Platelet Hemostasis and Bleeding Disorder 2024 PDF

Dr Zariyantey Abdul Hamid DrZarAH 2 What is HEMO-STASIS? HEMO-Blood + Stasis-Not Flow Seal-up wound DrZarAH 3 Hemostasis : General Concept Cellular System Protein-Based System * Fakulti...

Dr Zariyantey Abdul Hamid DrZarAH 2 What is HEMO-STASIS? HEMO-Blood + Stasis-Not Flow Seal-up wound DrZarAH 3 Hemostasis : General Concept Cellular System Protein-Based System * Fakulti Activation of bath Platelet ~ Alam Bina Coagulation bata Factor Platelet Plug on Simen damaged vessel Fibrin Mesh (Unstable) Stable Blood Clot DrZarAH 4  Normal Vessel Injury Platelet Plug Fibrin Mesh + Platelet Plug ② ① Gto stabilize platelet ↳ Plug macam jaring (to Stable Blood hold platelet plug) DrZarAH Clot 5 NORMAL HEMOSTASIS 1. VASCULAR PHASE 2. PLATELET PHASE 3. COAGULATION PHASE 4. FIBRINOLYTIC PHASE DrZarAH 6  Vascular Phase Vascular Damage Expose circulating platelet to sub endothelium substances (collagen) Reduce Blood Loss Contact to Collagen activate Circulating Platelet Reduce Blood Flow Activated platelet produce Epinephrine Thromboxane A2 (vasocontrictor) & Adenosine Diphospahte (ADP) ① How ? Vasoconstriction DrZarAH Thromboxane A2 + epinephrine 7 = vasoconstriction  Platelet Phase Endothelium Expose circulating platelet to sub release Von Vascular Damage endothelium substances (collagen) Willebrand Factor (vWF) * Platelet Aggregation Activated platelet Contact to Collagen & Adenosine Diphospahte produce Thromboxane activate Circulating (ADP) & vWF Promote A2 (vasocontrictor) & Platelet platelet aggregation Adenosine Diphospahte (ADP) * Platelet Adherence Provide surface * Provide surface receptors / molecules attachment for for coagulation cascade coagulation factors * 3 Primary Platelet Function DrZarAH 8 What make platelet remain inactive in healthy vessel? DrZarAH 9  Coagulation Phase Key Points in blood injury at the injury Extrinsic, Intrinsic and Common Pathways (outside) Vessel wall tissue -- Extrinsic = Tissue Factor Pathway * Intrinsic = Contact Activation Pathway A cascade of activation process of clotting factors COMPLEX! Prothrombin thrombin fibrinogen fibrin fibrin mesh DrZarAH 10  COAGULATION CASCADE : Complex Pathways Damage to blood vessel Damage to Tissue outside blood vessel common pathway DrZarAH 11  Important Notes ❑ Coagulation factors are indicated by Roman numerals with a lowercase a to indicate an active form. ❑ The coagulation factors circulate as inactive zymogens. ❑. FVIIIa is the co-factor of FIXa, and together they form the "tenase’’ complex, which activates FX; and so the cycle continues. ("Tenase" is a contraction of "ten" and the suffix "-ase" used for enzymes.) DrZarAH 12  Coagulation Phase: Simplified Factor 10 needs cofactor 5 to activate factor 2 Intrinsic Pathway TWELVE In the presence of cofactor Q (TEN) Eleven NINE - cofactor 13 convert , fibrinoge, to fibrin 8 5 Protrombin 13 ~ clot 12 11 9 10 2 1 Fibrin Clot bringen Common pathway 7 ~ SEVEN Extrinsic Pathway (S) DrZarAH 13 Coagulation Phase DrZarAH 14  Fibrinolytic Phase ANTICLOTTING MECHANISMS ARE ACTIVATED TO ALLOW CLOT DISINTEGRATION AND REPAIR OF THE DAMAGED VESSEL.  t-PA : Tissue plasminogen activator DrZarAH 16 So…Factors Affecting Hemostasis Vessel Wall Integrity Adequate Numbers of Platelets Proper Functioning Platelets Adequate Levels of Clotting Factors Proper Function of Fibrinolytic Pathway DrZarAH 17  Wrap Up! Thromboxane A2 Extrinsic Pathway Plasmin Factor X ADP Factor XII Ca2+ Factor VII Tromboplastin Factor VIII Prothrombin Fibrinogen Factor XIII Factor V DrZarAH 18 FBC kira je, tab boleh bezakan ~ release granule to promote v platelet normal vasoconstriction , tak normal platelet aggregation Wf Dr Zariyantey Abdul Hamid  ABNORMAL BLEEDING CAUSE FACTORS: - that can leadtobringin Vascular disorder Acquired - ED4 - Ehlers & - simple bruising Danlosandrone serveimpressurpura Henoch-Schonlein Syndrome Steprascur Thrombocytopenia < Failure platelet production (common ) ITPXChronice Defective platelet i aute drug induced - function anza & Inherited I Bernard Soulier Dissase Storage pool dobersh Von Willebrund Defective coagulation AcquiredDatea Disease DrZarAH 20 Myeloproliferative Myeloplastic Disease  VASCULAR BLEEDING DISORDERS Easy bruising and spontaneous bleeding of small vessel – mainly in skin and mucous membrane: Petechiae, purpura, ecchymoses. small macan largerram yg lebam besar Can be inherited or acquired disorders Lgenetic factor I due to other Commonly due factors throughout to mutation life ) drug , infection, age factor) DrZarAH 21 