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Data Interpretation Series: Clotting Abnormalities Dr. Acute Medicineman Trust Grade DoctorSocial Medias Intro Learning Objectives • Haemostasis • INR and APTT (activated partial thromboplastin time) • Touch on bleeding disorders • Touch on procoagulant disorder • Thrombotic Microangiopathies Case 1 Question A 50-year-old gentleman presents to the ED with bleeding following a sawing injury to his arm, cutting through the radial artery. The bleed has been managed and a full blood count. His platelet count is abnormally low (<150) but the cause is not known. What is the first step to haemostasis? A. Clot Formation B. Vasospasm C. Clot dissolving & repair D. Platelet plug formation E. Don’t know Case 1 Answer What is the first step to haemostasis? A. Clot Formation B. Vasospasm C. Clot dissolving & repair D. Platelet plug formation E. Don’t know Case 1 Haemostasis 2.Platelet plug 1.Vasospasm formation (primary haemostasis) Primary Haemostasis 1. Damaged blood vessel = collagen exposure 2. VWF binds to GP receptors = platelet adhesion 3. Platelet activation = vasoconstrictio2)(TXA & dense granule release 4. Serotonin = further vasoconstriction. 5. ADP = platelet activation via purinergic (P2Y) 3.Clot receptors & activates fibrinogen receptors 4. Clot dissolve formation (GPIIb/IIIa). & repair haemostasis) 6. Sticky platelets & aggregation = soft platelet plug formation Case 1 Secondary Haemostasis Initiation Phase Amplification Tissue Factor (IIIa) IX VII VIIa XIa IXa iCa+ Xa X VIIIa iCa+ Prothrombin (II) Thrombin (IIa) + Feedback Va Mesh Fibrin Fibrinogen D-Dimer Propagation Phase Case 2 Question A 60-year-old lady presents to her GP for her regular INR check. She is on warfarin for AF – her target INR is 2.5. The measure INR is 4 but she is well otherwise. Which clotting factors does the INR assess? A. VIII, IX, XI, XII B. I, II, V, VII, X C. III, IV D. I, II, III E. Don’t know Case 2 Answer Which clotting factors does the INR assess? A. VIII, IX, XI, XII B. I, II, V, VII, X C. III, IV D. I, II, III E. Don’t know I = Fibrinogen INR & APTT II = Prothrombin INR = Fibrinogen, Prothrombin, V, VII, X III = Tissue Factor APTT = VIII, IX, XI, XII IV = Ca+ PT (Prothrombin Time) & INR Ratio of patient’s PT to a normal PT Case 3 Question A 25-year-old gentleman presents to the ED following excessive bleeding post- dental extraction. He is otherwise normally fit and well. He states his sister had a have?ar issue in the past. Which bleeding disorder does this patient most likely A. Haemophilia A B. Haemophilia B C. Von Willebrand’s Disease D. Factor V Leiden E. Don’t know Case 3 Answer Which bleeding disorder does this patient most likely have? A. Haemophilia A – 2 ndmost common UK B. Haemophilia B – 3 most common C. Von Willebrand’s Disease D. Factor V Leiden – Procoagulant disorder E. Don’t know Typical history of VWD includes easy Epidemiology bruising, epistaxis > 10mins and Most common in the UK is VWD, followed bleeding following dental extractions. by Haemophilia A and then B.Case 3 Bleeding Disorders Features Haemophilia Haemophilia VWD A B Deficiency VIII FIX VWF Inheritance X-Linked X-Linked Autosomal Dominant APTT Increased Increased Increased Case 4 Question A 35-year-old gentleman presents to the ED following with a red hot swollen leg. His FBC and CRP are normal, however he has a positive D-Dimer. He is otherwise patient could have?ll. What is the most likely procoagulant disorder that this A. Factor V Leiden B. Protein C deficiency C. Antithrombin deficiency D. Prothrombin Mutation E. Don’t know Case 4 Answer What is the most likely procoagulant disorder that this patient could have? A. Factor V Leiden B. Protein C deficiency C. Antithrombin deficiency D. Prothrombin Mutation E. Don’t know Protein C & S are anticoagulant All procoagulant conditions are more proteins that are vitamin K common compared to the bleeding dependent. Factor V Leiden is