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Topics Covered •Anaemias: 3 Types •Bleeding disorders •LeukaemiaHaematopoietic Stem Cells Anaemia Definition • A reduction in haem and/or globin. Normal Hb variant Structure Percentage % HbA A2B2 90 HbA2 A2D2 <2 HbF A2G2 <2-5 Anaemia Microcytic <80 fL Normocytic (80-95fL) Macrocytic >95fL Iron deficiency Hereditary spherocytosis B12 Anaemia of CD G6DP Folate Thalassemia Autoimmune Alcohol Sideroblastic Non haemolytic Thyroid Liver General Principles Investigations: Symptoms Signs Hx= Ask about any bleeding from anywhere ?bowel symptoms SOB Tachypnoea ? Rash ?Chronic conditions Chest pain Tachycardia Bloods: FBC, Blood films, Haematinics, TFT, BM Palpitation Pallor biopsy Imaging: Dizziness Hypotension Endoscopy CT SBA: complaining of dyspnoea, and feelingc A)Blood film noticed his bowels are looser thano normal. B)Ferritin Below are his blood results. C)OGD Hb- 70 MCV - 70 D)Serum Iron likely investigation you would do to E) CXR find the underlying cause ? SBA: complaining of dyspnoea, and feelingc A)Blood film noticed his bowels are looser thano normal. B)Ferritin Below are his blood results. C)OGD Hb- 70 MCV - 70 D)Serum Iron likely investigation you would do to E) CXR find the underlying cause ? Iron Deficiency Reduced intake, consumption or increased loss. absorbed inn duodenum. • Reduced intake- Malabsorption,coeliac • Increased consumption-Pregnancy • Increased loss- Menstruation,Colon caner, Bound to PUD transferrin. • IDA IN THE ELEDERLY = COLON CANCER. Stored bound to ferritin.Symptoms • Pica • Glossitis • Angular stomatitis Management Investigation: Treatment: • FBC: Microcytic anaemia <80fL Conservative: Increase dietary iron + address • Blood film: Hypochromic red cells, target the underlying cause cell. • Iron studies Iron replacement:PO/IV Ferrous Fumarate- Monitor Hb 2-4 weeks and • Ferritin: Low then 2-4 months • Transferrin Sat: Low • TIBC: high Blood: Consider: <70 g/L • Endoscopy (>= 60yr old with IDA) <80 g/L- Longstanding cardiac pathology • Coeliac serologyTarget cells Alpha vs β-thalassemia • Alpha= Asian + African- 4 alleles on CH16 responsible for Alpha globin- Gene deletion • Beta= Asians, Middle eastern and Mediterranean-Point mutation Features: • Neonatal Jaundice • Hepatosplenomegaly • Chipmunk facies • Failure to thrive SBA: What is the A. destruction B. Malignant invasion mechanism behind frontal C. Secondary Haematoma bossing? D. Extramedullary haematopoiesis E. Intrauterine growth retardation SBA: What is the A. destruction B. Malignant invasion mechanism behind frontal C. Secondary Haematoma bossing? D. Extramedullary haematopoiesis E. Intrauterine growth retardation Electrophoresis Deletions HBA HBA2 HBF Carrier 1 Normal Normal Normal Asymptomatic Trait 2 Mild HBH 3 Marked symptoms HB Barts 4 Absent Absent Absent Hydrops fetalis Genetics HBA HBA2 HBF Trait β/β + Normal Normal Normal No/Mild symptoms Major β 0 /β 0 Marked anaemia Gene mutations • Reduced production (β+) • Absent production (β0 ) Management Treatment Investigation: • Regular Blood transfusions • FBC: Microcytic anaemia <80fL • Blood film: Hypochromic red • Iron chelation- Deferoxamine bodies target cells, Howell Jolly • Folate supplement: Haemolysis • Splenectomy • Hb Electrophoresis. • Stem cell transplant- Curative SBA: A 17 year old finish A)Globin boy has had recurrent B)Spectrin gall stones. A C)Band 2 diagnosis of D)Protein 2.2 spherocytosis was made. E)Satellite What protein is associated with this