DrZarAH 22 DrZarAH 23  VASCULAR BLEEDING DISORDERS a. INHERITED genetic factor (can't treat - manage only) , can bleeding condition due to vasodilation of Hereditary haemorrhagic telangiectasia vessel) macrovascular Esmall blood 1. Autosomal dominant genetic disorders darah terbentule dyn sempura salur x 2. Abnormal blood vessel formation (vascular dysplasia) that can lead to: treat laser ↓ i to swelling i. Dilated microvascular swellings (telangiectasia) to ii.Arteriovenous Malformation (AVM) – associated -lead more serious complication with morbidity and mortality of HHT patients (bigger blood vessel G develop recurrent bleeding 3. Develop in skin, mucous membrane and internal organ such asperiod for long lung and brain iron- lead to deficiency IDA sebab anamis o breeding 4. Complications : nosebleeds, GIT bleeding and other organ involvement: Long term haemorrhage can lead chronic iron deficiency anaemia. DrZarAH 24 Hereditary haemorrhagic telangiectasia 5. Etiology is not fully understood and still in active research. But it has been shown to be associated with the mutation of few HHT proteins that lead to malformation of blood vessels. 6. Symptoms of HHT: most common is nose bleed (epistaxis) and telangiectasia on the skin, lips, tongue and internal organ such as liver and GIT. Others are pulmonary and cerebral AVM that can be life-threatening. Rarely spine AVM. 7. Treatment : No treatment for HHT. But the symptom and complications can be managed through iron supplementation, blood transfusion and surgery / laser. DrZarAH 25  affect large- bloodresse , - Ccapil ary dah mac am clump Vascular anomaly = Abnormal connection between arteries and veins. interfere with O2 & CO2 exchange, nutrient supply and waste removal from surrounding cells. Symptoms are varies among different families due to variation in genetic mutation DrZarAH 26  VASCULAR BLEEDING DISORDERS Connective tissue disorders body X produce collagen ~ due to mutation thataffectgene collagen 1. Ehlers – Danlos Syndrome (EDS): A group of genetic disorders affecting connective tissue. 2. In vascular EDS, hereditary collagen abnormalities due to type II procollagen gene (COL3A1) mutations. blood vessel weak > blood - vessel blood vessel x elastic > - wall form X collagen > - blood vessel-encurysm bleeding[ rupture 3. Type III collagen is found in extensible connective tissues such as skin, lung, uterus, intestine and the vascular system. It provides strength and elasticity. DrZarAH 27 4. Common symptoms : purpura and superficial bruising, easy bruising/hematomas, thin skin, and joint hypermobility. 5. Life-threatening complications associated with arterial, intestinal and organ fragility – Aneurysms (anywhere) rupture of vessels. 6. Less common intestinal and uterine rupture, significant vaginal bleeding after intercourse and lung collapse DrZarAH 28  VASCULAR BLEEDING DISORDERS b. Acquired vascular defects Serang lebam simple bruising – benign disorder : no significant trauma has occurred to the skin or soft tissue to cause the bruise / no significant clinical consequence. elderly problem declined Senile purpura – atrophy of the supportive tissues of cutaneous blood vessels – mainly forearms and hands – causing vascular fragility Purpura due to infections – vascular damage due to immune complex formation; eg; dengue fever DrZarAH 29  VASCULAR BLEEDING DISORDERS Henoch – Schonlein syndrome hinok shonloin (pronounce) common in children with respiratory infection an IgA-mediated vasculitis: an inflammation triggered by immune complex deposition on blood vessel which is developed normally soon after infection manifested by puprpura , localized oedema , itching, painful joint swelling, haematuria. Scurvy – Vit C deficiency lead to reduced collagen synthesis leading to vascular fragility – petechiae, bruising and mucosal haemorrhage. Steroid purpura – due to longterm steroid therapy leading to vascular fragility DrZarAH 30  THROMBOCYTOPENIA ↓ platelet in blood 1. Abnormal bleeding due to thrombocytopenia and manifested by spontaneous skin purpura, mucosal haemorrhage and prolonged bleeding. rashes macam small stat (purple,a) 2. Cause bleeding symptoms: petechiea, - purpura, ecchymoses, haemorrhage, bruising, menorrhagia, mucosal bleeding, epistaxis - - menstrual rose bleed heavy bleeding DrZarAH 31  THROMBOCYTOPENIA Failure of platelet production ❑ common cause of thrombocytopenia Precursor of platelet ❑ Selective megakaryocytes depression due to drug toxicity, viral infection or bone marrow suppression ❑ Diagnosis : clinical