Big Robbins BLEEDING DISORDERS (Page 662) To do i) ITP, ii) Hemophilia, iii)DIC Ca BEXTRUNSIC PATHWAY J (Sure contac) (Tanve damage) ay nn ab » ce ase tat, VLC vce. [COMMON PATHWAY x ” fe veer, Protheombin (i!) — Thrombin (la) oe ie ’ ys gure 13:5 @ Pathways of blood coaguation, Rrinclyc system and partcipaton of platelets in activation of the cascade and their role In ‘emostate plug formation. Hemorrhagic Disathesis: Diathesis = Susceptibility/ Predisposition Causes of Excessive Bleeding: i) Fragility of Blood Vessels ii) Plt Deficiency iii)Pathology of Coagulation “Defect in Extrinsic Pathway > 7 PT” “Defect in Intrinsic Pathway > 7’ APTT” “Defect in Both > Elevation of Both”i)PT Plasma Clotting after adding tissue thromboplastin + Calcium = PT Time Raised in: Dysfunction of factor V, Factor VII, Factor X, Prothrombin or Fibrinogen Normal : 10-14 Sec Raised in: Dysfunction of Factor V,VIII,IX,X,XI,XIl, prothrombin or fibrinogen Normal : 30-40 Sec iii)Bleeding Time Normal Plt Count = 150 — 350 x 10° plt/microlitre 1 Plt-> Systemic Inflammation Normal range(BT) is 3-8 minutes. A prolonged bleeding time may be due to following causes: i) Thrombocytopenia. ii) Disorders 6f platelet function. iii) von Willebrand’s disease. iv) Vascular abnormalities\(e.g. in Ehlers-Danlos syndrome). v) Severe deficiency of factor Vand XI iv)Clotting Time 3 Bleeding Time (BT) is the time interval between the skin puncture ‘and spontaneous, unassisted (i.e. without pressure) stoppage of bleeding, The BT test is an in vitro test of platelet function. © Clotting time (CT) is the time interval between the entry of blood into the glass capillary tube, or a syringe, and formation of fibrin threads. Normal Clotting Time = 2-10 minsDISORDERS: i)Thrombocytopenia ii)Defective Plt Function iii) Abnormalities in Clotting Factors i)THROMBOCYTOPENIA(¥, Pit Count) ‘* Pit 20,000-50,000 > Bleeding After Trauma * Pit <20,000 > Bleeding without trauma(Spontaneous) ‘* Common sites for hemorrhage: Skin, GIT, Genitourinary Tract Tete 169 cases TrombooropniAcute Immune Thrombocytopenic Purpura ‘Acute ITP seen mainly in children between 2-4 years. ‘Acute ITP: Autoimmune disease, sudden onset, shorter duration and usually resolves within 6 months. © Self-limited disease. © Children: 2-4 years and seen equally in both sexes. * Presents 1-3 weeks after viral (measles, rubella, EBV) infection. * Platelet destruction by antiplatelet autoantibodies. * Platelet count is decreased, sometimes even below 10,000/cu mm (10x 10°/L). Clinical Features Sudden onset. Petechiae, gum bleeding, epistaxis and mild fever. Usually resolve spontaneously within 6 months. Excellent prognosis. Chronic Immune Thrombocytopenic Purpura: Persistent thrombocytopenia for more than 6-12 months. Cause: Autoantibody Mediated Destruction of Pit Conditions: SLE) HIV, B cell. Neoplasm(CLL) > Diagnosis of Exclusion Pathogenesi: © AutoAb against Plt Membrane Glycoproteins IIb-IIla or Ib-IX * Phagocytes Express IgG Fc Receptors >Antiplt Ab recognized by Fc Receptors © Antiplt Ab are of IgG Class * Thrombocytopenia Improved by splenectomy(as Splenic Red Pulp rich in Plasma cells > AutoAb Production)@ ee 4 4 Ss Sihipesmesen et tocensmMorphology: Main Changes: i)Spleen : Size > Normal Sinusoids > Congestion Splenic Follicles > Enlarged, ProminentGerminal Centres ii)Marrow: 4 Megakaryocytes ‘* Secondary Changes: >Petechial skin, mucous membrane bleeds > Megathrombocytes Clinical Features: ‘* AdultWoman <40 Yrs * Pinpoint Hemorrhage(Petechiae) in dependent areas (where capillary pressure is) * Petechiae confluent > Ecchymoses(Bruise) * H/O Easy Bruising, Nose Bleeds, Gingival