disease? SBA: A 17 year old finish boy has had recurrent gall Hereditarydiagnosis of A.Globin spherocytosis was B.Spectrin made. What protein is C.Band 2 associated with this D.Protein 2.2 disease? E.Satellite Macrocytic: Haemolytic vs Non-Haemolytic Hereditary spherocytosis: Abnormal membrane proteins. Abnormal membrane Northern Europe and North America proteins Spectrin Ankyrin Band 3 Spherocytes Protein 4.2 High yield associations • Jaundice • Gall stones Extravascular haemolysis • Splenomegaly (Splenomegaly) Management Investigation: Treatment • FBC: Normocytic anaemia, ➢ Phototherapy or exchange: Neonatal Increased reticulocytes jaundice • Blood film: Spherocytes ➢ Blood transfusion • LFT- Raised bilirubin ➢ Folate replacement ➢ Splenectomy: >6yrs old • LDH- Raised Consider: EMA binding Osmotic FragilitySpherocytes SBA: A. Sickle cell anaemia A 22 year old male has been B. B12 deficiency treated for salmonella with C. Iron deficiency anaemia he starts to complain of severe lethargy, jaundice and slight D. G6DP deficiency shortness of breath. A blood E. Steven-Johnson bite cells.ne which reveals Syndrome patient have?n does the SBA: A 22 year old male has been A. Sickle cell anaemia treated for salmonella with he starts to complain of severe B. B12 deficiency lethargy, jaundice and slight C. Iron deficiency anaemia shortness of breath. A blood bite cells.ne which reveals D. G6DP deficiency E. Steven-Johnson Syndrome patient have?n does theGlucose-6-phosphate Dehydrogenase Deficiency • X-linked recessive • Decreased G6DP > Decreased glutathione > Damage from oxidative species > RBC membrane damage > Intravascular haemolysis. • Antimalarials • Ciprofloxacin • Sulpha drugs e.g. sulfonylureas • Infection • Fava beans Fun Fact: 50-70% Kurdish Jews. Management Investigation: Treatment • FBC: Normocytic anaemia, ➢ Phototherapy or exchange: Neonatal Increased reticulocytes jaundice • Blood film: Bite cells and ➢ Blood transfusion Heinz body. ➢ Folate replacement ➢ Splenectomy: >6yrs old- less common • LFT- Raised bilirubin • LDH- Raised • Haptoglobin- Reduced Consider: Enzyme assay Blood film Heinz body, precipitation of HB Biting out of the Heinz body in secondary to oxidative stress the spleen. SBA: A. Thalassemia A 2 year old baby has been B. Psoriasis brought into E.D by his mother C. TB mum believes he’s more tiredThe than usual in the last 5 hours D. Sickle cell disease and looking more yellow. On E. Bacterial infection fingers look like this.his His observationsare Hb: 100 HR: 130 O2: 92% What condition does this child have? SBA: A. Thalassemia A 2 year old baby has been B. Psoriasis brought into E.D by his mother C. TB mum believes he’s more tiredThe than usual in the last 5 hours D. Sickle cell disease and looking more yellow. On E. Bacterial infection fingers look like this.his His observationsare Hb: 100 HR: 130 O2: 92% What condition does this child have? Sickle Cell Anaemia • Sub-Saharan Africa- protective against falciparum malaria. • Beta chain has a mutation at point 6 from Glutamic acid---valine • Leads to sickling in low Pa02. Genetic HbA HbA2 HbF HBs Trait One gene 55% <2% <2% 40% Normal Disease Both genes Absent <2% 8% 90% AnaemiaInvestigation • Newborn heel prick test. • FBC: Normocytic anemia • Blood film: Sickle cells, Howell-Jolly bodies. • LFT- Raised bilirubin • Hb Electrophoresis SBA: A. Ciprofloxacin B. Phenoxymethylpenicillin What is the one C. Labetalol important long D. Gentamicin term medication E. Prednisolone that sickle cell