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Kate Larard kml20@ic.ac.uk Slides adapted from Isobel Elliiott BLEEDING DISORDERS MedEd Y3 Written Exam Lectures 2023SESSION STRUCTURE Aetiology RFs Presentation Investigations Management = Gold Standard = High YieldSESSION CONTENT BLEEDING DISORDERS Primary haemostasis • ITP • TTP • DIC Secondary haemostasis • HAEMOPHILIA • DIC • VWDSESSION CONTENT BLEEDING DISORDERS Primary haemostasis • ITP • TTP • DIC Secondary haemostasis • HAEMOPHILIA • DIC • VWDPRIMARY HAEMOST ASIS Formation of temporary platelet plug 1. Endothelial injury → Vascular spasm 2. Ecollagen→ damaged endothelial cells make VWF which binds to exposed 3. Adhesion → circulating platelets bind to VWF via Gp1b receptor VWF 4. Activation → change shape and expose GpIIb/IIIa receptor, secrete Ca Serotonin, ADP, Thromboxane A2 (positive feedback loop) 5. Aggregation → bind to collagen and fibrinogen binds other platelets together Undamaged endothelium secrete prostaglandin and nitric oxide which inhibit platelet activation to limit platelet plug to the area of injuryPRIMARY HAEMOSTASISPRIMARY HAEMOST ASIS SUPERFICIAL BLEEDING EPISTAXIS (gums, GIT)EDING ECCYMOSES PETECHIAE/PURPURA PROLONGED BLEEDING TIMEPRIMARY HAEMOST ASIS Haematological cancers – Reduced production acute leukaemias Reduced Plts Destruction of Plts ITP Increased consumption HUS, TTP, DIC Antiplatelet drugs Aspirin, clopidogrel. Defect in function of Plts Bernard-Soulier syndrome, Congenital Glanzmann thrombasthenia, and storage pool disordersSESSION CONTENT BLEEDING DISORDERS Primary haemostasis • ITP • TTP • DIC Secondary haemostasis • HAEMOPHILIA • DIC • VWDImmune thrombocytopenic purpura AETIOLOGY Investigations • Auto-Abs against platelets • Isolated thrombocytopenia • Depletion in platelets • Prolonged bleeding time • Acute ITP: Children • Normal PT and APTT • Often follows an infection (cross reactivity) and resolves • Autoantibodies found • Chronic ITP: Adults • Associated with other autoimmune conditions and doesn’t resolve spontaneously Management • Generally self limiting CLINICAL FEATURES • If Plt under 20 in children or 50 in adults • Purpuric rash/petechiae • Meninor symptomaticcaemia • Epistaxis • HSPFFE• SteroidsOR PURPURIC RASH? • Bleeding gums • Von wi• IVIgnds disease • Menorrhagia • TPO RA - Eltrombopag • Fatigue Haemolytic Uraemic Syndrome TRIAD Investigations 1. Microangiopathic haemolytic anaemia 2. Acute kidney injury FBC: 3. Thrombocytopenia • Low Hb Anaemia caused by • Thrombocytopenia rbc being ‘cut up’ in Blood film: Schistocytes blood vessels U+Es – AKI Classic presentation Young child, bloody diarrhea, rash, abdo pain Causes E.coli (STEC) 0157:H7Thrombotic thrombocytopenic purpura AETIOLOGY • Defect in thADAMTS13 enzyme that breaks down VWF CLINICAL FEATURES – PENTAD 1. Acute kidney injury 2. Microangiopathic haemolytic anaemia 3. Thrombocytopenia 4. Temperature 5. SwingingCNS signs Investigations • Thrombocytopenia Management • Haemolytic anaemia • Plasmaphoresis (removes anti-ADAMTS13 • Reduced ADAMTS13enzyme +/- anti-Abs Abs and replaces ADAMTS13 enzyme) • Prolonged bleeding time • Normal PT and APTTDisseminated Intravascular Coagulation AETIOLOGY widespread activation of coagulation leads to the formation of microvascular thrombi, consuming platelets • Infection • Malignancy – acute promyelocytic leukaemia • Obstetric complication • Trauma CLINICAL FEATURES Bleeding – Mucosal, GI, Haematuria, bleedingfrom cannula sites Thrombotic – digital ischaemia, DVT/PE, Renal failure INVESTIGATIONS • Thrombocytopenia • Prolonged PT and aPTT MANAGEMENT • Lowfibrinogen Treat underlying cause Supportative therapy – plt? FFP? • Elevated D-DimerAntiplatelets Aspirin Arachidonic acid Platelet aggregation Clopidogrel ADP SBA 1 (question) A 14-year-old woman presentswith new-onset bruisingand gum bleeding for the past few days. She recently recovered from a mild viral illness. She is hemodynamically stable.Labs show: •Platelet count: 15,000/µL •Hemoglobin: 13.2g/dL •WBC: 6,000/µL •PT/aPTT: Normal Given the diagnosis, how should she be managed? A.Oral prednisone B.Platelet transfusion C. Splenectomy D.No treatment needed unless plateletsdrop further SBA 1 (answer) A 14-year-old woman presentswith new-onset bruisingand gum bleeding for the past few days. She recently recovered from a mild viral illness. She is hemodynamically stable.Labs show: •Platelet count: 15,000/µL •Hemoglobin: 13.2g/dL •WBC: 6,000/µL •PT/aPTT: Normal Management • Generally self limiting Given the diagnosis, how should she be managed? • If Plt under 20 in children or 50 in adults or symptomatic A.Oral prednisone • Steroids B.Platelet