disorders. resistant to the anticoagulant effect of protein C. Case 4 Bleeding Disorders Features Factor V Protein C/S Antithrombin Prothrombin Leiden deficiency Deficiency Mutation Disease Protein C Decrease Decreased Excess unable to anticoagulant inhibition of Prothrombin inhibit Factor proteins factors II, V, (II) V IX, X, XI, XII Inheritance Autosomal Autosomal Autosomal Autosomal Dominant Dominant Dominant Dominant APTT Decreased Decreased Decreased Decreased Case 5 Question A 21-year-old gentleman presents to the ED with fever, headache and photophobia. He is being treated for presumed meningococcal septicaemia. As part of his VTE prophylaxis he is receiving Dalteparin (LMWH) .Three days into his treatment he is bleeding from both of his cannula sites. His bloods are seen below. What is the most likely cause of his abnormal haem results? Value Range A. Haemolytic Uraemic Syndrome Hb 121 130-180 WCC 5.5 4-11 B. Disseminated Intravascular Platelets 57 150-400 Coagulopathy C. Thrombotic Thrombocytopaenic INR 2.5 1.1-1.3 aPTT 45s 21-35s purpura Fibrinogen 0.5 2-4 D. Heparin Induced Thrombocytopaenia D-Dimer 750 <250 E. Don’t know Blood film Schistocytes Case 5 Answer What is the most likely cause of his abnormalhaem results? A. Haemolytic Uraemic Syndrome B. Disseminated Intravascular Coagulopathy C. Thrombotic Thrombocytopaenic purpura D. Heparin Induced Thrombocytopaenia E. Don’t know DIC = consumption coagulopathy Acute DIC both increased risk with bleeding and Thrombocytopaenia thrombosis in acute DIC. How it High INR & aPPT differs from other TMAs is the High D-Dimer & Low Fibrinogen coagulation factor consumption (i.e. Blood film = RBC Fragments (Schistocytes) raised INR and aPPT). Case 5 DIC • DIC is a clinical and laboratory diagnosis Investigations Aetiology FBC Malignancy • systemic process that causes thrombosis and bleeding Coagulation Obstetric (AFE • unlike other TMAs with normal coagulation studies. Fibrinogen & HELLP) • DIC is associated with microvascular thrombi that contain IV Haemolysis fibrin as well as platelets D-Dimer (ABO) Blood film Sepsis • Acute DIC- AML, sepsis, intravascular haemolysis & trauma • Chronic- Malignancy (mucin producing adenocarcinomas) Trauma (Head) Management Features Complication • Treat underlying cause & supportive care Thrombosis Organ injury • Consider transfusion of blood product (not routine) Bleeding Purpura • Fibrinogen<1 = CCP Fulminans • PT & APPT remain elevated = FFP reduce bleeding not to normalise tests • Purpura fulminans = protein C administration Case 6 Question A 27-year-old gentleman presents to his GP with fatigue, abdominal pain and a rash over his trunk. O/E the rash appear to be petechiae. He states he was in hospital recently with an IBD flare-up and had received prophylactic dalteparin 14 days ago. He is otherwise afebrile and has no other symptoms. His FBC was sent a week earlier, the GP had found some abnormalities. Following haemotology advice a coag, d-dimer, fibrinogen and blood film have also been sent. What is the most likely cause of his abnormal haem results? A. Haemolytic Uraemic Syndrome Value Range Hb 111 130-180 B. Disseminated Intravascular Coagulopathy WCC 7.0 4-11 Platelets 41 150-400 C. Thrombotic Thrombocytopaenic purpura INR 1.2 1.1-1.3 aPTT 23 21-35s D. Heparin Induced Thrombocytopaenia Fibrinogen 3 2-4 E. Don’t know D-Dimer 300 <250 Blood film Schistocytes Case 6 Answer What is the most likely cause of his abnormalhaem results? A. Haemolytic Uraemic Syndrome B. Disseminated Intravascular Coagulopathy C. Thrombotic Thrombocytopaenic purpura D. Heparin Induced Thrombocytopaenia E. Don’t know TMA like DIC but does not consume TTP coagulation factors and rarely Thrombocytopaenia involves kidneys in regard to end Normal INR & aPPT organ damage. High or normal D-Dimer & Normal Fibrinogen Blood film = RBC Fragments (Schistocytes) Case 6 Question Features Investigations • TTP (medical emergency) is caused by