patients should have? SBA: A. Ciprofloxacin B. Phenoxymethylpenicillin What is the one C. Labetalol important long D. Gentamicin term medication E. Prednisolone that sickle cell patients should have? Long-T erm Management • Avoid precipitants: e.g. infections, dehydration,hypoxia, cold • Pain management: regularly prescribed medicationsto manage chronic pain • Hydroxycarbamide: ↑ HbF; indicated for patientswith recurrent chest or pain crises • Folic acid supplementation: 5mg once weekly • Lifelong phenoxymethylpenicillin:patientsare at risk of infection from encapsulated bacteria due to hypo-splenism from auto splenectomy • Regular vaccinations: pneumococcal vaccine every 5 years and yearly influenza Sickle Cell Crisis Sickling Intravascular Extravascular Haemolysis haemolysis Sickle crisis Sickle Cell Crisis CRISIS Manifestation Aplastic B19- reduced reticulocytes Sequestration crisis Sickle cells get trapped in the spleen: Increased destruction Abdominal Plain Repetitive episodes = autosplenctomy Vaso occlusive Pain- depending on where- Fingers, bone, hips. Dactylitis= Crisis until proven otherwise Chest- Sob, chest pain, Pulmonary infiltrates on Xray. Haemolytic Breakdown of RBC- Increased reticulocytes.CrisisManagement INVESTIGATECAUSE: SUPPORTIVE:REHYDRATION, BLOODTRANSFUSION– EXCHANGETRANSFUSION- INFECTIONSCREEN,ABG, ANALGESIA, ABX, CHEST SEVERECASES LIFE THREATENINGE.G. GROUP & SAVE, CXR PHYSIO,OXYGEN ORGAN DAMAGE. SBA: A.Idiopathic Raynaud’s A 27 year old healthy male B.Scleroderma came into the hospital with a C.Antibiotic reaction cough and dyspnoea.ductive D.Cold Haemolytic anaemia has Mycoplasma pneumonia.Ahe E. Warm autoimmune few days later he noticed he's startingto get a triphasic Haemolytic anaemia colour change to his fingers. causing this?nderlying disease SBA: A.Idiopathic Raynaud’s A 27 year old healthy male B.Scleroderma came into the hospital with a C.Antibiotic reaction cough and dyspnoea.ductive D.Cold Haemolytic anaemia has Mycoplasma pneumonia.Ahe E. Warm autoimmune few days later he noticed he's startingto get a triphasic Haemolytic anaemia colour change to his fingers. causing this?nderlying disease Autoimmune Haemolytic Anaemia Idopathic Warm IgM binds M. Idopathic IgG Pneumoniae EBV SLE CLL Cold Drugs- Complement fixation Penicillin, Cephalosporin Extravascular haemolysis Extravascular (Splenomegaly) haemolysis/Intravasuclar Autoimmune Haemolytic Anaemia Bloods: Treatment: Do not really need to know. FBC: Normocytic Anaemia, • Treat underlying condition Raised Reticulocytes. • Avoid cold Blood Film: Spherocytes • Plasmapheresis • Blood transfusion LDH: Raised • Immunotherapy. Haptoglobin: Decreased Bilirubin: Increased. Special test: CoombsDecreasedProduction Myelopathicprocess- Malignancy over taking the bone marrow Aplastic anaemia- Bone marrowis empty Causes: Idiopathic, Drugs- chloramphenicol Virus- Parvovirusb19 Chronic renal failure- Reduced epo SBA: A.Prescribe ferrous complaining of lethargy and weird sulphate tingling sensations in her lower B.IM hydroxocobalamin gets dizzy more often. The GPels she decides to run some bloods and C.Folate 5mg they are given below. D.Dietary advice Hb 80 MCV 110 E. Blood Transfusion Folate 3.5 ( >4) B12:100 (180-1000) What is the initial management for this patient? SBA: A.Prescribe ferrous complaining of lethargy and weird sulphate tingling sensations in her lower B.IM hydroxocobalamin gets dizzy more often. The GPels she decides to run some bloods and C.Folate 5mg they are given