Bleeding Disorders Dr. Farjah H.AlGahtani Assistant Professor of Internal Medicin,Consultant Hematology Director of transfusin Medicin and Blood Bank Department,KSU

Stable Hemostatic Plug Hemostasis CBC-Plt BT,(CT) PT PTT BV Injury Neural Damage/contact. Contact Coagulation Cascade Blood Vessel Constriction Platelet Aggregation Primary hemostatic plug Reduced Blood flow Platelet Activation Fibrin formation Platelet study Antibody tests Factor Assay Stable Hemostatic Plug

HEMOSTASIS Primary Hemostasis Secondary Hemostasis Tertiary Hemostasis Blood vessel contraction Platelet Plug Formation Secondary Hemostasis Activation of Clotting Cascade Deposition & Stabilization of Fibrin Tertiary Hemostasis Dissolution of Fibrin Clot Dependent on Plasminogen Activation

Classification: Disorders of Blood vessels Disorders of Platelets Scurvy, senile purpura, Henoch-Schonlein syndrome. Disorders of Platelets Thrombocytopenia ITP, TTP, HUS, DIC. Aspirin therapy, Thrombasthenia, Disorders of Coagulation Extrinsic, intrinsic, combined. Other disorders Post transfusion purpura, MPS, MDS.

Tests of Hemostasis: Screening tests: Specific tests: Bleeding.T - 10m. Platelet & BV function Prothrombin.T – Extrinsic, aPTT – Instrinsic Thrombin.T – common path. (DIC) Specific tests: Factor assays – hemophilia. Tests of thrombosis – TT, FDP, DDA, Platelet function studies: Adhesion, Aggregation, Release tests. Bone Marrow study

Bleeding: Clinical Features Local - Vs - General, spontaneous . . Hematoma / Joint Bleeds- Coag Skin / Mucosal Bleeds – PLT wound / surgical bleeding – Immediate - PLT Delayed - Coagulation

Platelet Coagulation Petechiae, Purpura Hematoma, Joint bl.

Vascular disorders: Petechiae, purpura, ecchymoses senile purpura vitamin C deficiency (scurvy) Connective tissue disorders Infections – Meningococcus Henoch-Schonlein Purpura-Immu

Senile Purpura

(Rocky Mountain Spotted Fever) Petechiae in Vasculitis (Rocky Mountain Spotted Fever)

Henoch-Schonlein purpura Immune disorder Children Follows infection Petechiae with edema and itching.

Henoch-Schonlein purpura 20y Male, fever, painful symmetric polyarthritis for a day. During the next two days, edema and palpable purpura developed.

Platelet Disorders - Features: Mucocutaneous bleeding Petechiae, Purpura, Ecchymosis. spontaneous bleeding after trauma CNS bleeding (severe  plt) Prolonged bleeding time (BT)

BLEEDING TIME vs. PLATELET COUNT

Idiopathic Thrombocytopenic Purpura (ITP) Acute - children (post infection) Chronic - adults ( females, 20-40 yrs) autoimmune disorder antiplatelet antibodies (IgG) IgG coated platelets removed by spleen Usually  megakaryocytes in BM

Platelet dysfunction: Inherited Disorders: Bernard-Soulier disease large platelets, failure of adhesion Glanzmann’s thrombasthenia normal size, failure of aggregation Acquired Disorders: Drugs - Aspirin, Alcohol, Uremia,

Platelet Aggregation Curves

Von-Willebrand Disease: Coagulation + PLT disorder: Congenital disorder Deficiency of vWF molecule Part of FVIII, Mediates platelet adhesion Prolonged Bleeding time Low Factor VIII & long aPTT Mucocutaneous bleeding

Von-Willebrand Disease vWF: F-VIII & PLT function. Defective Platelet Adhesion Skin Bleeding Prolonged Bleeding time. Low Factor VIII levels.

Coagulation disorders: Deficiencies of Clotting factors Onset - delayed after trauma Deep bleeding Into joints - Hemarthroses Into deep tissues – Hematoma large skin bleed – Ecchymoses

Blood Coagulation & Tests

CT- Large hematoma of psoas muscle

Coagulation Disorders Laboratory findings: Normal bleeding time & Platelet count Prolonged prothrombin time (PT) deficiencies of II, V, VII, X Prolonged time (aPTT) all factors except VII, XIII Mixing studies - normal plasma corrects PT or aPTT

Factor VIII Deficiency Classic hemophilia (hemophilia A) X-linked disorder (affects 1º males) Most common - severe bleeding Spontaneous hematomas < 1, 5, 75% Abnormal aPTT – Intrinsic path. Diagnosis - factor VIII assay Treatment - factor VIII concentrate Cryoprecipitate (less desirable)

Factor IX Deficiency Christmas disease (Hemophilia B) X-linked recessive disorder Indistinguishable from classic hemophilia (F VIII) Requires evaluation of factor VIII and IX activity levels to diagnose Treatment - factor IX concentrate Cryoprecipitate if factor IX unavailable

Secondary Hemostatic Disorders Acquired coagulation disorder: Vitamin K deficiency - neonates - decreased intestinal flora and dietary intake - oral anticoagulants (coumadin) - fat malabsorption syndromes Required for factors II, VII, IX, X Prolonged PT and aPTT

Combined Primary and Secondary Hemostatic Disorders (DIC) Disseminated Intravascular Coagulation Major pathologic processes - obstetric complications, neoplasms, infection (sepsis), major trauma Primary - platelet consumption ( bleeding time,  platelets) Secondary - factor consumption ( PT, aPTT)

Combined Primary and Secondary Hemostatic Disorders 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

Summary Hemostatic Disorders BT Plt PT PTT Vascular Dis -  - - - PLT Disorder -  -  - - Factor 8/9 *Congenital - - -  Vit K / Liver *Acquired - -  - Combined (DIC)   - 

Summary

CLL-Thrombocytopenia Lymphoid cells Smear cells (Fragile)

Dengue Hemorrhagic fever Platelet deficiency..

Thrombocytopenia-TTP

Summary Complex system to keep blood fluid To block leakage on injury. BV, PLT & Coagulation Complex inhibitory mechanisms Complex thrombolysis mechanisms. Screening tests: BT, CT (PT, aPTT) Special tests: Factor assay, PLT function etc.

Disorders of Hemostasis Vascular disorders – Scurvy, easy bruising, Henoch-Schonlein purpura. Platelet disorders Quantitative - Thrombocytopenia Qualitative - Platelet function disorders – Glanzmans Coagulation disorders Congenital - Haemophilia (A, B), Von-Willebrands Acquired - Vitamin-K deficiency, Liver disease Mixed/Consumption: DIC