet adhesion, activation and aggregation • Coagulation Cascade • Anticoagulants and fibrinolytic factors

  11. vWF, Platelet Adhesions and Aggregation NB. This image were obtained from the following site: http://www.orthosupersite.com/images/content/obj/0803/kroonen_fig1.gif

  12. Coagulation cascade

  13. PT/PTT

  14. Assays for Von Willebrand factor Quantitative or qualitative defects: • von Willebrand Ristocetin Cofactor • von Willebrand Antigen • Factor VIII level Qualitative defects: • Von Willebrand multimer gel analysis • Ristocetin-induced platelet aggregation (RIPA)

  15. Case 1: Labs NB. Normal chemistry panel and normal LFT

  16. Labs Other data: The serum iron level was 27 µg per deciliter (4.8 µmolper liter), the ferritin level 76 ng per milliliter, and thetotal iron-binding capacity 314 µg per deciliter (56.2µmol per liter). Levels of vitamin B12 and folate werenormal. The reticulocyte count was 2.7%, and the peripheral-bloodsmear showed mild erythrocyte anisocytosis but was otherwisenormal.

  17. What is your refined DDx? Acquired Von Willebrand disease

  18. Acquired Von Willebrand disease Causes: • Hypothyroidism • Mechanical/Shear stress, • Lymphoproliferative diseases/ collagen vascular diseases • Pancreatitis, DIC, Decompensated cirrhosis • Tumor

  19. Von Willebrand disease • Quantitative • Type 1 partial vWF deficiency • Type 3: complete vWF deficiency • Qualitative • Type 2: • 2A: decreased affinity of vWF for platelet • 2B: increased affinity of vWF for platelet • 2M: decreased platelet dependent function • 2N: defective factor VIII binding site

  20. Lab Findings

  21. Case 2 • HPI: A 2-year old boy was brought to the emergency department by his mother for oozing blood from his mouth following a fall nearly 6 hours ago. His mother related that he tended to bleed for prolonged periods from his immunization sites, but there was no history of bruising or hematomas. The patient was on antibiotics for a recent ear infection. There was no known family history of a bleeding disorder. • PE: • Gen: Alert, in no apparent distress, development appropriate for age • HEENT: Two small lacerations on the inside of lower lip, oozing bloodRemainder of exam within normal limits (notably, no petechia, bruises, joint swelling)

  22. What is your DDx? • Von Willebrand disease • Factor VIII and IX deficiency (Hemophilia A, B) • Lupus anticoagulant, factor VIII inhibitor (rare) • Factors XI and XII deficiency (rare)

  23. Initial lab results

  24. Additional Work up

  25. Final Diagnosis Von Willebrand Disease

  26. References • Cuker A, Connors JM, Katz JT, Levy BD, Loscalzo J; A Bloody Mystery, N Engl J Med 2009; 361:1887 - 94 • Haberichter SL, Balistreri M, Christopherson P, Morateck P,Gavazova S, Bellissimo DB, Manco-Johnson MJ, Gill JC, Montgomery RR; With type 1 von Willebrand disease with decreased VWF survival Assay of the von Willebrand factor (VWF) propeptide to identify patients, Blood 2008; 108:3344 - 3351 • Robbins and Cotran Pathological Basis of Human Disease, 7th ed. Chapter 13 (pg 649 - 659) • Harrison’s Principles of Internal Medicine, 16th ed. Chapter 102 • http://path.upmc.edu/cases/case325.html • Kroonen LT, Gillingham BL Provencher MT, Orthopedic Manifestations and Management of Patients With von Willebrand Disease, Orthopedics 2008; 31:263

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