below. D.Dietary advice Hb 80 MCV 110 E. Blood Transfusion Folate 3.5 ( >4) B12:100 (180-1000) What is the initial management for this patient? Methionine Cycle Homocysteine B12 Methionine Folate DNAMacrocyticAnemia • Megaloblastic= Impaired DNA synthesis, FOLATE, B12. • Non-Megaloblastic= DNA synthesis intact Alcohol, Hypothyroid, Liver disease • Most common cause: Pernicious anemia, Intrinsic factor and gastric parietal cells antibodies, leads to chronic gastritis and decreased absorption. Macrocytic Anaemia VitB12 bound to animal protein- Cause Pathology this binds R binder in saliva Reduced intake • Vegan diet, • Malabsorption Liberated in the stomach by Reduced absorption • Pernicious anaemia gastric acid • Crohn's • Drugs: Antiepileptic, metformin • Gastrectomy Duodenum- R binder detaches from B12 Via pancreatic enzyme • Fish tapeworm Increased requirement • Lactation • Pregnancy BiAbsorbed in the ileumr andInvestigation: Treatment : • FBC- Macrocytic anaemia • Diet- Milk, egg, meat, salmon, • Blood Film- megaloblast,Hyper cod. segmented nuclei. • IM Hydroxocobalamin • B12 • Loading regime-1g 3x for first 2 • Folate weeks. • Antibodies:IF antibodiesmore specific Not diet related: Life long IM Anti-parietal cells more sensitive every 2-3m Diet related: Oral life long for • Homocysteine-increased. vegans and others until corrected. Complications oNeurological: • Peripheral neuropathy • Subacute combined degeneration of SC cord. • Dementia oPancytopenia oGastric cancer oNT defects Folate Deficiency Polyglutamate form Cause Pathology in green vegetables Reduced intake • Malabsorption and animal proteins. Reduced absorption • Coeliac • Crohn's • Phenytoin- Conjugasei Converted to • Alcohol Monoglutamate • COCP- absorption form by conjugase Increased requirement • Lactation • Pregnancy Absorbed in jejunum Methotrexate and trimethoprim: inhibit dihydrofolate reductase Management Investigation: • FBC- Macrocytic anaemia • Blood Film- megaloblast, Hyper segmented nuclei. • B12 • Folic acid reduced Treatment: • Food: Chickpea, brown rice, • Homocysteine- Increased peas, Broccoli • Replacement:5mg for 4 months. • VB12 REPLACEMENT BEFORE FOLIC ACID IF DEFFICENT. Pregnancy and Haematology Pregnancy: •400mcg until week 12 •High risk women from conception to wk 12 (5mg) •High risk: Previous child with NTD, Fhx of NTD, anti- epileptic use, DM, Obese. Others Alcohol: Toxic to RBC progenitor Liver disease: Lipid synthesis impaired Hypothyroid: Interferes with EPOMalignancies Symptoms Component affected Symptoms RBC Anaemia- SOB, fatigue, pallor dizziness White cells Infection- Abnormal non functional Platelet High risk of bleeding Infiltration Gum Lymphadenopathy Hepatosplenomegaly. SBA: A. AML B. ALL Which of these is most commonly C. CML associated with D. CLL E. Lymphoma Gum Infiltration SBA: A. AML B. ALL Which of these is most commonly C. CML associated with D. CLL E. Lymphoma Gum InfiltrationAcute Myeloid Leukaemia: Neoplastic Proliferation of Myeloblast • Chemo, radiotherapy • Myelodysplasia • Advancing age9 Subtypes- M3 & M5 • Acute promyelocyticleukaemia • T(15;17) • Associated with DIC • Good prognosis Acute monocytic leukaemia • Accumulation of monoblastic • Gum infiltration Management Investigations • FBC: Leucocytosis, anaemia and thrombocytopenia • Blood film: Myeloblast with aue rods. • Bone marrow biopsy: >= 20% blast cells • Clotting screen- deranged DIC • Cytogenetic studies (15;17) Management • Induction- all-trans retinoic acid. • Consolidation. Myelodysplasia • Neoplastic proliferation of myeloblast with evidence of dysplasia • Blast cells <20% • Precursor lesion Acute Myeloid Leukaemia: Neoplastic Proliferation of Myeloblast Investigations: • Chemo, radiotherapy • FBC: Leucocytosis, anaemia and • Myelodysplasia thrombocytopenia • Advancing age. • Blood film: Myeloblast with aue rods. 9 Subtypes- M3 & M5 • Bone marrow biopsy: >= 20% • Acute promyelocytic leukaemia blast cells Myelodysplasia: • Clotting screen- deranged DIC • Neoplastic proliferation of • T(15;17) • Cytogenetic studies (15;17) • Associated with DIC myeloblast with evidence of • Good prognosis dysplasia • Blast cells <20% Management • Precursor lesion Acute monocytic leukaemia Induction- all-trans retinoic acid. • Accumulation of monoblastic Consolidation. • Gum infiltration Chronic myeloid leukaemia- NeoplasticProliferation of Granulocytes • BCR-ABL gene (95%) product: Constitutive activity Tyrosine kinase. Investigations: • FBC: Leucocytosis(granulocytes), anaemia and thrombocytopenia • Bcellsfilm: Increased granulocytes <10% blast • Bone marrow biopsy: Increased granulocytes Blast transformation- • Cytogenetic studies (9;22) CML turns to acute leukaemia- poor Management: prognosis Tyrosine kinase Inhibitor- Imatinib 2/3 AML 1/3 ALLOther Myeloproliferative Disorders: JAK2 V167F Myelofibrosis: • Neoplastic proliferation of Megakaryocytes- • Platelet derived growth factor • Fibrosis and extramedullary haematopoiesis Investigation: • FBC: Anaemia. • Blood film: Tear drop • Bone Marrowaspirate: Dry tap • BM biopsy: Fibrosis • Genetic: 60-65% Treatment : complex - chemo Polycythaemia Vera • Neoplastic proliferation of RBC- • Symptoms: Hyper viscosity • extremities,lushing, palmar erythema, Blurred vision, Burning of • Itching after bath (Release of histamine Investigation: • FBC: raised HB and haematocrit • EPO: Low • Genetic: 95% Treatment : • Weekly Venesection: Haematocrit <45% • Aspirin Essential Thrombocytosis • Neoplastic proliferation of Megakaryocytes- Investigation: • FBC: Thrombocytosis (>600,00) • BM biopsy: Increased megakaryocytes • Genetic: 50-60% Treatment : • Antiplatelet- Aspirin • Hydroxycarbamide Other Myeloproliferative disorder . JAK2 V167F Myelofibrosis: Polycythaemia Vera Essential • Neoplastic proliferation of • Neoplastic proliferation of RBC- Thrombocytosis Megakaryocytes- • Platelet derived growth factor • Symptoms: Hyper viscosity • Neoplastic proliferation of • Headaches, Flushing,palmar erythema, Megakaryocytes- • Fibrosis and extramedullary Blurred vision, Burning of extremities, haematopoiesis • Itching after bath (Release of histamine Investigation: Investigation: • FBC: Thrombocytosis (>600,00) Investigation: • FBC: Anaemia. • FBC: raised HB and hematocrit • BM biopsy: Increased • Blood film: Tear drop megakaryocytes • EPO: Low • Genetic: 50-60% • Bone Marrow aspirate: Dry tap • Genetic: 95% • BM biopsy: Fibrosis • Genetic: 60-65% Treatment : Treatment: • Weekly Venesection: Haematocrit <45% • Antiplatelet- Aspirin Treatment : complex - chemo • Aspirin • HydroxycarbamideALL: Neoplastic Proliferation of Lymphoblasts Lymphoblast • Most common malignancy in children! (t12;21) • Down syndrome 20x risk • 75% cases <6 • Bimodal distribution- childhood and adults Tcell Bcell • Extramedullary disease- Spleen, liver, lymph, testicles, CNS, parotid. Management Investigations • FBC: Lymphocytosis, anaemia, thrombocytopenia • BM: >= 20 % lymphoblasts • Cytogenetic studies: 12;21 • Immunophenotype- tells you which