history, CBC, blood film and BME. DrZarAH 32  THROMBOCYTOPENIA Increased destruction of platelets a. Autoimmune (idiopathic) thrombocytopenic purpura (ITP) i. Acute ITP ii. Chronic ITP DrZarAH 33  CHRONIC ITP Introduction ▪ Common cause of thrombocytopenia without anemia or neutropenia ▪ may associate with SLE, HIV, CLL, Hodgkin’s disease and autoimmune haemolytic anemia ▪ slow onset and can last for minimum 6 months and up to a year. Pathogenesis ▪ platelet sensitization with auto-antibodies ▪ Premature removal from circulation by macrophages ▪ reduced lifespan of platelet ▪ Increased platelet turn over and megakaryocytes mass DrZarAH 34  CHRONIC ITP Clinical features ▪ bleeding symptoms such as petechiea, haemorrhage, bruising, menorhagia, mucosal bleeding : normal platelet Diagnosis 150 400X109/2 ▪ platelet count 10-50 x 109 / l (very low) - ▪ BM – increased or normal numbers of megakaryocytes Treatment ▪ To maintain platelet count by giving steroid (immunosuppression), medications for infections / slower down immune activity ▪ Platelet transfusion will not be effective. DrZarAH 35  ACUTE ITP mostly affecting children Due to non-specific immune complex attachment – after vaccination / chicken pox sudden onset and short term manifestation (less than 6 months) DrZarAH 36  Thrombocytopenia..cont.. b. Post-transfusion purpura if patient receive blood/platelet transfusion -. Thrombocytopenia after about 10 days blood transfusion Due to developed antibody in recipient against the human platelet antigen – 1a (HPA-1a) on transfused platelet c. Drug-induced immune thrombocytopenia drug-dependent antibodies against platelet in serum of some patients works WF always d. Thrombotic thrombocytopenic purpura as protease active ~ Due to caspase deficiency (ADAMTS-13) – no breakdown of vWF – stimulate platelet aggregation – causing formation of microthrombi – can lead to the presentation of schistiocyte on blood smear platest thrombus) -promote unecessary aggregation > - UWF + ATP >platelet aggregation - ↓ platael DrZarAH level 37  Thrombocytopenia..cont.. e. DIC increased rate of platelet consumption in DIC elevated level of D-dimer – unique to DIC. I thrombus formation - - D-dimer , f. Massive transfusion syndrome DILUTED PLASMA with transfused stored blood containing low quality of platelet * difference between all diff types of DrZarAH 38 thrombscytopenre DISORDER OF PLATELET FUNCTION PROLONGED BLEEDING TIME WITH NORMAL PLATELET COUNT! Hereditary a. Glanzmann Thrombasthenia b. Failure platelet aggregation due to deficiency of membrane glycoproteins IIb and IIIa (receptor for fibrinogen) c. Treatment : platelet transfusion DrZarAH 39 DISORDER OF PLATELET FUNCTION b. Bernard –Soulier syndrome larger platelets deficiency in glycoprotein Ib (receptor for vWF) Defective binding to vWF, vascular and defect platelet adhesion and aggregation Treatment : platelet transfusion c. Storage pool diseases Larger platelets Deficiency of dense granules (ADP) Treatment : platelet transfusion DrZarAH 40 DISORDER OF PLATELET FUNCTION > - promote platelet d. Won Willebrand Disease UWF aggregation functionCarrier for vWF deficiency factor f defect in platelet adhesion and aggregation No activation of factor VIII – thus no factor X activation – fail coagulation Treatment : First line is by administration of Desmopressin which can induce vWF and VIII production. In severe cases, platelet transfusion. DrZarAH 41 DISORDER OF PLATELET FUNCTION Acquired disorders a. Antiplatelet drug inhibitors of glycoprotein receptor sites Inhibition of platelet aggregation Eg: Aspirin b. Hyperglobulinaemia Interfered platelet adherence, release and aggregation c. Myeloproliferative and myelodysplastic disorders d. Uremia high urea in blood – coating platelet – inhibit platelet function DrZarAH 42  DIAGNOSIS OF PLATELET DISORDERS Platelet count FBC and blood film Bone marrow examination Platelets autoantibodies Platelet functionHow long does it take Bleeding time for blood to stop Ristocetin-induced platelet aggregation– to measure platelet aggregation Flowcytometry : Glycoprotein receptor study DrZarAH 43 Ristocetin-induced platelet aggregation Principle: antibiotic ristocetin causes von Willebrand factor to bind the platelet receptor glycoprotein Ib (GpIb) In VWD, BSS and GT: no agglutination of platelet will be observed. However, addition of normal plasma to patient sample can normalize the result of ristocetin – induced platelet aggregation tests only for the case of VWD. No normalization occurs for BSS and GT. DrZarAH 44 DrZarAH 45 DrZarAH 46