Coagulation Disorders. Dr. Muhammad Shamim Assistant Professor, BMU
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1 Coagulation Disorders Dr. Muhammad Shamim Assistant Professor, BMU 1
2 Introduction Local Vs. General Hematoma & Joint bleed Coagulation Skin/Mucosal Petechiae & Purpura PLT wound / surgical bleeding Immediate PLT Delayed Coagulation 2
3 Hemostasis Neural BV Injury Tissue Factor Lab Tests CBC-Plt BT,(CT) PT PTT Blood Vessel Constriction Reduced Blood flow Platelet Aggregation Primary hemostatic plug Platelet Activation Stable Hemostatic Plug Coagulation Cascade Fibrin formation Plt Study Morphology Function Antibody 3
4 Platelet Coagulation Petechiae, Purpura Hematoma, Joint bl. 4
5 Primary Hemostatic Disorders 5
6 Defect of platelet plug formation 1. platelets 2. small vessels or capillaries 3. plasma proteins required for adhesion to subendothelium 6
7 Petechiae 7
8 Vascular defect - fragility Petechiae, purpura, ecchymoses senile purpura vitamin C deficiency (scurvy) connective tissue disorders Infectious and hypersensitivity vasculitides - Rickettsial & meningococcal infections - Henoch-Schonlein purpura (immune) 8
9 Senile Purpura 9
10 Henoch-Schonlein purpura 10
11 Platelet disorders platelets (thrombocytopenia) petechiae spontaneous bleeding after trauma CNS bleeding (severe plt) Platelet dysfunction mucocutaneous bleeding Prolonged bleeding time (BT) 11
12 Bleeding time test Timer is started upon incision Bleeding time = time to complete cessation of free blood flow from incision 12
13 Thrombocytopenia - Causes Marrow injury/failure - aplastic anemia - drugs, infections - megaloblastic anemia Decreased survival - immune (ITP, drugs, infections) - nonimmune (DIC, TTP) Splenic sequestration 13
14 Idiopathic Thrombocytopenic Purpura Acute - children (post infection) Chronic - adults ( females, yrs) - autoimmune disorder - antiplatelet antibodies (IgG against platelet glycoproteins) - IgG coated platelets removed by spleen ( platelet survival) Usually megakaryocytes in BM 14
15 Thrombotic Thrombocytopenic Purpura (TTP) Endothelial injury and activation of intravascular thrombosis Microvascular occlusion by thrombi (fibrin surrounding platelet aggregates) Ischemic dysfunction of multiple organs Hemolytic uremic syndrome (HUS) - toxin released by E coli 0157:H7 15
16 Pentad features 1. Thrombocytopenia (fibrin surrounds plt aggretates thrombi) 2. Neurologic deficits (CNS ischemia) 3. Renal failure (renal ischemia) 4. Microangiopathic hemolytic anemia (vessel narrowing) 5. Fever 16
17 Platelet dysfunction Inherited - autosomal recessive Bernard-Soulier disease - large platelets - lack of glycoproteins (1b-IX complex) - failure of platelet adhesion Glanzmann s thrombasthenia - normal platelet morphology - lack of glycoproteins (IIb-IIIa complex) - defect of platelet aggregation 17
18 Acquired - common Aspirin and NSAID - cyclo-oxygenase inhibitors - lack of thromboxane A 2 and PGE - failure of platelet aggregation Systemic disorders - i.e. uremia 18
19 Plasma proteins defect (for adhesion to subendothelium) von Willebrand disease - quantitative or qualitative deficiency of vwf molecule - binds to exposed subendothelial collagen - mediates initial platelet adhesion 19
20 20
21 Exposure of blood to collagen membrane Left - vwf deficient; Right - addition of vwf 21
22 Secondary Hemostasis Consolidates initial platelet plug into stable clot Disorders deficiencies of plasma clotting factors Clinical bleeding from large vessels into joints (hemarthroses), muscles, deep soft tissues (hematomas, large ecchymoses) Onset delayed after trauma 22
23 CT scan showing large hematoma of right psoas muscle 23
24 Secondary Hemostastic Disorders 24
25 Laboratory findings Normal bleeding time, platelet count Prolonged prothrombin time (PT) deficiencies of II, V, VII, X Prolonged activated partial thromboplastin time (aptt) all factors except VII, XIII 25
26 Screening Tests of Blood Coagulation 26
27 Classic hemophilia (hemophilia A) Factor VIII Deficiency X-linked disorder (affects males) Most common hereditary disease with severe bleeding 30% new mutations (non-hereditary) Spontaneous hemorrhages 27
28 Clinical grading severe = <1% circulating factor VIII Moderate = 1-5% mild = 5-75% Abnormal aptt Diagnosis factor assays Treatment factor VIII concentrate - cryoprecipitate (less desirable) 28
29 Christmas disease (hemophilia B) X-linked recessive disorder Similar to classic hemophilia Requires evaluation of factor VIII and IX activity levels to diagnose Treatment factor IX concentrate cryoprecipitate if factor IX unavailable 29
30 Acquired coagulation disorder Vitamin K deficiency neonates decreased intestinal flora & dietary intake oral anticoagulants (coumadin) fat malabsorption syndromes Required for factors II, VII, IX, X Prolonged PT and aptt 30
31 Combined Primary & Secondary Hemostatic Disorders 31
32 von Willebrand s Disease Autosomal dominant (or recessive) Primary defect platelet adhesion prolonged bleeding time Secondary defect deficiency of factor VIII; normally stabilizes factor VIII in circulation prolonged aptt 32
33 Clinical often mild - excessive bleeding from wounds - spontaneous bleeding from mucosa Different types quantity or loss of selective multimers Diagnosis ristocetin induced plt aggregation or multimer analysis 33
34 Disseminated Intravascular Coagulation Primary platelet consumption ( bleeding time, platelets) Secondary factor consumption ( PT, aptt) Major causes obstetric complications Neoplasms infection (sepsis) major trauma 34
35 Multiple initiating factors Tissue factor Thromboplastic substances Activates extrinsic pathway Tissue injury, Hemolytic anemia Widespread endothelial injury platelet aggregation Activates intrinsic pathway Microvascular thrombosis plasmin Fibrinolysis Clotting factor consumption Fibrin split products Bleeding 35
36 Acute DIC bleeding - occur in major trauma - give fresh frozen plasma Chronic DIC thrombosis - occur in cancer - give heparin or anticoagulant Treat underlying disease 36
37 Severe Liver Disease Primary dysfunctional platelets and/or thrombocytopenia ( BT) Secondary decrease in all coagulation factors except vwf ( PT, aptt) Vitamin K will promote synthesis of factors II, VII, IX, X 37
38 Summary BT Plt PT PTT 1 o hemostasis o Factor VIII/IX deficiency o Vitamin K deficiency - - Combined - 38
39 Thank you! 39
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