cell lineage it's from • Treatment: chemotherapy SBA: A. Age at diagnosis 6 B. Age at diagnosis 8 Which of these is associated with C. T (9;22) poor prognosis in D. T (15;17) E. WCC- 25 at diagnosis ALL? SBA: A. Age at diagnosis 6 B. Age at diagnosis 8 Which of these is associated with C. T (9;22) poor prognosis in D. T (15;17) E. WCC- 25 at diagnosis ALL? Poor Prognosis in ALL Poor prognosis T(9;22) WCC >30 at diagnosis Extramedullary disease CNS involvement: <1 and >10 years ALL: Neoplastic Proliferation of Lymphoblast • Most common malignancy in children! (t12;21) Lymph oblast • Down syndrome 20x risk • 75% cases <6 • Bimodal distribution- childhood and adults • Extramedullary disease- Spleen, liver, lymph, testicles, CNS, parotid. Tcell Bcell Poor prognosis T(9;22) Investigations: WCC >30 at diagnosis FBC: Lymphocytosis, anaemia, thrombocytopenia BM: >= 20 % lymphoblasts Extramedullary disease Cytogenetic studies: 12;21 CNS involvement: Immunophenotype- tells you which cell lineage its from <1 and >10 years Management- chemotherapy. Chronic Lymphocytic Leukemia • Neoplastic proliferation of mature B cell, • Commonest leukaemia in adults • Male and white ethnicity RF • Can undergo Richter transformation Richter T ransformation Neoplastic proliferation Lymphoma: Diffuse large B cell B symptoms:Fever, Night sweats,WL Accumulation in CLL: accumulation lymph nodes, small in blood lymphocytic Infections:Reduced IG lymphoma. Warmautoimmune haemolytic Anaemia Richter transformation Management • FBC: Lymphocytosis, anaemia, thrombocytopenia • Blood film: Increased lymphocytes and smudge cells • Bone marrow not necessary for diagnosis: Increased lymphocytes and few immature cells. • Immune phenotype: CD markers • IG: Hypogammaglobulinemia Treatment: Monitor Chemo (Late stage) CRAB: Myeloma • Neoplastic proliferation of one type of plasma cells • MGUS has a rate of transformation 1% per year • Afro-Caribbean IgG/A Neoplastic proliferation Light chains@Bitemedicine Management Bedside: Treatment: • Urine dip • Bisphosphonates: All patients to Bloods: • FBC: Pancytopenia protect against bone disease. • Chemotherapy • Blood Film : Rouleaux formation • Bone marrow biopsy: >=10% plasma cells. • Stem cell transplant <70 with good • Bone profile: Raised ALP & hypercalcemia. performance status • U&E: renal failure • Serum Electrophoresis: Paraprotein band (M-spike) • Urinary Electrophoresis: Bence jones proteins. Imaging: • WHOLE BODY MRI(Bone marrow infiltration)Electrophoresis MGUS • MGUS= Monoclonal gammopathy of undetermined significance • Plasma cell proliferation- <10% on bone marrow biopsy • Paraprotein- lower than myeloma any class • Asymptomatic. • Precursor to Myeloma. Bleeding Disorders Primary Haemostasis vsSecondary Haemostasis GP1B Symptoms-PH Early bleeding Epistaxis Petechiae post traumaPrimaryHaemostasias • Bedside: OBS • Bloods: • FBC: Anemia, Low plt • Bleeding time • Blood film: Assess number of plt. • Further • Imaging or endoscopy: localise bleeding point Qualitative vs Quantitative Defect Quantitative Qualitative • Bernard-Soulier • Idiopathic ThrombocytopaenicPurpura disease • Thrombotic Thrombocytopaenic Purpura • Haemolytic Uraemic Syndrome • Glanzmann disease • Heparin Induced Thrombocytopaenia • Medications ITP (Idiopathic/Immune thrombocytopenic purpura) • Type II hypersensitivityreaction: IgG directed against PLT antigens e.g. GpIIb/IIIa causing splenic consumption • Acute vs Chronic • infection- Self limitingn post immunisation/Viral • Most