transfusion • IVIg • TPO RA - Eltrombopag C. Splenectomy D.No treatment needed unless plateletsdrop further SBA 2 (question) A 5-year-old boy presentswith pallor,decreased urine output, and abdominal pain.His mother reports a recent episode of bloody diarrhea after a family barbecue. Labs show: •Platelets: 30,000/µL •Hemoglobin: 7.5 g/dL •Creatinine: 3.0 mg/dL •LDH: Elevated •Peripheral smear: Schistocytes •Coagulation profile: Normal What is the most likely cause of thiscondition? A.Shiga-toxin-producing E. coli (STEC) B.Group AStreptococcus C. Influenza virus D.Parvovirus B19 SBA 2 (question) A 5-year-old boy presentswith pallor,decreased urine output, and abdominal pain.His mother reports a recent episode of bloody diarrhea after a family barbecue. Labs show: •Platelets: 30,000/µL •Hemoglobin: 7.5 g/dL •Creatinine: 3.0 mg/dL Thrombocytopenia •LDH: Elevated MAHA •Peripheral smear: Schistocytes AKI •Coagulation profile: Normal What is the most likely cause of thiscondition? A.Shiga-toxin-producing E. coli (STEC) B.Group AStreptococcus C. Influenza virus D.Parvovirus B19 SBA 3 (question) A 23-year-old man presents to the emergency department after a road traffic accident. He has a skull fracture, tension pneumothorax, rib fractures, humeral fractures, splenic lacerations and a femoral fracture. He is anaemic and is also noted to have epistaxis, with purpura and ecchymoses overlying his arms, legs and torso. What is the most likely complication? A. Antiphospholipid syndrome B. Haemophilia A C. Pulmonary embolism D. DIC E. ITP SBA 3 (answer) A 23-year-old man presents to the emergency department after a road traffic accident. He has a skull fracture, tension pneumothorax, rib fractures, humeral fractures, splenic lacerations and a femoral fracture. He is anaemic and is also noted to have epistaxis, with purpura and ecchymoses overlying his arms, legs and torso. What is the most likely complication? A. Antiphospholipid syndrome B. Haemophilia A C. Pulmonary embolism D. DIC E. ITPSESSION CONTENT BLEEDING DISORDERS Primary haemostasis • ITP • TTP • DIC Secondary haemostasis • HAEMOPHILIA • DIC • VWD SECONDARY CLOTTING the coagulation cascade forms a fibrin mesh that reinforces the platelet clot TwelvE EleveN NinE EighT TenSESSION CONTENT BLEEDING DISORDERS Primary haemostasis • ITP • TTP • DIC Secondary haemostasis • HAEMOPHILIA • DIC • VWDCOAGULATION DISORDERS INHERITED: AQUIRED: Liver failure Autoimmune HaemophiliaA (I,II,VII,VIII, IX, destruction of a Factor 8 Deficiency X,XI, XIII) clotting factor Haemophilia B Vitamin K Disseminated deficiency intravascular Factor 9 Deficiency (II,VII, IX, X) coagulation (MENTI CODE: ) INHERITED HAEMOPHILIA X-linked recessive disorder CLINICAL FEATURES Haemarthrosis - bleeding into joints – swollen and painful(hallmark) Haematoma - bleeding into muscles Severe: will present <2yrs, bleeding into joints Milder: present later in life after surgery ortrauma MANAGAMENT INVESTIGATIONS: • avoid high impact sports Bloods: • avoid blood thinning medications • Desmopressin • APTT → prolonged (fVIII and IX part of • Stimulates release of stored fVIII INTRINSIC pathway) and VWF • Factor assay • Recombinant factor8/9 • Bleeding time, PT/INR and plt count will all be NORMALDisseminated Intravascular Coagulation AETIOLOGY widespread activation of coagulation leads to the formation of microvascular thrombi, consuming platelets • Infection • Malignancy – acute promyelocytic leukaemia • Obstetric complication • Trauma CLINICAL FEATURES Bleeding – Mucosal, GI, Haematuria, bleedingfrom cannula sites Thrombotic – digital ischaemia, DVT/PE, Renal failure INVESTIGATIONS • Thrombocytopenia • Prolonged PT and aPTT MANAGEMENT • Lowfibrinogen Treat underlying cause Supportative therapy – plt? FFP? • Elevated D-DimerVon Willebrand’s disease Type 1 Binds to Facilitates Reduced levels of normal vWF plateletsvia platelet Gp1b and aggregation activates Type 2 Normal levelsof defective vWF Binds to fVIII and Type 3 preventsits Complete deficiency in vWF MIX OF PRIMARY AND SECONDARY HAEMOSTASIS degredation and marked reduction of fVIII DYSFUNCTION!Von Willebrand’s disease Most common inherited bleeding disorder Investigations: Type 1and 2 – Autosomal Dominant • Prolonged bleeding time Type 3 – Autosomal Recessive • Prolonged APTT • Low fVIII Presentation: • PT normal • Superficial bleeding (primary • Normal platelet count haemostasis) • Epistaxis MANAGAMENT • Petechiae • Gum bleeding • Desmopressin • Deep bleeding • Releases stored vWF and fVIII into • haematomas the blood • Menorrhagia • Treatment of bleeds RFs: • Tranexamic acid • Give combined vWF and fVIII • Family history concentrates SBA 4 A 2 year