deficiency of the ADAMTS13 protease, which results in MAHA FBC accumulation of very long "ultra-large" von Thrombocytopaenia Coagulation Willebrand factor multimers on the endothelial Bleeding ADAMST13 surface that are capable of binding platelets. Neuro Haemolysis labs • This leads to the formation of platelet rich Gastro Blood film microthrombi that can lead to thrombocytopaenia, Renal (rare) MAHA (Schistocytes) PLASMIC (acquired) • Can be acquired (more dramatic) (ADAMST13 Platelets<30 Management autoantibody) or hereditary (ADAMST13 gene L Haemolysis mutation) 1. Plasma exchange Active cancer (Tx <12/122. Gluccocorticoids • Testing ADAMST13 activity if <10% = severe TTP and Solid organ or stem cell 3. Rituximab supports diagnosis. For pre-test probability use transplant PLASMIC scoring. MCV<90 INR<1.5 Creatinine<177 Case 7 Question A 9-year-old child presents non-specifically unwell to the emergency department. The mother stated she had seen some blood in her child’s urine. The urine was dipped and was positive for blood and protein. The mother further added her child had recovered recently from bout of bloody diarrhoea two days earlier but was otherwise normally fit and well. The bloods can be seen below. What is the most likely cause of the haem abnormalities? A. Haemolytic Uraemic Syndrome Value Range Hb 92 130-180 B. Disseminated Intravascular Coagulopathy WCC 7.0 4-11 Platelets 37 150-400 C. Thrombotic Thrombocytopaenic purpura INR 1.3 1.1-1.3 aPTT 28 21-35s D. Heparin Induced Thrombocytopaenia Fibrinogen 2.5 2-4 E. Don’t know D-Dimer 500 <250 Blood film Schistocytes Case 7 Answer What is the most likely cause of the abnormalhaem results? A. Haemolytic Uraemic Syndrome B. Disseminated Intravascular Coagulopathy C. Thrombotic Thrombocytopaenic purpura D. Heparin Induced Thrombocytopaenia E. Don’t know STEC HUS HUS commonly due to STEC (Shigella Thrombocytopaenia Toxin producing E.Coli). More common Normal INR & aPPT in younger childer <10years old but can High or normal D-Dimer & Normal Fibrinogen affect adults. There are causes of HUS Blood film = RBC Fragments (Schistocytes) other than E.Coli but less common Renal involvement (including non-infective). Recent bloody diarrhoea? Case 7 HUS • Complement-mediated HUS is thought to be caused by complement-induced damage to the endothelium. • Non-bloody to blood diarrhoea and apyrexial during the early stage STEC. • Shiga toxin producing E. Coli – shiga toxin 1 and/or 2 – 2>1. UpToDate • Triad non-immune haemolytic anaemia, thrombocytopaenia and kidney injury. • 1/5 of kids<10 with high risk STEC develop HUS, happens in adults but rarer or misdiagnosed • 5-10 days post onset of diarrhoea • Typical (STEC/Shigella) Vs Atypical HUS. • Supportive care- tranfusse blood if needed, fluid replacement, organ support, control BP, CNS involvement ?eculizumab . Extra HIT • Platelet factor 4 and heparin form a complex., viewed as foreign and IgG (HIT) antibodies are produced. Features • Antibody binding activates the platelets- causing thrombus Thrombosis formation. Thrombocytopaenia • Rapid drop in platelets due excessive clot formation. • Usually 5-10 days after exposure Bleeding (uncommon) Organ damage • Thrombosis due to platelet activation and bleeding related to the anticoagulant given. • No global coagulation abnormalities like DIC other than those Diagnosis related to the given anticoagulant or because of VTE (raised D- Platelets<150 or >50% Dimer) decrease • HIT type I (HIT I) is a mild, transient drop in platelet count that Thrombosis (V or A) typically occurs within the first two days of heparin exposure, not clinically significant. Injection site necrosis Antibody test (E.g. ELISA) • HIT type II (HIT II) is a clinically significant syndrome due to antibodies to platelet factor 4 (PF4) complexed to heparin, referred Constitutional symptoms to as "HIT antibodies" or "PF4/heparin antibodies" Feedback & Socials Feedback Follow our Instagram page for MCQs!