commoncause of thrombocytopeniain children • remitting course child bearing age, relapsing Management:Steroids, IVIG, Splenectomy. SBA: A 20 year old female has come to E.D, she seems confused and you notice she has pinpoint red marks all over her body. Below are her observations. Hb 100 ( 115-160) Sodium 136 (135-145 mmol/L) What is most likely underlying condition responsible for her Potassium 4.0 (3.5 - 5.0 manifestation. mmol/L) Urea 17 (2.0-7 mmol/L) A. Haemolytic anaemia Creatinine 70 (55-120 umol/L) B. ALL C. Hemolytic Uremic Syndrome D. Thrombotic Thrombocytopenic Purpura E. Immune thrombocytopenic purpura SBA: A 20 year old female has come to E.D, she seems confused and you notice she has pinpoint red marks all over her body. Below are her observations. Hb 100 ( 115-160) Sodium 136 (135-145 mmol/L) What is most likely underlying condition responsible for her Potassium 4.0 (3.5 - 5.0 manifestation. mmol/L) Urea 17 (2.0-7 mmol/L) A. Haemolytic anaemia Creatinine 70 (55-120 umol/L) B. ALL C. Hemolytic Uremic Syndrome D. Thrombotic Thrombocytopenic Purpura E. Immune thrombocytopenic purpuraThrombotic Thrombocytopenic Purpura (TTP) • ADAMTS13: Gets rid of VWF- Usually acquired • More VWF more clots (abnormal) and platelet degradation. • FEMALES!! •Macroangiopathic haemolytic anaemia.nal failure, CNS deficit, Management: Plasma exchange Steroids Immunosuppression Splenectomy.HUS(HemolyticUremic Syndrome) • Most commonly caused by Shiga toxin by ECOLI 0157:H7 (Undercooked red meat) • Causes endothelial damage and abnormal platelet activation and hence thrombocytopenia. • TRIAD: Macroangiopathic haemolytic anaemia, Thrombocytopenia, AKI Management • Supportive-Fluids, Analgesia. • Plasma Exchange • AVOID ABx HIT (Heparin Induced Thrombocytopenia) • Heparin binds platelet via PF4 • Ig binds this complex causing platelet destruction • This complex can also damage endothelial cells • Occurs 1-2 weeks post starting Diagnosis: HIT antibody screen Management: STOP HEPARIN.QualitativeDefects • Bernard-Soulier disease- Genetic deficeny Gp1B • Glanzmann disease- Genetic deficiency- Gp2b/3a • Medications-Antiplatelets • Aspirin- TXA2 inhibitor • Tirofiban- Gp2b/3ainhibitor • Clopidogrel- PreventsADP binding to P2Y12SecondaryHaemostasis • Bedside: OBS • Bloods: • FBC • Clotting screen • PT- Extrinsic Pathway • APTT- Intrinsic pathway • Further • Imaging or endoscopy: localize bleeding point Secondary Haemostasis Deep tissue bleeding • Haematomas Ecchymoses Late bleeding post • Hemarthrosis trauma • Retroperitoneal bleed 12a Intrinsic 11a Extrinsic pathway 7a .TF pathway 9a 10a 2 2a Fibrin SBA: What is the most A. Haemophilia common B. vWD bleeding C. TTP D. HUS disorder? E. ITP SBA: What is the most A. Haemophilia common B. vWD bleeding C. TTP D. HUS disorder? E. ITP Haemophilia A- factor 8 Deficiency Deep tissue Bloods: Raised X recessive bleeding APTT Management • F8 concentrate • Desmopressin Von Willebrand Disease Bloods • Raised APTT Autosomal • Increased bleeding time • Reduced F8 dominant • Ristocetin assay: failure Most Common of agglutination hereditary coagulopathy Management Stabilises F8- • Desmopressin reduces half-life • F8 concentrate • vWF concentrate Acquired Drugs: Heparin- Promotes activity of AntithrombinIII- X and II (Inc others) • UFH (IV)- APTT to monitor • LMWH- Longer acting Warfarin- Vit K epoxide reductase Inhibitor • 2,7,9,10,C,S – Measure activity PT DOAC- Apixaban- Xa inhibitor Dabigatran- 2a inhibitorThank you☺ QR CODE FOR FEEDBACKFORM