Bleeds ‘© First Manifestation : Melena, Hematuria, Menorrhagia © Splenomegaly and lymphadenopathy NOT present in Primary Disease Lab Findings: © YPlt count© Bone Marrow: Normal or “S megakaryocytes © Peripheral Blood : Large Plt © PT PTT Normal Complications: © Subarachnoid Hemorrhage * Intracerebral Hemorrhage Treatment: * Glucocorticoids * Splenectomy Hemorrhagic Diasthesis related to Abnormalities in Clotting Factors 1)Factor Vill-vWF Complex: © Factor VIll-vWF Complex Qualitative Defect> Hemophilia A © Factor VIll-vWF Complex Quantitative Defect > von Willebrand Disease Normal Physiology: i)Factor VIL *) Cofactor for factor IX © Factor IX converts Factor X > Factor Xa © Synthesized by Endothelial Cells ii)Von Willebrand Factor * vWF Made by Endothelial Cells & Megakarytocytes © Functions: a)Promote Platelet Adhesion to subendothelium b)Interacts with collagen, heparin,plt membrane glycoprotein etc in homeostasis> Adhesion of pit to subendothelium involves: Interaction b/w collagen, plt glycoprotein Ib-IX and vWF Factor VI hours) inds to WWE > ‘Stability of VIII, 1 Half Life(From 2.4 hrs > 12 2)Von Willebrand Diseas: MOST Common INHERITED BLEEDING disorder(Autosomal Dominant) >Clinical Features: * Spontaneous bleeding after dental extraction or epistaxis © Menorrhagia * Excessive wound bleeding Type 1 & 3 : Quantitative Defects (Ass. With 1} PTT as Factor VIII Stability) Type 2 :Qualitative Defects Treatment: a) Type 1 2 > Desmopressin( vWF Release), Recombinant vWF or Plasma Concentrates having factor VIII b)Type 3 is associated with severe bleeding so > Prophylactic Treatment(same as of Type 1,2) 3)Hemophilia A (Factor Vill Det ienc) MOS COMMON Inherited disorder associated with LIFE THREATENING bleeding >X Linked Recessive Severity of Disease < 1% of Normal Level Severe Disease 2-5% of Normal Level Moderate Disease 6-50% of Normal Level Mild Disease >Clinical Features:© Easy Bruising * Massive Post traumatic/Operation Hemorrhage © Hemarthroses(Bleeding in joint) © PETECHIAE ABSENT Lab Findings: © PTT © Normal PT Treatment: © Infusions of recomb factor VIII 3)Hemophilia B: (Christmas Disease] > Deficiency of factor IX > X linked recessive PTT , PT NormalDISSEMINATED INTRAVASCULAR COAGULATION : © Thrombohemorrhagic Disorder * Excessive Activation of Coagulation * Thrombi formation Signs: * Microthrombi > Hypoxia > Infarction * Depleted Coagulation Factors > Hemorrhage Pathophysiology: Matetee |) roaeea Proto sepia Please ot tee acer a. meer ee Aateton ot mn Mioangpatic — Vesedar ona ese “oct Proteolysis of 4 Scar aces (oom oof ‘samage Fst proaucs Innitton of tortie, ptt. | _ Bleeding _| ‘aggregation and ton polymerisation Fqure 14.27 Pathophyslony of esorinated rravascuarcoapuaton, Morphology: © Thrombi in Brain, Lungs, heart, Kidney, Spleen, Liver * Kidneys: Small thrombi > Microinfarcts or Bilateral renal cortical necrosis Clinical Features: Hemolytic Anemia Dyspnea Cyanosis Respiratory Failure eo 0 ea) Platelet agregation* Convulsions, coma © Oliguria,Renal Failure © Circulatory Failure * Shock Laboratory Findings in DIC Screening Assays * Coagulation abnormalities — APTT: Increased as a result of consumption andiifhibition of thelfunction of clotting factors. ~ Prothrombin time: Increased. — Thrombin time (TT): Increased because of decreased fibrinogen. ~ Fibrinogen: Decreased. * Bleeding time: Increased due to decréased platelet\count. * Platelet count: Decreased due to utilization of platelets\in microthrombi. * Peripheral smear: Microangiopathic hemolyti¢ anemia with schistocytes DiC laboratory findings + Increased: APTT, PT, BT, D-dimer + Decreased: Platelets, fibrinogen