old boy presents to the GP with his father following development of severe bruising after minor trauma. On examination there is a large, deep ecchymosis along the patient’s left thigh. On specific questioning, it is revealed that his maternal uncle suffers from a similar “bleeding disorder”. Blood tests reveal a normal blood count, urea & electrolytes and liver function. A coagulopathy prolonged. What is the most likely diagnosis? PT (INR) and normal fibrinogen; but the APTT is A. Von willebrands disease B. Haemophilia A C. Haemophilia B D. ITP E. DIC SBA 4 (answer) A 2 year old boy presents to the GP with his father following development of severe bruising after minor trauma. On examination there is a large, deep ecchymosis along the patient’s left thigh. On specific questioning, it is revealed that his maternal uncle suffers from a similar “bleeding disorder”. Blood tests reveal a normal blood count, urea & electrolytes and liver function. A coagulopathy screen reveals a normal bleeding time, normal PT (INR) and normal fibrinogen; but the APTT is prolonged. What is the most likely diagnosis? A. Von willebrands disease 80% of B. Haemophilia A Hameophilias C. Haemophilia B are A D. ITP E. DIC SBA 5 A 19-year-old woman presents to the emergency department after a tooth extraction earlier in the day. She has a history of heavy periods since menarche, but is otherwise fit and well. She has a family history of a bleeding disorder. On examination, there is still bleeding from the tooth extraction site, but no other abnormalities are noted. What is the most likely diagnosis? A. Haemophilia A B. Haemophilia B C. Von Willebrands disease D. ITP E. Factor V leiden SBA 5 (answer) A 19-year-old woman presents to the emergency department after a tooth extraction earlier in the day. She has a history of heavy periods since menarche, but is otherwise fit and well. She has a family history of a bleeding disorder. On examination, there is still bleeding from the tooth extraction site, but no other abnormalities are noted. What is the most likely diagnosis? A. Haemophilia A Factor V Leiden – Mutation B. Haemophilia B making FV resistant to C. Von Willebrands disease Protein C - Thrombophilia D. ITP E. Factor V leiden SBA 6 A 28-year-old man with a known history of Hemophilia A presents to the emergency department after sustaining a fall while skiing. He reports persistent swelling and pain in his left ankle. On physical examination, there is significant swelling and tenderness in the left ankle joint What is the most appropriate treatment for this patient’s bleeding episode? A. Fresh frozen plasma (FFP) B. Platelet transfusion C. Factor VIII concentrate D. Desmopressin (DDAVP) SBA 6 (answer) A 28-year-old man with a known history of Hemophilia A presents to the emergency department after sustaining a fall while skiing. He reports persistent swelling and pain in his left ankle. On physical examination, there is significant swelling and tenderness in the left ankle joint What is the most appropriate treatment for this patient’s bleeding episode? A. Fresh frozen plasma (FFP) B. Platelet transfusion C. Factor VIII concentrate D. Desmopressin (DDAVP)Feedback Please, Please, Please fill in the feedback form!SUMARY SLIDE BLEEDING DISORDERS Primary haemostasis – formation of platelet clot • HUS – AKI, MAHA, thrombocytopenia • TTP - AKI, MAHA, thrombocytopenia + fever and neuro signs • DIC - activation of coagulation leadsto the formation of microvascular thrombi, consuming platelets and clottingfactors – Infection, Malignancy, Obstetric complication, Trauma Secondary haemostasis • HAEMOPHILIA – A (VIII), B (IX) – Prolonged APTT, normal Bleeding time and PT • DIC • VWD - Prolonged bleeding time,Low fVIII, Prolonged APTT, normal PT SBA 16 (question) A 6 year old boy presents to the GP with large bruises on his knees. His mother says that he is very active and enjoys playing outside but his bruises appear to be a lot bigger and last a lot longer than his older sister's do. He also gets painful, swollen joints. Haemophilia A is suspected as the cause of his symptoms. Which of the following would confirm this diagnosis? A. BM biopsy B. Prolonged APTT C. Factor VIII assay D. Blood film SBA 16 (answer) A 6 year old boy presents to the GP with large bruises on his knees. His mother says that he is very active and enjoys playing outside but his bruises appear to be a lot bigger and last a lot longer than his older sister's do. He also gets painful, swollen joints. Haemophilia A is suspected as the cause of his symptoms. Which of the following would confirm this diagnosis? A. BM biopsy B. Prolonged APTT C. Factor VIII assay D. Blood film