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Bleeding disorders

Dairion Gatot, Soegiarto Gani, Savita Handayani Div Hematology-Medical Oncology, Dept of Internal Medicine School of Medicine, Sumatera Utara Unversity 2009

HEMOSTASIS, (Virchow’s Triad) Kerjasama 3 komponen : pembuluh darah, aliran darah dan darah

Function of HEMOSTASIS
• ARREST BLEEDING • MAINTAIN BLOOD IN FLUID STATE

HOMEOSTATIC HEMOSTASIS adalah mekanisma fisiologis yang mempertahankan darah dalam bentuk cairan di dalam sirkulasi, yang menggambarkan suatu kesetimbangan yang baik antara perdarahan dan pembekuan

Hemostatic Balance

PAI-1 Antiplasmin Tissue factor* Clotting Factors

Prot. S

Prot. C TFPI
Fibrinolytic System

ATIII

Procoagulant

Anticoagulant

HEMOSTASIS • Primary 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 .

Hemostasis BV Injury Tissue Factor Lab Tests •CBC-Plt •BT.(CT) •PT •PTT Neural Platelet Adhesion and Activation Blood Vessel Constriction Platelet Aggregation Primary hemostatic plug Coagulation Cascade Reduced Blood flow Fibrin formation Plt Study Stable Hemostatic Plug Morphology Function Antibody .

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The primary haemostatic system: haemostasis and platelet plug formation Primary haemostasis Platelet aggregation trombosit endothelial cells sub endothelial tissue Activation Aggregation White clot Adhesion Vascular injury Formation of platelet plug exposed sub endothelial tissue .

fibrin Coagulation cascade leads to clot formation Clot growth Fibrin threads . in turn.The haemostatic system: secondary haemostasis and clot formation Prothrombin Factor Xa Intrinsic pathway Extrinsic pathway Fibrinogen Fibrin Thrombin Activation of the coagulation cascade leads to generation of thrombin and.

The haemostatic system: Tertiary haemostasis and clot formation .

Coagulation balance: endogenous activators : the core role of factor Xa Intrinsic system XII XIIa XI IX XIa IXa VIIIa Ca2+ PL Xa X Cellular thromboplastin VIIa Ca2+ VII Extrinsic system II Xa Va Ca2+ PL Fibrinogen Thrombin IIa Soluble fibrin XIIIa Fibrin (clot) Boneu B. et al. 10:291–313. Sang Thrombose Vaisseaux 1998. .

making it an anticoagulant which then activates anticoagulant protein C. Protein C cleave factors Va and VIIIa .Coagulation cascade Hemophilia A (classic)is due to reduced amount or reduced activity of Factor VIII Hemophilia B (Christmas Disease) results from deficiency of factor IX Heparin is a cofactor that allows antithrombin III to inactivate thrombin and Factor Xa Thrombomodulin binds to thrombin.

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Clinical Manifestation of Hemostatic defect • • • • • • • • • • Ptechia Purpura Echymosis Haematoma Haematemesis Melena Haemathrosis Haematophysis Hematuria Epistaxis .

trachea.• Petechia : a minute. the color gradually changing to brown green and yellow • Hematemesis : the vomiting blood • Hemoptysis : the spitting of blood from larynx . rounded spot of haemorrhage on a surface. It is marked by purple discoloration of the skin. such as skin. mucous membrane. bronchi or lung .pharynx. serious membrane • Purpura : a condition in which haemorrhage occur in the skin • Ecchymosis: extravasasion of blood into the subcutaneous tissue.

• Hematoma : a focalized extravasation of blood which soon clot to form a solid mass and readily became encapsulated by connective tissue • Melena : the discharge of stool colored black by altered blood • Hemathrosis : extravasation of blood into a joint • Hematuria : the discharge of urine containing blood • Epistaxis : bleeding from nose • Hematoschezia : the discharge of stool colored red or brown .

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

VASCULAR .

Vascular • • • • Purpura. vasculitis . echymosis Connective tissue Ehler-Danlos Syndrome Aging process senile purpura (Bateman’s disease) Infectious Meningococcus Rocky Mountain’s syndrome typhoid fever Roseola spot • Vit C deficiency scurvy • Immunologic Henoch-Schonlein purpura • ↑ fragility capillary infectious.

Senile Purpura .

Petechiae in Vasculitis (Rocky Mountain Spotted Fever) .

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

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

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Vascular • Non palpable purpura senile purpura scurvy use corticosteroid • Palpable purpura Henoch-Schonlein syndrome .

THE ROLE OF PLATELET IN HEMOSTASIS .

THE ROLE OF PLATELET IN HEMOSTASIS .

.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.

aplastic anemia .acute leukemia .Platelet dysfunction • Quantitatif : .hypersplenism .thrombocytemia .ITP .DHF .

Platelet Disorders . Ecchymosis. Purpura.Features: • • • • • Mucocutaneous bleeding Petechiae. Spontaneous bleeding after trauma CNS bleeding (severe. ↓ plt) Prolonged bleeding time (BT) .

..Dengue Hemorrhagic fever Platelet deficiency.

angiomas) Not palpable (cf.Petechiae (typical of platelet disorders) Do not blanch with pressure (cf. vasculitis) .

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

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

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Ecchymoses (typical of coagulation factor disorders) .

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

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

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 .

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

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

dysfunctional platelets and/or thrombocytopenia (↑ BT) Secondary .decrease in all coagulation factors except vWF (↑ PT. IX. VII. X .Combined Primary and Secondary Hemostatic Disorders Severe Liver Disease: Primary . aPTT) Vitamin K will promote synthesis of factors II.

platelet consumption (↑ bleeding time. major trauma Primary . infection (sepsis).Combined Primary and Secondary Hemostatic Disorders (DIC) Disseminated Intravascular Coagulation: Major pathologic processes obstetric complications. aPTT) . ↓ platelets) Secondary . neoplasms.factor consumption (↑ PT.

muscles) Site of bleeding Petechiae Ecchymoses (“bruises”) Hemarthrosis / muscle bleeding Bleeding after cuts & scratches Bleeding after surgery or trauma No Large. GI tract) Yes Small. vaginal. gum.Clinical Features of Bleeding Disorders Platelet disorders Skin Mucous membranes (epistaxis. usually mild Coagulation factor disorders Deep in soft tissues (joints. often severe . deep Common No Delayed (1-2 days). superficial Extremely rare Yes Immediate.

Joint bl.Platelet Coagulation Petechiae. Purpura Hematoma. .

Summary Symptom Petechiae Sites Time Ecchymoses /Hematomas Platelet Yes Skin & Mucosa Immediate Yes Coagulation No Deep Tissue Delayed Yes .